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Bazhora Yu. I.,
Bulyk R. Ye.,
Chesnokova M. M.,
Shevelenkova A. V.,
Smetyuk O. O.,
Lomakina Yu. V.
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Medical
Biology
Vinnytsia
Nova Knyha
2018
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Recommended by the High Scientific Board of Odessa National Medical University,
as a textbook for 1st year students of medical and pharmaceutical faculties of higher educational
establishments of Ukraine (Report No 4 of November 21, 2018)
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Authors:
Bazhora Yu. I., Bulyk R. Ye., Chesnokova M. M., Shevelenkova A. V.,
Smetyuk O. O., Lomakina Yu. V.
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Reviewers:
Z. D.Vorobets, Head of the Department of Medical Biology, Parasitology and Genetics of the
Lvov National Medical University named after Daniil Galytskyi, Doctor of Biological Sciences,
Professor.
O. A.Slusarev, Head of the Department of Medical Biology, Microbiology, Virusology and
Immunology of the Donetsk National Medical University, Candidate of Medical Sciences,
Docent.
O. A. Raksha-Slusareva, Professor at the Department of Medical Biology, Microbiology,
Virusology and Immunology of the Donetsk National Medical University, Doctor of Biological
Sciences.
Медична біологія = Medical Biology : handbook / Bazhora Yu. I.,
Bulyk R.Ye., Chesnokova M. M. [et al].–Vinnytsia : Nova Knyha, 2018.
– 436 p. : il.
ISBN
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ISBN
The basic questions of general and medical biology are highlighted in this textbook.
The general laws of life, the study of the cell including fundamentals of the human
cytogenetics, the study of heredity and variability including the human genetics, laws of
phylogenetic development of organisms, fundamentals of general parasitology, biology of
the most meaningful human parasites, way of transmission, diagnosis and prophylaxis of
parasitogenic diseases are presented. The content of textbook is organized according to the
Program on Medical Biology for the first year students using English.
УДК
© Authors, 2018
© Nova Knyha, 2018
CONTENS
PREFACE...............................................................................................................................................................................
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Chapter 1. Introduction into
1.1. Introduction into the course of medical
the course of medical biology.
biology..........................................................................................
Levels of organization and
1.2. Levels of organization and fundamental
fundamental characteristics of
characteristics of living matter..................................
living matter. Chemical compo- 1.3. Chemical composition of the cell..........................
sition of the cell
Tasks & Questions........................................................................
Chapter 2. Classification of
living organisms. Non-cellular
and cellular organisms. Prokaryotic cell
2.1. Non-cellular infectious particles. Viruses,
viroids, prions...........................................................................
2.2. Cellular organisms. Prokaryotic cell.......................
Chapter 3. Morphology of the
eukaryotic cell
3.1. Structural components of eukaryotic cell.
Cell membrane.......................................................................
3.2. Cytoplasm. Cell organelles...........................................
3.3. Nucleus. Human karyotype.........................................
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Tasks & Questions........................................................................
Tasks & Questions........................................................................
4.1. Notion of cell metabolism. Assimilation and
dissimilation..............................................................................
4.2. Information flow. Molecular basis of
heredity. Nucleic acids.....................................................
4.3. Gene and its structure. Genetic code..................
4.4. Expression of genes. Protein biosynthesis.......
4.5. Regulation of gene expression in
prokaryotes and eukaryotes........................................
4.6. The human genome..........................................................
4.7. Energy flow in a cell...........................................................
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Chapter 4. Organization of
information and energy flow
in the cell. Molecular basis of
heredity
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Chapter 5. Reproduction on
the cellular and organismic
level
Tasks & Questions........................................................................
5.1. Mitotic cycle. Mitosis. Cell death..............................
5.2. Mitotic cycle regulation. Genetic basis
of tumour growth................................................................
5.3. Meiosis...........................................................................................
5.4. Organisms reproduction................................................
5.5. Gametogenesis. Fertilization.......................................
5.6. Cloning of organisms........................................................
Tasks & Questions........................................................................
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6.1. Ontogenesis. Embryonic period of
ontogenesis..............................................................................
6.2. Critical periods of embryogenesis.
Congenital defects..............................................................
6.3. Postnatal period of ontogenesis..............................
6.4. Aging and death...................................................................
6.5. Regeneration and transplantation.........................
6.6. Homeostasis. Biological rhythms.............................
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Chapter 6. Human ontogenesis. Prenatal and postnatal
periods of ontogenesis
Tasks & Questions........................................................................
7.1. Mono–and dihybrid cross. Mendel’s laws........
7.2. Multiple alleles. Blood groups.
Immunogenetics..................................................................
7.3. Allelic and non-allelic gene interactions
7.4. Chromosomal theory of heredity...........................
7.5. Inheritance of sex. Sex-linked
inheritance.................................................................................
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Chapter 7. Regularities of heredity in human
Tasks & Questions........................................................................
8.1. Phenotypic variation.........................................................
8.2. Genetic variation. Recombination and
mutations....................................................................................
Chapter 9. Methods of human
genetics
9.1. Peculiarities of human genetics.
Notion of hereditary disorders..................................
9.2. Pedigree analysis (genealogic method)
9.3. Twins method of genetics............................................
9.4. Cytogenetic methods. Chromosomal
disorders......................................................................................
9.5. Single gene disorders. Biochemical method
of medical genetics. DNA diagnosis.....................
9.6. Population statistic method........................................
9.7. Prophylaxis of hereditary disorders.
Medical genetic counselling.
Prenatal diagnosis................................................................
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Chapter 8. Variation, its forms
and manifestation
Chapter 10. General notions
of parasitology. Protists as human parasites
Tasks & Questions........................................................................
10.1. General notions of parasitology............................
10.2. General characteristic of protists.
Parasitic amoeboid protozoa...................................
10.3. Parasitic Ciliates...................................................................
10.4. Parasitic flagellates...........................................................
10.5. Apicomplexa parasites..................................................
Tasks & Questions........................................................................

11.1. General characteristics of flat worms.
Flukes (Trematodes)........................................................
11.2. Tapeworms (Cestodes) as human
parasites....................................................................................
11.3. General characteristics of Roundworms
(Nematodes). Roundworms –
geohelminthes....................................................................
11.4. Roundworms – biohelminthes..............................
11.5. Methods of laboratory diagnosis of
helminthoses........................................................................
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Chapter 11. Helminthes. Flat
worms and round worms as
human parasites
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Tasks & Questions........................................................................
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Chapter 12. Arthropodes as
12.1. General characteristics of Arthropods.............
poisonous animals, vectors and 12.2. Medical importance of Crustaceans and
Arachnida. Spiders and ticks.....................................
agents of human diseases
12.3. General characteristic of Insecta. Insects
as vectors and agents of human diseases....
Tasks & Questions........................................................................
13.1. Evolution theory................................................................
13.2. Phylogenesis of organ systems
in chordates...........................................................................
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Chapter 13. Evolution theory.
Phylogenesis of organ systems
in Vertebrates
Tasks & Questions........................................................................
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Chapter 14. Ecology. Bio14.1. Ecological factors. Ecosystems...............................
sphere as human environment. 14.2. Ecological systems. Biosphere................................
Poisonous organisms
14.3. Human ecology..................................................................
14.4. Poisonous organisms.....................................................
Tasks & Questions........................................................................
REFERENCES....................................................................................................................................................................
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KEY ANSWERS................................................................................................................................................................
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PREFACE
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Last decades of XX and beginning of XXI century are characterized by intensive development of molecular biology, introduction of molecular technologies into different branches
of medicine, pharmaceutics, agriculture and industry. Understanding of pathogenesis of
human disorders, modern approaches to diagnosis and mechanisms of treatment requires
basic knowledge of human biology.
Course of medical biology is the basis for successful mastering of future theoretical and
clinical disciplines. Studying biology provides clear understanding of complex processes
and activities of living being, including humans as an integral part of biosphere. Our present knowledge of biology has reached to such extend that it has become a multi-disciplinary branch of science involving participation of the fundamental knowledge of all the
basic sciences of medicine.
This textbook of medical biology is intended for the first year students of medical universities and includes information about main questions concerning the medical application of biology. It is composed according to the modern program of medical biology
and includes questions of cell biology; molecular and cellular basics of heredity, variation,
human genetics, medical parasitology (protozoology, helminthology, and archnoentomology), questions of comparative evolution of vertebrates and human ecology. The matter of
each chapter is designed to provide comprehensive and relevant information in a manner
easy to understand and recapitulate. The book includes figures and tables, each chapter is
accompanied with multiple choice questions for self-control. Language used is very simple
and within the easy comprehension of the students.
Suggestions for the further improvement of this textbook are solicited from the teachers and inquisitive students.
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Chapter 1.
Introduction into the course of medical
biology. Levels of organization and
fundamental characteristics of living matter. Chemical composition of the cell
1.1. Introduction into the course of medical biology
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Biology is the science of life and living organisms. The word biology comes from the
Greek word: bios – “life” and the suffix–logia–“study of”. It is the study of life and living organisms, including their structure, function, growth, evolution, distribution, and taxonomy.
Biology is a vast rapidly developing subject, composed of many branches and disciplines,
such as molecular biology, cytology, genetics, parasitology, ecology and many other subjects. In general, biology recognizes the cell as the basic unit of life, genes as the basic unit
of heredity, and evolution as the engine that moves the synthesis and creation of new
species.
Medical biology (Biomedicine) is a field of biology that has practical applications in
medicine, health care and laboratory diagnostics. It concerns a wide range of scientific and
technological approaches: from an in vitro diagnostics to the in vitro fertilization, from the
molecular mechanisms of a cystic fibrosis to the population dynamics of the HIV, from the
understanding molecular interactions to the study of the carcinogenesis, from a single-nucleotide polymorphism (SNP) to the gene therapy. It includes many biomedical disciplines
and areas that typically contain the “bio-” prefix such as:
`` Molecular biology, biochemistry, biophysics, biotechnology, cell biology, embryology.
`` Nanobiotechnology, biological engineering, laboratory medical biology.
`` Cytogenetics, Genetics, Gene therapy.
`` Bioinformatics, Biostatistics, Systems biology.
`` Microbiology, Virology, Parasitology.
`` Ecology.
`` Physiology.
`` Pathology and many others that generally concern life sciences as applied to medicine.
How Medical Biology Has Shaped Medicine?
Last decades of XX century are characterized by intensive development of molecular biology, introduction of molecular technologies into practical medicine, pharmaceutics, ag-
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Chapter 1. Introduction into the course of medical biology. Levels of organization and fundamental ...
Pharmacogenomics
mRNA
Peptide
Protein
Metabolism
genomics
transcriptomics
peptidomics
proteomics
metabolomics
Genetic medicine
Evidence-based medicine
H-NMR
spectroscopy
Methods for
evaluating organs
and systems
functions
Predictive
Medicine of the ХХІ century
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Harmonization
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DNA microarrays
2D-gel
electrophoresis
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RNA microarrays
MALDI-TOF
spectroscopy
Function
polysystem
monitoring
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Gene
Preventive
Personalized
Fig. 1.1. Genomics gives new tools for medicine development. MALDI-TOF – matrix assisted laser desorption/ionization; SELDI – surface-enhanced laser desorption/ionization; H-NMR – protein nuclear magnetic
resonance
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riculture and other. The achievements of molecular biology and nanotechnology give the
new conception of medicine, making it predictive, personalized and preventive (Fig. 1.1).
`` Basing on modern biochemistry and biophysics data, medicine gets new more deep
understanding of normal cellular processes and molecular mechanisms of human
diseases.
`` Achievements of medical genetics help to understand etiology of hereditary disorders, including the multifactorial ones. Multifactorial (complex) disorders develop
as a result of complex interaction of hereditary predisposition and unfavorable environmental factors. It is the most common group of disorders in human population.
Examples are arterial hypertension, bronchial asthma, diabetes mellitus and many
others. Early detection of hereditary predisposition permits to prevent manifestation of the disease, postpone its onset, choose adequate therapy, and improve the
life quality.
`` Practical medicine uses new methods of diagnosis based on studying of DNA and
RNA molecules. Molecular-genetic methods are used in medical genetics, infectious
disorders, oncology, forensic medicine.
1.2. Levels of organization and fundamental characteristics of living matter
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`` Modern biotechnology creates new medicines for treatment of many diseases. Human enzymes, hormones, and vaccines are produced by genetically modified bacteria, animals, and plants.
It is possible to choose individual treatment regimen, based on the peculiarities of genetically determined metabolism of a patient.
Modern biology also influences many aspects of science and everyday life.
For example, molecular genetics studies stimulate development of evolution theory. It
explains some evolutionary puzzles of anthropogenesis, demonstrates relationships between species and clarifies classification of living organisms.
Synthetic biology (combines biology and engineering) permits to create artificial
biological systems and redesign naturally existing ones. Modified bacteria can be
used in diagnostics of diseases, detection of chemical agents, cleaning up environmental pollutants and have many other applications. Genetically modified plants are
cultivated in many countris, giving an excellent crops and raw material for industry.
However, ecologists are afraid of unpredictable influence of such organisms on the
ecosystems.
Our knowledge of proper nutrition, healthy life style, prolongation of life span is based
on the achievements of medical biology.
Practical work of the first year students in the field of medical biology begins with study
of a chemical organization of a cell, its morphology and physiology, bases of genetics and
reproduction, peculiarities of a special interaction between organisms – parasitism, later it
continues into understanding of human ecology and biosphere with a glance on evolution.
1.2. Levels of organization and fundamental characteristics
of living matter
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Living organisms are the opened self-regulated, self-renewing and self-reproduced
systems composed of biological polymers – proteins and nucleic acids.
All living organisms share several common principle characteristics:
1. Sensitivity or response to stimuli – organisms respond to changes in their environment.
2. Reproduction – organisms produce offspring similar to themselves.
3. Growth and development – organisms grow in size and change.
4. Metabolism – organisms carry out different chemical reactions, exchange energy
and matter with outer environment (is an open system).
5. Homeostasis – organisms maintain a relatively constant internal environment.
6. Heredity and variation – organisms can transfer its characteristics to next generations and get new features.
Living organisms are characterized by combination of these properties. The only one
property is not enough to characterize an entity as alive.
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Chapter 1. Introduction into the course of medical biology. Levels of organization and fundamental ...
Levels of organization of life
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All living organisms follow a hierarchy of organization in which simpler structures combine to form the more complex structures of the next level. This hierarchy can be examined
on a scale from small to large.
The atom is the smallest and most fundamental unit of matter. It consists of a nucleus
surrounded by electrons. There is no difference between atoms of living organisms and
nonliving matter.
Atoms form molecules which are chemical structures consisting of at least two atoms
held together by one or more chemical bonds. Set of molecules in living and nonliving
entities is not the same. Dissimilarity became apparent starting from molecular level. Many
molecules that are biologically important are macromolecules, large molecules that are
typically formed by polymerization (a polymer is a large molecule that is made by combining smaller units called monomers, which are simpler than macromolecules). An example
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Biosphere
System of organs
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Organ
Ecosystem
Tissues
Cells
Fig. 1.2. Levels of organization of living matter
Population
Organism
Molecules
1.2. Levels of organization and fundamental characteristics of living matter
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of a macromolecule is deoxyribonucleic acid (DNA), which contains the instructions for the
structure and functioning of all living organisms. So, the first level of organization of life is
molecular-genetic level (Fig. 1.2).
1. Molecular-genetic level. Its elementary units are DNA, RNA and proteins. Elementary
phenomena at this level are DNA replication, protein biosynthesis (gene expression).
The processes at this level are studied by biochemistry, molecular biology, and molecular genetics. Mistakes at this level, like DNA mutations, cause single gene disorders.
2. Cellular level. Cell is the main structural and functional unit of life. A cell cycle and cell
metabolism are elementary phenomena of the level. All main characteristics of living
things are observed at this level. This level is studied by cytology and histology. Cellular pathology is underlying basis of any human disease manifestation. Failure of cell
cycle regulation causes tumor growth.
3. Organism level. Its elementary structure is an organism, having organ systems. Elementary phenomenon of this level is a complex of physiological processes that provides
organism functioning and its adaptation to environment. Human organism is studied
at this level by histology, anatomy, physiology, medical genetics and pathology. Any
disorder (started as aberrant gene expression and dysfunctions on the cellular level)
eventually manifests at the level of organism. Practical medicine deals with organism
of a patient.
4. Population and species level. Elementary unit of species is population. Important genetic characteristic of population is gene pool (set of genes in population). Elementary evolution processes (mutations, recombination, migration, waves of life, natural
selection and others) are elementary phenomena. Demographic characteristics of a
population reflect the problems of health state. The main laws of heredity manifest in
populations. This level is studied by population genetics, medical statistics, evolution
theory and ecology.
5. Ecosystem or biogeocenotic level. It is dynamic system of populations of different
species (elementary unit) interacting with each other and the inanimate environment. Biochemical cycling of matter and energy flow and interaction of populations of different species are elementary phenomena. Infectious and parasitic diseases are the result of such interactions (parasite and its host). Endemic disorders
are specific for certain ecosystems. Main problems of this level are studied by ecology; epidemiology and parasitology deals with medical aspects.
6. Biosphere. Its elementary structure is ecosystem. Global cycling of matter and energy
is elementary phenomenon. Modern problem that realizes at this level is increased
anthropogenic influence (destruction of natural ecosystems, eradication of species,
biosphere pollution). Biosphere is studied by ecology.
Levels of organization of life reflect one of the general principles of philosophy: increasing complexity creates new properties that exceed the sum of the parts used to form the
structure.
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Chapter 1. Introduction into the course of medical biology. Levels of organization and fundamental ...
1.3. Chemical composition of the cell
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Matter is composed of a limited number of chemical elements. All living organisms are
made of the same chemical substances that perform the same general tasks.
Chemical elements
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Chemical elements are substances that can not be broken down into any simpler
chemical substances or converted into other substances by chemical reaction. There are
92 naturally occurring elements, each differing from the other in the number of protons
and electrons in its atoms. Both living and inanimate matter is composed of same chemical
elements, about 25 of which are essential to life.
According to its content in an organism (i.e. human body), all elements are divided into
several groups:
`` “Organic” elements make up to 98 % of living matter as they form organic biomolecules and are the components of many inorganic substances. These are Oxygen
(O) – 65–75 %, carbon (C) – 15–18 %, hydrogen (H) – 8–10 % and nitrogen (N) – 1,5–
3 %.
`` Major elements (macroelements). These are phosphorus (P), sulfur (S), chlorine (Cl),
sodium (Na), potassium (K), calcium (Ca), magnesium (Mg) and iron (Fe). Major elements total make up about 1,9 % of living organism.
`` Minor elements or trace elements (about 0,1 % in sum): iodine (I), manganese (Mn),
zinc (Zn), copper (Cu), fluorine (F) and other. Concentration of each of them is less
than 0,001 %, but they are important components of hormones, enzymes, vitamins
and other biologically active molecules.
Various inorganic elements are dietary “essential” and its deficiency causes different disorders. Role of some major and minor (trace) chemical elements is given in Table 1.1.
Chemical compounds
Combination of chemical elements form chemical compounds. There are two principle
types of chemical compounds present in cells:
`` Inorganic compounds.
`` Organic compounds.
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Inorganic compounds
Inorganic compounds in human body are water and inorganic salts.
Water comprises 66–67 % of adult human body weight. Water has unique chemical and
physical properties that allow it to sustain life. It is a polar molecule consisting of 2 positively charged hydrogen atoms (H+) and 1 negatively charged oxygen atom (O2–). Thus, water molecule attracts other water molecules, forming weak electrostatic hydrogen bonds
between oppositely charged atoms (Fig. 1.3).
1.3. Chemical composition of the cell
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Table 1.1. Role of some chemical elements in living organism
Medical
aspects
0,04–2,0 %
Is a primary component of the
skeletal system and teeth;
Is required for muscle contraction and blood clotting,
regulates heart rhythm
Calcium deficiency is hypocalcemia.
Insufficient Ca leads to rickets in
children and osteoporosis (weak
bones) in adults
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Calcium (Ca)
Role
Weight
percentage
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Element
Is found in the bones and
teeth, nucleic acids (DNA,
RNA), ATP, phospholipids and
other molecules
Phosphorus deficiency in blood is
hypophosphatemia.
It may cause rickets in children;
improper balance of P and Ca
may cause osteoporosis
Potassium (K)
0,15–0,4 %
An essential cation important
for nerve transmission and
muscle contraction;
Regulates heart rhythm
Deficiency of potassium in blood
is known as hypokalemia.
It causes muscle weakness and
irregular heart beat
Sulfur (S)
0,15–0,2 %
Is found in several amino acids
(cysteine, methionine), vitamins (thiamine, biotine);
Is important for detoxication
(is a component of antioxidant
glutathione)
Sulfur deficiency affects synthesis
of connective tissue proteins,
causes itching, brittleness of hair
and nails
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Phosphorus (P) 0,2–1,0 %
0,02–0,15 %
Is a principal extracellular
cation, important for nerve
transmission
Deficiency in blood is hyponatremia. The symptoms are weakness,
headache, nausea and vomiting
Chlorine (Cl)
0,05–0,15 %
An essential anion important
for regulation of osmotic pressure and acid-base balance;
Is a component of gastric
secretion (in the form of hydrochloric acid)
Deficiency in blood is hypochloremia. It leads to alkalosis (excess
base), muscle weakness
0,02–0,05 %
Is an important cofactor for
many enzymatic reactions,
including protein synthesis;
Has an important impact on
the balance of potassium and
calcium
Deficiency leads to irritability and
nervousness, muscle twitching
or spasm, cramps, irregular heart
beat
0,01–
0,015 %
Is a component of hemoglobin
in red blood cells and myoglobin in muscles (delivery and
storage of oxygen);
Is an important cofactor for
many enzymatic reactions
Deficiency causes anemia
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Sodium (Na)
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Magnesium
(Mg)
Iron (Fe)
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Element
Weight
percentage
Medical
aspects
Role
0,0001–
0,014 %
Is necessary for synthesis of
thyroid hormones
Deficiency in diet causes goiter
(enlargement of thyroid gland).
Hypothyroidism (insufficient
production of thyroid hormones)
causes weakness, depression,
poor memory, weight gain
Fluorine (F)
0,0001–
0,0037 %
Is required for strength of
teeth and bones
Deficiency leads to caries and
weak bones
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Iodine (I)
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Hydrogen bonds give such properties as
Н
Н
high cohesion of water molecules and high
heat of vaporization. Cohesion is tendency of
–
molecules to stick together, that, for example,
+
Hydrogen
helps water to move against the force of gravbonds
Н
ity in the vascular tissues in plants. Evaporative
cooling prevents overheating in humans by
–
evaporation of sweat.
Н
+
Polarity of water molecules explains also
+
Н
Н
ability of water to be a versatile solvent.
–
The importance of water in the cell:
Н
` It is a medium for biochemical reactions
Н
and its participant.
` It helps cells to keep their size and shape
Fig. 1.3. Water molecules with hydrogen bonds
(turgid pressure).
` It is a solvent for many polar molecules.
Water-soluble molecules are called hydrophilic, water-insoluble molecules are hydrophobic.
` Water helps in the maintenance of a stable internal environment within a living organism. The concentration of water and inorganic salts that dissolve in water is important in maintaining the osmotic balance between the blood and interstitial fluid.
` Water keeps temperature of cells from changing rapidly.
` It is the transport medium in the blood.
` It helps in lubrication.
Inorganic salts mainly exist in form of ions (anions and cations). The most important
are K+, Na+, Ca2+, Mg+, Cl–, HCO3–, HPO42–. Inorganic salts support osmotic pressure, form
buffer system for maintaining of pH (CO32– and HCO3–; HPO42– and H2PO4–), activate enzymes
and perform many other important functions. Anion HCO3– is a main form of CO2 transport
in blood. Salts of Ca and P are important components of human bones.
1.3. Chemical composition of the cell
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Organic compounds
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Organic compounds are complex molecules that have carbon chain as a molecular
backbone. The main organic compounds in living organisms are carbohydrates, proteins,
lipids and nucleic acids.
Carbohydrates are organic substances with molecular formula Cn(H2O)n or Cn(H2O)m.
Principles groups of carbohydrates are monosaccharides, oligosaccharides (disaccharides)
and polysaccharides (Fig. 1.4).
Monosaccharids or simple sugars are single molecules. They are categorized according
to the number of carbon atoms. Pentose sugars (five-carbon sugars) ribose and deoxyribose are components of nucleic acids RNA and DNA. Hexose sugars (six-carbon sugars)
glucose, fructose and galactose are involved in the production of energy.
Disaccharides consist of two monosaccharide molecules joined by glycosidic bond. Examples are sucrose (table sugar), maltose and lactose (milk sugar).
Polysaccharides are polymers formed by chains of monosaccharides (usually glucose).
Well known examples in plants are starch and cellulose, in animals – glycogen.
Carbohydrates are one of the main nutrients in our diet.
The main functions of carbohydrates:
`` Supply immediate energy for cell processes (monosaccharides, particularly glucose).
`` Serve as a material for synthesis of other organic molecules.
`` Store energy. Glycogen accumulates in liver and skeletal muscles and brakes down
into glucose when required.
Lipids are a group of hydrophobic molecules that include fats (neutral lipids), waxes,
sterols, fat-soluble vitamins (such as vitamins A, D, E, and K), phospholipids, and others.
Some functions of lipids:
`` Store large amounts of energy over long periods of time. Neutral lipids are stored in
adipose tissue of skin.
Cellulose
Source
Plant
Starch
Amylose
Amylopectin
Plant
Plant
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Diagram
Shape
Fig. 1.4. Polysaccharides that contain glucose as a monomer
Glycogen
Animal
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`` Act as an energy source. Complete oxidation of lipids releases more than twice energy produced by carbohydrates and proteins.
`` Phospholipids play a major role in the structure of the cell membranes.
`` Act as a source of metabolic water.
`` Steroid hormones and fat-soluble vitamins are involved in regulation of different
metabolic processes.
Proteins are the polymers composed of 20 main types of amino acids. The amino acids
are joined by peptide bonds into a polypeptide chain. A number of amino acids in polypeptide chain varies greatly. An average number of amino acids in human proteins is 447.
Proteins have four levels of structural organization: primary, secondary, tertiary and
quaternary. The primary structure is a polypeptide chain (linear order of amino acids). Secondary structure is of two types: alfa helix or beta sheet. Both variants are supported by
hydrogen bonds. Tertiary structure is a globular-shaped molecule with a complex internal
organization. It is held by different types of bonds, like ionic, hydrogen, disulfide ones and
hydrophobic interactions between amino acids’ radicals. Tertiary conformation of the protein is of the utmost importance for its function, conformational changes contribute to
various activities of the proteins. Quaternary structure is formed when protein is composed
of several polypeptide chains (Fig. 1.5).
Structural conformation of a protein depends on its primary structure. Sequence of
amino acids is encoded in genes. Genetic (hereditary information) is realized by synthesis
of proteins, and in fact it is an information about a set of proteins in organism.
Proteins are building blocks of life. Cells generally contain a greater variety of proteins
than any other type of macromolecules.
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H3N+
COO–
A
B
alfa helix
C
D
beta sheet
Fig. 1.5. Levels of structural organization of proteins: A – primary structure; B – secondary structure;
C – tertiary structure; D – quaternary structure
1.3. Chemical composition of the cell
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The main functions of proteins:
`` They are structural components of cell and intercellular matter.
`` Most of enzymes are proteins. They catalyze reactions of cellular metabolism, growth
and repair.
`` Some hormones, which control growth and metabolism, are proteins.
`` Such proteins as antibodies and clotting factors provide defense of an organism.
`` Recognition and signaling are provided by receptors of cell membrane.
`` Proteins provide different kinds of movements.
`` Transport of different molecules is provided by transmembrane proteins and blood
plasma proteins.
Nucleic acids are biopolymers composed of nucleotides. There are two types of nucleic
acids: DNA and RNA. DNA is the largest biomolecule in a cell.
Nucleic acids contain the genetic information and play a vital role in protein synthesis.
More information about nucleic acids is given in Chapter 4.
Most of human diseases are result of defects in biomolecules, failure of chemical reactions or biochemical pathways.
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TASKS & QUESTIONS
`` MULTIPLE CHOICE QUESTIONS (Choose one correct answer)
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EC
1. The mechanism by which organisms maintain the stability of internal environment is
known as:
D. Osmoregulation
A. Homeostasis
B. Normal health
E. Blood circulation
C. Structural adaptation
2. The ability to move is an example of:
D. Adaptation
A. Homeostasis
B. Reproduction
E. Response to stimuli
C. Growth and development
3. The amount of sugar in our blood is always maintained 3.2 – 6.1 mmol/l. It is an example of:
A. Homeostasis
D. Adaptation
B. Reproduction
E. Response to stimuli
C. Growth and development
4. The next higher level of biological organization above the organism is:
C. Population-species
E. Biosphere
A. Molecular genetic
B. Cellular
D. Ecosystem
5. What level of life organization is studied by epidemiology and parasitology?
B. Cellular
A. Molecular genetic
8.
9.
10.
11.
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7.
C. Population and species
E. Biosphere
D. Ecosystem
One of the lipid functions is:
A. Provide different kinds of movements
B. Store large amount of energy over long period of time
C. Contain genetic information
D. Provide lubrication
E. Play role of enzymes
Which of the following is a major element found in cell:
A. Copper
C. Sulfur
E. Fluorine
B. Zinc
D. Iodine
Which of the following is a minor element found in cell:
A. Oxygen
C. Sulfur
E. Sodium
B. Carbon
D. Zinc
The most prevalent compound in a living cell:
A. Protein
C. Water
E. Polysaccharide
B. Nucleic acid
D. Lipid
The largest biomolecule in a living cell:
A. Glycogen
D. Deoxyribonucleic acid
E. Triglyceride
B. Protein
C. Cholesterol
Amino acid is a structural component of:
C. Sucrose
E. Fat
A. Nucleic acid
B. Protein
D. Starch
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6.
Chapter 1. Introduction into the course of medical biology. Levels of organization and fundamental ...
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18
`` FILL IN THE BLANKS:
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1. Water is a polar molecule which contains ___ hydrogen and ___ oxygen atoms.
2. Organic elements are ________.
3. Calcium is primary component of __________.
`` TRUE OR FALSE:
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1. Oxygen is a micro element in cell.
True
False
2. Sulfur is a trace element in cell.
True
False
3. Carbohydrates supply immediate energy for cell processes.
True
False
4. Magnesium serves as a cofactor for enzymes.
True
False
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Chapter 2.
Classification of living organisms.
Non-cellular and cellular organisms.
Prokaryotic cell
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According to modern point of view, there are non-cellular infectious particles and living organisms, which have cellular organization. Non-cellular infectious particles include
viruses, viroids and prions.
All cellular organisms are divided into prokaryotes and eukaryotes by the cell structure, peculiarities of gene expression and basic metabolic pathways.
Prokaryotic cell lacks nucleus and membrane-enclosed organelles. There are two domains of prokaryotes – Archaea (Archaebacteria) and Bacteria (Eubacteria). Archaebacteria are bacteria of extreme environments,
such as hot springs and salt lakes (the Dead
Fungi
Plantae
Sea) or methanogenic Archaea. They have
Ciliates
unique properties and features, which difAnimalia
fer them from other bacteria. Eubacteria is
Ameboids
the large group of bacteria, including pathPROTISTS
ogenic for humans.
Flagellates
The cells of eukaryotes contain nucleus.
Eukaryotes
There is one domain of eukaryotes, called
Eukarya. It is divided into several kingdoms:
the Protists (unicellular eukaryotes) and
Archaebacteria
three kingdoms of multicellular eukaryEubacteria
Prokaryotes
otes – Fungi, Plantae, and Animalia. The
exact number of protists kingdoms is still
under debate (Fig. 2.1).
Fig. 2.1. Main systematic groups of cellular organisms
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2.1. Non-cellular infectious particles. Viruses, viroids, prions
Non-cellular infectious particles require host cell for existence. They include viruses, viroids and prions.
Viruses. The first virus (tobacco mosaic virus – TMV) was discovered by the Russian scientist D. I. Ivanovsky in 1892. In 1898, Friedrich Loeffler and Paul Frosch found evidence
that the cause of foot-and-mouth disease in livestock was an infectious particle smaller
than any bacteria.
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Chapter 2. Classification of living organisms. Non-cellular and cellular organisms. Prokaryotic cell ...
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For a long time it was believed that the viruses are living organisms because they have
genetic material, reproduce, are able to adapt to the changing of environmental conditions and evolve trough natural selection. However, molecular biological studies revealed
significant differences between viruses and cellular organisms. Thus, the genetic material
of viruses is represented by only one type of nucleic acid (DNA or RNA). Viruses lack cell
membrane, cytoplasm. They do not have their own protein synthesis system and other
enzyme systems providing metabolism. They are incapable reproducing themselves and
exist on the borderline between the living and the inanimate, non-biological world.
Currently, viruses are considered to be infectious agents that can infect all types of living organisms including eukaryotes and prokaryotes. They are obligate intracellular parasites and reproduce by using the host cell to synthesize viral nucleic acids and proteins.
The free viral particle is called virion (Fig. 2.2). Size of most viruses varies from 20 to
300 nm. Virion consists of nucleic acid (either DNA or RNA) and a protein coat or capsid. In
some viruses, capsid is surrounded by membranous envelope. While in this form outside
the host cell, the virus is metabolically inert.
When it comes into contact with a
host cell, a virus can insert its genetic
Envelope
Nucleocapsid
material into the cell. An infected cell
Capsomers
produces more viral protein and geCapsid
netic material instead of its usual prodNucleic
ucts. Some viruses may remain dormant
acid
inside host cells for long periods, causNucleic
ing no obvious change (a stage known
acid
as the lysogenic phase). But when a dorCapsid (composed
of capsomers)
mant virus is stimulated, it enters the
lytic phase: new viruses are formed, selfassemble, and burst out of the host cell, Fig. 2.2. Structure of virion: naked virus (left) and envelkilling the cell and going on to infect oped (right)
other cells.
Role of Viruses:
`` Viruses are the important factors
of molecular evolution as they
can transfer hereditary information between organisms of same
or different species.
`` Many viruses are pathogenic (can
cause diseases). Diseases caused
by viruses in humans include: flu,
herpes, polio, rabies, chickenpox,
rubella, mumps, Ebola, AIDS and
many other (Fig. 2.3). Even some Fig. 2.3. Human immunodeficiency virus on the surface
types of cancer have been linked of T-lymphocytes (microphotography)
2.2. Cellular organisms. Prokaryotic cell
21
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to viruses. Viruses have the capacity to cause death and devastation to large populations in epidemics and pandemics. This has led to the concern that viruses could be
used for biological warfare.
`` Viruses have been used extensively in genetic research and for studying of genes
organization, DNA replication, transcription, translation and basics of immunology.
`` Viruses (mostly adenoviruses and retroviruses) are used as vectors for genetic modifications of the host cells, creation of transgenic organisms and gene therapy of human disorders.
IC
Viroids are the smallest known agents of infectious disease. They are found in plants only.
The first identified viroid was the agent of potato spindle tuber disease Potato spindle tuber
viroid (PSTVd) (Theodor Otto Diener, 1971). Viroids are small (246 to 467 nucleotides) circular
non-coding single-stranded RNA molecules. They lack external protein coat. There are over 30
determined viroid species in plants. Avocado sunblotch and citrus exocortis are the examples.
Prions are proteinaceous infectious particles (prion proteins, PrP) that cause diseases
in animals. Prions were isolated and named by Stanley Prusiner in 1982, while he studied
scrapie disease of sheep. Unlike other infectious agents, prions have no DNA or RNA.
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The Nobel Prize in Physiology or Medicine 1997 was awarded to Stanley B. Prusiner “for his discovery
of Prions – a new biological principle of infection”.
EC
Normal cellular prions (PrPC) that present in brain cells are mainly of alfa-helical structure. Pathogenic prions (PrPSc, from scrapie disease) are misfolded forms of normal protein.
They have a higher proportion of beta-sheet structure, thus form insoluble protease resistant aggregates in nervous cells. Accumulation of PrPSc in these cells leads to cell death and
loss of brain tissue (spongiform encephalopathy).
Prion disease can be hereditary or acquired. Acquired diseases are transferred through
meat of affected animals. Agents are abnormal proteins PrPSc, which enter cells and turn
normal prions into pathological misfolded version. Examples of such diseases are mad cow
disease (bovine spongiform encephalopathy), and kuru. Hereditary variants are caused by
mutations of prion protein gene (PRNP), localized on short arm of human chromosome 20.
Examples are Creutzfeldt-Jakob disease (CJD), and fatal familial insomnia (FFI).
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2.2. Cellular organisms. Prokaryotic cell
Cell is a structural and functional unit of living organisms. The cell was discovered in
1665 by English scientist Robert Hooke, who described a network of “cellulae” in cork slice
using primitive compound microscope. In 1838 German scientists Theodor Schwann and
Matthias Schleiden formulated Cell Theory that is one of the basic principles of biology. The
theory was complemented later by Rudolph Virchow, who noted that all cells come from
maternal cells.
22
Chapter 2. Classification of living organisms. Non-cellular and cellular organisms. Prokaryotic cell ...
Nucleus
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Prokaryotic Cell
Eukaryotic Cell
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Nucleoid
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The modern Cell Theory states that:
`` All living things are composed of cells, cell is the basic structural and functional unit
of life.
`` All cells have the same basic chemical composition and morphology.
`` Cells arise from preexisting cells.
`` In multicellular organisms cells are specialized and form tissues and organs, that are
controlled by neural and humoral regulation.
The two principle categories of cells are prokaryotic and eukaryotic cells (Fig. 2.4).
Membranous organelles
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Fig. 2.4. Principle difference between prokaryotic and eukaryotic cells
Prokaryotic cell
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Prokaryotes are two different groups of bacteria: the Archaebacteria and Eubacteria,
which scientists believe have unique evolutionary lineages.
Most prokaryotes are small, single-celled organisms that have a relatively simple structure. They are about 0.2 µm in diameter and 2–8 µm in length. Prokaryotes differ from
eukaryotes by the absence of a nucleus and membrane-bound organelles.
Prokaryotic cell consists of cell envelope, cytoplasm and a single circular DNA molecule
(Fig. 2.5).
The DNA in prokaryotes is contained in the central area of the cell called the nucleoid.
This single circular DNA (bacterial chromosome), is not associated with histone proteins
and is not bound by a nuclear membrane. As a result, transcription and translation can be
carried out simultaneously.
2.2. Cellular organisms. Prokaryotic cell
23
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Some bacteria have plasmids (additional small circular extrachromosomal
1 μm
7
DNA). Plasmids have a few thousand
base pairs, carry one or several genes
6
8
and replicate separately from bacterial
5
chromosome. Genes of plasmids give
9
some advantage to bacterial cell, like an4
tibiotic resistance, ability for sexual process (conjugation) and other. Plasmids
are widely used in genetic engineering
3
10
for gene cloning and transferring.
Cytoplasm of bacterial cell contains
2
various organic and inorganic molecules
and cell components. Membrane bound
1
9
organelles are absent. There are ribosomes, which are smaller than the ribo- Fig. 2.5. Structure of typical prokaryotic cell: 1 – nuclesomes in eukaryotic cells.
oid; 2 – cytoplasm; 3 – inclusions; 4 – ribosomes; 5 – cell
Cell envelope consists of plasma membrane; 6 – cell wall; 7 – flagellum; 8 – capsule; 9 –
membrane and cell wall. Cell membrane plasma membrane folds; 10 – pili or fimbriae
has typical lipid-protein structure. Some
functions of the cell (ATP synthesis, photosynthesis if present) are performed by enzymes
of plasma membrane folds. Cell wall is an outer covering that protects the bacterial cell
and provides its rigidity. It is chemically complex and includes peptidoglicans. Some bacterial cells have capsule. This is additional outer covering, which protects the cell when it
is engulfed by other organisms, assists in retaining moisture, and helps the cell adhere to
surfaces and nutrients.
Bacterial cell has pili – hair-like structures on the surface of the cell that are used
for attachment to other bacteria cells. Shorter pili called fimbriae help bacteria attach
to surfaces. Some bacteria have flagella (are not made of tubulin) for cellular locomotion.
Most prokaryotes reproduce asexually by binary fission. Bacterial recombination takes
place by the processes of conjugation, transformation, and transduction. Conjugation is
the exchange of hereditary material (plasmids or fragments of bacterial chromosome)
between bacterial cells through direct contact. Transformation occurs by direct uptake of
exogenous free DNA from the surrounding. Transduction is provided by bacterial viruses
(bacteriophages) that insert DNA into bacterial chromosome. All these processes are the
variants of horizontal gene transfer.
In unfavorable conditions bacterial cells transform into dormant highly resistant stages
called spores.
The main differences between prokaryotic and eukaryotic cells are given in Table 2.1.
24
Chapter 2. Classification of living organisms. Non-cellular and cellular organisms. Prokaryotic cell ...
Table 2.1. Eukaryotic Cell versus Prokaryotic Cell
Prokaryotic Cell
Eukaryotic Cell
Bacteria and Archaea
Animals, Plants and Fungi
First evolved
Approximately 3.5 billion
years ago
Approximately 2.1 billion
years ago
Size
About 0.2 µm in diameter and
2–8 µm in length
10–100 µm
Nucleus
Absent
Present
Chromosomes
Single circular chromosome in nucleoid region; plasmids in cytoplasm
Several linear chromosomes
in nucleus
Membranous organelles
Absent
Present
Microtubules
Absent or rare
Ribosomes
Smaller in size; have a sedimentation
value of 70 when centrifuged.
Larger in size; have a sedimentation value of 80 when
centrifuged
Flagella
Submicroscopic in size, composed of
only one fiber, other than tubulin
Microscopic in size; membrane
bound; usually arranged as
nine doublets surrounding two
singlets of tubulin microtubules
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Organisms
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Present
Present, usually chemically complex
and includes peptidoglicans
Present only in plant cells and
fungi, includes cellulose and
chitin accordingly
Cell division
Binary fission
Mitosis and meiosis
Genetic Recombination
Horizontal gene transfer
Meiosis and fusion of gametes
EC
Cell wall
TASKS & QUESTIONS
`` MULTIPLE CHOICE QUESTIONS (Choose one correct answer):
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1. The virus capsid is composed of:
A. DNA
C.
B. RNA
D.
2. Disease(s) caused by viruses:
A. Influenza
C.
B. Rubella
D.
3. Viroid consists of:
A. Protein
C.
B. DNA
D.
Proteins
Both DNA & RNA
E. None
Polio
Ebola
E. All are correct
RNA
Peptidoglycan
E. Lipid
2.2. Cellular organisms. Prokaryotic cell
25
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4. Prion is a molecule of:
A. Protein
E. Lipid
C. RNA
B. DNA
D. Peptidoglycan
5. Example of prion disease is:
A. Creutzfeldt-Jakob disease
D. Scrapie
B. Fatal familial insomnia
E. All are correct
C. Kuru
6. Viruses range in size from:
A. 1–100 nm
C. 10–100 μm
E. 1–10 μm
B. 20–300 nm
D. 400–1000 nm
7. A fully formed infectious viral particle is called:
A. Viroid
C. Virion
E. Prion
B. Virusoid
D. Capsid
8. Which of the following statements applies to viruses?
A. They can be observed using a light microscope
B. They can multiply outside the host cells
C. Release of a virus from its host cell is always associated with lysis of the cell
D. Viruses are complexes of nucleic acid and proteins
9. Which of the following statements is not true of prokaryotes?
A. Most prokaryotes are multicellular
B. Prokaryotic cells do not have a nucleus
C. Prokaryotic cells have circular DNA
D. Prokaryotic cells have flagella
E. Prokaryotic cells have ribosomes
10. The prokaryotic genome is contained in the:
A. Capsule
C. Pilus
E. Ribosomes
B. Endospore
D. Nucleoid region
11. Genetic recombination has led to antibiotic resistance through the transfer of:
A. Pili
C. Plasmids
E. All of the above
B. Spores
D. Enzymes
12. In bacteria genetic recombination is provided by:
A. Binary fission
C. Conjugation
E. Recombination is
B. Meiosis
D. Fertilization
absent
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`` FILL IN THE BLANKS:
1.
2.
3.
4.
5.
The free viral particle is called ______________.
Kuru and Creutzfeldt-Jakob diseases are caused by ____________.
The smallest known agents of infectious diseases are ______________.
There are over ______ known species of viroid.
Statement, that all organisms are composed of one or more cells, and that those cells
have arisen from preexisting cells was proposed by ________________.
26
Chapter 2. Classification of living organisms. Non-cellular and cellular organisms. Prokaryotic cell ...
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`` TRUE OR FALSE:
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6. Prokaryotes lack a ________ and other membrane-bound organelles.
7. ____________ have a few thousand base pairs and reproduce independently from
bacterial chromosome.
8. Scientists believe that two groups of bacteria – ____________ and __________ are
unique evolutionary lineage.
9. ______________ is the area of cytoplasm that contains the single bacterial DNA molecule.
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1. All viruses are obligate parasites of cells and therefore all viruses cause disease.
True
False
2. Viroids are composed of small covalently closed, circular single-stranded RNA molecules.
True
False
3. There is a gene in our DNA, on chromosome 10, that contains instructions telling
each cell how to make PrP.
True
False
4. The capsid encloses DNA or RNA which codes the virus elements.
True
False
5. Both prokaryotes and eukaryotes have a nucleus.
True
False
6. Both prokaryotes and eukaryotes have a plasma membrane.
True
False
Chapter 3.
Morphology of the eukaryotic cell
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Animals (including human being), plants and fungi are Eukaryotes. The main characteristic of eukaryotic cell is the presence of nucleus surrounded by nuclear membrane and
membranous organelles.
Eukaryotic cells vary in size, shape, and complexity, but they share at least three components: cell membrane, cytoplasm with organelles and nucleus.
3.1. Structural components of eukaryotic cell. Cell membrane
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Cell membrane isolates the cytoplasm from the exterior environment; regulates the
flow of molecules and substances into and out of the cell; allows communication with
other cells. Through this thin membrane, approximately 10 nm thick, the cell selectively
interacts with its surroundings.
Chemical components of the biological membrane are lipids (phospholipids, cholesterol) and proteins (Fig. 3.1).
4
5
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3
2
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6
5
5
1
7
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Fig. 3.1. Structure of cell membrane: 1 – cytoplasm; 2 – lipid bilayer; 3 – glycoprotein; 4 – glycolipid; 5 – proteins; 6 – cholesterol; 7 – cytoskeleton
28
Chapter 3. Morphology of the eukaryotic cell...
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Structure of the cell membrane is described by the fluid mosaic model, which was
proposed by Seymour Jonathan Singer and Garth L. Nicolson in 1972. According to this
model, membrane consists of two layers of phospholipids stabilized by specific oriented
proteins. The phospholipid molecules and proteins are “fluid” because they move around
and jostle one another in reaction to the surrounding water molecules. The word “mosaic”
refers to the assemblage of proteins in membrane that help to stabilize the lipid layer and
create various passages and channels through it.
Phospholipid molecule consists of glycerol molecule, two fatty acid chains and a phosphorus- and nitrogen-containing group each covalently bonded to the glycerol molecule.
The nitrogen- and phosphorus-containing group is polar, making one end, the “head”, of the
phospholipid molecule water-soluble, or hydrophilic. The two nonpolar fatty acid chains make
the other end (the “tail”) of the phospholipid water-insoluble, or hydrophobic. When phospholipids are placed in water, the polar region of the phospholipid molecules form hydrogen
bonds with the surrounding water molecules. The nonpolar tails, or fatty acid chains, will be
“pushed away” from the water molecules. Water spontaneously organizes the phospholipids
into two layers. The hydrophilic heads are toward the water, and the hydrophobic tails
are toward each other and therefore away from the water. The result of this organization is called a phospholipid bilayer. Phospholipid bilayer is the framework of all biological
membranes. Because the interior portion of the bilayer is non-polar, it repels water-soluble
molecules, polar molecules, or electrically charged ions that attempt to pass through it.
Cholesterol molecules lie parallel to hydrophobic fatty-acid groups. At physiological
temperature, cholesterol stabilizes the membrane by reducing fluidity.
Proteins are embedded in the phospholipid bilayer. Depending on their function these
proteins either partially or completely penetrate the bilayer. According to its position proteins are divided into integral, semi-integral and peripheral. Integral proteins traverse the
membrane one or several times and have intracellular and extracellular domains. Peripheral proteins are associated with either cytoplasmic or extracellular side of the lipid bilayer.
Semi-integral proteins are partially embedded into membrane but do not cross it.
Functions of membrane proteins. The most important membrane proteins are the
transport proteins (channel, carrier or pump), receptor, recognition (cell identity makers),
adhesion proteins and enzymes (Fig. 3.2).
Channel proteins allow water molecules and small water-soluble molecules to pass
across the lipid bilayer. Channel proteins are selective. Some channel proteins can attract
or repel particular ions. Other channel proteins are always open, and some close or open in
response to changing conditions in the cell (gated channels).
Carrier proteins are enzyme-like proteins that facilitate transport of certain molecules
through the lipid bilayer down their concentration gradient. Conformational changes in
carrier proteins translocate molecules across the membrane.
Pump proteins utilize energy to move specific molecules across the cell membrane
against their concentration gradient.
Receptor proteins, also known as cell-surface receptors, are embedded in the cell membrane and transmit information into the cell. The end of the receptor protein exposed to
Enzyme
Receptor site
Cell identity maker
Cell adhesion
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Transport channel
29
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3.1. Structural components of eukaryotic cell. Cell membrane
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Attachment of cytoskeleton
Fig. 3.2. Functions of plasma membrane proteins
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EC
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the cell surroundings fits specific signal molecules (hormones or other molecular messengers). When a signal molecule encounters the receptor protein, it chemically bonds to it.
This makes receptor protein to change the shape of inner part of molecule and, in turn,
shifts some aspect of cell activity by modifications of secondary messengers (cAMP and
other).
Recognition proteins (antigens) embedded in the phospholipid layer indicate to the immune system that the cell is not foreign.
Adhesion proteins protrude from the exterior surface of the cell membrane, allowing
cells to form connections with one another.
Proteins arranged on the inner surface of the cell membrane are secured to certain
internal proteins, constituting a web like network that helps to maintain cell shape and
makes movement possible in some cells.
Glycocalyx (supramembrane structure of animal cell). Some proteins and lipids of outer membrane surface have carbohydrate molecules attached to them (glycoproteins and
glycolipids). These carbohydrate-rich molecules form a covering of plasma membrane of
animal cell termed glycocalyx. Oligosaccharide portions of glycolipids and glycoproteins
are exposed on the surface of cell membrane and are very important in cell-cell interactions (adhesion, recognition, communication and other).
The main functions of cell membrane are protection and isolation of the cytoplasm
from the exterior environment, regulation of molecular passage, recognition and signaling,
cellular adhesion.
Transport across the cell membrane. Cell membrane is selectively permeable. It means
that some molecules are allowed to pass through the cell membrane while other can not.
Fat-soluble molecules pass through the phospholipids. Polar molecules can not diffuse
Chapter 3. Morphology of the eukaryotic cell...
Transported molecules
a
b
Extracellular fluid (outside of cell)
Carrier protein
Phospholipid bilayer
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30
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Pump protein
Energy
Cytoplasm
ATP
a – simple diffusion; b – facilitated diffusion
Active Transport
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Passive Transport
Fig. 3.3. Types of transport across the cell membrane
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EC
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through the lipid bilayer and pass by the assistance of the proteins embedded in the membrane.
There are two principle types of transport across cell membrane: passive transport and
active transport (Fig. 3.3).
Passive transport is transport of the molecules along the electrochemical gradient
without energy expenditure.
`` Simple diffusion is the random movement of molecules or ions down their concentration gradients from an area of higher concentration to an area of lower concentration. Examples of the important molecules that move by simple diffusion across
the cell membrane include oxygen and carbon dioxide, cholesterol and steroid hormones, vitamin D, some ions. Lipid-soluble substances pass through phospholipids.
`` Osmosis is the diffusion of water across a selectively permeable membrane. Diffusion of water across lipid bilayer is very slow, so membrane has specific water channels aquaporins.
The osmosis is affected by tonicity (the relative concentration of solutes in two fluids on
both sides of the membrane).
The solution is said to be hypotonic when solute concentration is less outside the
membrane. Water moves from the outside into the cell. The cell swells and can rupture
(lysis). The solution is said to be hypertonic when solute concentration is greater outside
the membrane. The net osmotic movement of water will be from the inside of the cell into
the outside, and the cell will shrink. When solute concentration is equal on both sides of
the membrane the solution is called isotonic. Movement of water into the cell is exactly
balanced by the movement of water out of the cell. Example of isotonic to human cell solution is 0,9% solution of NaCl.
31
3.1. Structural components of eukaryotic cell. Cell membrane
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Because of the channel proteins and molecular size, water easily moves through the cell
membrane in response to solute concentration. (About 100 times the volume of water in
a cell crosses the cell membrane every second.) Even though water is rapidly entering and
leaving cells, the cells normally do not swell up or shrink because the solute concentration
in the solution surrounding the cells is maintained at the same level as the solute concentration in the cell.
With the exception of water molecules, soluble polar molecules, such as amino acids or
glucose, can not cross the cell membrane on their own. They can be transported by facilitated diffusion.
`` In facilitated diffusion there is a carrier or channel protein embedded in the cell
membrane specific to the molecule to be transported. The carrier protein facilitates,
or helps, the molecule pass into or out of the cell. On contact the molecule (amino
acids, glucose, some ions) chemically bonds to the carrier protein. This enables the
molecule to pass through the cell membrane in the direction of its concentration
gradient, either into or out of the cell.
Active transport is the transport of molecules against their concentration gradients or
transport of large molecules. It requires energy in the form of ATP.
`` Ion pumps are integral proteins that transport ions up the concentration gradient.
Example of such transport is sodium-potassium pump (Fig. 3.4) that transfers Na+
outside and K+ inside the cell (uphill their concentration gradient). Cytoplasmic Na+
binds to a pump protein that stimulates breakage of ATP and phosphorylation of the
pump. This makes the protein to change its conformation and translocate Na+ outside the cell. Extracellular K+ binds to the pump, stimulating its dephosphorylation.
The pump regains its original shape transporting K+ inside. For each used ATP molecule three Na ions are pumped out and two K ions are pumped in simultaneously. It
enables the cell to maintain much higher concentration of Na+ outside and K+ inside
providing normal physiological activities of the cell.
K+
Na+
P
P
Na
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+
ATP
Cytoplasmic Na binds to
the protein. This stimulates
phosphorylation by ATP
+
K+
P
ATP → P + ADP
ADP
Phosphorylation makes the
protein to change its shape
and release Na+ to outside
Extracellular K+ binds to the protein, this release off
the phosphate group. Loss of the phosphate restores
the protein original conformation and K+ enters the
cell. The cycle repeats
Fig. 3.4. Sodium-potassium pump
32
Chapter 3. Morphology of the eukaryotic cell...
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`` Endocytosis is engulfment of large polar molecules, particles, and dissolved molecules by the
cell membrane. During endocytosis the cell membrane first completely surrounds the substance to
be taken into its interior and then pinches off. This
creates a vesicle that encloses the engulfed material within the cell. If the material brought into
the cell is a particle, such as a bacterium or some
cell fragment, the process is called phagocytosis (Fig. 3.5). In humans phagocytosis is one of
the immune reactions, provided by leukocytes. If
the material is liquid and contains dissolved molecules, the process is called pinocytosis. Selective
endocytosis stimulated by interaction of transferred substance with certain receptor is termed
as receptor-mediated endocytosis. For example,
liver cells engulf low-density lipoproteins (LDL)
Fig. 3.5. Phagocytosis
just after interaction with specific LDL receptors.
`` Exocytosis is reverse to endocytosis. It is discharge of substances within membrane-bound vesicle by fusing with the cell membrane. After fusing the vesicle opens to the exterior, and its content diffuse out. Exocytic vesicles are formed mostly by the Golgi apparatus.
3.2. Cytoplasm. Cell organelles
1
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Cytoplasm – a semifluid material that contains water,
proteins, sugars, amino acids, ions and other molecules
necessary for cell maintenance, growth, and reproduction. It consists of an aqueous cytoplasmic matrix
(hyaloplasm or cytosol) (Fig. 3.6). Matrix contains cell
organelles, inclusions and is the seat of many metabolic
pathways. Often the external cytoplasmic layer under
the cell surface is more dense and called ectoplasm. The
internal cytoplasm is termed endoplasm.
The cytoplasm is crisscrossed by a network of protein
fibers – cytoskeleton. The cytoskeleton is responsible for
maintaining cell shape, anchoring the organelles found in
the cytoplasm and for the cellular and intracellular movements. Cytoskeleton includes three types of fibers (Fig. 3.7):
`` microtubules composed of tubulin. Its diameter is
25 nm;
Fig. 3.6. Eukaryotic cell: 1 – cytosol
(hyaloplasm)
3.2. Cytoplasm. Cell organelles
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B
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Fig. 3.7. Cytoskeleton (A – schematic representation; B – microphotography): 1 – cell membrane; 2 – mitochondrion; 3 – endoplasmic reticulum; 4 – ribosomes; 5 – microtubules; 6 – microfilaments
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`` microfilaments composed of actin mainly. These are fibrils 8 nm in diameter;
`` intermediate filaments composed of non-motile structural proteins (keratin, desmin,
vimentin and other). Intermediate filaments are 8–10 nm thick.
The cytoplasm contains organelles and inclusions. Organelles are permanent cytoplasmic entities with certain structure and functions. Inclusions are temporary structures,
like granules or droplets of secretory products or stored nutrients. Example of inclusions is
glycogen granules in liver cells.
Organelles are permanent subcellular structures that perform specialized tasks. Organelles separate different chemical reactions in the space of cytoplasm and in time.
According to the structure organelles are divided into membranous and non-membranous. Membranous organelles are covered by a single or double membrane which has
principally same structure as a cell membrane.
Single-membranous organelles are endoplasmic reticulum, Golgi apparatus, lysosomes and peroxisomes.
The endoplasmic reticulum (ER) is an extensive membranous system of interconnected fluid-filled tubules and flattened sacs located between the plasma membrane and
nuclear membrane (Fig. 3.8). There are two types of endoplasmic reticulum: rough and
smooth. Rough ER when viewed under an electron microscope appears grainy. The grains
are ribosomes attached to the membrane surface of the ER. Function of rough endoplasmic reticulum is manufacturing and transport of proteins destined for export from the cell.
Other portions of the ER membrane do not have ribosomes and are called the smooth endoplasmic reticulum. The smooth ER is involved in the synthesis, storage, and intracellular
transport of lipid containing substances and carbohydrates. In some cells the enzymes of
the smooth ER are responsible for steroid synthesis. In the other cells, such as those of the
liver, the smooth ER contains enzymes that detoxify a variety of drugs and toxic substances.
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Chapter 3. Morphology of the eukaryotic cell...
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Fig. 3.9. Golgi complex: 1 – cisterna;
2 – tubules; 3 – vesicles
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Fig. 3.8. Eukaryotic cell: 1 – nucleus; 2 – rough endoplasmic reticulum; 3 – smooth endoplasmic reticulum; 4 – ribosomes
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The Golgi apparatus or Golgi complex is a stack of flattened, slightly curved, membranebound sacs (cisternae) and associated with them vesicles (Fig. 3.9). Cisternae are thin in the
middle but have enlarged edges. Each cisterna usually is 1µm in diameter and 25 nm thick
in the center. There are about 5–10 cisternae in a single stack. Such stack is a structural unit
of Golgi apparatus and is called dictyosome or Golgi body. The ER and Golgi apparatus are
functionally related. Most of the newly synthesized molecules produced by the ER migrate,
via vesicles, to the Golgi apparatus. Here these molecules are modified, packed into vesicles
and secreted by exocytosis. The Golgi complex is also involved in the restoration of plasma
membrane. One of the important functions of this organelle is biogenesis of lysosomes.
Lysosomes are membrane-bound vesicles
0.2–0.4 µm in diameter (Fig. 3.10). They contain
1
different digestive enzymes synthesized by the
ER and packaged in Golgi complex. Lysosomes
are the primary organelles of intracellular digestion. The lysosomal digestive enzymes are able
to break down proteins, nucleic acids, lipids, and
carbohydrates. A newly formed in Golgi apparatus lysosome with digestive enzymes only is
called primary lysosome. Lysosomes are able to
digest material brought into the cell through
endocytosis, including phagocytosis of bacteria. The primary lysosomes carry out their tasks
by fusing with the vesicle containing the newly
introduced material and releasing digestive
enzymes into it. Lysosome with material to be Fig. 3.10. Eukaryotic cell: 1 – lysosome
3.2. Cytoplasm. Cell organelles
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digested is referred to as a phagolysosome or heterophagosome (secondary lysosome or
digestive vacuole). A secondary lysosome containing indigestible matter is known as the
residual body or post-lysosome. Residual bodies may be stored in the cells or are released
by exocytosis.
In the same way, lysosomes also fuse with aged or damaged organelles, forming autophagosome.
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The Nobel Prize in Physiology or Medicine 2016 was awarded to Yoshinori Ohsumi
“for his discoveries of mechanisms for autophagy”.
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There is a group of hereditary disorders, known as lysosomal storage disorders, in which
a deficiency in one of the lysosomal enzyme leads to the failure of the macromolecules
breakage. Macromolecules accumulate in cells and intercellular matter of different organs
and tissues, causing disturbance in their function. Children born with these disorders are
normal at birth. With time disease becomes symptomatic, progresses and eventually leads
to death. Examples of lysosomal storage disorders are glycogenenosis type II (Pompe disease), caused by accumulation of glycogen in skeletal muscles, heart, liver, and Tay-Sachs
disease, caused by accumulation of gangliosids (certain type of lipids) in nervous tissue.
If a whole cell is damaged or dies, the lysosomes rupture and release their enzymes into
the cytoplasm, ultimately digesting the whole cell. This process is called autolysis.
Peroxisomes are vesicles limited by a single membrane, rich in different enzymes involved in oxidation of different substances (Fig. 3.11). They are 0.3–1.5 µm in diameter.
Peroxisomes oxidize fatty acids, amino acids and other substances with production of
hydrogen peroxide (H2O2). By this molecule
peroxisomes detoxify many toxins. One of
the functions of peroxisome is degradation of
H2O2 into water and oxygen by enzyme catalase. They also participate in synthesis of fatty
acids, cholesterol, myelin and some other lipids. Hereditary deficiency of peroxisomal en1
zymes causes peroxisomal disorders.
Double membranous organelles are mitochondria.
Mitochondria appear under the microscope as sausage-shaped structures 0.5µm
2
thick and 7–60 µm long (Fig. 3.12). The main
function of mitochondria is production of
energy (ATP synthesis). It occurs as a result of
oxidation of organic substances (mitochondria use O2). The mitochondria number per
cell varies, depending on the energy requireFig. 3.11. Eukaryotic cell: 1 – lysosome;
ments of each particular cell type.
2 – peroxisomes
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Chapter 3. Morphology of the eukaryotic cell...
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Each mitochondrion has an outer and inner
membranes. The outer membrane surrounds the
mitochondrion itself, and the inner membrane
6
forms a series of folds called cristae. Enzymes of
electron transfer chain embedded in the cristae
bring about oxidative phosphorilation linked
1
with synthesis of ATP. The interior space of the
mitochondria are filled with a semifluid substance called matrix. The matrix is a mixture of
enzymes necessary to prepare the nutrient molecules for the final extraction of usable energy
2
in cristae (Krebs cycle). It also contains circular
7
5
DNA molecules, ribosomes so, mitochondrion is
3
able to produce some proteins. Due to presence
of DNA molecules mitochondria transfer some
hereditary information to next generation (cytoplasmic inheritance). Hereditary dysfunction of
mitochondria leads to mitochondrial disorders,
4
in which nervous system, heart, skeletal muscles
and eyes are mostly affected. As zygote gets all
the mitochondria from ovum mitochondrial dis- Fig. 3.12. Eukaryotic cell: 1 – mitochondrion;
orders are inherited from affected mother by all 2 – external membrane; 3 – internal membrane; 4 – crista; 5 – matrix; 6 – ribosome;
her children.
7 – intermembrane space
Mitochondria are semi-autonomic organelles
as they have their own DNA, system for protein manufacturing, and are able for multiplication. This fact is explained by endosymbiotic theory according to which mitochondria are
evolved from certain bacteria engulfed by eukaryotic cell more than 1.45 billion years ago.
This theory is confirmed by circular shape of DNA, size of ribosomes similar to prokaryotic
and data of DNA-analysis.
Non-membranous organelles are ribosomes and centrosome (centrioles).
Ribosomes are spheroid bodies (Fig. 3.13) formed of two subunits – a large subunit
and a small subunit consisting of proteins and rRNA. Large subunit of eukaryotic ribosome
contains about 50 proteins and 3 types of rRNA, the small one – 30 proteins and one type
of rRNA. The size of eukaryotic ribosome is 25 × 20 × 20 nm, so it is the smallest among the
organelles. When centrifuged, ribosomes have 80S sedimentation coefficient in Svedberg
units (40S for small and 60S for large subunit).
In eukaryotic cells the process of biogenesis of ribosomes is complicated. The proteins needed for ribosomal structure are manufactured in the cytoplasm and transported into the nucleus. The rRNA is synthesized in nucleolus, and here ribosome subunits
are formed.
Ribosomes are described as “protein factories” of the cell since they are the only sites of
protein biosynthesis.
3.3. Nucleus. Human karyotype
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Small subunit
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Fig. 3.13. Eukaryotic cell: 1 – ribosomes;
2 – subunits of ribosome
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Recent studies have indicated that the two
subunits of the ribosome usually exist freely in
the cytoplasm and unite only during protein
synthesis. The ribosome complex may be attached to the endoplasmic reticulum (rough
ER), nuclear membrane or floats in cytoplasm.
Centrosome consists of two centrioles
(Fig. 3.14). Centrioles are two short cylindrical Fig. 3.14. Eukaryotic cell: 1 – centrosome
structures (0.15µm in diameter and 0.3–0.5 µm
in length) that lie at right angle to one another near the cell nucleus. Each centriole is composed of nine microtubule triplets, which lie in a ring. A small portion of cytoplasm around
centrioles is called centrosphere. The centrioles help to organize spindle fibers and act as
anchoring points for them during the cell division.
3.3. Nucleus. Human karyotype
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The nucleus (from Latin nux – nut) is the most significant component of the cell. Main
functions of the nucleus are:
`` contains the genetic material – DNA;
`` controls various metabolic activities of the cell;
`` produces ribosomes;
`` produces all types of RNA.
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Chapter 3. Morphology of the eukaryotic cell...
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Morphology of the nucleus
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The nucleus was discovered by Robert Brown in 1831. The nucleus is found in all eukaryotic
cells. However, certain highly specialized cells such as the mature sieve tubes of higher plants
and mammalian erythrocytes have nucleus at the early stages of development only.
The prokaryotic cells of the bacteria do not have nucleus, i.e., the single, circular and
large DNA molecule (bacterial chromosome). It is disposed in a region that is not membrane-enclosed, called the nucleoid.
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Usually the cells contain single centrally located nucleus but their number may vary
from cell to cell (mononucleate, binucleate or polynucleate cells).
The nucleus has following structures (Fig. 3.15):
(1) The nuclear envelope (nuclear membrane); (2) the nuclear sap or nucleoplasm; (3)
the chromosomes; (4) the nucleolus.
1. The nuclear envelope separates the nucleoplasm from the cytoplasm. The electron
microscopy of the nuclear envelope have shown that it is composed of double membrane
perforated with large pores. So, the major structural elements of the nuclear envelope are:
`` the outer and inner nuclear membranes. Each membrane is about 7.5 to 9 nm thick
and has a typical structure. The intermembranous space is called the perinuclear
space. The inner nuclear membrane is associated with the chromatin. The outer nuclear membrane often looks rough due to attached ribosomes. It is connected with
the membranes of the endoplasmic reticulum.
`` nuclear pore complexes, that control the passage of molecules in and out of the nucleus.
`` nuclear lamina. The nuclear lamina
is a structure near the inner nuclear
2
membrane. It is composed of lamins
3
(intermediate filament proteins)
and lamin-associated proteins. The
7
nuclear lamina is an essential com5
4
8
ponent of eukaryotic cells. Chromosomes are fixed to the lamina, by this
it is involved in most nuclear activi6
ties including DNA replication, RNA
1
transcription, nuclear and chromatin
organization. Specific mutations in
nuclear lamina genes cause a wide
range of hereditary human diseases.
Famous example is Hutchinson-GilFig. 3.15. Nucleus: 1 – nuclear envelope; 2 – exterford progeria syndrome (premature nal membrane; 3 – internal membrane; 4 – periaging of children), caused by muta- nuclear space; 5 – nucleolasm; 6 – chromatin;
tion of lamin A gene.
7 – nucleolus; 8 – nuclear pores
3.3. Nucleus. Human karyotype
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2. Nucleoplasm or karyolymph is transparent, semi-solid, granular and slightly acidophilic content of the nucleus. The nucleoplasm is composed of different types of RNA, nucleotides, proteins, enzymes, ATP, lipids and ions such as phosphorus, potassium, sodium, calcium and magnesium. It contains nuclear matrix – a network of protein fibers that provides
the basic shape and structure of the nucleus. The nuclear matrix, along with the nuclear lamina, aids in organizing the chromatin within the nucleus. It is a central element in the formation of DNA loop domains and important in regulation of DNA replication and transcription.
3. Chromosomes (from Greek chrome – color) are constant components of the nucleus,
that contain hereditary information and play a vital role in heredity, variation and evolutionary development of the species.
Chromosomes consist of DNA and proteins (basic histone proteins and acidic non-histone proteins). DNA and protein complex is called chromatin. Number of DNA molecules in
chromosome is determined by the phase of the cell cycle. From anaphase of mitosis until
S-period of interphase each chromosome has one DNA molecule. In S-phase DNA doubles,
so from this stage until anaphase each chromosome has two DNA molecules.
The structure of the chromosomes also depends on the cell cycle stage. During interphase chromosomes are decondensed (dispersed) and look like long chromatin fibers.
They are invisible in light microscope. During the cell divisions (mitosis and meiosis) chromosomes condense and become thick “X-shaped” structures.
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Levels of chromatin condensation
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There are four levels of chromatin condensation (Fig. 3.16).
`` The first one is nucleosome level.
The proteins that participate in the structure of chromatin at this level are basic proteins called histones. These are low molecular weight proteins with high proportion of basic amino acids – arginine and lysine. There are five different types of histones: H1 (large
proteins about 200 amino acids), H2A, H2B, H3 and H4 (each of them is formed of about
102–135 amino acids).
Each nucleosome is disc-shaped body about 11 nm in diameter (Fig. 3.17). It consists of
8 histone molecules (two copies of H2A, H2B, H3 and H4) and DNA strand having 146 base
pairs and tightly wrapped around protein core (core DNA). A part of DNA, which does not
connect to histone proteins, is called linker DNA. It connects two adjacent nucleosomes
and has 15 to 100 base pairs. Complex interdependent modifications of the histones (acetylation, phosphorilation, ect) are responsible for controlling gene activity (“histone code”
theory of gene regulation).
The nucleosome fiber is approximately 10–11 nm in diameter. After coiling with histones the DNA shortens 7 times. Nucleosomes are the fundamental packing units of chromatin and give chromatin the “beads-on-a-string” appearance.
`` Chromatin fibers with a diameter of about 30 nm.
It is three-dimensional zig-zag structure. The histone H1 helps in this level of the chromatin condensation. In cells that are not actively dividing the 30 nm fiber is probably the
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Chapter 3. Morphology of the eukaryotic cell...
Short region of
DNA doublehelix
2 nm
Nucleosome
fiber
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11 nm
30-nm chromatin fiber
30 nm
700 nm
200–300 nm
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Chromosome scaffold
Radial loop
domains of
interphase
chromosome
Condensed scaffoldassociated form
Metaphase
chromosome
1400 nm
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Fig. 3.16. Levels of chromatin organization
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Histones
most organized state of chromatin in the nucleCore DNA
H1
us. The DNA becomes 6-fold shorter (42 in sum).
H2B
H2B
`` Radial loop domains.
H2A
This level of chromatin condensation involves
H2A
11 nm
interaction of 30 nm fibers and nuclear matrix.
Chromatin fibers are connected with proteins
H4
H4
of nuclear matrix and lamina (non-histone proH3
H3
teins), packing into loops with 200–300 nm diameter. This is interphase chromosome level. The
DNA shortens 1600 times.
Linker DNA
The attachment of radial loops to nuclear
5.5 nm
matrix organizes the chromosomes within the
Fig. 3.17. Structure of nucleosome
nucleus and plays important role in gene regulation.
The degree of chromatin condensation during the interphase differs (heterochromatin
and euchromatin).
Heterochromatin is darkly stained and highly condensed. It is supposed to be metabolically and genetically inert. Constitutive heterochromatin is permanently inactive and plays
a structural role. It is located around the centromere and at the tips of all chromosomes.
Facultative heterochromatin contains genes in the transcriptionally inactive state. Example
3.3. Nucleus. Human karyotype
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of facultative chromatin is a Barr body (highly spiralized X chromosome in the mammalian
females).
Euchromatin is light and diffused portion of the chromatin. The euchromatin contains
comparatively large amount of actively transcribed DNA.
`` Condensed chromosomes during the cell division.
This is the highest fourth level of packing takes place only during cell division when chromosomes become visible. The 30 nm fiber takes up a conformation with supercoiled loops
radiating from a core comprising non-histone proteins. The width of the structure is about
500–600 nm. Maximal level of condensation is observed at metaphase stage of cell division.
Morphology of Metaphase Chromosome
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The size of the chromosomes varies from species to species and remains constant for a
particular species. The length of the human metaphase chromosomes is from 2.3 to 11 µm.
Each pair of chromosomes have specific morphological characteristic (rule of individuality).
Metaphase chromosome has “X”-like
appearance (Fig. 3.18). It consists of two
sister chromatids (future daughter chro2
mosomes) attached at the site of primary
constriction or centromere. Position of
4
primary constriction is constant for given
chromosome and forms a feature of iden6
tification. The microtubules of the spindle
fibers are attached to the protein complex
1
on the centromere known as kinetochore.
The centromere divides the chromatid
into two parts, each part is called an arm. The
short arm is designed as p, long one – as q.
The tips of the chromosomes are rounded and sealed and are called telomeres.
These provide stability to the chromosomes and protect their individuality. Chro5
mosomes with broken ends become sticky
and may easily join other chromosomes.
Telomeres are considered now to be involved in the process of aging by controlling number of cell divisions.
3
Besides having the primary constriction, some chromosomes have secondary
Fig. 3.18. Structure of metaphase chromosome:
constriction. The terminal part of the chro1 – centromeric region; 2 – telomeric region;
mosome beyond secondary constriction
3 – sister chromatids; 4 – short arm; 5 – long arm;
is called satellite. Secondary constriction
6 – kinetochore
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Chapter 3. Morphology of the eukaryotic cell...
Satellite
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Secondary
constriction
Fig. 3.19. Shapes of metaphase chromosomes (scheme): 1 – metacentric; 2 – submetacentric; 3 – acrocentric; 4 – telocentric; 5 – acrocentric sat-chromosome
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possesses genes for rRNA and participates in the formation of nucleolus during interphase,
therefore, is known as nucleolar organizer region. The chromosomes with satellite are
known as sat-chromosomes.
The position of centromere determines shape of metaphase chromosomes (Fig. 3.19):
`` Metacentric are chromosomes in which centromere lies in the middle of chromosome so that the two arms are equal.
`` Submetacentric are chromosomes with centromere slightly away from the mid-point
so that the two arms are unequal.
`` Acrocentric are chromosomes having subterminal centromere. All human acrocentric chromosomes are sat-chromosomes.
`` Telocentric are chromosomes with centromere occupying a terminal position. One
arm is very long and the another one is absent. In humans telocentric chromosomes
are observed.
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The number of the chromosomes is constant for a particular species (rule of constancy).
For example, the organism with the lowest number of the chromosomes is round worm
Ascaris megalocephalus which has only two chromosomes in the somatic cells; Drosophila
melanogaster (fruit fly) has 8, Musca domestica (house fly) – 12, Rana esculenta (frog) – 26,
Gorilla gorilla – 48, Homo Sapiens – 46 chromosomes.
The chromosomes can be matched in pairs (rule of double number). The chromosomes
of each pair are similar in length, shape and staining pattern and carry genes controlling the
same inherited characters. One chromosome of each pair is inherited from mother, another
one – from father. These two chromosomes making up a matched pair are called homologous chromosomes. Cells whose nuclei contain paired set of the chromosomes are called
diploid cells, and the total number of chromosomes is called the diploid number (2n).
The set of chromosomes of the gametes such as sperm and egg is a single or haploid
(n). Somatic cells get the diploid set of the chromosomes in the process of fertilization by
the fusion of the haploid male and female gametes.
3.3. Nucleus. Human karyotype
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Karyotype and Idiogram
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The karyotype is the diploid set of chromosomes characteristic for a certain species. It
is characterized by the constant number, size and shape of the chromosomes (Fig. 3.20).
The karyotype is represented by a diagram where chromosomes are arranged according to
their size and shape. Laboratory investigation of the karyotype is termed as karyotyping.
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A
B
2
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1
3
6
7
8
13
14
15
19
20
9
21
22
4
5
10
11
12
16
17
18
X
Y
Fig. 3.20. Human karyotype: A – metaphase plate; B – human karyotype (male)
For chromosome analysis, cells which grow and divide rapidly in culture are chosen. The
most commonly used cells are leukocytes (lymphocytes), skin fibroblasts, red bone marrow
cells, cells of amniotic fluid, placenta and chorion. Stages of karyotyping are as follows:
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Chapter 3. Morphology of the eukaryotic cell...
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1. Peripheral blood is cultivated in the nutrient medium containing phytohemagglutinin (PHA), which agglutinates erythrocytes and stimulates the lymphocytes to divide. The cells are cultured under sterile conditions at 37 °C for about 72 hours. During this period the cells divide.
2. Three hours before the end of incubation a small amount of colchicine is added to
the culture. Colchicine prevents the assembling of the spindle fibers and arrests mitosis at the stage of metaphase.
3. After an hour hypotonic solution of KCl is added. This makes the cells swell and chromosomes spread out.
4. Next step is fixation, staining and analyses of the karyotype. Routine staining by
Romanovsky-Gimsa makes chromosome intensively dark along its length. Differential staining demonstrates the banding appearance of the chromosomes (alternation of dark and light bands). Banding pattern is specific for each pair of the chromosomes that helps in identification of chromosomes and detection of structural
aberrations.
The set of chromosomes of one cell on the slide is termed as metaphase plate
(see Fig. 3.20).
Schematic representation of the chromosomes arranged by size, form and banding pattern is called ideogram (Fig. 3.21).
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Characteristics of human karyotype
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Human karyotype includes 46 chromosomes (23 pairs). From them 44 (22 pairs) are
autosomes and 2 (1 pair) – sex chromosomes. Autosomes are same in males and females.
Sex chromosomes (heterochromosomes) determine sex of a person. Woman has XX sex
chromosomes and man has XY.
The main principles of classification of the chromosomes were worked out by famous
geneticist Klaus Patau, who proposed to take into account size and shape of the chromosomes. The first international classification of chromosomes (nomenclature of human
chromosomes) was adopted in 1960 at the international genetic conference in Denver.
The nomenclature of human chromosomes has been revised several times on the bases of
modern staining techniques and molecular-genetic data (the last one – in 2013).
Under this classification, pairs of chromosomes are numbered from the 1st to 23rd (see
Fig. 3.20). The 1st to 22nd chromosome pairs are autosomes, the 23rd pair is sex chromosomes. A female karyotype is marked as 46, XX and male karyotype as 46, XY.
According to the position of centromere and size of the chromosome 22 pairs of autosomes are divided into 7 groups from “A” to “G”, 23rd pair (sex chromosomes) forms a separate group.
Group “A” (1–3). The largest chromosomes. Chromosomes 1 and 3 are metacentric,
chromosome 2 is submetacentric.
Group “B” (4–5). Large submetacentric chromosomes. The 4th and 5th pairs are not distinguished without differential staining.
3.3. Nucleus. Human karyotype
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3
p
2
D
1
1
q
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p
2
3
4
1
2
3
7
8
4
2
1
1
2
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10
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p
1
1
q
2
3
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13
p
1
q
1
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20
6
5
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q
11
12
15
16
17
18
21
22
Y
X
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Fig. 3.21. Ideogram of human (male) represents the banding pattern in each chromosome at the stage of
metaphase (left chromatid) and early prometaphase (right chromatid) of mitosis
Group “C” (6–12). Chromosomes of medium size, submetacentric. At routine staining
X-chromosome can’t be differed from chromosomes of this group.
Group “D” (13–15). Chromosomes are medium acrocentric. All three pairs have satellites on the short arm.
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Chapter 3. Morphology of the eukaryotic cell...
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Group “E” (16–18). Small submetacentric chromosomes.
Group “F” (19–20). Small metacentric chromosomes.
Group “G” (21–22). The smallest acrocentric chromosomes. A short arm bares satellite.
Sex chromosomes (23). Y-chromosome is small acrocentric; X-chromosome is submetacentric, and routinely stained is similar to chromosomes of the group “C”.
4. Nucleolus. The nucleus contains a large, spherical and acidophilic dense granule
known as the nucleolus (see Fig. 3.15). The number and the size of the nucleoli are related
with the synthetic activity of the cell. The position of the nucleolus in the nucleus is eccentric.
The nucleolus is composed of DNA, rRNA and proteins. It is formed on the secondary
constriction of the chromosomes (nucleolar organizing center).
The main function of nucleolus is the synthesis of rRNA and biogenesis of the ribosomes.
TASKS & QUESTIONS
`` Multiple Choice Questions (Choose one correct answer):
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1. Organelles present in both prokaryotic and eukaryotic cells are:
B. Ribosomes
D. Mitochondria
A. Endoplasmic
reticulum
C. Lysosomes
E. All of the above
2. As a rule DNA in eukariotyc cells is in chromosomes. Some cell organelles contain
DNA also. These are:
C. Endoplasmic
D. Ribosomes
A. Lysosomes
B. Golgi complex
reticulum
E. Mitochondria
3. Centrioles were removed from the cell by micromanipulator. Which cell process is
destroyed?
A. Protein synthesis
C. Carbohydrate
D. Cell division
B. Cell respiration
E. Fat metabolism
metabolism
4. Golgi complex consists of tubules, vesicles, and cisternae. It produces:
D. Secondary lysosomes
A. Chromosomes
B. Ribosomes
E. Mitochondria
C. Primary lysosomes
5. Ribosomes consist of proteins and rRNA. What is the place of biogenesis of ribosomes:
D. Microtubules
A. Golgi complex
B. Smooth endoplasmic reticulum
E. Nucleolus
C. Rough endoplasmic reticulum
6. There are two types of endoplasmic reticulum: smooth and rough. Which function is
common for both?
3.3. Nucleus. Human karyotype
10.
11.
12.
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8.
A. Protein synthesis
D. Synthesis of glycogen
B. Biosynthesis of carbohydrates
E. Transport
C. Lipid biosynthesis
What do we call the double set of chromosomes, specific for the species?
A. Genome
C. Metaphase plate
E. Genotype
B. Idiogram
D. Karyotype
Ten human chromosomes have nucleolar organizer regions, which are responsible
for the formation of nucleoli. These chromosomes are:
A. Telocentric
C. Metacentric
E. Acrocentric
B. Submetacentric
D. Centromeric
There are several types of the chromosomes in human karyotype. Chromosomes
with slightly unequal arms are:
A. Submetacentric
C. Acrocentric
E. Telocentric
D. Metacentric
B. Centromeric
There are different types of the chromosomes in photo of metaphase plate. Which of
them have equal arms?
A. Metacentric
C. Acrocentric
E. Centromeric
D. Telocentric
B. Submetacentric
Chemical composition of the chromosomes is:
E. Nucleoproteids
A. Polypeptides
C. Glycolipids
B. Amino acids
D. Glycoproteids
The similar chromosomes in males and females are termed as:
A. Autosomes
C. Heterosomes
E. Non-homologous
B. Sex chromosomes
D. Homologous
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7.
47
`` FILL IN THE BLANKS:
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1. The presence of __________ and ________________________________ is the main
characteristic of eukaryotic cell.
2. Structure of the cell membrane is described by the ________________ model.
3. Chemical components of the biological membrane are lipids (_____________,
______________) and ____________.
4. Molecule of amino acid chemically bonds to the carrier protein and is transported by
___________________ diffusion.
5. A newly formed ___________ lysosome containing ____________ enzymes after fusing with vacuole with introduced material is referred to as ___________________ or
___________________.
6. Production of energy occurs in ______________ as a result of ____________ of organic substances.
7. Each nucleosome is a disc-shaped body that consists of 8 __________ molecules and
__________ tightly wrapped around protein core.
48
Chapter 3. Morphology of the eukaryotic cell...
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8. The metaphase chromosome consists of two ______________________ attached at
the site of ______________________ or ________________.
9. Secondary constriction is present in human ____________ chromosomes, possesses
genes for ______ and participates in the formation of nucleolus during interphase,
therefore, is known as ______________________ region.
`` TRUE OR FALSE:
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EC
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1. Phagocytosis is an engulfment of dissolved molecules by the cell membrane.
True
False
2. Single-membranous organelles are endoplasmic reticulum, Golgi apparatus, ribosomes, lysosomes and centriols.
True
False
3. The smooth ER is involved in the synthesis, storage, and intracellular transport of lipid
containing substances and carbohydrates.
True
False
4. DNA and protein complex is called chromatin and is a chemical matter of chromosomes.
True
False
5. Telocentric chromosomes are chromosomes with only one arm and can be found in
normal human karyotype.
True
False
6. The nucleolus is formed on the secondary constriction of the chromosomes and is
responsible for the synthesis of rRNA and biogenesis of the ribosomes.
True
False
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CHAPTER 4.
Organization of information and energy
flow in the cell. Molecular basis of heredity
4.1. Notion of cell metabolism.
Assimilation and dissimilation
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All the chemical processes taking place within a cell (an organism) are called metabolism. Metabolism is a complex of antagonistic reactions of assimilation (anabolism) and
dissimilation (catabolism).
Assimilation reactions are the processes of synthesis of complex molecules. These are
endothermic reactions (need ATP energy). Examples are synthesis of proteins, carbohydrates, lipids, nucleic acids. These processes cause growth and differentiation of cells and
an increase in body size.
According to assimilation peculiarities, all organisms are divided into autotrophs and
heterotrophs. Autotrophs can construct the complex organic molecules from simple inorganic molecules like carbon dioxide and water (plants, some bacteria). They can use sunlight or exothermic chemical reactions as the source of energy (photoautotrophs or chemoautotrophs respectively). Heterotrophs can not construct the organic molecules from
simple inorganic ones, thus they must use organic molecules of food to produce own complex molecules (animals, fungi, bacteria).
Dissimilation is the set of metabolic pathways that breaks down large molecules into
smaller units with releasing of energy (exothermic reactions). Reactions of assimilation and
dissimilation are interrelated with each other. Cells use the small molecules and energy
released for assimilation reactions. Catabolism therefore provides the matter and chemical
energy necessary for the maintenance and growth of cells. Assimilation is seen as constructive metabolism and dissimilation as destructive metabolism.
All these highly coordinated sets of different metabolic pathways provide flows of information, energy and matter in a cell (organism).
Information flow creates certain organization of a cell (organism), permits to
maintain it in time and transfer to next generations. In this process are successively
involved DNA that stores information, mRNA that transports information into cytoplasm, and cytoplasmic translation complex (ribosomes, tRNAs, enzymes). The result
of information flow is synthesis of different proteins and manifestation of characteristics.
50
CHAPTER 4. Organization of information and energy flow in the cell. Molecular basis of heredity...
4.2. Information flow. Molecular basis of heredity.
Nucleic acids
Deoxyribonucleic Acid (DNA)
TE
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Leading role in the storage and realization of hereditary information belongs to nucleic
acids.
For the first time the nucleic acid was isolated from the nuclei of pus cells by Friedrich
Meisher in 1868 and was named nuclein. The name nucleic acid was given to it after knowing its acidic property. There are two types of nucleic acids: deoxyribonucleic acid or DNA
and ribonucleic acid or RNA.
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EC
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Function. DNA stores and transfers hereditary (genetic) information needed for the synthesis of proteins.
Location. DNA is located in the nucleus and is the main component of the chromosomes.
It is combined with proteins thus forming deoxyribonucleoprotein. DNA also occurs in mitochondria and plastids as a circular molecule resembling prokaryotic DNA.
Chemical composition. DNA is a biopolymer consisting of nucleotides (Fig. 4.1). Each nucleotide consists of 3 components: phosphate group, deoxyribose sugar and a nitrogenous base. The
nitrogenous base may be adenine (A) and guanine (G), which are 9-membered double ringed
purines; cytosine (C) and thymine (T) – 6-membered single ringed pyrimidines. Thus, DNA consists of 4 types of nucleotides – adenosine monophosphate (AMP), guanosine monophosphate
(GMP), cytidine monophosphate (CMP), and thymidine monophosphate (TMP).
DNA structure. In 1953 James Watson and Francis Crick discovered space organization of
DNA molecule.
DNA is a double helix in which two polynucleotide chains are spirally coiled around a
common axis. Helix is right handed. The diameter of the molecule is 2 nm; its one turn is
3.4 nm long and has 10 base pairs (Fig. 4.2).
–
Phosphate
O
NH2
H
O
P
O–
Fig. 4.1. Structure of DNA nucleotide
C
H
O
5'
4'
CH2
C
C
Nitrogenous base
(Cytosine)
N
C
N
O
O
C H
H C
C
H
3'
OH
C
H
2'
H
1'
Deoxyribose
4.2. Information flow. Molecular basis of heredity. Nucleic acids
51
Sugar-phosphate
backbone
The length of DNA varies greatly. In E. coli
the ring-shaped DNA has a length of 1.2 mm.
5'-end
In humans, the total length of DNA is about
190 cm (the average length 1 DNA molecule
is more than 4 cm). The length of the certain
Minor
Bases
DNA fragment is measured in pairs of nuclegroove
otides or base pairs (b.p.).
Nucleotides forming a polynucleotide
chain are joined by phosphodiester bonds
(Fig. 4.3). A phosphodiester bond is formed
Major
between hydroxyl group of the carbon atom
groove
at position 3’ of the sugar in one nucleotide
and phosphate group carried by carbon atom
in 5’ position of the sugar in the next nucleoHydrogen
tide. Thus, one end of the chain has a free
bonds
phosphate group and the other end has a free
between
hydroxyl (-OH) group. These ends are called 5’
bases
(“five prime”) and 3’ (“three prime”) respectively. New nucleotides are added to 3’ end.
5'-end
3'-end
The alternating sugar-phosphate-sugar
groups form the backbone of the DNA chain.
Fig. 4.2. Watson and Crick model of DNA structure
Two deoxyribonucleotide chains are held
together by hydrogen bonds between nitrogenous bases according to the complementary principle. Adenine of one chain is always joined to thymine of the other chain by two hydrogen bonds and cytosine is always
joined to guanine by three hydrogenous bonds. So nitrogenous bases project inward and
sugar-phosphate backbone is located on the outside of the molecule (Fig. 4.4).
The two polynucleotide chains are antiparallel: 5’ end one strand is joined to 3’ end of
another one.
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3'-end
The 1962 Nobel Prize in Physiology or Medicine was awarded to Francis Harry Compton Crick, James
Dewey Watson and Maurice Hugh Frederick Wilkins “for their discoveries concerning the molecular
structure of nucleic acids and its significance for information transfer in living material”.
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Main properties of DNA molecule
Complementary base pairing (strict matching of nitrogenous bases of two DNA
strands) explains Chargaff’s rules which were discovered by Austrian chemist Erwin Chargaff (born in Czernowitz, Austria-Hungary, which is now Chernivtsi, Ukraine) in 1950. The
rules state that in DNA molecule:
1. Amount of Adenine equals to the amount of Thymine; and Cytosine equals to Guanine.
52
CHAPTER 4. Organization of information and energy flow in the cell. Molecular basis of heredity...
T
O–
O
O
P
C
5'
O
D
–
O
3'
Phosphodiester bond
O
O
P
O
C
5'
O
O
OH
G
IC
3'
TE
C
O–
O
P
O
C
5'
O
TR
O
3'
Fig. 4.3. Formation of phosphodiester bond
OH
5'-end
P
EC
Deoxyribose
A
T
P
Deoxyribose
T
P
A
P
R
Deoxyribose
G
3'-end
Fig. 4.4. The scheme of DNA structure
C
Deoxyribose
P
C
P
Deoxyribose
3'-end
Deoxyribose
Deoxyribose
P
G
Deoxyribose
P
5'-end
4.2. Information flow. Molecular basis of heredity. Nucleic acids
53
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2. Amount of purines (A + G) equals to pyrimidines (T + C), so (A + G) / (T + C) = 1.
The ratio (A + T) / (G + C) varies from one species to another. This ratio known as coefficient of DNA specificity is constant for given species and can help in identification of the
source of DNA. This ratio in humans, for example, equals 1.53.
Complementary principle gives to a DNA molecule several very important properties:
1. DNA can undergo denaturation (melting) and renaturation (annealing).
If DNA molecule is exposed to high temperature or changing of pH two strands unwind and separate by breakdown of hydrogen bonds between the base pairs (denaturation). In physiological conditions separated strands re-associate to restore double strand DNA (renaturation). Strands find each other under the complementary
principle. This DNA property is widely used in the methods of molecular genetics.
2. A DNA molecule is able of replication. Replication is the process by which a cell
copies its DNA.
Replication of DNA occurs in interphase period before the cell divides. In cell division
each of daughter cells gets one copy of the DNA molecule. Thus, hereditary information
can be passed on to daughter cells.
During the replication process DNA unwinds and each strand of maternal DNA serves
as a template for construction of the complementary daughter strand. Thus, each copied
DNA molecule contains one strand derived from the parent molecule and one newly synthesized. Such kind of replication is called as semi-conservative (Fig. 4.5). Complementary
principle of base pairing provides genetic identity of daughter DNA molecules.
EC
1
4
R
3
2
3
Fig. 4.5. Semi-conservative
mechanism of DNA replication:
1 – parental DNA molecule;
2 – new daughter DNA
molecule;
3 – maternal strand;
4 – daughter strand
54
CHAPTER 4. Organization of information and energy flow in the cell. Molecular basis of heredity...
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Replication includes the following stages:
`` Initiation. Unwinding of the double helix begins at a distinct position called the replication origin. Replication origin contains sequences rich in A-T pairs. DNA replicated
from a single origin is called replicon. A typical mammalian cell has 50–100 000 replicons. Separation of parental strands creates a replication bubble. The region, where
the helix unwinds and new DNA is synthesized, is called the replication fork. Each
replication bubble has two replication forks which move in opposite directions (replication is bidirectional). Such enzymes and proteins, like topoisomerase, helicase, single-strand binding proteins (Fig. 4.6) work at the region of replication fork (Table 4.1).
`` Elongation is a synthesis of DNA strand by DNA polymerase. This enzyme requires
a short pre-existing double-stranded region to initiate or prime DNA synthesis. So
first step is synthesis of RNA primer (about 18-22 nucleotides) that is produced by
an RNA polymerase (primase). DNA polymerase adds new nucleotides to the 3' end
of the primer (synthesis occurs in the 5' to 3' direction) (Fig. 4.7). As DNA strands are
antiparallel, replication of the maternal strands is asymmetrical. One strand is copied
in the same direction as the helix unwinds and so can be synthesized continuously
(leading strand). Another one is synthesized in the opposite direction and is copied
discontinuously (as a series of short Okazaki fragments) and requires primer for each
fragment (lagging strand) (Fig. 4.8).
Energy reach deoxyribonucleotide triphosphates (ATP, GTP, CTP, TTP) are required for
replication.
`` Termination. At the finishing of replication primers are removed simultaneously with
synthesis of DNA to fill the gaps. DNA ligase seals the remaining nicks in the sugarphosphate back-bone. Two DNA molecules separate and pack with histone proteins.
EC
The 1959 Nobel Prize in Physiology or Medicine was awarded to Severo Ochoa and Arthur Kornberg “for their discovery of the mechanisms in the biological synthesis of ribonucleic acid and
deoxyribonucleic acid”.
4
2
5
3
3'
5'
3'
R
3'
5'
1
7
8
3'
5'
6
2
3' 5'
5'
10
3'
5'
9
Fig. 4.6. The process of DNA replication: 1 – leading strand; 2 – DNA polymerase; 3 – helicase; 4 – topoisomerase; 5 – single strand binding proteins; 6 – primase; 7 – primers; 8 – Okazaki fragments; 9 – DNA ligase;
10 – lagging strand
4.2. Information flow. Molecular basis of heredity. Nucleic acids
55
Table 4.1. Enzymes and proteins for DNA replication
Enzymes
Functions
Separates the two parental DNA strands at the replication fork. It has
an ATP-ase activity and breaks down 2 ATP molecules for each base
pair separated
Bind to the newly exposed single strand regions and prevent their reassociation
Prevents overwinding (supercoiling) of DNA by introduction of transient single or double-strand breaks into DNA
Makes primers (short RNA fragments) that DNA polymerase can extend
by adding nucleotides to their 3’ end
Synthesis of daughter DNA strands
Removing of the primers (have exonuclease and endonuclease activity)
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Helicase
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Single-strand binding
proteins
Topoisomerase
Primase
DNA polymerase (α, δ, ε)
MF1(maturation factor)
and RNAse H
DNA polymerase β
Ligase
IC
Fills the gaps after primers are removed
Seals the nick between two adjacent nucleotides by forming phosphodiester bonds
2
O
O P O
O
O
H2C
TR
5'
1
EC
O OH
O P O
O
O
H2C
3'
O
–
O
O
O
OH OH
P O P O P O H2C O
O–
O–
O–
OH OH
R
3
4
3'
O
H
CH2
O
O
O P O–
H O
CH2
O
O
O P O–
H O
CH2
O
O
O P O–
H O
CH2
O
O
O P O–
H O
O
CH2
O
5'
Fig. 4.7. Elongation – the main reaction in the synthesis of new DNA molecule: 1 – a new synthesized strand;
2 – the template DNA strand; 3 – incoming deoxyribonucleotide triphosphate; 4 – the nitrogenous base
CHAPTER 4. Organization of information and energy flow in the cell. Molecular basis of heredity...
3' 5'
3'
5'
1
2
3'
3
5'
1
3
1
4
2
5' 3'
5' 3'
TE
1
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5' 3'
IC
Fig. 4.8. Replication of leading and lagging DNA strands:
1 – primer; 2 – leading strand; 3 – lagging strand; 4 – Okazaki fragments.
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3. A DNA molecule is able to repair. It is processes by which a cell identifies and corrects damage to the DNA molecules and maintains stability of hereditary information.
There are different mechanisms of DNA repair:
`` Replicative repair.
DNA polymerase has both polymerase and exonuclease activities. It checks itself during
the replication process. If non-complementary nucleotides are incorporated into growing
strand, they are removed by DNA polymerase and replaced by complementary ones. This
process is termed as proofreading. It provides 10-fold reduction of the replication mistakes (from 1 in 100 000 nucleotides to 1 in 1 000 000).
`` Pre-replicative repair corrects mistakes before DNA replication. The examples are
photoreactivation (photorepair) and excision repair.
Photoreactivation corrects DNA damages caused by UV rays. The major alteration of
DNA by UV rays is intra-strand linkage of adjacent pyrimidines, usually thymines, called
thymine dimers. It creates distortion in helix and affects replication and transcription. Enzyme photolyase, with cofactor folic acid, binds to thymine dimer. When light shines on a
cell, folic acid absorbs the light and uses the energy to break the bond between thymines.
This kind of direct DNA repair is common to a variety of prokaryotes, yeasts, some species
of animals and plants but not to humans.
In excision repair, the damaged DNA is recognized and removed (Fig. 4.9). The resulting gap is then filled in by synthesis of a new DNA strand, using the undamaged complementary strand as a template. Many enzymes, including nucleases, helicase, polymerase
and others, are involved in this process. Excision repair is the most important DNA repair
mechanisms in both prokaryotic and eukaryotic cell.
`` Post-replicative repair corrects incomplete DNA replication or mismatched nucleotides.
4.2. Information flow. Molecular basis of heredity. Nucleic acids
Dimer recognized
and cut off by
nuclease
Dimer excised
If pyrimidine dimers or some other types of
damage are not corrected before replication,
DNA polymerase can not copy the damaged region. Replication is initiated again downstream of
the dimer so daughter strand has a gap opposite
the site of damage. At the same time undamaged
strand is replicated normally. Recombination between normal and damaged DNA allows repairing the gap.
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DNA with dimer
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Excision repair
57
The Nobel Prize in Chemistry 2015 was awarded to
Tomas Lindahl, Paul Modrich and Aziz Sancar
”for mechanistic studies of DNA repair”.
Nick sealed by
DNA ligase
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DNA Iigase
Defects of DNA repair in the cell cause the accumulation of mutations that eventually leads to
the rapid aging of the cells and development of
tumours. For example, hereditary non-polyposis
colorectal cancer results from mutations of genes
that control mismatch DNA repair.
There is a group of hereditary disorders known
as disorders of DNA repair. The most known studied of these diseases is xeroderma pigmentosum
that manifest with freckles, pigmentation spots,
photophobia, and skin cancer developing in
100 % of cases.
IC
Gap filled by
DNA polymerase
DNA
polymerase
EC
Fig. 4.9. Principle of excision repair
Ribonucleic Acid (RNA)
R
Function. RNA provides the process of protein biosynthesis, thus provides the realization of hereditary information. In some viruses it stores genetic information.
Location. RNA occurs in nucleus and cytoplasm.
Chemical composition. A RNA molecule is a single chain of ribonucleotides. A ribonucleotide consists of three molecules: phosphate, ribose sugar and nitrogenous base. The
nitrogenous base may be adenine, guanine (purines), cytosine and uracil (pyrimidines).
The main differences in chemical composition of RNA and DNA are:
1. RNA is a single polynucleotide chain.
2. It has uracil instead of thymine.
3. It contains ribose sugar.
RNA is formed on the DNA template. In a RNA molecule neither adenine and uracil nor
cytosine and guanine are necessary in equal amounts.
58
CHAPTER 4. Organization of information and energy flow in the cell. Molecular basis of heredity...
3'
OH
8
7
8
6
1
2
5'
CCA
3'
D
5' P
7
TE
1
2
A
5
3
IC
4
B
3
2
TR
Fig. 4.10. tRNA: A – secondary structure; B – tertiary structure. 1 – pseudouridine loop; 2 – dihydrouridine loop;
3 – anticodon loop; 4 – variable loop; 5 – anticodon; 6 – acceptor stem; 7 – acceptor site; 8 – hydrogen bonds
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There are several types of RNA – messenger or template (mRNA), ribosomal (rRNA),
transfer (tRNA), small nuclear and nucleolar (snRNA, snoRNA), microcytoplasmic RNA (miRNA) and other.
mRNA carries genetic information about the sequence of amino acids from DNA to ribosome and serves as a template for protein biosynthesis. Its length varies and usually
contains several thousand nucleotides. It forms about 0.5–5 % of total RNA of a cell.
rRNA forms structural carcass of ribosomes and participates in the protein synthesis
in ribosomes. In eukaryotes large subunit of ribosome has three rRNAs (28S, 5.8 S, 5S) and
small subunit has one rRNA (18S). It forms about 90 % of the total RNA of a cell.
tRNAs carry amino acids to the ribosomes. They act as adapters during protein synthesis
and link the nucleotide sequence of the messenger RNA to the amino acid sequence of the
polypeptide. Each tRNA can combine with only one specific to it amino acid. tRNA is a small
molecule (70–100 nucleotides) folded as clover leaf (two-dimensional secondary structure)
(Fig. 4.10). The clover-leaf structure has stems and loops. These include the acceptor stem
for amino acid attachment and anticodon loop with three nucleotides (anticodon). Anticodon binds to a matching codon of mRNA for recognition. Tertiary structure of tRNA is
L-shaped. Peculiarity of tRNA is presence of modified nitrogenous bases as dihydrouridine
and pseudouridine. It forms about 10% of total RNA of a cell.
snRNAs (100–220 nucleotides) are involved in maturation (processing) of mRNA, snoRNAs participate in processing of rRNA.
4.3. Gene and its structure. Genetic code
59
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miRNAs are small molecules (21–23 nucleotides) that suppress expression of the gene
at the level of translation in the ribosomes. These are single-stranded RNA molecules that
are complementary to regions of one or more messenger RNA molecules. They down regulate the expression of some genes by complementary pairing with mRNA that blocks translation and speeds degradation of mRNA.
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4.3. Gene and its structure. Genetic code
EC
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The unit of hereditary information is a gene.
A gene is a fragment of a DNA molecule, which encodes the primary structure of protein, rRNA, tRNA and other RNAs, or regulates the transcription of another gene.
According to this definition genes are divided into structural and regulatory ones.
Structural genes encode proteins and all types of RNA. Regulatory genes (regions) regulate
transcription of structural genes. Structural genes conventionally are divided into “housekeeping” genes (are active in all types of the cells and maintain their existence) and genes
of terminal differentiation or “genes of luxury” (are active just in certain type of the cells or
certain period of ontogenesis, provide specific functions of the cells).
Protein coding gene has a coding region and regulatory regions at 5’ and 3’ ends of the
gene (Fig. 4.11). Regulatory regions are promoter, terminator, enhancers and silencers.
Promoter region is situated upstream (5’ end) of the coding region. It has conserved
DNA sequences (GC-box, CAAT-box and TATA-box) recognized by RNA-polymerase and
other proteins (transcription factors), thus it regulates expression of the gene.
Terminator region is a DNA sequence just downstream of the coding segment of
a gene (3’ end), which is recognized by RNA polymerase as a signal to stop transcription.
Enhancers or silencers are regulatory regions that enhance or suppress transcription.
They may be situated upstream or downstream of the gene, near or far from it and even in
another chromosome.
Coding region in eukaryotes consists of exons and introns. Exons (from the word expressed) encode amino acids. Introns (from the word intervening) – do not specify amino
acids, so are transcribed but not translated. In prokaryotes coding regions lack introns.
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Start point of transcription (+1)
Promoter
Intron 1
Exon 1
5'
GC-box
CAATbox
TATAbox
Region that terminates RNA synthesis
Intron 2
Intron 3
Exon 2
Exon 3
Exon 4
Terminator
3'
protein-coding region
5'-leader
Fig. 4.11. Structure of the eukaryotic gene
3'-trailer
Transcription unit
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CHAPTER 4. Organization of information and energy flow in the cell. Molecular basis of heredity...
The 1993 Nobel Prize in Physiology or Medicine was awarded to Richard J. Roberts and
Phillip A. Sharp “for their discoveries of split genes” (exons and introns).
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A typical human gene is composed of approximately 28 000 bases and has 8 exons. It
encodes a polypeptide consisting of an average of 447 amino acids. The longest human
gene encodes protein dystrophin of the muscle cells and contains 2.4 × 106 b.p.
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Genetic code
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IC
Hereditary (genetic) information is information about the structure of proteins and the
peculiarities of protein synthesis. This information is kept in DNA as a system of genetic code.
Genetic code is a sequence of nitrogenous bases in a DNA molecule which determines
the sequence of amino acids in a protein molecule (Fig. 4.12).
Main features of the genetic code are following:
1. Triplet nature – one amino acid is specified by three adjacent nucleotides. A group
of three nucleotides that specify one amino acid is called codon or triplet. There are
20 amino acids and only 4 nitrogenous bases. American theoretical physician and
cosmologist George Gamow (was born in Odessa, Russian Empire) suggested three
letter code, i.e. each codon (code word) consists of three nitrogenous bases. This will
give 43 = 64 code words, which is enough to code all amino acids.
SECOND LETTER
U
G
ucu
UCC Serine (S)
UCA
UCG
UAU Tyrosine (Y)
UAC
UAA stop codon
UAG stop codon
UGU Cysteine (C)
UGC
UGA stop codon
UGG Tryptophan (W)
U
C
A
G
C
CUU
CUC Leucine (L)
CUA
CUG
CCU
CCC Proline (P)
CCA
CCG
CAU Histidine (H)
CAC
CAA Glutamine (Q)
CAG
CGU
CGC Arginine (R)
CGA
CGG
U
C
A
G
A
AUU
AUC Isoleucine (I)
AUA
AAU Asparagine (N)
AAC
AGU Serine (S)
AGC
AUG Methionine* (M)
ACU
ACC Threonine (T)
ACA
ACG
GUU
GUC Valine (V)
GUA
GUG
GCU
GCC Alanine (A)
GCA
GCG
AAA Lysine (K)
AAG
GAU Aspartic acid (D)
GAC
GAA Glutamic acid (E)
GAG
AGA Arginine (R)
AGG
GGU
GGC Glycine (G)
GGA
GGG
U
C
A
G
EC
R
L
E
T
T
E
R
A
UUU Phenylalanine (F)
UUC
UUA Leucine (L)
UUG
U
F
I
R
S
T
C
G
T
H
I
R
D
L
E
T
T
E
R
U
C
A
G
* The start codon encodes the amino acid methionine
Fig. 4.12. Genetic code. Full names and one letter amino acid abbreviations are given
4.3. Gene and its structure. Genetic code
61
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2. Degeneracy or redundancy – most of the amino acids are specified by more than
one codon (2–6 triplets) as number of possible triplets is more than number of amino
acids. Codons that specify same amino acid are called synonyms. As usual, such codons differ by the third nucleotide. Degeneracy of genetic code minimizes the consequences of mutations and base pairing errors.
3. The code is specific (nonambiguous) – particular triplet codes a certain one amino
acid.
4. There are 61 meaning triplets that specify amino acids. Three triplets – UAA, UAG,
UGA – do not specify any amino acid, so, are called nonsense (meaningless) codons.
They are also called termination codons as are the signals of termination of the translation. AUG codon (Met) is called starting or initiation codon as it initiates the synthesis of polypeptide chain.
5. Universality of genetic code – the genetic code is the same in all living organisms.
There are some exceptions to the rule (several codons in mitochondrial DNA specify
other amino acids comparing with nuclear DNA).
6. The code is commaless – there is no punctuation (gaps) between the adjacent codons.
7. The code is nonoverlapping – each nucleotide is a part of only one codon.
8. Collinearity of genetic code – a linear arrangement of the codons in mRNA determines a linear arrangement of amino acids in a protein molecule.
The 1968 Nobel Prize in Physiology or Medicine was awarded to Robert W. Holley,
Har Gobind Khorana and Marshall W. Nirenberg “for their interpretation of the genetic code
and its function in protein synthesis”.
Molecular mechanisms of variation
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EC
Changes in the nucleotide sequence in DNA molecule are called gene mutations. Such
mutations can cause synthesis of abnormal proteins.
Main molecular mechanisms of gene mutations are: replacement, deletion, duplication and insertion of nucleotides. They are results of mistakes in natural processes
(modification of nitrogenous bases, mistakes in DNA replication and so on) or action
of different mutagenic factors. If not corrected by repair mechanisms they become
the source of variation on molecular level. As genetic code is specific replacement of
the first or the second nucleotide in the codon usually causes replacement of amino
acid in the protein. Replacement of the third nucleotide is not accompanied with the
replacement of amino acid in most of cases due to degeneracy of genetic code. If stopcodon is formed as a result of mutation, it causes premature arrest of protein synthesis
and production of truncated protein. Deletion or duplication not a multiple of three
nucleotides leads to the shifting of all codons downstream the mutation (frame shift
mutations).
Molecular mechanisms of variation will be discussed in details in the Chapter 8.2.
62
CHAPTER 4. Organization of information and energy flow in the cell. Molecular basis of heredity...
4.4. Expression of genes. Protein biosynthesis
DNA
D
Gene expression is the realization of hereditary information. It is a process by which
information from a gene is used in the synthesis of a functional gene product. These products are proteins or functional RNA.
In realization of hereditary information DNA encodes the proteins, and the proteins determine characters:
character
TE
protein
The 1958 Nobel Prize in Physiology or Medicine was awarded to George Wells Beadle and Edward
Lawrie Tatum “for their discovery that genes act by regulating definite chemical events”.
Protein biosynthesis goes on according to the scheme:
transcription
translation
mRNA
Protein.
IC
DNA
TR
Protein biosynthesis includes several steps (Fig. 4.13):
`` Transcription.
`` Activation of amino acids.
`` Translation.
`` Post-translational modification.
promoter
EC
DNA
leader
cap
leader
R
hemoglobin β-chain
exon-1
exon-2
intron-2
exon-3
trailer
Transcription
leader exon-1 intron-1
pre mRNA
mRNA
exon-1
intron-1
exon-2 intron-2
exon-3
trailer
poly-A site
Poly AAAA-
processing
exon-2
exon-3
trailer
AAAA
translation
H2N
COOH
posttranslational modification
hemoglobin
transport of gases (character)
expression
Fig. 4.13. Stages of hemoglobin β-chain gene expression
terminator
4.4. Expression of genes. Protein biosynthesis
General transcription factors
63
DNA coding strand
3'
3'
D
5'
5'
3'
Promoter
mRNA
DNA template strand
RNA polymerase
TE
5'
Fig. 4.14. Transcription
IC
Transcription is the process of mRNA synthesis on DNA template. After the local uncoiling of DNA mRNA is synthesized according to complementary principle. This process
is carried out by enzyme RNA polymerase and requires associated proteins (general transcription factors) for initiation (Fig. 4.14).
The DNA strand that serves as a template in transcription is called template strand. Its
complementary strand is termed coding or sense strand.
5’ T A C G T T C G A T C C 3’
3’ A T G C A A G C T A G G 5’
TR
Coding or sense or
Nontemplate strand of DNA
Template strands
Transcription of template strand
EC
mRNA
5’ U A C G U U C G A U C C 3’
R
Transcript is complementary to a template strand and has same sequence of nucleotides as a nontemplate coding strand (but contains U instead of T).
As in eukaryotes genes have exons (coding sequences) and introns (non-coding
sequences) mRNA which is formed is a precursor mRNA (pre-mRNA). Pre-mRNA has
same sequence of nucleotides as DNA has, so consists of exons and introns. The process
of pre-mRNA maturation is termed processing (Fig. 4.15). It includes splicing, capping
and polyadenylation. Special enzymes in complex with small nuclear RNA (snRNA) cut
off the introns and binds exons. This process is called splicing. The newly formed mature mRNA consists of exons and is shorter than pre-mRNA. In some cases, the exons
can be put together in different ways to generate several types of mRNAs (alternative
splicing). Thus, one gene can control synthesis of several proteins with different functions.
Capping is modification of the head (5’ end) of mRNA by adding of 7-methylguanosine
triphosphate. Polyadenylation is addition of up to 250 adenines to the 3’ end of the mRNA
64
CHAPTER 4. Organization of information and energy flow in the cell. Molecular basis of heredity...
Gene
Intron 1
exon 1
pre-mRNA
exon 3
Intron 2
Transcription
(RNA synthesis)
exon 2
exon 3
D
Chromosomal DNA
exon 2
TE
exon 1
RNA Splicing
Fig. 4.15. Processing of mRNA
exon 2
exon 3
AAAA
poly A-tail
IC
cap
exon 1
Messenger RNA
TR
(formation of poly-A tail). The same gene may have multiple polyadenylation signals thus
gives several types of mature mRNA (alternative polyadenylation).
Capping and polyadenylation protects mRNA from degradation in cytoplasm, are required for interaction with the ribosomes. Mature mRNA leaves the nucleus and is transported into cytoplasm towards the ribosomes.
2. Activation of amino acids is charging of tRNA with amino acids. Amino acids in the
cytoplasm occur in inactive stage and cannot take part in protein synthesis. Activation of
amino acids takes place in cytoplasm in two steps:
`` adenylation of the amino acid, which forms aminoacyl-AMP and diphosphate
EC
amino acid + ATP → aminoacyl-AMP + PP
`` after this amino acid residue is transferred to the tRNA
aminoacyl-AMP + tRNA → aminoacyl-tRNA + AMP
R
Aminoacyl-tRNA complex (charged or loaded tRNA) becomes reach with energy to
form peptide bonds in a process of translation.
The charging of tRNA is under the control of specific for each type of amino acid enzyme aminoacyl-tRNA-synthetase. For twenty amino acids 20 different enzymes and at
least 20 different types of tRNA molecules are required (usually more due to degeneracy
of genetic code).
3. Translation is the process in which sequence of nucleotides in mRNA is translated
into the sequence of amino acids of a polypeptide chain. Process occurs in ribosomes and
involves following stages: initiation, elongation and termination. Each ribosome has a
binding site for mRNA on its small subunit. Large ribosomal subunit has binding sites for
4.4. Expression of genes. Protein biosynthesis
Ala
5
Met*
65
3
P
1
D
Met*
Met*
A
2
4
TE
6
Fig. 4.16. Initiation of translation – assembling of a protein-synthesis complex:1 – mRNA; 2 – small ribosomal subunit; 3 – initiator tRNA; 4 – start codon of mRNA; 5 - large ribosomal subunit; 6 – active ribosome
R
EC
TR
IC
tRNA: the peptidyl site and the aminoacyl one. The peptidyl site (P site) holds the tRNA carrying the growing polypeptide chain, while the aminoacyl site (A site) holds a tRNA carrying the next amino acid to be added to the chain. So two codons of mRNA complementary
to anticodons of two tRNAs participate in translation simultaneously.
During initiation, the mRNA, the initiator tRNA with Met and the ribosome associate
with each other to form a translation complex (Fig. 4.16). Small ribosomal subunit binds to
mRNA. Initiator tRNA with methionine attaches to the start codon AUG of mRNA. A large
ribosomal subunit binds to the small one creating a functional ribosome in such manner
that initiator tRNA with methionine occupies P site of large subunit. This process requires
set of assistant proteins (eukaryotic initiation factors) and energy.
Elongation is adding of amino acids and growing of the polypeptide chain (Fig. 4.17).
tRNA anticodon pairs with the mRNA codon in the A site of the ribosome. If they are complementary two adjusted amino acids in A and P sites bind by peptide bond. By this one
more amino acid is added to the chain and polypeptide from P site is translocated to the
tRNA in A site. Free tRNA releases from P site and the ribosome moves along the mRNA one
triplet forward. The tRNA with growing polypeptide is translocated from A site to the P site.
A site becames vacant and next charged tRNA enters the ribosome and occupies it. Elongation requires eukaryotic elongation factors and energy.
Termination of translation occurs when A site of the ribosome reaches the stop (termination) codon. There are no tRNAs able to bind to the termination codons. Special proteins
(eukaryotic release factors) enter the ribosome and cause polypeptide to be released.
mRNA can be translated by several ribosomes at once forming a polysome (polyribosome). Ribosomes, mRNA , tRNAs are used for translation many times.
4. Post-translational modification. Ribosome produces a polypeptide strand which
is a primary non-functional structure of the protein. After translation the polypeptide
coils and folds, assuming its secondary, tertiary or for some proteins quaternary structure.
Chemical modification may involve cleavage of polypeptide chain, methylation, acetylation and other processes. Quite often post-translational modification occurs in endoplasmic reticulum and Golgi complex.
66
CHAPTER 4. Organization of information and energy flow in the cell. Molecular basis of heredity...
4.5. Regulation of gene
expression in prokaryotes
and eukaryotes
Proline
A
G
P
A
UA C
3'
AUG C C U
mRNA
B
Methionine
Proline
5'
A
UA C G GA
IC
P
3'
A UG C C U
mRNA
TR
C
Methionine
tRNA
Proline
A
P
G GA
5'
3'
A UG C CU
EC
mRNA
Arginine
D
Proline
Methionine
R
P
5'
A
G GA
A complex system of protein biosynthesis regulation is present in every cell.
In prokaryotes most of structural
genes are present in one copy and combined into operons. Operon is a group
of functionally related structural genes
and associated control genes that regulate certain metabolic process.
The concept of operon was proposed by Francois Jacob and Jacques
Monod in 1961. While studying the
catabolism of lactose in E. coli, Jacob
and Monod paid attention that several enzymes required for lactose utilization appear only in the presence of
lactose. Based on this fact they created
concept of operon regulation by the
feedback principle. Lactose operon
includes three structural genes for lactose metabolic pathway and common
regulatory regions. These are regulator, promoter, operator and terminator
(Fig. 4.18).
1. The regulator gene specifies
protein which acts as a repressor
substance. This repressor protein
binds to the operator gene and
suppresses operon activity.
2. The promoter gene is the DNA
segment at which RNA-polymerase binds. It initiates the transcription of structural genes.
3. The operator gene is the DNA segment, which lies downstream the
promoter and close to the structural gene. It controls the transcription by binding repressor protein.
TE
5'
GA
D
Methionine
3'
A UG C CU U CU
Fig. 4.17. The mechanism of the polypeptide chain
elongation
4.5. Regulation of gene expression in prokaryotes and eukaryotes
67
Structural genes
Promoter
Operator
DNA
B
C
Transcription is blocked.
Enzymes are not synthesized
RNA-polymerase
mRNA
A
Repressor protein
A
DNA
RNA-polymerase
mRNA
Repressor
protein
Inactivated
repressor
B
C
B
C
Transcription
A
Formation of mRNA
Translation. Synthesis of enzymes that breakdown lactose
IC
II
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I
Terminator
D
Regulator gene
Inducer (Lactose)
A
B
C
TR
Fig. 4.18. Functioning of E. coli lactose operon: I – supression; II – induction
EC
4. The terminator gene is the DNA segment at the end of operon, which gives a signal
to stop transcription.
If bacteria are cultured without lactose repressor protein binds to the operator site and
prevents the transcription. As a result, enzymes encoded by structural genes are not formed.
When lactose is introduced in the nutritive medium it binds to the repressor protein
and removes it from operator site. Free operator allows transcription, so enzymes necessary for lactose catabolism are formed. In this case lactose (substrate of reaction) works as
the inducer for operon switching on.
The 1965 Nobel Prize in Physiology or Medicine was awarded to François Jacob, André Lwoff and
Jacques Monod “for their discoveries concerning genetic control of enzyme and virus synthesis”.
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Regulation of gene expression in eukaryotes
In eukaryotes operon control of gene expression is absent. Each gene has its own
regulatory elements as promoter, terminator, enhancers and silencers. Human genome
is characterized by complex organization. There are about 22 000 structural genes in 24
linkage groups (22 autosomes and 2 sex chromosomes) that specify synthesis of more
than 250 000 different proteins. It is explained by several mechanisms. Some of them
are:
CHAPTER 4. Organization of information and energy flow in the cell. Molecular basis of heredity...
A
NH2
N
O
NH2
Methylated DNA
DNA methylCH3
transferases N
5'–CpG–3' O
3'–GpC–5'
N
N
Methylation
Acetylation
D
68
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Unmethylated
transcription
IC
B
Histone Acetylation
Ас
Ас
Ас
Ас
Ас Ас
Ас
Ас
Ас
Ас Ас
TR
Ас
Ас
Histone Deacetylation
Ас
Ас Ас
Ас
Ас Ас
Ас
Ас
Ас
Ас
Ас Ас
Ас Ас
Ас
Ас
Ас
Ас Ас
Fig. 4.19. Mechanisms of epigenetic regulation: A – methylation of DNA switchs off transcription; B – acetylation of histones permits transcription.
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`` both strands of DNA can be used as a template for transcription. As they are copied
in opposite directions resulting RNAs are completely different and are translated into
different proteins;
`` large introns of some genes can code small proteins (genes inside the genes);
`` same gene in different tissues can be transcribed from different promoter regions;
`` alternative splicing and alternative polyadenylation can give different mature mRNAs from the same primary transcript (pre-mRNA);
`` in the cytoplasm mRNA can pass through the RNA edition (replacement of the nucleotide with stop-codon forming). By this mechanism long and short protein versions
are formed in different tissues.
Control of gene expression occurs at different levels. It might be amplification (multiple
replication) of certain region for intensification of protein biosynthesis.
On the transcription level the most important mechanisms are methylation of cytosine
in CpG dinucleotide sequences upstream the promoter (switches off the transcription) and
acetylation of histone proteins (Fig. 4.19). Acetylation removes the positive charge of the histones and transform chromatin complex into a more relaxed structure that is associated
4.6. The human genome
69
D
with greater level of transcription. Modification of DNA and chromatin that shifts gene
activity without changes in the nucleotide sequence is termed as epigenetic regulation.
Hormones, factors of transcription, enhancers and silencers also influence intensity of transcription.
Example of regulation of gene expression on the post-translation level is RNA interference. MicroRNA molecule binds to target mRNA and stimulates its degradation with
ribonucleases.
TE
The Nobel Prize in Physiology or Medicine 2006 was awarded jointly to Andrew Z. Fire and Craig
C. Mello “for their discovery of RNA interference–gene silencing by double-stranded RNA”.
4.6. The human genome
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EC
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IC
The genome is a set of hereditary material (DNA) of the cell including coding and noncoding regions of DNA. In humans, the genome contains the sequence of DNA within the
24 chromosomes (22 autosomes and two sex chromosomes X and Y) and in a circular DNA
molecule in mitochondria.
The Human Genome Project. The DNA sequence has been identified in the performance of the international research project “Human Genome” that started on 1 October
1990. The main goals of the Human Genome Project were to determine the nucleotide
sequence of human genome and to construct genetic maps. A preliminary version of the
human genome sequence was published in 2001 and the almost completed version in
2003. In process of project implementation, the genomes of many prokaryotic and eukaryotic organisms have also been sequenced and methods of molecular genetic testing have
been perfected.
Despite the human genome is successfully sequenced now, the functions of some DNA
regions have not yet been fully clarified. Currently, the human transcriptome (set of all synthesized RNAs) and proteome (set of all synthesized proteins) are being intensively studied.
Deciphering the functions of all synthesized RNA and proteins of the human body will help
to understand the functions of all parts of the genome.
The completion of Human Genome Project has important applications for the theory
and practice of medicine. The resulting data allowed to understand the etiology of hereditary diseases and to improve methods of diagnosis and treatment. They are now used in
medicine, forensics, anthropology, etc.
Online information about human genome is given on Human Genome Website: https://
www.ncbi.nlm.nih.gov/ and website of United States National Human Genome Research
Institute (NHGRI: http://www.nhgri.nih.gov/).
Organization of human genome. The genomes of all eukaryotes, including man, are
characterized by the presence of a large amount of non-coding and repetitive DNA.
The human genome contains 3.2 billion (3,2 × 109) pairs of nucleotides (bp). The protein-coding sequences (exons) occupy only 1.5 % of the genome. More than 98 % of the hu-
70
CHAPTER 4. Organization of information and energy flow in the cell. Molecular basis of heredity...
LTR retrotransposons
DNA transposons
SINEs
Miscellaneous
heterochromatin
2.9 %
8.3 %
13.1 %
IC
Simple sequence repeats
3%
Segmental duplications
TE
D
man genome is non protein-coding DNA with different functions. These sequences either
participate in regulation of gene expression and contain signals of epigenetic control or
are important in organization of chromosome structure. It has been established recently
that about 75 % of the human genome is transcribed into RNA molecules. Functions of
most of this RNAs are still unknown.
About 45 % of DNA sequences are seen only ones in genome (single-copy DNA sequences) and about 55 % are repetitive DNA sequences.
According to their functions, sequences of human DNA can be classified into several
types (Fig. 4.20):
5%
8%
20.4 %
LINEs
1.5 %
TR
11.6 %
25.9 %
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Miscellaneous
unique sequences
0
10
20
30
% C or G
R
50
Introns
60
41
21%
LINEs
40
Exons of
protein-coding
genes
70
80
90
100
% A or T
34% 42%45%48%53%
90.5% 92% 100
DNA
transposon
'fossils'
Retrovirus-like Segmental
elements
duplications
Simple sequence repeats
Heterochromatin
Introns Protein coding
regions
SINEs
Repeats
Fig. 4.20. Principle organization of human genome
Genes
Unique
4.6. The human genome
71
D
1. Protein-coding genes and gene-related sequences (sequences which lie between
genes, areas of transcription regulation, pseudogenes).
2. Genes for non-protein-coding RNAs.
3. Repetitive DNA sequences:
`` dispersed repetitive DNA;
`` satellite DNA.
4. Mitochondrial DNA.
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EC
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IC
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Protein-coding genes and gene-related sequences. The human genome contains
approximately 22 000 protein-coding genes that can encode up to 250 000 or even more
proteins.
As noted above coding sequences of the genes (exons) account for only a very small
fraction of the genome (1.5 %). Non-coding introns occupy about 26 % and known regulatory sequences occupy about 5–8 % of the human genome.
The protein-coding genes are not equally distributed in the chromosomes. Some human chromosomes are gene-rich and others are gene-poor. For example, chromosomes
13, 18, and 21 are relatively gene-poor. Trisomy on these chromosomes are compatible
with the livebirth. In general, euchromatic regions of chromosomes (light bands under Gdifferential staining method) are gene rich and heterochromatic regions (dark bands) are
gene-poor.
Most protein-coding genes and gene related sequences belong to a single-copy DNA.
Their mutations cause monogenic disorders (single gene disorders). Complete information
about genes and associated monogenic disorders can be found on the website OMIM –
Online Mendelian Inheritance in Man (https://www.ncbi.nlm.nih.gov/omim).
Some protein-coding genes form gene families. It is group of genes with similar biochemical structure, formed by duplication of a single gene. They specify proteins with
common function. Examples include the globin, immunoglobulin, histones, and olfactory
receptors gene families. The members of the gene families are located in a single cluster,
multiple clusters, or are dispersed in the genome.
Gene-related sequences include sequences which lie between genes (spacers), areas of transcription regulation (enhancers, silencers, etc) and pseudogenes. The human
genome contains about 13.000 pseudogenes. These are functionally inactive copies of
the genes due to absence of promoter region or accumulation of inactivating mutations.
Some pseudogenes are not transcribed, some can be transcribed, but not translated
into proteins or give non-functional protein. Most pseudogenes belong to repetitive sequences.
Many pseudogenes are members of gene families. For example, the family of olfactory
receptor genes includes about 350 functional genes and about 600 pseudogenes.
2. Genes of non-protein-coding RNA. Non-protein-coding RNA genes encode functionally important RNAs such as ribosomal RNAs (rRNAs), transfer RNAs (tRNAs) and other
types of RNAs. They participate in RNA processing and protein synthesis. The functions of
many types of RNAs are still unknown.
72
CHAPTER 4. Organization of information and energy flow in the cell. Molecular basis of heredity...
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There are 497 nuclear genes encoding cytoplasmic tRNA molecules. They are grouped
into 49 families according to their anticodon features. These genes are found in all chromosomes, except 22 and Y chromosome.
The human genome contains about 650-900 genes for ribosomal RNAs (rRNAs) of the
large and small subunits. Most of them are located in clusters in the short arms of the five
acrocentric chromosomes (13, 14, 15, 21, and 22).
There are approximately 100 genes for small nuclear RNA (snRNA) and 200 genes for
small nucleolar RNA (snoRNA) in the human genome. Most of them are grouped in clusters.
More than 700 genes for miRNAs have been identified.
3. Repetitive DNA sequences account about 55 % of the human genome. They play a
major role in the maintenance of chromosome structure. The human genome has a much
greater portion of repeat sequences comparing with many other organisms (i.e., in mustard weed – 11 %, in round worm Caenorhabditis elegans – 7 % , and in fruit fly Drosophila
melanogaster – 3 %).
There are two main classes of repetitive DNA: satellite DNA and dispersed repetitive
DNA.
Satellite DNA are repetitive regions clustered together in certain chromosome locations, where they form tandem repeats (one after another). It occupies about 8 to 10 % of
the human genome and includes α-satellite DNA, minisatellites and microsatellites.
Α-Satellite DNA (alphoid sequence) is located near the centromeres of chromosomes. It
reaches several million pairs of nucleotides or more with repeating fragment of 171 pairs of
nucleotides. This region is important for attachment of spindle fibers during mitosis or meiosis.
Minisatellites (also known as variable number tandem repeats – VNTRs) are tandem repeats with total length usually a few thousand base pairs. The repeating fragment consists
of 14 to 500 bp.
Microsatellites (short tandem repeats – STRs) contain usually multiple copies of bi-,
tri- , or tetranucleotide repeat sequences. The repeat unit varies from 1 to 13 bp. The total
length of these repeats is usually less than a few hundred base pairs. Among the microsatellite sequences, trinucleotide repeats sometimes occur within protein-coding genes. The
number of this repeats can increase (expansion of trinucleotide repeats) and may lead to
genetic disorders. Telomeres of human chromosome consist of a microsatellite hexanucleotide repeats of the sequence (TTAGGG)n.
Minisatellites and microsatellites account for about 3 % of the genome. The number
of copies in clusters of mini–and microsatellites is highly individual (tandem repeat polymorphism) and inherited according to the laws of Mendel. Both types of tandem repeats
are useful in forensic practice for paternity testing and identification of individuals (DNA
fingerprinting).
Dispersed repetitive DNA sequences occupy about 45 % of the genome and are scattered singly throughout the genome (they do not occur in tandem). It belongs to transposable (mobile) elements. A transposable element is a DNA sequence that can change its
position within a genome (jumping genes). Jumping genes were discovered by Barbara
McClintock in 1949.
4.7. Energy flow in a cell
73
The Nobel Prize in Physiology or Medicine 1983 was awarded to Barbara McClintock “for her discovery of mobile genetic elements”.
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Genomic variability
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Dispersed repetitive DNA includes short interspersed nuclear elements (SINEs) and long interspersed nuclear elements (LINEs). They were formed due to reverse transcription. SINEs are
represented by fragments of 100–300 bp in length, which are present in about 1.5 million
copies (13 % of the human genome). LINEs are fragments with a length of 5–8 kbp that occur in about 850 thousand copies in genome. They take about 21 % of the human genome.
Originally transposable elements had the ability to move within the genome, but many
have lost this ability as a result of inactivating mutations. Some elements retain the ability to generate copies of themselves, which can then be inserted into other parts of the
genome. These insertions can inactivate the protein-coding genes and cause hereditary
diseases.
Mitochondrial DNA is a circular DNA (mtDNA) that consists of 16568 bp. It has 13 protein-coding genes, 22 genes of tRNAs, and 2 genes of rRNAs. The mitochondrial genes are
important for energy generation in the cell. Human mtDNA has a mutation rate ~20 times
higher than nuclear DNA due to presence of mutagens and absence of repair system. Mutations of mtDNA can cause mitochondrial diseases with a maternal type of inheritance
(transmission from the mother to all children with cytoplasm of egg).
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The human genome sequence is almost exactly (99.9 %) the same in all people. However, 0.1 % of the DNA sequence is different. It means that each human haploid DNA sequence (the sequence inherited from one parent) differs from any other human haploid
sequence by 0.1 % of DNA base pairs. Difference among individuals in DNA sequence is
called genetic polymorphisms. The most common type of polymorphisms is the single nucleotide polymorphism (SNP). It is a variation in a single nucleotide that occurs at a specific
position in the genome. On average two haploid genomes differ in about 3 000 000 SNPs
(one SNP in about 1000 nucleotides). Other types of polymorphisms are variations in number of tandem repeats (STRs, VNTRs) and insertion/deletion polymorphisms (indels).
Genetic polymorphisms can occur in both genes and non-coding regions. They are the
molecular bases of genetic variability and individuality of the people. Some of the polymorphisms are harmless but other cause predispositions to such common complex (multifactorial) diseases as cancer, diabetes, cardiovascular diseases and some forms of mental
disorders or associated with susceptibility to certain drugs, toxins, infectious agents.
4.7. Energy flow in a cell
A cell gets energy for performing of any function by dissimilation process.
Dissimilation in animals includes anaerobic and aerobic stages.
74
CHAPTER 4. Organization of information and energy flow in the cell. Molecular basis of heredity...
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Food serves as a source of matter and energy. In gastrointestinal tract food is digested:
proteins split into amino acids, polysaccharides to simple sugars, fats to fatty acids and
glycerol molecules. Small molecules are absorbed and pass into cells. Some of them are
used for synthesis of macromolecules, and some enter anaerobic stage of dissimilation.
Anaerobic stage takes place in cytoplasm. Anaerobic breakage of glucose is called glycolysis. The result is production of two pyruvic acid molecules, hydrogen atoms and two
ATP molecules. Pyruvic acid is used in aerobic stage.
Aerobic stage occurs in mitochondria. Pyruvic acid is transported into mitochondrion
and converted into smaller molecule acetyl coenzyme A (acetyl Co-A). It is completely oxidized to water and carbon dioxide in the citric acid or Krebs cycle (in matrix) and electron
transport chain (in cristae). Released energy is accumulated by synthesis of 36 ATP molecules (oxidative phosphorylation).
Total per mole of glucose under aerobic conditions cell generates 38 high-energy phosphate bonds of ATP molecules.
TASKS & QUESTIONS
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`` Multiple Choice Questions (Choose one correct answer):
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1. There are 100 monomers in a protein molecule. How many nucleotides (fragment of
double strand DNA) specify this protein?
A. 100
C. 300
E. 900
B. 200
D. 600
2. All amino acids, with the exceptions of methionine and tryptophan are encoded by
more than one codon. This feature is referred to as:
A. Universality of genetic code
D. Specificity of genetic code
B. Colinearity
E. Triplet nature of genetic code
C. Degeneracy of genetic code
3. Action of some antibiotics on microorganisms is based on the arrest of translation. It
means the arrest of synthesis of:
A. DNA
C. rRNA
E. mRNA
B. tRNA
D. Polypeptide chain
4. Both DNA and RNA consist of nucleotides. RNA differs from DNA by the presence of:
A. Adenine
C. Guanine
E. Phosphate group
B. Ribose
D. Cytosine
5. The majority of structural genes in eukaryotes consist of sequences coding the information (exons) and intervening noncoding sequences (introns). Which molecule is
formed on these genes directly after transcription?
A. Pre-mRNA
C. snRNA
E. rRNA
B. mRNA
D. tRNA
4.7. Energy flow in a cell
75
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D
6. In eukaryotes, pre-mRNA produced directly after transcription should be transformed in mature mRNA. This process of maturation is referred to as:
A. Translation
C. Splicing
E. Reparation
B. Processing
D. Termination
7. Monomer of a DNA molecule is:
A. Amino acid
E. Nucleotide
C. Polypeptide
B. Nitrogenous base
D. Deoxyribose
8. mRNA molecule has 200 nitrogenous bases. How many nucleotides does it have?
A. 50
C. 200
E. 600
B. 100
D. 400
9. Three triplets (UAA, UAG, UGA) do not specify amino acids. These triplets are termed
A. Introns
C. Anticodons
E. Exons
B. Codons
D. Terminators
10. All types of RNA are synthesized on DNA template. Enzyme that carries out the transcription is:
C. Nuclease
E. Polimerase
A. Phosphatase
B. Lipase
D. Protease
11. Recognizing of mRNA triplets (i.e., deciphering of genetic code) during the translation occurs under the complementary principle by three-nucleotide sequence of
tRNA. This sequence is:
A. Anticodon
C. Promoter
E. Intron
B. Codon
D. Exon
12. Synthesis of primary protein structure is termed:
A. Transcription
C. Replication
E. Reparation
B. Translation
D. Termination
13. Ribosomes synthesize polipeptides (translation). In post-translation period the following occurs:
A. Replication
E. Reparation
C. Splicing
B. Processing
D. Folding
14. Which cell organelles provide formation of primary protein structure?
A. Ribosomes
C. Lysosomes
E. Nucleus
B. Golgi complex
D. ER
15. A cell contains three types of RNA: mRNA, tRNA, rRNA. Synthesis of all these molecules occur in:
A. Lysosomes
C. Nucleus
E. Golgi complex
B. Ribosomes
D. Smooth ER
16. A mRNA molecule has 110 phosphate groups. How many nucleotides does it consist
of?
A. 55
C. 220
E. 440
B. 110
D. 330
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CHAPTER 4. Organization of information and energy flow in the cell. Molecular basis of heredity...
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17. Structural genes of eukaryotes have exons and introns. Introns are removed during
the maturation of mRNA. This process is termed:
A. Processing
C. Reparation
E. Replication.
B. Splicing
D. Termination
`` FILL IN THE BLANKS:
`` TRUE OR FALSE:
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1. Two deoxyribonucleotide chains are held together by ______________ bonds between nitrogenous bases according to the ______________________________.
2. During DNA replication __________ strand is synthesized continuously and
__________ strand is synthesized discontinuously as a series of short __________
fragments.
3. _______ are involved in maturation (processing) of mRNA.
4. Translation occurs in __________ and involves following stages: ___________,
_____________, ______________.
5. Trisomy on chromosomes _____, ______ and _______ is compatible with life birth as
these chromosomes are relatively gene-poor.
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1. A gene is a fragment of a RNA molecule, which encodes the primary structure of
protein and DNA.
True
False
2. Amount of Adenine in DNA equals to the amount of Thymine and Cytosine equals to
Guanine.
True
False
3. Photoreactivation corrects DNA damages caused by UV rays.
True
False
4. On the transcription level the most important mechanism of gene regulation is acetylation of cytosine in CpG dinucleotide sequences upstream the promoter.
True
False
5. Mutations of mtDNA can cause mitochondrial diseases with a paternal type of inheritance.
True
False
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Chapter 5.
Reproduction on the cellular
and organismic level
TE
5.1. Mitotic cycle. Mitosis. Cell death
Cell (mitotic) cycle
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The growth and development of every multicellular organism is provided by the multiplication, growth and differentiation of its cells. The asexual and sexual reproduction of the
organisms also depends on cell division.
There are the following ways of cell division in animals and plants:
1. Mitosis or indirect cell division.
2. Meiosis or reduction division.
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Cell cycle is the period from forming of the new cell up to the end of the next division or
cell death. It includes all the events that happen during this period like growth, differentiation, functioning of the cell, preparing for division and the division itself.
In continuously dividing cells, an individual cell passes through the following two main
phases of mitotic cycle (Fig. 5.1):
A. Interphase.
B. Mitotic phase (mitosis).
Interphase. A stage between the two mitotic divisions is called an intermitotic phase or
interphase (from Latin inter – between; from Greek phasis – appearance). The interphase
is the longest phase of the mitotic cycle and occupies about 90 % of the cell cycle. At this
period:
`` The nuclear envelope remains intact.
`` The chromosomes are diffused, long, coiled and indistinctly visible chromatin fibers.
`` The nucleus and cytoplasm remain metabolically active. There is active synthesis
of RNA, proteins, enlargement of the organelles size and number, so offspring cells
grow to maternal size.
Interphase is divided into three sub-phases:
1. G1-phase (G from the word gap) is post-mitotic or pre-synthetic phase. The main
events include growth, differentiation of the cell, synthesis of different proteins including enzymes required for DNA-synthesis. Set of hereditary information is 2n2c
(n – number of chromosomes, c – number of chromatids (DNA molecules). It means
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Chapter 5. Reproduction on the cellular and organismic level ...
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rs
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Prophase
Me
tap
has
e
G 2 5 Hou
2–
Mitosis (M)
that each chromosome has just a single
One hour
chromatid (one DNA molecule). In somatic
human cell it is 46 chromosomes, 46 DNA.
2. S-phase is synthetic phase. Replication
S
(synthesis) of DNA molecules occurs, so at
se
6–8 H
pha
a
n
ours
A
the end of this phase each chromosome
Telophase
has two chromatids. Set of hereditary inG0
formation at the end of this phase is 2n4c.
G1
In somatic human cell it is 46 chromo12 Hours
somes, 92 DNA. Another important event
of this stage is doubling of the centrioles.
3. G2-phase is post-synthetic or pre-mitotic
phase. Accumulation of energy (ATP) and
Interphase (I)
synthesis of tubulin proteins occurs. Set of
Fig. 5.1. Cell cycle
hereditary information remains 2n4c. In
somatic human cell it is 46 chromosomes,
92 DNA molecules.
G0 resting phase and cell death. If cell quits dividing it is considered to stay at G0
resting phase. G0 resting phase or cell quiescence phase is a phase of cell differentiation. It can be reversible or irreversible. Liver, pancreatic, kidney and some other cells can
return to the cell cycle for restoration of cell number after injuring. Irreversible G0 stage is
characteristic for the terminally differentiated cells like neurons, cardiomyocytes, cells of
striated muscles.
Senescent cells do not divide also. Cellular senescence is a state that occurs in response
to DNA damage or degradation that would make a cell’s progeny nonviable. Such cells are
eliminated by apoptosis (from Greek apoptosis – falling off ).
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Cell death: apoptosis, necrosis
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There are two mechanisms of cell death – apoptosis and necrosis (Fig. 5.2).
Apoptosis is a process of programmed cell death. It is highly regulated process with
distinct morphological characteristics and energy-dependent biochemical mechanisms.
Morphologically apoptosis is characterized by: a) cell shrinkage; b) chromatin condensation followed by fragmentation of the nucleus; c) extensive plasma membrane
blebbing and separation of cell fragments into apoptotic bodies. The organelles and
nuclear fragments remain enclosed within an intact plasma membrane, so apoptotic
cells do not release their cellular constituents into the surrounding and do not provoke inflammatory reactions. Apoptotic bodies are quickly phagocyted by macrophages.
On the biochemical level apoptosis is characterized by activation of specific proteolytic
enzymes – caspases. Caspases are widely expressed in an inactive form in most cells (procaspases). Being activated they break down such targets as proteins of cytoskeleton and
5.1. Mitotic cycle. Mitosis. Cell death
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NORMAL
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Apoptolic body
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Phagocyte
Enzymatic digestion and leakage
of cellular contents
NECROSIS
Phagocytosis of apoptotic cells
and fragments
APOPTOSIS
Fig. 5.2. Apoptosis and necrosis
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nuclear envelope, enzymes of DNA replication and repair, transcription and translation factors and others. More than 60 proteins have been shown to be substrates of one or more
caspases in mammalian cells. DNA breakdown by activation of specific endonucleases also
occurs resulting in DNA fragments of 180 to 200 base pairs. mRNA is rapidly and globally
degraded also. Activation of caspases occurs by two main pathways:
1. The extrinsic one is activated by extracellular activation of cell-surface death receptors (death receptor pathway). For example, T lymphocytes are able to kill cells infected by virus via the extrinsic pathway.
2. Intrinsic signaling pathways initiate apoptosis by non-receptor-mediated stimuli that
act directly on targets within the cell and are mitochondrial-initiated events (mitochondrial pathway). The stimuli that initiate the intrinsic pathway are factors of physical and chemical stress (radiation, hyperthermia, hypoxia, etc), viral infections, nonrepaired DNA damage, absence of external signals from certain hormones and other.
All of these stimuli cause changes in the inner mitochondrial membrane that results
in it's increased permeability, loss of the mitochondrial transmembrane potential
and release of factors that initiate apoptosis into the cytosol.
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Once activated caspases can activate other procaspases, allowing initiation of a protease cascade. This proteolytic cascade, in which one caspase activates the other, amplifies
the apoptotic signaling pathway and thus leads to rapid cell death.
Apoptosis as physiological process is observed in embryogenesis, regulation of immune response and other. Inappropriate apoptosis is a factor in many human conditions
including neurodegenerative diseases, ischemic damage (too much), autoimmune disorders and many types of cancer (too little).
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The 2002 Nobel Prize in Physiology or Medicine was awarded to Sydney Brenner, H. Robert Horvitz
and John E. Sulston “for their discoveries concerning genetic regulation of organ development and
programmed cell death”.
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The alternative to apoptotic cell death is necrosis (from Greek necros – dead).
Necrosis is an uncontrolled toxic process where the cell is a passive victim and follows
an energy-independent mode of death. Necrotic cell injury is mediated by two main mechanisms: interference with the energy supply of the cell and direct damage to cell membranes. The major morphological changes that occur with necrosis include cell swelling,
disrupted membranes of the organelles, including mitochondria and lysosomes, disaggregation of ribosomes, and eventually disruption of the cell membrane. The release of the
cytoplasmic contents into the surrounding tissue causes inflammation and damage of the
neighboring cells.
Mitotic phase (mitosis)
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Mitotic cell division occurs during mitotic phase or M phase of the cell cycle. The mitosis (from Greek mitos – thread) is an indirect cell division that occurs in the somatic cell.
Fundamentally, it remains related with the growth of an individual from zygote to adult
stage and provides repair in multicellular organisms. Single-celled eukaryotic organisms
reproduce via mitosis.
The most important characteristic of mitotic cell division is that it distributes identical
sets of chromosomes to daughter cells, so one maternal cell gives rise to two genetically
identical daughter cells, which resemble each other and the parent cell qualitatively.
The basic outline of mitosis remains the same in all living organisms. The division of the
nucleate cells is achieved by two integral activities: 1) division of the nucleus (karyokinesis) and 2) division of the cytoplasm (cytokinesis). Usually the karyokinesis is followed by
the cytokinesis. If the cytokinesis does not occur multinucleate cell is formed.
Mitotis includes the following phases (Fig. 5.3):
1. Prophase. The prophase (from Greek pro – before, phasis – appearance) is the first
phase of the mitosis. During the prophase the following events occur:
`` Centrosomes separate and migrate towards the opposite poles of the cell. Microtubules gradually assemble between them to form spindle fibers.
`` The disintegration of nuclear envelope starts. The nucleolus disappears.
5.1. Mitotic cycle. Mitosis. Cell death
Centrioles
Chromosomes (indistinct)
Nucleus
Cytopiasm
Cell membrane
Aster
Interphase cell
Nucleolus
(appearing)
Nuclear membrane
(reappearing)
Early telophase
Nucleolus
(disappearing)
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Chromosomes
(thin and long)
Constriction in
cytoplasm
Astral rays
(disappearing)
Chromosomes
(thin and long)
Centromere
D
Daughter cell
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Early prophase
Nuclear
membrane
(disappearing)
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Spindle (disappearing)
Midprophase
Chromosomes
(short and thick)
Chromosomal fibre
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Chromosomal fibre
(contracting)
Polar fibres
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Late anaphase
Early anaphase
Polar fibres
Late prophase
Chromosomes are
in cytoplasm
Chromosomes in equatorial plate
Metaphase
Chromatids became daughter chromosomes
Fig. 5.3. Scheme of mitosis in animal cell
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`` The chromosomes start to condense, so become shortened, thickened and visible.
Due to the DNA duplication in the interphase each chromosome possesses two
chromatids, connected with each other by the centromere and remain closely associated along their entire lengths. Set of hereditary information remains 2n4c (46
chromosomes, 92 DNA molecules in somatic human cell).
Stage at which nuclear membrane completely disintegrates and the chromosomes move
towards the equator (a clear zone in between the mid-line of the spindle and the nucleus) is
known as prometaphase. At this stage microtubules of the spindle start to find centromeric
regions of the chromosomes and attach to the kinetochore (Fig. 3.15, Chapter 3).
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Chapter 5. Reproduction on the cellular and organismic level ...
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2. Metaphase. The metaphase (from Greek meta – middle) follows the prometaphase
and during this phase the following events occur in the cell:
`` Each chromosome reaches the equator and becomes aligned on the equatorial
plate of the cell forming metaphase plate. Set of hereditary information remains
2n4c (46 chromosomes, 92 DNA molecules in somatic human cell).
`` Spindle is completely formed and consists of several types of microtubules.
There are kinetochore microtubules that attach the centromere (through the kinetochore) to the poles, the polar microtubules or continuous spindle fibers that
connect pole to pole and overlap at the equator (but do not attach to any chromosome), the aster microtubules that extend from the pole to cell membrane.
Fibers appear between the chromosomes also and are known as interzonal fibers
or interchromosomal fibers.
As at metaphase chromosomes are maximally condensed, mitosis is usually arrested at
this stage for analysis of the karyotype.
3. Anaphase. At the anaphase (from Greek ana – backward) the following changes occur in the cell:
`` The centromere of each chromosome splits, the sister chromatids of each chromosome separates and form two daughter chromosomes.
`` The chromatids (daughter chromosomes) migrate towards the opposite poles of
the cell. The migration is achieved by the shortening (disassembly) of kinetochore
microtubules. Polar microtubules slide past one another in the region of overlap,
thereby extending the cell and pushing the poles further apart.
As each chromosome divides into two, cell becomes tetraploid for the short time with the
4n4c set of hereditary information (92 chromosomes, 92 DNA molecules in somatic human cell).
4. Telophase. The telophase (from Greek telo – end) is the final stage of mitosis and
during this phase the following events occur:
`` The chromosomes that reach the opposite poles of the cell decondense, and become thread-like.
`` New nuclear envelope around the chromosomes is formed. The nucleolus reappears.
`` The microtubules of the aster and mitotic spindle rearrange and disappear. Thus,
after the telophase two daughter nuclei are formed due to the karyokinesis. Each
nucleus has 2n2c set of hereditary information.
`` The karyokinesis is followed by the cytokinesis. At the process of cytokinesis the
cytoplasm splits from the equatorial region and the two daughter halves of the
cytoplasm are separated. In animal cells it involves formation of a contractile ring
from actin and myosin proteins.
As a result 1 cell 2n4c set gives 2 cells with 2n2c set of hereditary information.
Significance of Mitosis:
1. Mitosis is the main mode of multiplication of the cells, including processes of growth
and regeneration. With few exceptions, all kinds of asexual reproduction are carried
out by mitosis.
5.1. Mitotic cycle. Mitosis. Cell death
83
2. In mitosis each daughter cell gets a complete set of chromosomes identical to that
of the parent cell. Thus mitosis provides exact transmission of hereditary information
to the daughter cells.
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Mitosis failure. Mitosis is a complex process in which cell goes through dramatic
changes in ultrastructure and organization of hereditary material. Occasionally, normal
distribution of daughter chromosomes may become altered. Damage of the spindle fibers results in a non-disjunction of daughter chromosomes, which fail to separate during
anaphase. One daughter cell will receive both sister chromatids and the other will receive
none (daughter cells will have trisomy and monosomy respectively). Abnormal cells must
be eliminated by activation of apoptosis; if aneuploid cell survives such condition is often
associated with cancer. Chromosomes also may become damaged. An arm of the chromosome may be broken and the fragment lost (deletion), incorrectly reattaches to another
(translocation) or to the original chromosome in reverse orientation (inversion), became
duplicated. The effect of these genetic abnormalities depends on the specific nature of the
error. It may range from no noticeable effect to cancer induction and organism death.
Mitotic index. Types of cell populations
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Mitotic index is a measure for the proliferation status of a cell population. It is defined as
the ratio between the number of cells undergoing mitosis (cell division) per thousand cells.
There are three principle types of cell populations according to its proliferation status:
1. Stable cell populations – mitosis is not detected. These are terminally differentiated
cells which number reduces during the course of life (examples are neurons, cardiomyocytes, rods and cones of the retina). These cells are characterized by high ability
of intracellular regeneration, but if seriously damaged they are replaced with connective tissue.
2. Growing cell population (the average mitotic activity, in mitosis are individual cells) –
specialized cells that are able to divide for restoration of cell number (kidney, liver,
thyroid gland, pancreas).
3. Upgrading cell population (high mitotic activity) – a high proportion of cells are in
the mitosis (skin epidermis, red bone marrow cells, spermatogonia and other). These
are cells with short life term that should be replaced constantly. For instance a lifespan of intestinal epithelial cells is about 2 days with 7 × 1010 daily dying. Such complexes are rich in stem cells that provides restoration of cell number.
Endomitosis and polyteny
Multiplication of chromosomes and DNA not always is followed by cell division.
`` Endomitosis is a kind of internal division, when duplication of the chromosome isn’t
followed by formation of spindle fibers and cytokinesis, resulting in polyploid cell
(multinucleated one or with single polyploid nucleus). By this cells intensify protein
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Chapter 5. Reproduction on the cellular and organismic level ...
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64N
2N
64N
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2N
Fig. 5.4. Endomitosis results in polyploid cell
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biosynthesis getting more templates for transcription. In human organism it is seen
in actively working cells as liver cells, megakaryocytes, giant trophoblast cells in the
placenta. Megakaryocytes (its fragmentation yields platelets), for example, may pass
through as many as seven S phases producing a giant cell with a single nucleus containing 128n chromosomes (Fig. 5.4).
`` Polyteny is a repeated DNA replication without subsequent cell division. It forms
giant chromosomes that consist of hundred DNA (chromonems) and look like long
thick threads easily distinguished with a low-power light microscope (Fig. 5.5). Giant chromosomes are found in the salivary glands of order Diptera (mosquitoes and
flies). For example, each of fruit fly’s 4 pairs of chromosomes can undergo 10 rounds
of DNA replication, so each chromosome contains 2048 identical strands of DNA. In
humans modified polyteny is observed in the cells of placenta.
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A
Chromosomal puff
Dark band
Inter band
B
Fig. 5.5. Polyteny. A – giant chromosome;
B – regions of intense gene transcription called "puffs"
5.2. Mitotic cycle regulation. Genetic basis of tumor growth
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Cultivation of cells beyond the organism
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Sites on the giant chromosomes that represent regions of intense gene transcription –
called “puffs” – are swollen and appear to have a looser structure. Puffs became a very important tool in studying of gene expression and chromosome mapping.
Having multiple copies of genes permits a high level of gene expression so endomitosis
and polyteny both are being associated with large, metabolically active cells.
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Cell culture is the complex process by which cells are grown under controlled conditions. Animal cell culture became a common laboratory technique in the mid-1900s.
A cell line is a permanently established cell culture that will proliferate indefinitely given
appropriate fresh medium and space. Cell lines are used in all kinds of ways, such as studying
the effects of diseases, developing medications and vaccines, and play an invaluable role in
medicine today. One of such laboratory-grown human cell lines is HeLa. In 1951, a scientist
George Gey at Johns Hopkins Hospital in Baltimore created the first immortal human tumor
cell line with a tissue sample taken from a young woman with cervical cancer, Henrietta Lacks.
HeLa cells have been used for the development of a polio vaccine, research into cancer, AIDS,
the effects of radiation and toxic substances, and many other scientific pursuits.
In biotechnology mass culture of animal cell lines is fundamental to the manufacture of
viral vaccines and complex human proteins (enzymes, monoclonal antibodies, interleukins
and others).
5.2. Mitotic cycle regulation.
Genetic basis of tumor growth
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Mitotic cycle regulation
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A cell’s progress through the cell cycle is determined by complex of two classes of regulatory molecules: cycline and cyclin-dependent kinase (cdk).
Cyclin-dependent kinase is an enzyme that can change activity of different proteins by
its phosphorilation. It is constantly present in the cytoplasm but in the inactive state; it is
considered to be a catalytic subunit of the complex. There are several types of CDK labeled
by numbers in order of its discovering.
Cyclin got its name as appears in the cytoplasm in cyclic manner. It activates cyclindependent kinase, and by this initiates the events of appropriate phase of the cell cycle;
it is considered to be a regulatory subunit of the complex. Types of cyclins are labeled by
letters of Latin alphabet.
Each stage of the cell cycle is characterized by a specific cyclin-Cdk association (Table 5.1). Each complex provides events of certain phase of the cell cycle and pushes cell to
the next phase according to a domino principle.
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Chapter 5. Reproduction on the cellular and organismic level ...
Table 5.1. Regulation of mitotic cycle by cyclin-Cdk complex
Phase
Cyclin-Cdk complex
Role of the complex
CyclineD/Cdk4
Inactivation (phosphorylation) of Rb protein that blocks transcription factor E2F (required for transcription of cyclin E gene).
It allows synthesis of cyclin E and by this initiates all subsequent
events of the cell cycle
G1/S
CyclineE /Cdk2
Activate synthesis of proteins required for DNA replication like
DNA polymerase and assembling of pre-replication complex
S
Cycline A/Cdk2
Cycline A/Cdk1
Initiation and progression of DNA replication, prevent more
than one round of replication
Activation of CyclinB/Cdk1 complex
G2/M
CyclinB/Cdk1 (MPF–
mitosis promoting
factor)
Initiate mitotic prophase by breakdown of nuclear envelope
protein, assembling of the spindle fibers and condensation of
the chromatin
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G0/G1
The Nobel Prize in Physiology or Medicine 2001 was awarded to Leland H. Hartwell, Tim Hunt and Sir
Paul M. Nurse “for their discoveries of key regulators of the cell cycle”.
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Initiation of Cyclin D production is activated by extrinsic signal from growth factors
through intracellular signalling pathway (Fig. 5.6).
Growth factors are peptide-hormone-like substances or hormones that can activate
cell division, so they are of outmost importance in process of embryogenesis, growth and
regeneration. Some growth factors stimulate many types of the cells but some are very
specific and confined to the certain type of the cells. Examples are:
`` insulin-like-growth factors (IGF or somatomedin) resemble insulin and have insulinlike action on some tissues. It is mainly secreted by the liver as a result of stimulation by growth hormone and has a lot of different physiological functions: promotes
longitudinal bone growth, supports hepatocyte proliferation, inhibits apoptosis and
others;
`` platelet-derived growth factor (PDGF) stimulates mitosis in a variety of cell types.
Platelets contain large amounts of growth factors that are released at the site of
injury when a clot forms and assist with wound healing. For example, it plays a significant role in blood vessel formation, stimulates division of fibroblasts, smooth
muscle cells;
`` epidermal growth factor (EGF) can also stimulate or inhibit proliferation or differentiation of a wide variety of cells. Salivary EGF is important in healing of oral
and gastric ulcers and protects the wall of intestinal tract from different injurious
factors. EGF-stimulated cell regulatory system plays an important role in tumor
formation.
Several growth factors are used in medicine to stimulate tissue repair, i.e., PDGF is applied for healing of chronic diabetic foot ulcers and in cases of severe periodontal disease.
5.2. Mitotic cycle regulation. Genetic basis of tumor growth
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Growth factor
Adaptor proteins (transduction factors)
Transcription factors
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Mitogen-activated protein kinases (MAP kinases)
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Receptor
Activation of genes that encodes cyclins and cyclindependent kinases
Activation of the mitotic cycle
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Fig. 5.6. Signal pathways from growth factor receptors
The Nobel Prize in Physiology or Medicine 1986 was awarded to Stanley Cohen and
Rita Levi-Montalcini “for their discoveries of growth factors”.
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Other important signals that control cell division come from the membrane proteins.
Absence of the open space on the border of cellular layer inhibits cell division (density
dependent inhibition). Most animal cells are allowed to divide if they are attached to the
extracellular matrix (anchorage dependence).
Cell cycle checkpoints
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Cell cycle is characterized by coordinated sequence of the events which provide equal
distribution of hereditary information (DNA replication is followed by segregation of chromosomes and cytokinesis).
Cell cycle checkpoints are the regulatory signaling systems that control progression
through the cell cycle (Fig. 5.7). DNA damage or uncompleted events of the appropriate
phase arrest the cell cycle. It gives time for DNA repair or completing cell cycle events, if it
does not happen, apoptosis becomes activated.
Currently, there are several known checkpoints:
`` G1 checkpoint is also known as the restriction or start checkpoint. Cell checks whether cell size and resources permit DNA replication and futher division. If a cell receives
a go-ahead signal at the G1 checkpoint, it will usually continue with the cell cycle,
otherwise it enters G0 phase. After passing the restriction point, cell irreversibly commits to the division process and completes division cycle even in the absence of
growth factors.
DNA damage or deficiency in nutrients or cellular components may cause the
cells to halt before progressing through G1 phase.
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M checkpoint
`` Intra S-phase checkpoint is activated to
delay progression through S phase when
G2/M checkpoint
cells are treated with DNA damaging
M
agents or inhibitors that interfere with
M
ongoing DNA replication, allowing time
G2
for DNA repair.
`` The G2/M checkpoint ensures all of the
G1
G0
chromosomes have been replicated and
DNA is not damaged before cell enters
mitosis.
`` M (metaphase) checkpoint, also known
I
as the spindle checkpoint. It determines
G1 checkpoint
whether each of the sister chromatids are
correctly attached to the spindle fibers Fig. 5.7. Checkpoints
before cell enters the anaphase.
The cell cycle is halted by negative regulators. Famous examples of the negative regulatory molecules are retinoblastoma protein (Rb), p53, and p21.
Rb protein (pRb) is responsible for a major G1 checkpoint, blocking S-phase entry and
cell division. Loss of pRb functions may induce cell cycle dysregulation, uncontrolled division and tumor development. Inactivation of pRB due to gene mutation causes retinoblastoma (malignant tumor of eye retina).
p53 is a multi-functional protein. If damaged DNA is detected, p53 halts the cell cycle
and recruits enzymes to repair the DNA. If the DNA cannot be repaired, p53 can trigger
apoptosis to prevent the multiplication of mutant cell. As p53 levels rise, the production of
p21 is also triggered. p21 enforces the halt in the cycle dictated by p53 by inhibiting the
activity of the Cdk/cyclin complexes. Role of p53 in a control of DNA quality is so important
that it is known as a “genome gatekeeper”.
Tumor growth. Genetic basis of tumors
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Tumor growth is characterized by rapid uncontrolled mitotic division of the cells and
inhibition of apoptosis. Morphological difference between tumor cells and cells of normal
tissue is called atypia. Based on degree of atypia, peculiarities of growth and influence on
the patient’s organism tumors are divided into benign and malignant. The main differences
between them are described in Table 5.2.
Tumors develop due to the mutations of genes controlling cell cycle and apoptosis. Most
tumors are the result of accumulation of somatic mutations of many genes. Mutations are
promoted by mutagenic factors called carcinogens. Examples of carcinogens are ultraviolet rays, ionizing radiation, polycyclic carbohydrates of tobacco smoke, and some viruses.
There are two main groups of genes that play a role in tumor development.
`` Oncogenes are excessively active proto-oncogenes. Proto-oncogenes normally
stimulate mitosis. Examples are genes for growth factors and its receptors, molecules
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5.2. Mitotic cycle regulation. Genetic basis of tumor growth
Table 5.2. Benign versus malignant tumors
Malignant tumors
Benign tumors
Cells retain morphological characteristics typical
for the tissue from which they originate
Rapid growth (mostly)
Slow growth
Invasive growth (invading into the neighboring
tissues and organs)
Expansive growth. Tumors usually have capsule,
that separate it from neighboring tissues
If tumor cells enter the blood stream or lymph
they get into other organs and produce daughter tumors – metastasis
Do not produce metastasis
Life-threatening
Compress neighboring tissue. Manifestation depends on the size of the tumor and its location.
Without intensive treatment lead to death
Without treatment often transform into malignant tumor
Carcinoma (malignant tumor from epithelium)
(Fig. 5.8), sarcoma (from connective tissue)
Examples are adenoma (benign tumor from
glandular epithelial tissue), lipoma (from fat tissue), myoma (from muscle tissue)
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Cells loose specialization and resemble embryonic cells. Sometimes it is even impossible to
determine from which organ they originate
1
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2
3
5
4
7
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6
Fig. 5.8. Lung carcinoma: 1 – tumor; 2 – respiratory epithelium; 3 – connective tissue; 4 and 6 – blood vessels;
5 – lymphatic vessel; 7 – metastatic cells
of intracellular transmission of the mitogen signal, protein-kinases and cyclins. When
a proto-oncogene becomes uncontrollably activated by mutation (either chromosomal rearrangements or gene mutations) or amplifies (by gene duplication or by
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viruses that bring additional gene copies) the cell multiplies out of control, which
can lead to cancer. One of the famous examples of such mutation is translocation
between chromosomes 9 and 22. Fusion of the broken end of chromosome 22 with
portion of chromosome 9 produces excessively active oncogene that stimulates cell
division. A mutant chromosome 22, known as Philadelphia chromosome, is associated with chronic myeloid leukemia.
Most cancer-causing mutations involving oncogenes are acquired, not inherited.
` ` Tumor suppressor genes are normal genes that slow down cell division. These
are genes of check points, DNA repair, or involved in apoptosis. When tumor
suppressor genes are inactive, cells, that normally should be destroyed, can survive, which often lead to cancer. For example, abnormalities of the TP53 gene
(which codes p53 protein) have been found in more than half of human cancers. Tumor suppressor genes are switched-off by chromosomal and gene mutations. Oncoviruses are involved in its inactivation also. For example, infection with the human T cell leukemia virus-1 (HTLV-1) leads to a cancer as virus
encodes a protein that blocks cellular proteins of the spindle checkpoint. The
leukemic cells in these patients show many chromosome abnormalities including aneuploidy.
Most tumor suppressor gene mutations are acquired, but some family cancer syndromes are caused by inherited abnormalities of tumor suppressor genes. Inherited mutation of TP53 causes Li-Fraumeni syndrome. It is a rare disorder characterized by development of multiple tumors in one organism (breast cancer, bone cancer, leukemia, brain
tumors) particularly in children and young adults.
Chance of mutation of genes involved in tumor genesis depends on other genes like
those of DNA repair and metabolism of chemical carcinogens.
Science that studies genetics of cancer is oncogenetics (from Greek oncos – mass, bulk
and genesis – origin).
5.3. Meiosis
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Meiosis (from Greek meiosis – diminution) is a specialized form of cell division that reduces the number of chromosomes in the parent cell by half and produces four haploid
cells. Gametes (sperm and egg cells) in animals and spores in plant and fungi are formed
by meiosis.
The meiotic division is of utmost importance for those organisms in which the fusion
of the haploid gametes takes place during the sexual reproduction. By reducing the number of chromosomes of the diploid germ cells into haploid gametes the meiosis maintains
a constant number of the chromosomes in the species from generation to generation.
In the process of meiosis the chromosomes divide once and the nucleus and cytoplasm
divide twice thus four haploid cells are formed from the single diploid cell.
The process of meiosis is fundamentally the same in all the animals and plants.
5.3. Meiosis
91
It occurs in two subsequent divisions. The first division is reduction and second one is
equation. Both meiotic divisions occur continuously and each includes prophase, metaphase, anaphase and telophase (Fig. 5.9).
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First Meiotic Division (reduction)
Prophase I
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The steps leading up to meiosis are similar to those of mitosis. At the beginning of the
first meiotic division the nucleus starts to swell up by absorbing water from the cytoplasm
and the nuclear volume increases about three times. The centrioles are replicated. The
amount of DNA in the cell has doubled, so cell has 2n4c set of hereditary information. After
these changes the cell passes to the first prophase.
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The prophase of the first meiotic division is very significant phase because the most
cytogenetic events such as synapsis and crossing-over occur during this phase. The prophase I is the longest meiotic phase, therefore, for the sake of convenience it is divided
into substages – leptotene (leptonema), zygotene (zygonema), pachytene (pachynema),
diplotene (diplonema) and diakinesis.
1. Leptotene or leptonema. At the leptotene stage the chromosomes become long and
thread-like. The chromosomes take up a specific orientation inside the nucleus; the ends
of the chromosomes converge towards that side of the nucleus where the centrosome lies
(the bouquet stage).
The centrioles migrate towards the opposite poles of the cell.
2. Zygotene or zygonema. At the zygotene stage, the homologous chromosomes are
attracted towards each other and pairing takes place. The pairing of the homologous chromosomes is known as synapsis (from Greek synapsis – union). The synapsis (conjugation)
begins at one or more points along the length of the homologous chromosomes. The homologous chromosomes are held together by the synaptonemal complex. The pairing is
very exact and specific process. Pair of homologous chromosomes closely joined together
in one complex unit is called bivalent because it actually contains a pair of chromosomes
or tetrad (four chromatids). Number of tetrads is equal to haploid set of chromosomes.
3. Pachytene or pachynema. At the pachynema stage the pairs of chromosome become
twisted spirally around each other.
During pachytene stage an important genetic phenomenon called “crossing-over”
takes place. The crossing-over (Fig. 5.9B) is the mutual exchange of chromatin material
(allele genes) between the non-sister chromatids of two homologous chromosomes. The
crossing over is accompanied by the chiasma (point of exchange) formation.
4. Diplotene or diplonema. At the diplotene stage, the homologous chromosomes repel each
other because the force of attraction between the two homologous chromosomes decreases.
The two homologous chromosomes thus separate from each other, however, not completely
because both remain united at the point of exchange or chiasmata, which can be seen at this
stage.
Chapter 5. Reproduction on the cellular and organismic level ...
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Cell membrane Paternal
chromosomes
Centrioles
Nucleolus
(disappearing)
Pachytene
Chromosomal fibre
Continuous
fibre
Metaphase-I
Tetrads in
equatorial plate
Leptotene
Diplotene
Interzonal fibre
Anaphase-I
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Daughter cells
Prophase-II
Aster (disappearing)
Cytoplasmic
Spindle
constriction (disappearing)
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Early telophase-II
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Tetrads
Centromer
Zygotene
Tetrad
Chromosomes
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Proleptotene
Nuclear membrane (disappearing)
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Bivalents
Aster
Nuclear membrane
(disappearing) Diakinesis
Nucleolus
Homologues
chromosomes
(appearing) Spindle (disappearing)
separate
Aster (disappearing)
Constriction in
cytoplasm
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Spindle
Centrosome
Maternal
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Nuclear
membrane
Nucleolus
Cytoplasm
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Chromosomes in
equatorial plate
Metaphase-II
Nuclear membrane
(appearing)
Telophase-I
Cromatids become
chromosomes
Anaphase-II
Nuclear membrane
(appearing)
Nucleolus
(appearing)
Gametes (totally four)
Late telophase-II
Fig. 5.9. Scheme of meiosis. A – Meiosis I; C – Meiosis II (note: see B on the next page)
5.3. Meiosis
93
Homologous
chromosomes
(wide apart)
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Kinetochore
Leptotene
Bivalent
Zygotene
Sister chromatids
Sister chromatids
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Kinetochores
Pachytene
Kinetochores
Nonsister chromatids
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Homologous
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(synapsed)
Noncross-over chromatid
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Tetrad
Cross-over chromatids
Noncross-over chromatid
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Anaphase
Chromosomes
Chromosomes
Homologous
Crossing-over
(in pachytene)
Telophase
Fig. 5.9. Scheme of meiosis (continuation). B – Behavior of chromosomes in Meiosis I including crossing-over
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5. Diakinesis. At the diakinesis stage the bivalent chromosomes become more condensed and evenly distributed in the nucleus. During diakinesis the chiasmata moves
from the centromere towards the ends of the chromosomes (terminalisation). The chromatids still remain connected by the terminal chiasma and these exist up to the metaphase I.
Metaphase I. At the metaphase I
`` the bivalents (tetrads) are at the equator;
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`` microtubules of the spindle are attached to the centromeres of the homologous
chromosomes. The centromere of each chromosome is directed towards the opposite poles. The repulsive forces between the homologus chromosomes increase
greatly and chromosomes become ready to separate.
Anaphase I
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Telophase I
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`` each homologous chromosome with its two chromatids and undivided centromere
moves towards the opposite poles of the cell due to the contraction of chromosomal
fibers or microtubules.
The actual reduction of chromosome number occurs at this stage. It should be carefully
noted here that the homologous chromosomes which move towards the opposite poles
are the chromosomes of either paternal or maternal origin. Moreover, as during the chiasma
formation out of two chromatids of a chromosome, the one changes its counter part, therefore, the two chromatids of a chromosome do not resemble each other in the genetic terms.
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`` the nuclear envelope around the chromosomes reforms and the nucleolus reappears.
`` cytokinesis takes place and two haploid cells form;
This stage is absent in some species.
In Meiosis I maternal cell with 2n4c set of hereditary information produces 2 cells with
1n2c set of hereditary information.
Meiosis I proceeds directly to meiosis II. Both cells pass through a short resting phase or
the interkinesis. DNA synthesis do not occur at this stage, so cell enter meiosis II with 1n2c
set of hereditary information.
Second Meiotic Division (equation)
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The second meiotic division is principally the same as mitotic division. In anaphase II
chromosome splits and chromatids (daughter chromosomes) move towards the opposite
poles of the cell.
After the karyokinesis, the cytokinesis occurs in each haploid meiotic cell and thus, four
haploid cells appear. In Meiosis II 2 cell with 1n2c set of hereditary information produce 4
cells with 1n1c set of hereditary information.
Thus, meiosis from 1 cell with 2n4c produces 4 cells with 1n1c set of hereditary information. These cells have different hereditary information due to the crossing-over at the
prophase I and independent assortment of maternal and paternal chromosomes at the
anaphase I.
Significance of Meiosis:
The meiosis has the greatest significance because of its following features:
1. Meiosis maintains a definite and constant number of chromosomes from generation
to generation in sexual reproduction.
5.4. Organisms reproduction
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2. Meiosis provides genetic variation by recombination of hereditary material. The
mechanisms of recombinations are:
`` crossing-over in prophase I. For example, in human being crossing-over occurs in
2–3 points in each pair of homologous chromosomes in average.
`` Independent assortment of maternal and paternal homologous chromosomes at
the anaphase I. In each pair of the chromosomes one homolog has maternal and
another one – paternal origin. In anaphase I, when each daughter cell gets one
chromosome from each homologous pair, maternal and paternal chromosomes
might be combined in 2n variants (n – haploid set of the chromosomes). Thus in humans exists 223 combinations of maternal and partenal chromosomes in a gamete.
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Meiosis failure. Non-disjunction of a pair of chromosomes in meiosis results in aneuploidy (numerical chromosomal aberration) in gametes. One gamete will receive both
homologous chromosomes and the another will receive none. After fusion with normal
gametes they will produce aneuploid zygotes with trisomy or monosomy respectively.
Aneuploid zygotes are eliminated or, if not, give children with chromosomal disorders.
Inadequate crossing-over results in structural cromosomal aberrations as deletions, duplications, inversions and translocations. These mutations are transmitted to next generation and may have no effect (balanced chromosomal aberrations) or causes chromosomal
disorders and death.
5.4. Organisms reproduction
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The reproduction is a process by which the living beings propagate or duplicate their
own kinds. The reproduction may be of the following two types:
1. Asexual reproduction.
2. Sexual reproduction.
Asexual Reproduction
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The development of new individuals without the formation and fusion of the male and
female gametes is known as asexual reproduction. The asexual reproduction in eukaryotes
occurs by mitotic division of the somatic (body) cells, therefore, it is also known as somatogenic or blastogenic reproduction. This way of reproduction involves only a single parent
and forming daughter organisms are genetically identical to it, i.e., they are clones. Asexual
reproduction ensures rapid increase in numbers.
The asexual reproduction is common in plants, fungi and lower animals.
In unicellular animals the most common types of asexual reproduction is fission.
Fission. In this way of reproduction the nuclear and cytoplasmic contents of the cell
divide or split completely into smaller daughter individuals. The fission itself may be of the
following types:
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Parent cell dividing
Nucleus
Constriction
Daughter cells
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Pseudopodium
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Fig. 5.10. Binary fission of amoeba: A – Schematic representation of the process; B – Scanning microphotograph of amoeba division: a – 0 min; b – 6 min; c – 8 min; d – 13 min; e – 18 min; f – 21 min
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`` Binary fission. At the binary fission an organism divides in to two equal daughter
cells. First of all the nucleus divides by mitotic division and the division of the nucleus
is followed by the division of the cytoplasm. The binary fission could be simple or
orthodox (the plane of division is difficult to observe as in Amoeba (Fig. 5.10), longitudinal as in Euglena or transverse as in Paramecium.
`` Multiple fission is the division of a parent cell into many small daughter individuals
simultaneously. The nucleus of a parent divides a few to many times without the
division of the cytoplasm. At later stage each daughter nucleus gets surrounded
by the little mass of the cytoplasm. Multiple fission occurs in Plasmodium (agent of
malaria).
In multicellular animals the most common types of asexual reproduction are budding
and fragmentation. It is provided by ability of organisms for regeneration.
Budding is an unequal division of a parent. A daughter individual is formed from
a small outgrowth, the bud, arising on a parent body. In certain multicellular animals, such
as Hydra (Coelentrates), the body gives out a single or many buds, which are supported by
the parent body and ultimately develops into a new individual. When full-grown, the new
individual may gets detached from the parent and becomes an independent animal or
may remain joined to the parent and becomes a part of the colony.
Fragmentation is a process by which an organism breaks up into two or more parts
and each part is capable of forming a complete individual. It is found in Planaria (Plathelminths) and some other lower animals.
5.4. Organisms reproduction
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In plants and fungi asexuall reproduction mostly occur by vegetative reproduction and
spores.
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Sexual Reproduction
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The sexual reproduction involves formation and fusion of the haploid sex cells – male
and female gametes, so a new forming organism is genetically different from both parents.
The sexual reproduction is the most common type of reproduction among the plants,
fungi and animals. It may be of the following types:
1. Syngamy (copulation). The syngamy is the most common type of sexual reproduction in the plants and animals. In syngamy (from Greek syn – together; gam – marriage) the
fusion of two gametes with zygote formation takes place completely and permanently. The
fusion of gametes is termed fertilization.
The following kinds of syngamy are prevalent among the organisms:
`` Isogamy (from Greek is – equal, gam – marriage). In this case the fusion of morphologically and physiologically identical gametes (isogametes) takes place.
`` Anisogamy (from Greek an – without, is – equal; gam – marriage) or heterogamy is
a fusion of morphologically different gametes. The form of anisogamy that occurs in
animals, including humans is oogamy. In this case the male gametes are mobile and
small sized, and known as the microgametes (sperm or male gamete). The female
gametes are passive, comparatively large and are known as the macro-or megagametes (ovum or female gamete).
Syngamy sometimes is followed by polyembryony. Polyembryony is a condition in
which two or more embryos develop from a single fertilized egg. Forming organisms in
this case are genetically identical (clones). Identical twins in humans are an example.
2. Conjugation is the temporary pairing of two parents which exchange their hereditary material. During this union both individuals known as conjugants exchange
certain amount of nuclear (DNA) material (male pronuclei) and then separate. The conjugation is the mode of sexual process in Ciliates, e.g., Paramecium, some algae, fungi
and bacteria.
3. Parthenogenesis. The parthenogenesis (from Greek parthenos – virgin, genesis – origin) is the special type of sexual reproduction. In case of parthenogenesis an ovum develops into a new individual without being fertilized by sperm (monoparental process). The
parthenogenesis occurs in certain insects (wasps and bees, etc), crustaceans, fishes, reptiles, birds. In complete (obligatory) parthenogenesis biparental sexual reproduction does
not exist. All individuals are females that develop exclusively by parthenogenesis (Caucasian rock lizard). In incomplete parthenogenesis both biparental and parthenogenic ways
of reproduction takes place. For example, in honeybee, unfertilized egg develops into haploid male bees and fertilized eggs give rise to diploid females.
Parthenogenesis provides quick and easy mode of reproduction, it eliminates need for
mating, but also reduces variability in a population.
Natural parthenogenesis has never been observed in mammals, including humans.
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Chapter 5. Reproduction on the cellular and organismic level ...
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Fig. 5.11. Guinea pig spermatogenesis. Сross-section of seminiferous tubule of testis: 1 – spermatogonia;
2 – primary spermatocytes; 3 – spermatids; 4 – newly formed spermatozoa
5.5. Gametogenesis. Fertilization
Gametogenesis
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Gametogenesis (from Greek gam – marriage; genesis – origin) is the process of gamete
formation. The male gamete is known as spermatozoon or sperm and the female gamete
is known as ovum or egg.
The sexually reproducing animals have two types of cells in their body, e.g., somatic
cells and germ cells.
The somatic cells form various organs of the body and provide the conditions for maturation, development and formation of the germ cells.
The germ cells give rise to the gametes. In humans, this cell line can first be distinguished
at 4 weeks of embryogenesis as a population of ovoid, poorly differentiated cells in the endoderm of the yolk sac wall. These cells are called the primordial germ cells and their lineage constitutes the germ line. Between 4 and 6 weeks the primordial germ cells migrate
by ameboid movement from the yolk sac to the wall of the gut tube and from the gut tube
to the dorsal body wall. When the germ cells arrive in the presumptive gonad region, they
stimulate cells of the adjacent coelomic epithelium and mesonephros (embryonic kidney)
to proliferate. These proliferating cells give rise to the tissue that will nourish and regulate
the development of the maturing sex cells. Together with germ cells they form the gonads
(testis and ovaries) of the animal body.
5.5. Gametogenesis. Fertilization
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In both males and females, the primordial germ cells undergo further mitotic division
within the gonads and commence gametogenesis, the process that converts them to mature male and female gametes. The basic sequence of gametogenesis events remains principally the same in males and females.
Spermatogenesis. The process of sperm production is known as spermatogenesis (from
Greek sperma – sperm or seed; genesis – origin). It occurs in male gonads or testis. The testis
of the vertebrates is composed of many seminiferous tubules, which are lined by the cells of
the germinal epithelium. The cells of the germinal epithelium (primordial germ cells) form
sperms by the process of spermatogenesis. Figure 5.11 represents the transverse section of
seminiferous tubule with several layers of cells showing successive stages of spermatozoon
development. In mammals, there are somatic Sertoli cells lying between germinal cells. The
Sertoli cells anchor the differentiating cells and provide nourishment to the developing
sperms. Leydig cells lay adjacent to the seminiferous tubules and produce testosterone.
The primordial germ cells pass through following phases (Fig. 5.12):
1. Multiplication phase. The undifferentiated germ cells multiply by repeated mitotic
divisions and produce the cells which are known as the spermatogonia (from Greek
sperma – sperm or seed, gone – offspring). Spermatogonia are diploid (2n).
2. Growth phase. At the growth phase the spermatogonia cells accumulate nutrition
material and replicate DNA. The formed cells are known as the primary spermatocytes
(2n4c set of hereditary information).
3. Maturation phase. The primary spermatocytes enter the first meiotic or maturation
division. First meiotic division forms two secondary spermatocytes. Each secondary sper-
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2
4
3
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6
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Fig. 5.12. Scheme for spermatogenesis: 1 – primary spermatocyte; 2 – meiosis I; 3 – secondary spermatocytes; 4 – meiosis II; 5 – spermatids; 6 – spermiogenesis; 7 – spermatozoa
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Chapter 5. Reproduction on the cellular and organismic level ...
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Fig. 5.13. Scheme of spermatozoon formation from the spermatid: 1 – centriol; 2 – nucleus; 3 – Golgi complex; 4 – mitochondria; 5 – flagellum; 6 – cytoplasm excess; 7 – mitochondria; 8 – centriol; 9 – tail;
10 – middle piece; 11 – head; 12 – acrosome; 13 – neck
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matocyte is haploid (n2c). It passes through the second maturation or second meiotic
division and produces two spermatids (nc). Thus, by the meiotic division a diploid primary spermatocyte produces four haploid spermatids. These spermatids cannot act directly as the gametes so they have to pass through the next phase, the spermiogenesis.
4. Spermiogenesis is the metamorphose of the spermatids into the sperms by losing
a great deal of cytoplasm, condensation of the nucleus into a head and formation of
flagellate tail. A modified Golgi complex forms acrosome, which contains enzymes
necessary for fertilization (Fig. 5.13).
Oogenesis. The process of production of ovum is known as oogenesis (from Greek
oon – egg; genesis – origin). It occurs in the cells of the germinal epithelium of the ovary,
such cells are known as primordial germ cells. The oogenesis is completed in the following
three successive stages (Fig. 5.14):
1. Multiplication phase. The primordial germ cells divide repeatedly to form the oogonia
(From Greek oon – egg). The oogonia multiply by the mitosis. Oogonia are diploid (2n).
5.5. Gametogenesis. Fertilization
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2. Growth phase. Oogonia enlarge and form the primary
oocyte. The growth phase of the oogenesis is comparatively longer than the growth phase of the spermatoA a B B
genesis. At the growth phase the size of the primary
1
oocyte increases enormously. In the primary oocyte,
2
large amounts of fats and proteins become accumulat4
3
ed in the form of the yolk and due to its heavy weight
(or gravity) it is usually concentrated in the lower part
of the egg forming the vegetal pole. The portion of
B
a B
A
the cytoplasm containing the egg pronucleus remains
often separated from the yolk and stays at the upper
5
side of the egg forming the animal pole. The cytoplasm
3
7
of the oocyte becomes rich in RNA, ATP and enzymes.
The DNA replicates. The nucleolus becomes large or
its number is multiplied due to excessive synthesis of
B
AB
ribosomal RNA on the nucleolar organizer region of
aB
A
chromosomes. When the growth of the cytoplasm and
6
nucleus of the primary oocyte (2n4c) is completed it
Fig. 5.14. Scheme of oogenesis:
becomes ready for the maturation phase.
1 – primary oocyte;
3. Maturation phase. The maturation phase is accom- 2 – meiosis I;
panied by the maturation or the meiotic division. After 3 – primary polocyte;
the first meiotic division of the nucleus the cytoplasm 4 – secondary oocyte;
of the primary oocyte divides unequally to form two 5 – meiosis II; 6 – ovum;
7 – secondary polocyte
haploid cells (n2c): a single large-sized secondary oocyte
and minute, nonfunctional, first polar body (polocyte).
In the second meiotic division secondary oocyte divides to form a large ootid or ovum
and second polar body. The first polar body passes through the second meiotic division
simultaneously. So, as a result of meiosis a primary oocyte gives rise to four haploid cells
(nc): one ovum and three polar bodies. The polar bodies ultimately degenerate.
Unequal divisions allow one cell out of the four daughter cells to contain most of the
cytoplasm and reserve food material which is sufficient for the developing embryo.
Actually, at ovulation (releasing from the ovary) secondary oocyte begins the meiosis II,
but progress only to metaphase. If the secondary oocyte is fertilized by a sperm, the second
meiotic division is completed and second polar body is formed.
The main differences between spermatogenesis and oogenesis are the following:
`` The timing of these two processes differs in the two sexes.
Spermatogenesis activates at puberty. The seminiferous tubules mature and the germ
cells differentiate into spermatogonia. Successive waves of spermatogonia undergo meiosis and mature into sperms. In human male each cycle of spermatogenesis takes about
74 days. Sperm cells are produced continuously from puberty until death.
In females oogenesis starts at embryonic period. The primordial germ cells differentiate into oogonia and then all begin meiosis by the fifth month of fetal development.
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Primary oocytes progress through the prophase of the first meiotic division until the
diplotene stage. After this all the primary oocytes become dormant as meiosis is arrested
in a long latent dictyotene phase. Each primary oocyte becomes tightly enclosed by a
single-layered capsule of epithelial follicle cells. Capsule with primary oocyte constitute
a primordial follicle. By 5th month, the number of primordial follicles in the ovaries peaks
at about 7 million. Most of these follicles subsequently degenerate. By birth only 700.000
to 2 million remain. Primary oocytes are maintained in prophase I stage until puberty.
There are about 40.000 follicules at this age and just 300 to 400 primary oocytes reach
the maturity per life. With the onset of menstrual cycles, groups of oocytes periodically
resume meiosis. Oogenesis continues until menopause at approximately 50 years old.
Thus, meiosis begins in the embryonic period, and finishes from 12 to 45–50 years later.
`` Testes produce 150–200 million sperm cells daily. Only one primary oocyte matures
into a secondary oocyte and is ovulated each month.
`` Four spermatids are formed from one primary spermatocyte but only one ovum (and
three polar bodies) is formed from one primary oocyte.
`` Spermatids undergo spermiogenesis to get transformed into sperm. Matching stage
in oogenesis is absent.
Morphology of the Gametes
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Sperm cell (spermatozoon) consists of the head, neck, middle piece and tail (Fig. 5.15).
`` The head contains compact haploid nucleus with densely packed DNA and a small
acrosome. The acrosome lies at the tip of the nucleus. It is formed from the Golgi complex and contains proteolytic enzymes (hyaluronidase, acrosin and others).
These stored enzymes are used to lyse the outer coverings of the egg and plays an
essential role in fertilization.
`` The neck is very short and contains two centrioles lying one behind and at right
angles to the other. The proximal centriole plays a role in the first cleavage of the
zygote. A distal centriole gives rise to the axial filament complex (motor apparatus of
the spermatozoon tail) of the sperm.
`` The middle piece contains large, helical mitochondria and generates the ATP for the
movement of the sperm in the female’s genital tract.
`` The tail (flagellum) contains the axial filament complex consisting of microtubules
that form part of the propulsion system of the spermatozoon.
Size of human spermatozoon is up to 70 µm. Most sperms do not survive more than
72 hours in female genital tract.
Ovum is a rounded, immotile cell. It has abundant cytoplasm, large nucleus and plasma
membrane (Fig. 5.16).
`` Nucleus is large, haploid and contains nucleolus.
`` Cytoplasm contains a lot of mRNA, tRNA and ribosomes for active protein biosynthesis, mitochondria (all mitochondria of zygote arise from the egg) and other or-
5.5. Gametogenesis. Fertilization
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Fig. 5.15. Spermatozoon (A – schematic image; B – microphotograph): 1 – acrosome; 2 – head; 3 – nucleus;
4 – centriol; 5 – neck; 6 – spiral mitochondria in middle piece; 7 – axial thread; 8 – flagellum (tail)
Corona radiata
B
Zona pellucida
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Cytoplasm
Polar bodies
Sperm
Cell membrane
Haploid nucleus of egg
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Fig. 5.16. Mammalian ovum. A – schematic image; B – microphotograph
ganelles. Asymmetric localization of cytoplasmic molecules (mostly proteins and
mRNAs) within the egg is known as ooplasmic segregation. The latter provides preconditions for differentiation in embryogenesis.
Nutritive substances (fats, albuminoids) are accumulated in yolk granuls. In humans the
ovum is almost free of yolk and is said to be alecithal.
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There are cortical granules with high levels of carbohydrates and proteinases near the
plasma membrane. These are regulatory secretory organelles (ranging from 0.2 µm to 0.6
µm in diameter) that prevent polyspermy (fertilization by several sperms).
Plasma membrane forms microvilli to absorb food materials from the follicular cells
during growth.
The ovulated secondary oocyte is surrounded by two additional coats: inner zona pellucida (acellular thin transparent glycoprotein coat) and outer thick corona radiata formed
by one or more layers of radially arranged follicular cells.
Size of the human egg is about 120 µm in diameter. Oocyte should be fertilized within
24 hours after ovulation. If it is not fertilized, it disintegrates.
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Fertilization is the process male and female gametes fusion to produce diploid zygote.
Fertilization in humans is internal as in other mammals. It takes place usually in the
ampulla of the fallopian tube.
The egg released during the ovulation is received by the fallopian tube. Actually, it is in
the secondary oocyte stage with the second meiotic division in progress (metaphase II). As
many as 40 to 100 million spermatozoa may be deposited in the vagina by a single ejaculation, but only about 200 reach the fallopian tube and just one sperm fertilizes the egg
(monospermy).
Within the female genital tract spermatozoa undergo capacitation, which is the final
step of the sperm maturation. Capacitation involves destabilization of the sperm head
membrane which becomes more fluid and fusigenic.
Fertilization is a complex sequence of several coordinated phases (Fig. 5.17).
1. Distant interaction – migration of sperm cells towards the egg. Spermatozoa move
by lashing of sperm tail (swimming) 2 to 3 mm per minute. Secondary oocyte secretes gynogamones that attract the spermatozoa and activate sperm movement
(chemotactic attraction). The process is assisted by uterine contractions.
2. Contact interaction includes
`` Acrosomal reaction. The sperm binds to a human-specific glycoprotein sperm
receptor molecule in the zona pellucida, which induces acrosome to release proteolytic enzymes. It causes lysis of the zona pellucida, thereby forming a path for
the sperm. When a spermatozoon successfully penetrates the zona pellucida and
reaches the oocyte, the cell membranes of the two cells fuse. The head and neck
of the sperm then enter the cytoplasm of the oocyte.
`` Cortical reaction. Entry of the sperm into egg causes cortical granules located
just beneath the oocyte cell membrane to release their contents into the space
between the oocyte and zona pellucida. Released substances interact with zona
pellucida, causing the zona to become impenetrable by additional spermatozoa.
This mechanism prevents polyspermy (fertilization of the oocyte by more than
one spermatozoon). Abnormal fertilization of the egg by two spermatozoa results
5.5. Gametogenesis. Fertilization
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4
5
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6
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8
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7
10
11
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Fig. 5.17. Fertilization: 1 – cytoplasm; 2 – cell membrane; 3 – spermatozoon; 4 – meiosis II;
5 – primary polar body; 6 – corona radiata; 7 – zona pellucida; 8 – perforations in the wall of the acrosome;
9 – acrosomal reaction; 10 – acrosome, 11 – nucleus
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in triploid cell (69 chromosomes in humans), that is not compatible with life in
most of the animals.
3. Karyogamy. The sperm entry stimulates the secondary oocyte to complete the second meiotic division. This produces a haploid mature oocyte (ovum) and the second
polar body. The nucleus of the mature oocyte growth and becomes the female pronucleus. At that time sperm nucleus enlarges also and become the male pronucleus
(Fig. 5.18). During growth both pronuclei replicate their DNA. Immediately after the
DNA synthesis chromosomes organize at the center of the cell and form metaphase
plate of the zygote. It initiates the first division of the zygote by mitosis.
Significance of Fertilization
`` Fertilization restores the diploid number of the chromosomes (46 in man) in the zygote.
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Chapter 5. Reproduction on the cellular and organismic level ...
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2
4
5
7
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8
8
6
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Fig. 5.18. Karyogamy: 1 – primary and secondary polar bodies; 2 – corona radiata; 3 – nucleus of spermatozoon; 4 – zona pellucida; 5 – nucleus of the ovum; 6 – centriole; 7 – male and female pronuclei; 8 – polar
bodies
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`` Combination of hereditary information of two parents introduces variation, which is
important in the genetic variability of population.
`` In humans the sex of child is determined at the moment of fertilization.
`` Fertilization activates metabolic processes in the cytoplasm of the egg and initiates
cleavage.
In vitro fertilization (IVF)
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In Vitro Fertilization (IVF) is the process of fertilization by manually combining an egg
and sperm in a laboratory dish, and then transferring the embryo to the uterus.
IVF is used in case of infertility. Female infertility is often due to damage of the Fallopian
tubes, obstructing a contact between the egg and the sperm. In this case IVF includes the following steps: 1) stimulation of egg production by fertility medication; 2) retrieving of the oocytes at the metaphase stage of meiosis II from the ovary through the minor surgical procedure;
3) collection of sperm, which is prepared for combining with the eggs; 4) mixing the thousands
of motile sperm in a small drop of media with eggs (insemination) for fertilization. Usually several embryos are produced. Embryos culture for 3 to 5 days; 5) transferring of the embryos into
the woman’s uterus three to five days following egg retrieval and fertilization.
5.5. Cloning of organisms
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Male infertility is linked to impaired sperm quantity and quality. In this case IVF is done
by intracytoplasmic sperm injection (ICSI). Through this procedure, a single sperm is injected directly into the egg. The procedure is done under a microscope. A single immobilized
sperm is picked by a delicate hollow needle and carefully inserted into the cytoplasm of
the mature egg held with a specialized pipette. After this procedure the oocyte is placed
into cell culture and checked on the following day for signs of fertilization.
Since 1978 when first baby, Louise Joy Brown, had been born through successful IVF
of human oocytes, new way to treat many forms of infertility is opened. Today, 2–3 % of all
newborns in some countries are conceived with the help of IVF.
The 2010 Nobel Prize in Physiology or Medicine was awarded to Robert G. Edwards “for the development of in vitro fertilization”.
5.5. Cloning of organisms
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Cloning is the development of offspring that are genetically identical to their parent.
Natural cloning is common among the plants and animals which reproduce asexually. In
sexually reproduced organisms natural clones are formed by polyembryony, when several
organisms develop from one fertilized egg. Identical twins are clones in mammals (including humans).
Artificial cloning is a modern technology that produces genetically identical copies
of an organism (reproductive cloning) or a cell (therapeutic cloning). The nucleus of
a somatic cell is removed and inserted into an unfertilized egg that has had its nucleus
removed (Fig. 5.19). This technique is known as somatic cell nuclear transfer (SCNT).
In case of reproductive cloning such egg is nurtured until it becomes an embryo. The
embryo is then placed inside a surrogate mother where it develops till birth. Dolly the
Sheep became famous for being the first successful case of the reproductive cloning of a
mammal from somatic cell in 1996 (Fig. 5.20). More than 20 species of different animals
has been successfully cloned today. These are cattle, pig, camel, mouse, goat, etc. Dogs
and cats are commercially cloned. The potential applications of reproductive cloning
are: to create clones of genetically modified (transgenic) animals for production of human proteins; for drug testing and treatment strategies; to restore or renew populations
of endangered or extinct species of animals. Despite the current achievements animal
cloning through the somatic cell nuclear transfer still has low efficiency with success rate
from 0.1 % to 3 %. One of the most important problems is an abnormal gene expression
patterns inadequate to one of the naturally-concieved embryo. Controlled and complete
re-programming of the transferred nucleus to an early embryonic state is an important
challenge for future researches.
Therapeutic cloning produces embryonic stem cells for creating tissues to replace injured or diseased tissues. It can be a tool for studying mechanisms of differentiation and
testing new therapeutic drugs.
Chapter 5. Reproduction on the cellular and organismic level ...
Donor of an unfertilized ovum
The donor of somatic cells
(the animal that is cloned)
Ovum
Donor of the fertilized egg
The donor cells
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The first transplantation
(the first nucleus transfer)
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Fertilized egg with
two nuclei –
own and derived
from the sperm
Removal of the nucleus
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The electrical discharge causes fusion
of the somatic cell with the “empty” ovum
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Activation of genes in the
nucleus of the somatic cell
Removal of the DNA of
the ovum and sperm
Removal of the nucleus
“Empty” ovum
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Second transplantation (second transfer of the nucleus)
Activated nucleus of the somatic cell fuses with the “empty” ovum
Fig. 5.19. Main stages of animal cloning
Surrogate
mother
Embryo is placed inside the surrogate mother
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5.5. Cloning of organisms
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Fig. 5.20. Dolly the Sheep and Ian Wilmut, who created the first cloned mammalian. Dolly was cloned from
udder cells of a sheep grown by an artificial method in a laboratory
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TASKS & QUESTIONS
`` MULTIPLE CHOICE QUESTIONS (Choose one correct answer)
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1. Active synthesis of proteins, carbohydrates and lipids in the cell takes place at the:
C. Metaphase
E. Prophase
A. Anaphase
B. Interphase
D. Telophase
2. Human somatic cells are diploid (2n), but polyploid cell of the red bone marrow
(megakaryocytes) may have 64 n chromosomes. What is the mechanism of its formation?
C. Mitosis
E. Meiosis
A. Endomitosis
B. Polyteny
D. Amitosis
3. An electron photomicrograph shows the cell with separating centrioles and forming
mitotic spindle. Chromatin threads are situated in the cytoplasm. The nuclear envelope and nucleoli are absent. This is typical for:
A. Anaphase
C. Metaphase
E. Prophase
B. Interphase
D. Telophase
4. At which phase of mitosis does a human cell have 92 single-chromatid chromosomes?
C. Metaphase
E. Anaphase
A. Interphase
B. Prophase
D. Telophase
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Chapter 5. Reproduction on the cellular and organismic level ...
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5. At which stage of the cell cycle do we usually study a human karyotype to diagnose
chromosomal disorders?
A. Interphase
C. Metaphase
E. Anaphase
B. Prophase
D. Telophase
6. Pairing of homologous chromosomes and crossing over take place in meiosis in:
A. Prophase I
C. Metaphase I
E. Anaphase II
B. Prophase II
D. Anaphase I
7. Meiosis is a reduction division. What set of hereditary information has a cell after the
second meiotic division?
A. 1n 2c
C. 2n 1c
E. 2n 2c
B. 1n 1c
D. 2n 4c
8. In humans, mammals and other chordates sexual reproduction takes place by fusion
of large immobile ovum and small motile sperm. This kind of sexual reproduction is:
C. Oogamy
A. Isogamy
E. Polyteny
B. Schizogony
D. Conjugation
9. Formation of egg in humans takes
C. 1–2 years
E. 12–45 years
A. 1 month
B. 28 days
D. 5–7 years
10. Tissue sample of the ovary shows large cells with paired homologous chromosomes
and points of crossing over in some of them. At what period of gametogenesis are
the cells?
A. Multiplication
C. Maturation
B. Growth
D. Formation
11. Oogenesis starts at embryogenesis but the cells don’t complete meiosis and become
dormant. At which stage of meiosis are oocytes stored in the ovaries?
A. Prophase I
C. Anaphase I
E. Interphase
B. Metaphase I
D. Telophase I
12. In some species ovum can start to develop without fertilization. Such way of reproduction is called:
A. Gametogenesis
C. Oogamy
E. Copulation
B. Parthenogenesis
D. Polyteny
13. Tissue sample of the ovary shows the resting cells that accumulate nutritive substances. At what period of gametogenesis are the cells?
A. Multiplication
C. Maturation
B. Growth
D. Formation
14. Process of oogenesis starts at the:
A. Embryonic period
C. 5th–7th year
E. 14th–6th year of life
nd
rd
th
th
B. 2 –3 year of life
D. 12 –13 year
15. Tissue sample of the fetal ovary demonstrate small cells. Some of them undergo mitotic division. What stage of ovogenesis is observed?
A. Multiplication
C. Maturation
B. Growth
D. Formation
5.5. Cloning of organisms
16. The stage of female gamete at the time of ovulation is:
A. Oogonium
C. Secondary oocyte
B. Primary oocyte
D. Polar body
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E. Mature ovum
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`` FILL IN THE BLANKS:
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1. Irreversible G0 is characteristic for the terminally differentiated cells like __________
___________________________.
2. In 1951 in Baltimore the first immortal human cell line called ____ was created from a
tissue sample taken from a young woman with ____________cancer.
3. ___________________ is the process by which polyploid cells are formed.
4. Apoptosis is characterized by activation of specific proteolytic enzymes – ________.
5. Examples of growth factors are _____________________, _________________,
______________.
6. Cyclin-dependent kinase is an enzyme that can change activity of different proteins
by its ____________________.
7. Tumor suppressor genes are normal genes that ______________________.
8. After the first meiotic division the primary oocyte divides to form two ________ cells
(n2c): a single large-sized ____________ and minute first _____________.
9. Fertilization restores the ______________ number of the chromosomes (___in man)
in the ________.
10. Artificial cloning produces genetically _______ copies of an organism (__________
cloning) or a cell (__________ cloning).
`` TRUE OR FALSE:
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1. Apoptotic cells release their cellular constituents into the surrounding and provoke
inflammatory reactions.
False
True
2. The interphase is the shortest phase of the mitotic cycle and occupies about 10 % of
the cell cycle.
True
False
3. The division of the nucleus is called karyokinesis.
True
False
4. Cells of kidney, liver, thyroid gland and pancreas belong to growing cell population.
True
False
5. The G2/M checkpoint ensures each of the sister chromatids are correctly attached to
the spindle fibers before cell enters the anaphase.
True
False
6. Cortical reaction prevents polyspermy (fertilization of the oocyte by more than one
spermatozoon).
True
False
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Chapter 6.
Human ontogenesis. Prenatal and postnatal
periods of ontogenesis
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6.1. Ontogenesis. Embryonic period of ontogenesis
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Ontogenesis (from Greek ontos – an essence, genesis – development) is individual development of an organism. It includes the set of consecutive morphological, physiological
and biochemical transformations from the fertilization up to death. From genetic point of
view ontogenesis is realization of hereditary information at the each stage of individual
development in certain environment.
The science which deals with the study of ontogenesis is called developmental biology.
The ontogenesis of multicellular organisms is divided into two periods: embryonic and
postembryonic. Period of gametogenesis or prezygotic period is very important for ontogenesis as the failure at this period (for instance, numerical or structural chromosomal
aberrations arising in meiosis) determines the further fate of an organism.
1. Embryonic period (embryogenesis). It starts immediately after fertilization and
completes with hatching or birth. In mammals including man this period is also termed
as prenatal. As in mammals embryonic development takes place in the uterus inside the
maternal organism, it is the intrauterine development.
The study of this period is called embryology.
In humans prenatal period lasts about 266 days or 38 weeks. Developing human organism is called embryo till the 9th week from fertilization. This period is characterized by active
morphogenesis. In 9 week after the fertilization the embryo acquires human features. Since
this time till birth it is called fetus.
In premature birth newborn child is considered to be viable from 23rd week of gestation
if it gets full-team medical attention in a neonatal intensive care unit. From 28th week of
gestation fetus is capable of spontaneous breathing, so can survive.
2. Postembryonic (in mammals and man – postnatal) period extends from hatching
or birth to death.
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Embryonic period of ontogenesis
The main consequent steps of embryogenesis are:
`` fertilization;
`` cleavage;
`` gastrulation;
`` histogenesis and organogenesis.
6.1. Ontogenesis. Embryonic period of ontogenesis
2-Cell
(1 day)
4-Cell
(2 days)
9-Cell
(21/2 days)
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Blastomere
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Polar body
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Trophoblast
58-Cell
(blastocyst)
(4 days)
Blastocoele
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16-CeII
(morula)
(3 days)
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Embryoblast
Zona pellucida
107-Cell
(blastocyst)
(5 days)
Fig. 6.1. Cleavage in humans
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I. Fertilization is fusion of haploid male and female gametes to form a diploid zygote.
It initiates cleavage.
II. Cleavage is the rapid mitotic division of the zygote. It ends with formation of a single
layered hollow spherical structure called blastula (Fig. 6.1). These divisions are not accompanied by cell growth, so size of the daughter cells called blastomeres became smaller
with each division. The embryo as a whole does not change in size and remains enclosed
in zona pellucida.
The type of cleavage depends on amount and distribution of yolk in the egg (ovum)
(Fig. 6.2). There are several types of the ovum:
`` Isolecithal is characterized by little amount of evenly distributed yolk. Such type of
the egg is present in Mollusks, Annelids, Mammals. In man ovum is almost completely lack yolk and is called as secondary alecithal.
`` Telolecithal eggs are characterized by accumulation of yolk at one of the poles (the
vegetal one). The opposite pole with the nucleus and most of cytoplasm is termed
as animal pole. Depending on amount of yolk there are moderately (amphibians and
some fishes) and extremely (most fishes, reptiles, birds) telolecital eggs.
`` Centrolecithal. Yolk is concentrated in the center of egg (Arthropods).
According to the pattern of distribution of yolk in the zygote, cleavage is of two main
types:
Chapter 6. Human ontogenesis. Prenatal and postnatal periods of ontogenesis
Extremely
telolecithal egg
Unequal holoblastic
cleavage
Blastocoel
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Blastocoel
Meroblastic discoidal
cleavage
Sea urchin
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Equal holoblastic
cleavage
Centrolecithal
egg
Meroblastic superficial
cleavage
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IsoIeсithaI egg
Moderately
telolecithal egg
Blastocoel
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Frog
Insect
Bird
Fig. 6.2. Types of ovum according to yolk distribution and patterns of cleavage
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A. Holoblastic. It is characteristic for isolecital and moderately telolecital eggs. In holoblastic cleavage the zygote divides completely into the blastomeres. Such a cleavage can
be either equal or unequal. Equal holoblactic cleavage produces approximately equal sized
blastomeres as in starfish. Unequal holoblactic cleavage produces blastomeres unequal in
size (human, frog).
B. Meroblactic. It is characteristic for centrolecital and extremely telolecital eggs. In
this case only a small, yolk-free, metabolically active part of the cytoplasm divides, leaving
the yolky part undivided. Meroblastic cleavage can be of two types. In discoidal cleavage
divisions are confined to the cytoplasmic disc at the animal pole. It is found in the heavily
yolky eggs of reptiles, birds, prototherian mammals. In superficial cleavage divisions are
confined to the peripheral yolk-free cytoplasm as in insects.
During cleavage, cellular activity is still mainly controlled by the molecules received
from the secondary oocyte’s cytoplasm, but some of the developing organism’s genes become active.
Cleavage in a human occurs during passage of embryo through the fallopian tube to
the uterus as in other mammals (Fig. 6.3). The type of the cleavage is holoblastic, unequal,
and asynchronous (blastomeres divide at different moment of time). The first cleavage
takes place about 30 hours after fertilization. It is meridional. The second cleavage occurs
6.1. Ontogenesis. Embryonic period of ontogenesis
115
cell division
2-cell
4-cell
embryo stage
embryo stage
8-cell
embryo stage
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morula
zona pellucida
nucleus of the spermatozoon
primary and
secondary polocytes
fertilization
Embryoblast
late blastocyst
Implantation
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early blastocyst
blastocyst cavity
trophoblast
secondary oocyte
ovulation
IC
ovary
fimbria
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Fig. 6.3. First week of human development. Cleavage
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within 60 hours after fertilization. It is at right angle to the plane of the first. Third cleavage
takes place about 72 hours after fertilization. Subsequent cleavage divisions follow one
after another in an orderly manner, but in a less precise orientation. Cleavage produces
a solid ball of small blastomeres. The embryo now looks like a mulberry, and is known as
morula. The morula consists of 16 to 32 cells, but it is not larger than zygote.
By 4 days of development the morula, consisting about 30 cells reaches uterus cavity and starts to absorb the fluid. As the quantity of fluid increases, the morula enlarges
rapidly and assumes the shape of a cyst. The embryo is now called the blastula. The human blastula is blastocyst (Fig. 6.4A). Blastocyst consists of two groups of cells and cavity
inside. The outer layer of cells is called the trophoblast and the inner cell mass is called
the embryoblast. The cavity inside contains fluid and is known as blastocoel. The side of
blastocyst to which embryoblast is attached is the embryonic or animal pole, and the opposite side is the abembryonic pole. The trophoblast does not take part in the formation
of the embryo proper. It remains external to the embryo and gives rise to the extra embryonic membranes (chorion and placenta) for protection and nourishment of the embryo.
Embryoblast gives rise to the embryo proper and fetal membranes except for chorion and
placenta (amnion, yolk sac and allantois).
As a blastocyst is formed, zona pellucida becomes thinner and finally disappears (5th
day after fertilization). It permits implantation.
Implantation is the embedding of the blastocyst to the uterine wall. It takes place
about six to seven days after fertilization.
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Chapter 6. Human ontogenesis. Prenatal and postnatal periods of ontogenesis
Inner cell mass or embryoblast
Uterine stroma
Uterine
epithelium
D
Trophoblast
cells
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Blastocist cavity
Embryoblast
Outer cell mass
or trophoblast
A
B
IC
Fig. 6.4. Human blastocyst: A – section of a 107-cell human blastocyst; B – schematic representation of a
blastocyst showing trophoblast cells at the embryonic pole of the blastocyst penetrating the uterine mucosa
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The function of the zona pellucida is to prevent the implantation of the blastocyst at
an abnormal site. Disappearing of zona pellucida enables the blastocyst to come in direct
contact of trophoblast cells with the mucosa of the uterus (endometrium) (Fig. 6.4B). This
contact stimulates rapid divisions of the trophoblastic cells, which destroy the endometrial
cells by releasing lytic enzymes. The blastocyst sinks into a pit formed in the endometrium
and then gets completely buried in the endometrium that grows around it. Thus, implantation involves activities of both the blastocyst and the uterus. The trophoblast of embedded
blastocyst forms villi all round it to obtain nourishment. Later, it projects into the uterine
cavity and loses villi from the free surface. Thus the trophoblast of the invading blastocyst
develops the chorion, which later forms placenta.
The chorionic cells secrete a hormone named human chorionic gonadotrophin (hCG).
A pregnancy test at this time may confirm conception by presence of hCG in urine.
III. Gastrulation is forming of germ layers. Gastrulation converts a single-layered, hollow blastula into a gastrula with germ layers. Germ layers are groups of cells that give rise
to specific tissues, organs and organ-systems of the young one to be developed. In fact, the
fate of the germ layers is the same in all triploblastic animals. This indicates their evolution
from a common ancestor.
There are three germ layers: ectoderm (external), mesoderm (medium) and endoderm
(internal). Ectoderm and endoderm are formed initially at the stage of early gastrulation.
Bilaminar embryo is known as gastrula. Mesoderm is formed after that (late gastrulation).
Gastrula can be formed by several ways:
`` Invagination. Local inward movement of blastula wall into blastocoel (Fig. 6.5).
By this process the single layered blastula is converted into gastrula with two layers
of cells and a new cavity which opens to the exterior. The outer layer is ectoderm
and the inner layer is endoderm. The cavity in the interior is called primary or embryonic gut (archenteron) and its opening is blastopore. Blastopore is limited by
6.1. Ontogenesis. Embryonic period of ontogenesis
117
B
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D
A
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Fig. 6.5. Scanning electron microphotograph of gastrula formation by invagination: A – inside view;
B – view from the outside
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lips. Such way of gastrulation is characteristic for one of the primitive chordates –
a lancelet.
`` Migration. Movement of individual cells over a substratum of other cells or extracellular material.
`` Epiboly. The spreading movement of a superficial cell layer to envelop a yolk mass
or deeper cell layer.
`` Delamination. Splitting of one layer of cells into two parallel layers.
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Most of animals have several ways of gastrulation during embryogenesis. For example,
amphibians demonstrate epiboly and invagination, birds and mammals – delamination
and migration.
Different combinations of these mechanisms yield a wide variety of morphogenetic
processes in different animals.
Mesoderm in most of animals is formed by one of two ways:
`` Teloblastic. Several cells from blastopore lips migrate between ectoderm and entoderm and multiply forming mesoderm. It is typical for mollusks, annelids and other
invertebrates.
`` Enterocoelic. Embryonic gut (archenteron) forms two pouches that invaginate between
ectoderm and endoderm and grow towards each other. It is typical for chordates.
Gastrulation and further stages of embryogenesis are connected to certain repertoire
of cellular behaviors, like cell division, cell movement, cell shape changes, intercalation and
adhesion of cells, and programmed cell death (apoptosis).
Gastrulation in Human occurs by delamination and migration of the cells.
At the beginning of the second week, the embryoblast splits into two layers (delamination): the epiblast or primary ectoderm and the hypoblast or primary endoderm (Fig. 6.6).
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Chapter 6. Human ontogenesis. Prenatal and postnatal periods of ontogenesis
Trophoblastic lacunae
Enlarged blood vessels
Syncytotrophoblast
D
Cytotrophoblast
TE
Amniotic cavity
Epiblast
Hypoblast
IC
Exocoelomic (Heuser's) membrane
Exocoelomic cavity (yolk sac)
Fiber coagulum
TR
Fig. 6.6. A 9-day human blastocyst. The bilaminar germ disc consists of a layer of columnar epiblast cells
and a layer of cuboidal hypoblast cells
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A cavity, called the amniotic cavity develops within the epiblast. Cells from hypoblast migrate to line the blastocyst cavity transforming it into yolk sac. Embryo looks now like a
bilaminar germ disc (epiblast and hypoblast) lying between the amniotic cavity and the
yolk sac.
By the beginning of the third week, the embryonic disc begins to elongate and broaden
at one end, becoming a pear shaped plate of the cells. A depression forms down the center
of the plate, called the primitive streak. Some cells of epiblast rapidly multiply and move
toward and into this groove (migration), forming mesoderm between epiblast and hypoblast. Some cells of epiblast migrate to replace original hypoblast cells and form endoderm. The remaining cells of the epiblast get arranged in a layer called ectoderm. Hence,
epiblast gives rise to all three germ layers of the embryo (Fig. 6.7).
VI. Histogenesis and organogenesis is the formation of tissues and organs from three
germ layers. It is the final phase of embryonic development, which involves the morphogenesis and differentiation of cells. In vertebrates it begins simultaneously with formation
of mesoderm.
On the third week of development formation of notochord and neural tube starts. By
the 17th day of development, the mesodermal cells beneath the primitive streak aggregate,
forming a solid rod of mesodermal cells called the notochord. It forms a midline axis, which
establishes bilateral symmetry, craniocaudal direction and will serve as the basis of the
axial skeleton. Chemical signals from the notochord stimulate the ectoderm overlying it to
thicken and form the neural plate. By day of 21 the raised edges of the neural plate form
6.1. Ontogenesis. Embryonic period of ontogenesis
119
Morula.
Embryo is a solid
ball of cells
produced by
cleavage
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Trophoblast
D
Human
Lancelet
Blastocoel
Embryoblast
Blastula.
Embryo has a cavity
Blastocyst cavity
Blastopore
IC
Amnionic cavity
Embryonic disk
Ectoderm
Endoderm
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Early gastrula.
Embryo has the
ectoderm and
endoderm
Archenteron
Yolk sac
Ectoderm
EC
Late gastrula.
Formation of
mesoderm
Mesoderm
Endoderm
Primitive streak
Archenteron
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Fig. 6.7. Stages of early animal development. All animals go through the stages noted. The appearance of
these stages in lancelets and human is compared
two neural folds. Two days later the raised edges of the neural plate come together and
fuse, forming a neural tube. Formation of the neural tube is called neurulation, embryo in
this stage – neurula (Fig. 6.8).
Paraxial mesoderm on the dorsal side (dorsal mesoderm) on either side of the notochord forms somites – a series of mesodermal segments. Each somite later subdivides into
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Chapter 6. Human ontogenesis. Prenatal and postnatal periods of ontogenesis
4
1
5
6
D
2
3
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7
8
A
IC
B
Ectoderm
Mesoderm
Endoderm
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Fig. 6.8. Human neurula. A – dorsal view; B – cross section: 1 – neural folds; 2 – pericardial area; 3, 5 – somites;
4 – neural tube; 6 – notochord; 7 – gut; 8 – coelom
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three parts: sclerotome (internal part), myotome (medial part) and dermatome (external
part). Sclerotome gives rise to the vertebral column, myotome develops into skeletal muscles and dermatome into dermis of skin. Ventral part of mesoderm is not segmented and
forms splanchnotome. Splanchnotome divides into parietal and visceral parts and gives
rise to the smooth muscles, blood vessels, blood cells, heart, coelom (pericardial, pleural
and peritoneal cavities) and some other organs.
Thus, each germ layer gives rise to the specific tissues, organs and organ systems
(Fig. 6.9). The germ layers have the same fate in all animals.
1. Ectoderm. It gives rise to skin epidermis and epidermal derivatives (glands, hair,
nails), nervous system, posterior and intermediate lobes of pituitary gland, pineal
gland, medulla of adrenal gland, eye (conjunctiva, cornea, lens, retina, iris and ciliary muscles), internal ear, nasal epithelium, epithelial lining of oral cavity and rectum, lining of external auditory canal, lacrimal glands, salivary glands, enamel of
teeth.
2. Mesoderm. It produces dermis of the skin, muscles, notochord, skeleton, connective tissues, cortex of adrenal glands, kidneys, gonads, urinary and reproductive
ducts, heart, blood and lymph vessels, spleen, dentine of teeth, wall of gut except
its lining epithelium, mesenteries, pericardium, pleura and peritoneum, sclera and
choroid of eye.
3. Endoderm. It forms lining of gut except that of oral cavity and rectum, tongue epithelium, gastric and intestinal glands, liver, pancreas, lining of trachea, bronchi and
6.1. Ontogenesis. Embryonic period of ontogenesis
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5
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7
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12
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Fig. 6.9. Formation of tissues and organs from germ layers: 1 – brain; 2 – heart; 3 – amniotic cavity; 4 – amnion; 5 – gastrointestinal tract; 6 – skin; 7 – spinal cord; 8 – chorion; 9 – tail; 10 – umbilical cord; 11 – placenta;
12 – yolk sac
lungs, anterior lobe of pituitary gland, thyroid gland, parathyroid glands, thymus, lining of urinary bladder, primordial germ cells, most of the prostate, lining of middle
ear.
By the 4th week after fertilization, the embryo has a simple heart, limb buds and eye
rudiments. It also has a tail and pharyngeal pouches, the vestiges of its early vertebrate
ancestors that disappear later in development (Fig. 6.10).
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Chapter 6. Human ontogenesis. Prenatal and postnatal periods of ontogenesis
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3
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2
4
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9
8
7
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6
5
Fig. 6.10. 5-week embryo: 1 – optical cup; 2 – umbilical cord; 3 – tail; 4 – hindlimb bud; 5 – gastrointestinal
tract; 6 – liver; 7 – heart; 8 – forelimb bud; 9 – brain
TR
By the end of the eight week, main organ systems are established and the embryo is
recognizable as a primate. From 9th week the embryo is called fetus. At fetal period growth
and differentiation of cells continues.
Period of pregnancy is called the gestation period. It is conventionally calculated from
the onset of the last menstruation making the gestation period approximately 280 days. Parturition, or giving birth to the baby, usually takes place within 15 days of the calculated date.
EC
Embryonic or Fetal Membranes
R
Embryonic or fetal membranes (provisory organs) are temporary organs, which provide
intrauterine development of an embryo. They include amnion, yolk sac, allantois, chorion
and placenta (Fig. 6.11).
The amnion is a thin extraembrionic membrane derived from ectoderm and mesoderm. It loosely envelops the embryo, forming an amniotic sac that is filled with amniotic
fluid. As the amniotic sac enlarges during the late embryonic period (at about 8 week),
the amnion gradually sheathes the developing umbilical cord with an epithelial covering.
The amniotic fluid performs following functions: helps to maintain a constant pressure and
temperature; cushions and protects from jolts that the mother may receive; allows the fetus to move freely, which is important for musculoskeletal development and blood flow.
The amniotic fluid is formed initially as an isotonic fluid absorbed from maternal blood
in the endometrium. Later, the volume is increased and concentration changed by the
urine excreted from the fetus into the amniotic sac. The amniotic fluid is normally swal-
6.1. Ontogenesis. Embryonic period of ontogenesis
Chicken
123
Human
Chorion
D
Amnion
Yolk sac
TE
Embryo
Allantois
Fig. 6.11. Extraembryonic membranes
IC
Fetal portion of placenta
Maternal portion of placenta
Umbilical
cord
R
EC
TR
lowed by the fetus and is absorbed into the blood from gastrointestinal tract. From fetal
blood the waste products of amniotic fluid pass through placenta into maternal blood.
The amniotic fluid also contains cells that are sloughed off from the fetus. Many hereditary disorders can be detected by aspirating this fluid and examining the cells. A procedure
of taking amniotic fluid is called amniocentesis.
Amniotic membrane ruptures at the beginning of labor and the amniotic fluid is released.
The yolk sac is formed during the end of the second week. The human yolk sac contains
no nutritive yolk. Attached to the underside of the embryonic disk, it is the first organ of
hematopoesis (produces blood cells) and produces the primordial germ cells. A portion of
the yolk sac is also involved in the formation of the primitive gut.
The stalk of the yolk sac usually detaches from the gut by the 6th week. Following this,
the yolk sac gradually shrinks as pregnancy advances.
The allantois forms as a small outpouching near the base of the yolk sac. In birds it is
the place of accumulation of the embryo’s metabolism products. In mammals and humans
it remains small but is involved in the formation of umbilical cord. It gives rise to the fetal
umbilical arteries and vein.
The chorion is the outermost extraembryonic membrane that develops from trophoblast and extraembryonic mesoderm. It contributes to the formation of the placenta as small
fingerlike extensions called chorionic villi, penetrate deeply into the uterine tissue. Initially,
the entire surface of the chorion is covered with chorionic villi. Villi on the surface toward the
uterine cavity gradually degenerate, producing a smooth area. The chorionic villi associated
with the uterine wall rapidly increase in number and branch out, becomes highly vascular
with embryonic blood vessels. This portion of the chorion is known as the villous chorion
and becomes the embryonic portion of placenta. The placenta is a vascular structure by
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Chapter 6. Human ontogenesis. Prenatal and postnatal periods of ontogenesis
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which fetus is attached to the uterine wall. The placenta is formed in part from maternal
tissue and in part from embryonic tissue. Blood does not flow directly between these two
portions but as their membranes are in close proximity, certain substances diffuse readily.
Placenta supplies fetus with all necessary substances, provides gas metabolism and removing of metabolic products. It also serves as a protective barrier and an endocrine organ
producing steroid hormones and chorionic gonadotropin.
Chorion and placenta develop from the same zygote as embryo, thus have same genetic information and can be used for prenatal diagnosis of hereditary disorders. The techniques for obtaining the cells are called chorionic villi biopsy (chorioncentesis) and placentocentesis respectively.
The umbilical cord connects embryo with placenta. It contains two umbilical arteries,
which carry deoxygenated blood from the embryo towards the placenta, and one umbilical vein, which carries oxygenated blood from the placenta to the embryo. Taking of umbilical blood for prenatal diagnosis is called cordocentesis. At parturition extraembryonic
membranes (placenta, umbilical cord) separate from the fetus and are expelled from the
uterus as the afterbirth.
Molecular and cellular mechanisms of differentiation
R
EC
TR
A multicellular organism composed of variable cells forming tissues and organs, develops from a single zygote. Embryonic development is characterized by active proliferation,
migration, apoptosis and differentiation of cells. At the end of prenatal period, human organism has about 350 types of cells with different functions and morphological features,
despite they share same set of genetic information. Availability of all genes required for
the development of whole organism from differentiated cell was demonstrated by John
Gurdon (Fig. 6.12). He transferred the nuclei of cells from a frog’s skin and tadpole’s intestine
into enucleated frog’s eggs and got normal frogs (clones of an organism whose nuclei were
used). Multiple successful experiments of different animals cloning also prove that the cells
of an adult organism genetically identical to the fertilized egg from which they are derived.
Ability of cell to differentiate into other cell types is known as cell potency (Fig. 6.13). Zygote is totipotent (from Latin totus – entire + potent – having power). It means that zygote
can give rise to all types of cells, both embryonic and extraembryonic.
Early blastomers are also totipotent, but after reaching the morula stage differentiation
into embryoblast and trophoblast cells starts. At blastocyst stage cells of the inner cell mass
(embryoblast) become pluripotent (from Latin plurimus – very many + potent). These cells
have the potential to differentiate into any of the three germ layers cells, but are unable to
form chorion and placenta. With further development potency restricts and cells become
multipotent (from Latin multus – much, many + potent). Multipotent cells can differentiate
into more than one, but discrete cell types.
The process of cell specialization at which cell gets chemical, morphological and functional peculiarities is called differentiation. Differentiation is explained by activation and inactivation of specific genes that leads to pattern of proteins, typical for certain cell type. The
6.1. Ontogenesis. Embryonic period of ontogenesis
125
IC
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Enucleated frog's leg
Nucleus from frog's intestine cell
TR
Fig. 6.12. Nuclear transplantation (Experiment by D. Gurdon)
Zygote
Totipotent
Morula
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Blastocyst
Germlines
Ectoderm
Pluripotent
Gastrulation
Mesoderm
Entoderm
Adult stem cells
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Precursor cells
Mature effector cells
Brain
Skin
Blood
Muscles
Intestine
Fig. 6.13. Types of stem cells, depending on the level of differentiation
Liver
Multipotent
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Chapter 6. Human ontogenesis. Prenatal and postnatal periods of ontogenesis
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point at which non-specialized cell becomes committed to a particular way of development
is called determination. Determination precedes differentiation and occurs when tissue
specific genes become active and synthesis of tissue specific proteins starts. Differentiation
depends on combination of molecular signals that switch on different genes in different cells.
The processes of early embryogenesis are controlled by proteins and RNA molecules
that have been accumulated in the cytoplasm of oocyte. Spermatozoon also delivers a set
of unique regulatory RNAs to oocyte upon fertilization. Own genetic program of developing organism activates from the 8-blastomere stage (there are experimental evidences that
separate genes become active earlier).
Cell differentiation in embryogenesis is very complex process caused by many factors.
Some of them are:
`` Reprogramming of DNA in maternal and paternal pronuclei after fertilization and
in early blastomeres. It occurs by shifting of DNA methylation pattern (epigenetic
reprogramming of genome), that helps to control which genes will be expressed
(maternal or paternal).
`` Ooplasmic segregation. Cytoplasm of an egg has heterogenous chemical organization. It is observed from maturation stage, but becomes prominent after fertilization.
As a result blastomeres get cytoplasm portions with different chemical “local determinants” that cause activation of different genes.
`` Concentration gradient of morphogens. Morphogens are signaling molecules that are
released by certain embryonic cells and diffuse through the embryo forming a concentration gradient. The gradient (difference in concentration of the morphogen) determines appropriate differentiation of cells according to their position within the tissue.
Morphogens also guide migration of the cells and are involved in regulation of apoptosis. Thus, dose of morphogen, which is gradually restricted, is important in establishment of spatial patterns during embryonic development. For example, retinoic acid is
an important morphogen involved in pattering of the anterior-posterior axis structures,
including neural plate, brain, foregut derivatives and paraxial mesoderm. Retinoic acid is
synthesizes in the posterior part of the embryo and its concentration decreases towards
the anterior end. Another famous morphogen is SHH (Sonic HedgeHog) protein. It is essential for dorso-ventral neural tube pattering, development of foregut and limbs.
`` Embryonic induction. It is the process in which one group of cells directs the development of another group of cells. The process was discovered by German embryologist Hans Spemann and his student, Hilde Mangold (1924) in experiments with embryos of newt (Fig. 6.14). He noted that the dorsal lip of blastopore induces formation
of the notochord, neural tube and mesoderm. H. Spemann transplanted group of the
cells from dorsal lip of one newt embryo to the ventral lip of another embryo at early
gastrula stage. As a result one more notochord, neural tube and after that a complete
secondary embryo was formed on the ventral side. So, dorsal lip region of blastopore
was called primary organizer. Embryonic induction is explained by synthesis of certain chemicals (inducers) by the cells of primary organizer. Inducers migrate to the
neighboring cells and stimulate differentiation.
6.1. Ontogenesis. Embryonic period of ontogenesis
127
Glass scalpel
Dorsal blastopore lip (Spemann organizer)
D
a
b1
Either way
b2
Receiver
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Donor: Early gastrula
Receiver
Primary neural plate
d
IC
c
Induced, second neural plate
Induced double body
Fig. 6.14. Scheme of Spemann-Mangold experiment (embryonic induction). b1 – blastocyst 1; b2 –blastocyst 2
TR
The Nobel Prize in Physiology or Medicine 1935 was awarded to Hans Spemann
“for his discovery of the organizer effect in embryonic development”.
R
EC
`` Growth factors – proteins or polypeptides that are secreted by some cells of embryo
into the surrounding space. They interact with specific receptors on the surface of
target cells and regulate cell proliferation, migration and differentiation. Examples
of growth factors involved in embryogenesis are the Fibroblast Growth Factor family
(FGF) and Transforming growth factor β (TGF β) family. The latter includes the bone
morphogenic protein (BMP) that is very important for bone formation.
Genes controlling growth factors, morphogens and their receptors are present in all
organisms from nematodes to mammals. These genes are highly conserved (share similar sequences of nucleotides) in different species and signaling pathways are principally
same. This fact permitted to study molecular mechanisms of human development on such
animal models as round worm Caenorhabditis elegans, fruit fly, zebrafish, frog, chicken and
mouse.
The Nobel Prize in Physiology or Medicine 1995 was awarded jointly to Edward B. Lewis, Christiane
Nüsslein – Volhard and Eric F. Wieschaus “for their discoveries concerning the genetic control
of early embryonic development” on animal model of fruit fly Drosophila melanogaster.
Mutations of genes for growth factors, their receptors and other factors involved in regulation of embryogenesis lead to hereditary congenital defects.
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Chapter 6. Human ontogenesis. Prenatal and postnatal periods of ontogenesis
6.2. Critical periods of embryogenesis. Congenital defects
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Critical periods of embryogenesis are the periods when an organism is the most sensitive to the factors of environment. There is a great chance of congenital defects or death
of the fetus at these periods (Fig. 6.15).
Congenital defects of development – are the morphological abnormalities that are
formed prenatally and cause dysfunctions of organs. Science about congenital defects is
teratology.
From the point of view of teratology, critical period is the period of the highest risk of
congenital defects. There are two critical periods.
The first 2 weeks after fertilization is called the first critical period of embryonic development. During this period, teratogenic factors act according to the principle “all or nothing”.
Few damaged cells can be replaced by others and embryo develops normally as cells are
toti- or pluripotent. Severe damage results in the death of the embryo. Congenital defects
are formed rarely. They are called blastopathies.
The second critical period lasts from 3rd to 8th weeks after fertilization. It is the period of
greatest sensitivity to teratogenic exposure as main processes of histogenesis and organogenesis take place. Congenital defects formed at this period are called embriopathies.
Classification and examples of congenital defects are given in Table 6.1.
Embryonic period (wk)
1
2
3
Eye
R
EC
Period of dividing
CNS
zygote, implantation
and bilaminar embryo Heart
4
5
6
7
8
Indicates common site of action of teratogen
Ear
Ear
Palate
Eye Heart
Leg
Limbs
Teeth
9
16
20–36
Brain
Full-term
fetus
38
External genitals
Central nervous system
Heart
Forelimbs
Eyes
Hindlimbs
Teeth
Palate
External genitals
Usually not susceptible to teratogens
Prenatal death
Fetal period (wk)
Ears
Major morphological abnormalities
Physiological defects and minor morphological abnormalities
Fig. 6.15. Sensitivity to teratogenic factors in embryogenesis. (dark boxes indicate periods of great sensitivity;
light boxes indicate states that are less sensitive to teratogens)
6.2. Critical periods of embryogenesis. Congenital defects
129
Table 6.1. Classification of congenital defects
Groups
of defects
Characteristic
Gametopathy Gametogenesis failure
Conjoined twins
TE
Embryopathy
Most of the defects (polydactyly,
heart defects and other)
Fetopathy
Pathology of fetal period (after
9th week from fertilization)
Cleft lip and palate, defects of
external genitalia
Hereditary
Caused by mutations (numerical and structural chromosomal
aberrations, gene mutations)
Congenital defects in chromosomal and single gene disorders
Teratogenic
Develop under the action of
external factors
Alcohol fetal syndrome
(Fig. 6.16); congenital defects
due to intrauterine infections
Multifactorial
Develop as a simultanious
result of hereditary predisposition (mutant alleles) and
environmental factors
Anencephaly (absence of brain),
cerebrospinal hernia, most congenital heart defects, club foot
TR
According to
etiology
Pathology of first two weeks
from fertilization
Pathology of 3rd–8th weeks from
fertilization
Blastopathy
Multiple defects in chromosomal
disorders due to non-disjunction
of chromosomes in meiosis
IC
According
to the time
when it is
formed
Examples
D
Principles of
classification
1
2
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3
4
5
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7
6
Fig. 6.16. Alcohol fetal syndrome. Children with alcohol fetal syndrome are born in 30–45 % of cases of alcohol consumption by mothers. Characteristic features: 1 – small head size (microcephaly); 2 – low nasal
bridge; 3 – epicanthal folds; 4 – short nose; 5 – reduced middle part of face; 6 – thin upper lip; 7 – smooth
and long philtrum (a vertical groove in the middle area between nose and upper lip); mental retardation
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Chapter 6. Human ontogenesis. Prenatal and postnatal periods of ontogenesis
Environmental factors that lead to the congenital defects are teratogenic factors.
Three groups of teratogenic factors are summarized in Table 6.2.
Alcohol,
some medicines (thalidomide (Fig. 6.17), tetracycline),
salts of heavy metals like
Pb, Hg
Biological
TORCH infections during the pregnancy.
TORCH from:
Toxoplasma,
Other (AIDS, syphilis and other)
Rubella
viral
Cytomegalovirus
infections
Herpes
TR
IC
Hyperthermia,
ionizing radiation,
mechanical
trauma
Chemical
TE
Physical
D
Table 6.2. Groups of teratogenic factors
EC
Fig. 6.17. Absence of hands as a result
of thalidomide embryopathy
From the point of view of embryology, the critical periods are the periods of the highest
risk of prenatal death. These are implantation, placentation (3–4 week), and delivery.
6.3. Postnatal period of ontogenesis
R
Postembryonic period is the period from hatching or birth to death. In mammals this
period often is termed as postnatal, it lasts from birth to death.
There are two principle types of postembryonic development: direct and indirect. In
the direct development nascent body is similar to the adult, but smaller in size. Direct
development is possible if egg accumulates enough amount of yolk (reptiles and birds)
or embryo gets nutrition directly from maternal organism (mammals). A human being has
direct postembryonic development.
6.3. Postnatal period of ontogenesis
131
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In the indirect development the larva, which is not like an adult, hatches of the egg. A
metamorphosis – the gradual transformation of the larva into an adult occurs in the postembryonic period. Such type of development is seen in animals with insufficient for direct
development amount of yolk in eggs (insects, bony fish, amphibians).
The important characteristic of postnatal period is age. Chronological or passport age
is time passed from a moment of birth. Biological age is estimated according to morphological and physiological state of an organism. In childhood biological age is determined
by body size and weight, ossification of bones, teeth eruption, psychological milestones,
motor skills, and, starting from 10-yars-old age by the level of sexual maturity. Chronological and biological age of a child should coincide. In some cases there is retardation
or acceleration of child’s development (biological age) comparatively with chronological
age. Normally, this difference shouldn’t be more than two years. In adults biological age
depends on intensity of aging process (state of nervous system, cardiovascular and other).
Difference between chronological and biological age can reach five years in adults and 20
years in elderly persons.
Postembryonic (postnatal) development includes pre-reproductive, reproductive and
post-reproductive periods.
Milestones of human postnatal ontogenesis are given in Table 6.3.
TR
Pre-reproductive period. Growth
R
EC
Pre-reproductive period is characterized by active growth and differentiation. Growth
is an irreversible and permanent increase in size, shape and mass, accompanied by an increase of dry weight of an organism. It occurs when anabolic activities exceed the catabolic
ones.
Growth is always associated with differentiation. Differentiation is a change in the anatomy or physiology of a single cell or group of cells in a multicellular organism as it matures
into a specialized cells and tissues.
At a molecular level the growth involves synthesis of new molecules and their aggregation.
At the cellular level the growth involves increase of cell size due to synthesis of cytoplasmic structures (hypertrophy), increase in the number of the cells by cell division (hyperplasia) and accumulation of extracellular matter.
At the organism level the growth manifests as increase in size and formation of the
body shape.
There are several classifications of growth:
1. According to the pattern of growth:
`` Isometric growth, when body and organs grow at the same rate. As the organism
grows, the proportions of the body does not change (fish);
`` Allometric growth. As the organism grows the external form and proportion of
the body changes (mammals). The growth rate of inner organs also is irregular
(Fig. 6.18).
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Chapter 6. Human ontogenesis. Prenatal and postnatal periods of ontogenesis
Table 6.3. Milestones of human postnatal ontogenesis
Period
Age
The main processes
Early childhood
Adapting to new conditions of life: breathing by
lungs, reorganization in blood circulation and
thermoregulation. Digestive system starts to work.
Newborn comes into contact with bacteria and
viruses of the environment
29 days – to
1 year
Rapid growth, teeth eruption, forming the spine
curves, closing fontanelles, the development of motor skills, psychological development (the formation
of conditioned reflexes, speech)
1st year to 3 years
Active growth and psychomotor development,
teeth eruption ends.
Intense development of the immune system
TE
Infancy
First 28 days of life
(The first 10 days
according to
another
classification)
IC
Newborns
(neonatal period)
D
Pre-reproductive period – intensive growth
First childhood
(preschool period)
4–7 years
A change of milk teeth to permanent begins,
changes in body proportions
Second childhood
(primary school age)
8–11 (♂12) years
Forming of abstract thinking.
Activation of gonads
Intensive sexual maturation, rapid growth
TR
Teenage years (puberty) ♀12–15; ♂13–16
Adolescence
(Youth)
♀16–20; ♂17–21
Maturation of reproductive function. Termination
of growth. Determination of the constitution type
and temperament
Reproductive period
22–35 year ♂,
21–35 уear ♀
36–55 year ♀
36–60 year ♂
EC
Adulthood I
Adulthood II
Reproduction
Implementation of creativity; the aging process
starts
Post reproductive period
60–74 years ♂,
55–74 years ♀
Old-aged
75–90 years
Centenarians
After 90
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Elderly
Aging-reduction of adaptive capacity and viability
of an organism
2. According to the duration of growth:
`` Limited or definite growth like in insects, birds and mammals. Their growth stops
when the characteristic for the species is attained.
`` Unlimited or indefinite growth is observed in fishes, reptiles. They keep growing
throughout all their life.
6.3. Postnatal period of ontogenesis
133
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D
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Size attained as percentage of total postnatal growth
200
`` Periodic or discontinuous growth
is observed in animals with the
180
inelastic exoskeleton. They grow
in spurts for short periods after
160
molts (cructacean).
Lymphoid
In man growth is limited and allo140
metric.
120
3. According to the mechanisms of
growth on the organ and tissue level
100
there are several types of growth:
Brain and head
`` Auxetic growth. The volume of
80
body increases due to the growth
of cells without increase in the
60
General
number of cells.
`` Multiplicative growth. The growth
40
of the body is due to increase in
20
Reproductive
the number of cells. The cells divide but their size remains the
0
same. The prenatal growth of
B 2 4 6 8 10 12 14 16 18 20
higher vertebrates at the period
Age, years
of cleavage is an example.
Fig. 6.18. Allometric pattern of growth
`` Accretionary growth. In postembryonic life the cells get differentiated for specific functions. These cells lose the capacity for division, but stem cells
remain in an undifferentiated state as reserve. In case of necessity, stem cells divide
by mitosis, differentiate and replace the worn out cells. Example is the epidermis of
the vertebrate skin.
`` Appositional growth. It involves the addition of new layers on the previously formed
layer. It is characteristic for growth of rigid materials like bones.
R
The growth curve is the graphic representation of height in centimeters against time intervals. The sigmoid or S-shaped growth curve is characteristic for all higher animals including man. It means that velocity of growth differs in postnatal ontogenesis. Alternation of
active growth period with periods of intensive differentiation is characteristic feature of ontogenesis. Deceleration of growth is accompanied with active differentiation and vice versa.
The process of growth is very intensive during the embryonic period, especially first
four months. Intensity of growth increases extremely after birth. The child’s birth weight
doubles by 4th–5th months and triples by one year (the first growth spurt). Infant becomes
24–28 cm longer by one year and adds 10–11 cm more by second year. Later growth slows
down. Next acceleration of growth is observed at 5–8 year age (the second growth spurt
caused by increasing of androgens production in adrenal cortex). Growth becomes very
intensive in puberty (the third growth spurt or adolescent growth spurt). It is explained
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Chapter 6. Human ontogenesis. Prenatal and postnatal periods of ontogenesis
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by activation of anabolic processes by sexual hormones that gonads start to produce. The
adolescent growth spurt starts at 11–12 years in girls and at 13–14 years in boys. It lasts up
to 16–17 years age. After this period, the growth rate starts declining and it almost stops at
about 18 years in females and 21–23 years in males. The growth rate in cm per year in boys
and in girls is shown on Fig. 6.19.
Growth regulation. Numerous endogenic – (primarily heredity) and exogenic (mainly
social and economic) factors produce a significant effect on the processes of growth and
development. It is very difficult to differentiate them as they interact as a single complex.
Peculiarity of individual growth is a polygenic character. More than 100 genes involved
in growth process are identified. These genes control production of hormones, growth
factors and their receptors, energy metabolism and other. Pituitary hormone somatotropin (growth hormone) is main in stimulation of growth. First years of life thymosin secreted by the thymus gland is very important in growth regulation and maturation immune
system. Growth acceleration at 5–8 years is explained by increasing of androgens secretion in adrenal cortex. During the puberty except for sexual hormones production the
enhanced activity of the thyroxine hormone from the thyroid gland and the somatotropin
is observed.
Many hereditary disorders affect growth and development of a human being, e.g., in
cases of abnormal number of sex chromosomes (XO, XXY, XXX, XYY). Persons with extra sex
chromosomes are usually tall and females with the single X chromosome (ShereshevskyTurner syndrome, 45, XO) are short. Disturbances of the endocrine system (both central
and peripheral glands) have a great influence on the processes of development. For exam20
16
R
EC
Growth rate of body length (cm/year)
18
14
12
10
Boys
I
Girls
8
6
С
A
J
4
2
0
M
2
4
6
8
10
12
14
16
18
20
22
Age, years
Fig. 6.19. Growth rate in cm per year in boys and in girls: I – infancy; C – childhood; J – juvenile age; A – adolescence; M – maturity
6.3. Postnatal period of ontogenesis
135
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EC
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ple, low production of growth hormone causes nanism (dwarfism) and hyperproduction
leads to gigantism.
Nutrition, family and living conditions, urbanization, morbidity rate have a key role
among the social factors. Malnutrition and hunger hamper physiologic and sexual development. There is a close relation between speed of skeleton growth and maturation and
protein deficiency. Urbanization is beneficial for psychological development acceleration
in childhood and juvenile age.
Prereproductive period includes:
1. Newborn or neonatal period. It lasts 28 days after birth (first 10 days according to
another classification). Adaptation to the new environment with the rearrangement of circulatory, respiratory digestive and other systems takes place.
2. Infancy. From 29 days to 1 year. Birth weight triples, length increases by a half. Increased brain growth, teeth begin to erupt. Active psychomotor development.
3. Childhood. From 1 year to 11 years of age in girls and to 12 in boys. It is subdivided into early childhood, first childhood, second childhood (see Table 6.3). At early
childhood children still have so-called infant body shape with comparatively large
head and short hands and legs. The division of trunk into chest and abdominal parts
is not clear. The flexures of the spinal column are not completely formed; the joints
are highly agile the jaws are poorly developed. Musculature is weak; muscles are not
ready for intensive and long contractions at that period. This is the period of “neutral
childhood” as body shape in boys and girls is same. At the end of the first childhood
body proportions change and by the age of about 9 years foreshadow those of the
adults.
The second childhood is considered to be pre-pubertal period. Despite secondary sexual characters are poorly promoted, differences between boys and girls in body structure
become apparent.
At 9–10 year of life brain size is almost same as in adults, but its slow growth continues
up to 15.
4. Puberty. Puberty refers specifically to the period of sexual development that culminates in the sexual maturity. It lasts from 12 till 15 years of age in girls and from 13 to 16 in
boys. The primary events associated with puberty include the development of secondary
sexual characters, growth and weight-gain acceleration (adolescent growth spurt) as it is
shown on Fig. 6.19.
Particularly the pubertal phase is characterized by the most significant changes of
morpho-functional properties. The main event of this period is maturation of the hypothalamic-pituitary body-gonads interactive system. It is supposed that the sensitivity of
hypothalamus centers to the inhibition influence of sex hormones (androgens and (or) estrogens) decreases and the sensitivity of gonads to gonadotropic hormones of pituitary
body increases.
Sex hormones have a distinct effect on biochemical metabolic process, activating anabolism, which creates the basis for intermittent growth in males and females at this stage.
Although muscle growth increases steadily in both sexes before the onset of puberty, mus-
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Chapter 6. Human ontogenesis. Prenatal and postnatal periods of ontogenesis
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cle growth is more dramatic in males because of increases in testosterone levels. Fat accumulation increases in females under the influence of estrogens.
Besides the morphologic and physiologic changes, a person undergoes certain psychological and sociological changes.
5. Adolescence occurs after puberty. Reproductive system matures completely at this
period. The ovulatory cycle sets in women and rhythms of testosterone secretion and production of mature sperm sets in men. Growth stops. Constitution and temperament types
become established.
Acceleration. The acceleration of somatic, sexual and psychological development
has been observes at the end of XIX and became significant in the XX century. The earlier maturation and an increase in average body size is a secular trend. The term “acceleration” has been suggested by a German pediatrician E. Koch (1935). The acceleration
reasons can hardly be explained by one fact and are obscure enough. Better nutrition,
improvement of environmental conditions, extending from better health care to a
smaller family size, dramatic increase in the migration of people and the subsequent
gene flow, influence of electromagnetic waves, urbanization are probably very important. The process is contradictive. The main difficulty consists in contradiction in speed
of biological and social development of a personality. Disharmony in the development
of different systems of the whole organism may be the reason of diseases of accelerated
children.
Reproductive period. Types of constitution
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Reproductive period is a period of adulthood. It is the period of maximal physical, psychological and social activity. According to WHO classification it is divided into I adulthood
(22–35 in males, 21–35 in females) and II adulthood periods (36–55 in females, 36–60 in
males). At the age of about 30, humans are at their peak physiologically. During the II adulthood period signs of aging appear.
Life style, social activity and predisposition to diseases at this period are greatly influenced by type of constitution. Constitution (habitus status) is genetically determined set
of relatively stable individual morphological, physiological and psychological properties of
the organism, which manifest as a variety of reactions towards the external factors. Constitution is an integrated human beings characteristic, variant of an adaptive norm. One of
the most common and simple classification of types of constitution (somatotypes) based
on body proportions was proposed by M. V. Chernorutskyi in 1927. He divided humans into
asthenics, hypersthenics and normosthenics. Another classification based on predominant
development of certain germ layer derivatives was proposed by W. Sheldon in 1954. According to Sheldon’s classification there are ectomorphic, endomorphic and mesomorphic
types of constitution (Fig. 6.20). The human somatotypes in these two classifications share
similar characteristics given in Table 6.4. Most of the people have some features mixed from
different types.
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A
B
C
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Fig. 6.20. Types of constitution: A – ectomorphic; B – mesomorphic; C – endomorphic
Table 6.4. Types of human constitution
Types of
constitution
Some morphological
and physiological characteristics
Predisposition
to disorders
Long limbs, tall torsos, slimmer hips and shoulders and
thin bones;
Small heart, long lungs, low position of diaphragm,
short bowel;
Low blood cholesterol, active dissimilation
Hypotonicity, lung
diseases, tuberculosis,
peptic ulcer
Endomorphic
(Hypersthenic)
Short limbs and torso with more rounded body shape,
more body fat;
Heart is relatively large with horizontal position, high
diaphragm, long bowel with large absorption surface;
High level of cholesterol and ureic acid in blood,
active assimilation
Hypertension, obesity, diabetes mellitus,
cholelithiasis, urolithiasis
Mesomorphic
(Normosthenic)
Square, sturdy bodies, with athletic stature;
Assimilation and dissimilation processes are
in balance
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Ectomorphic
(Asthenic)
The periods when the organism is most sensitive to adverse environmental factors are
the postnatal critical periods. At these periods occurs rearrangement of physiological
processes that makes the likelihood of diseases and death higher. In humans, the critical
periods are:
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`` Neonatal period (newborn) – adaptation to life in the outer environment.
`` Puberty – the reorganization of gonads work, the maturation of reproductive function.
`` Post-reproductive period (over 55–60 years) – reduction in the adaptive capacity and
viability of the organism, involution of gonads.
6.4. Post-reproductive period. Aging and death
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Post-reproductive period includes elderly age (61–74 in males, 56–74 in females), old
aged period (75–90) and centenarians (after 90). From a biological point of view aging is
universal and natural process, which ends with death. Effects of aging tend to become
more apparent after about age of 40.
Aging afflicts all levels of organization from molecular-genetic up to the organismic.
On molecular-genetic level aging is characterized by poor DNA repair with accumulation of somatic mutations (both gene and chromosomal mutations). On the cellular and
tissue level occurs reduced cell division, problems with cell cycle regulation that often
leads to tumors, decreasing of basic metabolism and protein synthesis rate, failure of
transmembrane transport, alteration of connective tissue and other. These changes explain decreased functional capacity of inner organs. On organismic level aging manifests
as decrease of the height (0.5–1.0 cm every year after 60), changes of the body stature
(kyphosis, redistribution of fat), decrease of face size due to the loss of teeth and alveolar
processes reduction, enlargement of the skull volume, skin changes (secretion of sebaceous glands and thickness of epidermis decreases, graying of hair). Changes of the main
organism’s systems functioning, primarily regulatory, are typical for the process of aging,
e.g., in the central nervous system both structural (decrease of brain mass, neurons size
and density) and functional (increase in the time it takes for neurotransmitter substances
to cross a synapse, changes of electroencephalogram) occur. The partial loss of sight,
hearing, taste, and tactile sensitivity takes place. Decrease of glands mass and its hormones producing function (thyroid, sexual glands) are typical for endocrine regulatory
system.
Changes take place in other systems also. The secretory activity of the digestive system, vital capacity of lungs, the chest movements amplitude, heart activity, main kidney
functions decrease. The lowering of immune system activity results in the autoimmune
processes and increase of tumor formation rate.
During the process of aging not only lowering of systems functions and their disintegration but the activation of counteracting compensatory mechanisms takes place, e.g., in
case of some hormones secretion rate lowering, the cell’s sensitivity to them increase, etc.
As well as initial stages of ontogenesis (growth and differentiation) aging passes unevenly.
Atrophy of the primary immunity organ – thymus – commences at the age of 13–15; gonads of women – at 48–52; changes of the skeleton system may start very early but develop gradually. First there can be no changes in the central nervous system, but if occur
develop rapidly.
6.4. Post-reproductive period. Aging and death
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As aging involves all systems of organs on different levels of organization over 200 hypotheses of aging have been created. The most popular among them were theories that
explained aging by morphological degradation of cells and tissues or dysregulation of organism’s functions. For example, collagen that surrounds the cells becomes impermeable
with age. This stops the diffusion of the substances to and from the cells, which start aging
(collagen theory). With advancing age there is a deposition of calcium in connective tissue, including joints and the wall of the arteries. This affects the physiological processes in
the cells and starts aging (elasticity loss theory). Wear-and-tear theory states that cells
and tissues continuously wear out due to internal and external stress factors. Hormonal
imbalance causes a malfunctioning and ageing of the cells of many tissues and organs
(hormonal theory). Immunity theory explains aging as a process, caused by weakening
of natural defense because of involution of the thymus gland. Neurogenic theory states
that overwork of nervous system, stress and neurosis leads to aging. Each of these theories explains the different mechanisms observed during the aging process.
The modern theory of aging is a genetic theory. It tries to explain basic underlying
mechanism of senescence. The genetic theory states:
1. Aging is a naturally programmed genetic process. Important conformation of this
idea is regulation of cell division by telomeres. Telomeres are tips of chromosomes. They
have specifically organized highly repetitive short DNA sequence (5´TTAGGG3´in humans).
In human somatic cells this sequence repeats up to 2,500 times and varies between 7 and
15 kb in size. Telomeric DNA replicates by special enzyme telomerase. It is active in germ
line cells, stem cells and in tumors. In the differentiated cells telomerase is inactive, so size
of this region becomes shorter with each cell division. The gradual loss of telomeric DNA
restricts number of cell divisions and can contribute to apoptosis and aging. Several researches demonstrated association of telomere shortening with age-related diseases and
early death. Centenarians usually have longer telomeres that can be expected at their
chronological age.
Genetic control of senescence should include several different mechanisms, many of
which are still unknown.
The Nobel Prize in Physiology or Medicine 2009 was awarded jointly to Elizabeth H. Blackburn,
Carol W. Greider and Jack W. Szostak “for the discovery of how chromosomes are protected
by telomeres and the enzyme telomerase”.
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2. Accumulation of somatic mutations disturbs cell processes and accelerates aging.
Some of this mutations “switch on” gene-controlled processes of senescence.
Hereditary disorders of premature aging illustrate role of mutations in aging. For example, mutation of WRN gene, which protein product is involved in DNA replication and
repair, leads to Werner syndrome (adult progeria or premature aging). Pubertal growth
spurt is absent. Signs of aging become visible at the beginning of third decade of life: hair
turns gray, age related diseases like atherosclerosis, diabetes mellitus, cataract and other
develop. Most of the patients die before 50-yars-old age.
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Intensity of aging also depends on polymorphism of genes for energy metabolism and
predisposition to age-related diseases like atherosclerosis, stroke, ischemic heart disease,
myocardial infarction.
Intensity of aging depends on environmental factors also. Such factors as peculiarities
of nutrition, physical activity, life style, occupational conditions influence biological age.
Accessibility of medical care, economic state of an individual and other social factors are
also important. Contact with environmental mutagens (ionizing radiation, chemical mutagens and other), stress can promote aging process.
The problem of process of biological, psychological and social involution slowing and
prolongation of active longevity is very important now as human life span becomes longer
and proportion of elderly people increases. Study of organism’s processes connected with
old age, i.e., the study of senescence and senility is called gerontology. Geriatrics is medical care of old people.
Life expectancy of a human being depends on many reasons but has limits as in
all biologic species. Life expectancy is defined as the life period of 80% of population,
though it is not an exact digit but a spectrum of fluctuations. A French biologist J. Bouffon had calculated that duration of life in human being should exceed his time of growth
6–7-folds and makes approximately 90–100 years. All the following calculations were
close to this formula. Maximal duration of life of a human being is supposed to be equal
to 130 years. The observations of the long-living people are very important for science.
It is established that they have delayed somatic and sexual maturation, the age related
involution of the skeleton, the low basic metabolism at the mature age as compared to
their populations. These facts confirm the role of constitution and genetic mechanisms
in duration of human life.
The final phase of ontogenesis is death (permanent cessation of all vital functions of an
organism). There is natural (physiologic) death, which occurs because of aging and premature (pathologic) one.
The science of death is thanatology.
The first few minutes after death (4–6 min) is the period of apparent (clinical) death.
This period is characterized by absence of life signs: absence of consciousness, reflexes,
spontaneous breathing and heartbeat. However, cells of the body stay alive and continue to
process more or less actively, so resuscitation (reanimation) is possible. Cells of the brain
cortex are the first to die as they are extremely energy-dependent. At low temperature or
in case of resuscitation measures (artificial breathing and indirect heart massage) cells can
survive longer. So hypothermia (lowering of the body temperature with its cooling) induced
as a means of decreasing metabolism of tissues and thereby the need for oxygen is used
to prolong the period of clinical death. A branch of medicine studying the revivification of
human beings at the stage of clinical death is called resuscitation (reanimation).
The biological death is the next stage after clinical death. It is irreversible process of
autolysis of cells. Autolysis occurs in different organs at different times. It depends on sensitivity of the cells to oxygen (energy) deficiency. The most sensitive are the nervous cells of
the cerebral cortex. Irreversible changes occur in them in 6–7 min after death.
6.5. Regeneration and transplantation
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6.5. Regeneration and transplantation
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Regeneration – is a natural ability of an organism to repair or replace damaged or lost
organs and tissues. It involves cell division, cell growth, differentiation and morphogenesis.
Regeneration occurs by several mechanisms depending on cells and tissues.
If specialized cells lost the ability for multiplication, as a rule they have high capacity for
intracellular renewing (replacement of molecules and organelles). Intracellular regeneration, for example, is typical for neurons, rods and cones of retina.
Non-dividing specialized cells of certain organs can return to mitotic cycle to restore
the number of cells. It is characteristic for hepatocytes, cells of kidney, thyroid gland and
some other.
Some organs and tissues have a pool of stem cells. They divide and differentiate to compensate loss of differentiated cells. This is typical, for example, for restoration of blood cells
(stem cells of red bone marrow), skin epidermis (germinal layer).
There are two types of regeneration:
1. Physiological – renewal of the naturally died cells (replacement of the blood cells,
skin epidermis, intestinal epithelium).
2. Reparative – recovery after injury (for example, wound healing). Reparative regeneration can be typical and atypical (abnormal). Typical regeneration produces the
same tissue or organ, which has been damaged. Example is forming of bone tissue
in the healing of bone fractures. Atypical regeneration produces other tissues or
organs at the injury site. For example, a false joint is formed at the fracture site, connective tissue replace cardiomyocytes after myocardial infarction.
Ways of reparative regeneration
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Morphallaxis is remodeling of remaining tissues or parts of the entire organism from
the body without cell division and little growth. Organisms that regenerate from each fragment are smaller in size. After restoration of organs they begin to grow. Morphallaxis is
not observed in humans, just in simply organized animals such as hydra, planarian (class
Turbellaria of flat worms).
Epimorphosis is the regeneration (growth) of a part of an organism by proliferation
of cells at the wound surface. Regeneration of limbs in newts occurs by epimorphosis.
Example in humans is the healing of bone fractures from the periosteum, healing of the
skin cuts.
Endomorphosis is the regeneration of organ without keeping its shape (regenerative
hypertrophy). For example, in removing part of the liver the remaining cells begin to divide
actively, restoring the mass and volume of the organ, but not its shape. Compensatory
hypertrophy is an increase in volume of organ or tissue due to the heavy load. As a kind
of regeneration it is observed in the paired organs. For example, surgical removing of one
kidney causes second kidney to increase in size and to intensify its function. It provides a
restoration of function of the excretory system.
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In humans, the capacity of regeneration of tissues and organs is limited. If organ or
tissue is damaged so severely, that it cannot be restored by an organism, the organs transplantation (grafting) can be performed.
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Transplantation
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Transplantation is the grafting of organs and tissues. It is a branch of surgical medicine. Organs that were transplanted first are cornea (V. P. Filatov in Odessa, 1930), kidney
(J. E. Murray, 1954, between identical twins), red bone marrow (E. D. Thomas, 1956, between identical twins), heart (C. Barnard, 1967). Now almost all tissues, organs and organ
complexes can be transplanted, including face, hands, lungs, liver, pancreas, and intestine.
Donor is an organism who gives the organ or tissue for transplantation. Recipient (acceptor) is an organism who receives the organ or tissue.
There are several types of transplantation (grafting):
`` Autotransplantation (autografting) is the transplantation of organs and tissues
(skin, bones, muscles, bone marrow stem cells) in the same individual. This plastic
surgery called autoplastics.
`` Isotransplantation (isografting) is the transplantation of organs and tissues between monozygotic twins.
`` Allo- or homotransplantation (allografting) is the transplantation of organs and
tissues between different organisms of the same species. Organs of living related
donor, living non-related donor or cadaveric organs are used. Plastic surgery is called
alloplastics.
`` Xenotransplantation (heterotransplantation or xenografting) is the transplantation
of organs and tissues between organisms of different species (for example, transplanting heart valves from pigs or liver from monkey to humans).
Organ or tissue, which is transplanted is called autograft, isograft, allograft or xenograft
respectively.
Despite idea to transplant organs was raised already during ancient times, attempts to
transplant organs were unsuccessful. At the beginning of XX century an idea was proposed,
that there is a biological force that prevents successful grafting between individuals. Nature of this force became clear with the discovering of human leukocyte antigens (HLA
antigens) by Jaen Dausse in 1958. The main reason for unsuccessful allotransplantation is
the immune incompatibility of organs and tissues of the donor and the recipient. The
HLA antigens (protein molecules) on the cell surface of transplanted organs are recognized
by immune defense of recipient and immune system tries to destroy the foreign cells and
reject the graft.
The Nobel Prize in Physiology or Medicine 1980 was awarded jointly to Baruj Benacerraf, Jean Dausset
and George D. Snell “for their discoveries concerning genetically determined structures on the cell
surface that regulate immunological reactions”.
6.5. Regeneration and transplantation
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HLA antigens (human leukocyte antigens) are specified by genes of major histocompatibility complex (MHC) located on the short arm of chromosome 6 (Fig. 6.21).
There are three groups of MHC genes, two of them encode HLA antigens of class I and
class II. Antigens of class I (HLA-A, HLA-B, HLA-C) are present on the surface of almost all
nucleated cells and give a signal to the immune system if cells are own or foreign. Class
II molecules (HLA-DR, HLA-DQ, HLA-DP) are expressed only on activated T lymphocytes
and some other cells of immune system (macrophages, B lymphocytes and other). They
are very important in presentation of antigens to immune system and activation of immune response. So, antigens of class I and II are six classical transplantation antigens.
The class III of MHC region does not encode HLA molecules, but contains genes for
some signaling molecules of immune system.
HLA genes form the most polymorphic genetic system in humans with many different variants in each locus (multiple alleles). Allelic variants are designed by gene (A, B, C or other) and
allele group. For example, more than 40 allele groups are
described in locus A, alleles are named as HLA-A1, HLAHLA
A2 and so on. Each individual has unique combination
MHC Complex
of HLA antigens. Combination of alleles on one chromosome is known as haplotype. Child inherits the one haplo- HLA-A
21.32p
type (entire combination) of HLA alleles from mother and
another one from father without recombination. Thus in21.31p
heritance of HLA genes demonstrates complete linkage.
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Possible random combinations of antigens from different HLA loci on an HLA haplotype are enormous, but certain
HLA haplotypes are found more frequently in some popula21.2p
tions. For example, HLA-A1, B8, DR17 is the most common
Centromere
HLA haplotype among Caucasians, with a frequency of 5 %. HLA-С
Immune system of recipient accepts the autograft HLA-B
very easily, because antigens of recipient cells and the
transplanted tissue are alike. Since development of identical twins takes place from a single zygote, twins share
same HLA haplotypes, and isograft is not rejected.
q
The HLA antigens of allograft and xenograft are
arm
dissimilar with the recipient antigens. If HLA antigens
of the transplanted organ do not coincide with HLA an- HLA-DR
HLA-DQ
tigens of the recipient, immune response activates resulting in rejection of graft (Fig. 6.22).
The main ways of solving the rejection problem are: HLA-DP
`` Choosing of the most HLA antigens compatible
“donor-recipient” pairs. Collection of information
Human chromosome 6
about all persons who require transplantation
and creation of international banks of organs help Fig. 6.21. Scheme of MHC complex
to solve this problem.
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Chapter 6. Human ontogenesis. Prenatal and postnatal periods of ontogenesis
Donor
Haplotypes:
Recipient
Haplotypes:
A3-B7-DR2
A1-B8-DR3
A2-B7-DR2
A1 -B8-DR3
Organ Graft
IgG
B8
IgG
A1
B8
Donor
Cell
B8
A3
A1
B7
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A3
B7
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B7
Fig. 6.22. Incompatibility in HLA antigenes
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`` The administration of immunosuppressive drugs (drugs that suppress the immune
response). These drugs people with transplanted organs must take throughout their
lifetime.
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The Nobel Prize in Physiology or Medicine 1990 was awarded jointly to Joseph E. Murray and
E. Donnall Thomas “for their discoveries concerning organ and cell transplantation in the
treatment of human disease”.
Nowadays several approaches to restore organs and tissues avoiding histocompatibility
problem have been elaborated:
`` One of the directions of surgical regenerative medicine is usage of artificial heart
valves, blood vessels, joints and other organs.
`` Usage of stem cell for organ regeneration.
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Stem cell therapy
Stem cells are non-differentiated cells that have a capacity for self-renewal and the ability to differentiate into different types of specialized cells. There are two types of stem cells:
embryonic stem cells and adult (somatic) stem cells.
Embryonic stem cells are the cells of inner mass of blastocyst. Under the appropriate
culture conditions they can divide for a prolonged period of time without differentiation.
Embryonic stem cells exhibit high level of telomerase activity and maintain normal karyo-
6.5. Regeneration and transplantation
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type. The cells are pluripotent and in certain conditions can differentiate into derivatives of
any germ layer (ecto-, ento- and mesoderm), including germ cells. It is possible to get embryonic stem cells from unused preemplantation blastocyst created for in vitro fertilization. Human embryonic stem cells line first was derived by James Thomson and colleagues in 1998.
Adult stem cells can be isolated from tissues of a human organism whatever their
age. They are multipotent and can differentiate into the cell types found in the tissue from
which they are derived. For example, hematopoietic stem cells of the red bone marrow
produce all types of blood cells, mesenchimal stem cells (originate from mesoderm, are
found in red bone marrow, adipose tissue and other) differentiate into the bone cells, cartilage cells and adipocytes (fat cells). Adult stem cells provide regeneration and are found in
almost all tissues, including gut epithelial stem cells, stem cells of brain, spinal cord, blood
vessels, dental pulp, liver, pancreas and so on. These cells are characterized by homing and
plasticity. Adult stem cells have a tendency to migrate specifically to damaged tissue from
which they originate, that is termed as homing. It allows using them in regenerative therapy: being injected intravenously adult stem cells will home to damage sites. Plasticity or
“transdifferentiation” is ability of a stem cell from one adult tissue to differentiate into the
cells of another type. For example, experimental studies have shown that bone-marrow
derived stem cells (both hematopoietic and mesenchimal) undergo transdifferentiation
into cardiac, vascular endothelial, neuronal or other cells. But unlike embryonic stem cells
they cannot give rise to every cell type.
Stem cells can be used in regenerative medicine for repairing and replacing tissues or
organs damaged by mechanical injuring or disease. Incomplete list of the disorders that
can be treated by stem cells therapy includes anemia, diabetes mellitus, myocardial infarction, spinal cord trauma, some neurodegenerative disorders.
There are several sources of cells for stem cell therapy.
`` Transplantation of blood stem cells obtained from adult donor, or, sometimes from
the patient himself. It is used to treat diseases and conditions of the blood and immune system, or to restore the blood system after treatment for specific cancers.
`` Blood of a newborn contains a lot of stem cells. It is possible to collect these cells
from umbilical blood at birth. Cells can be stored at low temperature in special institutions and used for autotransplantation in future if required.
`` Therapeutic cloning permits to get embryonic stem cells using the nucleus of adult organism cells. Such approach includes nuclear transferring from cell of adult person into
enucleated oocyte; development of early embryo for several days in vitro, collecting
of embryonic stem cells and their usage for regenerative therapy of the person whose
nucleus was taken. It is considered non-ethic by many scientists as created zygote that
theoretically can develop into human organism is used just as a source of cells.
`` Reprogramming of specialized cells into pluripotent stem cells. For example, artificial activation of just four genes in mature fibroblast can reprogram it into immature
stem cells. Induced pluripotent stem cells (iPS cells) can give rise to all the different
cell types of the body and open new opportunities in medicine. Such cells can be
used in tissue and organ engineering.
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The Nobel Prize in Physiology or Medicine 2012 was awarded jointly to Sir John B. Gurdon and Shinya
Yamanaka “for the discovery that mature cells can be reprogrammed to become pluripotent”.
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`` Tissue and organ engineering is making of artificial organs from scaffolds, cells and
biological active molecules. A scaffold is created from proteins or different polymers
(tri-D-printing is offered). Cells of the patient are collected and cultured in vitro. Tridimensional scaffold is seeded with the cells and usually treated with growth factors.
If the environment is right, the cells differentiate to appropriate tissue and after that
the construction is transplanted to the patient. Skin, cartilage, outer ear (as a model)
has been created now.
Despite significant progress of stem cell research in recent years, there are several questions that have to be solved before wide usage of stem cell therapy in practice. These are
optimal sources of cells and routs of administration for treatment of different disorders,
safety control and other.
Culturing of stem cells also is used for studying of cell differentiation and genome regulation mechanisms.
6.6. Homeostasis. Biological rhythms
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Homeostasis is a property of organisms to maintain constant characteristics of internal
environment. The purpose of homeostasis is to provide a consistent internal conditions for
set processes to occur.
Homeostasis was first defined by a prominent French physiologist Claude Bernard in
1865. С. Bernard came up with this idea based on numerous biological observations. To
his mind, the manifestations of life were dictated by the organism's constitution and an
outer environment influence. The life process in the organism is displayed in the form of
synthesis and decay. On а basis of these processes organisms adapt to the environmental
conditions: thus, adaptation is а harmonious equilibrium between organism and environment. According to the ability for adaptation there are three types of life: latent, oscillating,
permanent (free).
Latent form of life is such а state when life has no outer signs and metabolic processes
are slow. The examples are seeds of the plants, cysts of the protists, bacterial spores. Under
favorable conditions they come back to active life.
Oscillating form of life – vital activities of an organism depend on outer environment. The example is cold-blooded vertebrates which metabolic processes are determined by environmental temperature. Some species of warm-blooded animals also
have periods of hibernation in winter or dormancy under unfavorable conditions.
Lowering of metabolic activities at this state makes animals less sensitive to oxygen
deficiency, injury, infections and intoxication.
On а basis of natural hibernation the methods of the artificial hibernation had been
worked out. It is widely used in heart, brain and lung surgery.
6.6. Homeostasis. Biological rhythms
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Permanent (free) life is typical for highly organized warm-blooded animals. Their life activities are not arrested even under the unfavorable changes of environment. The organs
are processing approximately on the same level of activity as conditions of internal environment do not change.
С. Bernard proposed an idea about internal environment inside highly organized species. According to С. Bernard these are liquids washing up all tissue elements, i.e., blood
plasma, lymph, tissue fluid. Despite changes of external environment the internal one remain relatively constant providing permanent vital activities. С. Bernard considered that
oxygen supply, nourishment and certain temperature limits are obligatory to support the
constancy of internal environment.
The term internal environment was introduced by a French physiologist Charles Robin,
but he did not realize its significance in the constancy of vital activities.
Later the idea of internal environment constancy had been developed due to the
work of Walter Cannon, а prominent American physiologist, who coined the term “homeostasis”. W. Cannon came up to the similar conclusions as С. Bernard by analysis of
physiologic experiments. He considered a living being as an open system actively interacting with surrounding. Environment factors either directly or indirectly influence
internal environment but it is not followed with significant deviation from the normal
state. Automatic self-regulating mechanisms keep the changes in narrow limits in “equilibrium”.
W. Cannon emphasized that the word “homeostasis” did not mean anything stable, but
the process leading to it. Thus, the term “homeostasis” determines physiological mechanisms which assure the stability of living systems. He identified two groups of homeostatic
factors. The first group includes material supporting cellular needs (glucose, proteins, fats
for the energy production, growth and regeneration), ions, oxygen, water and products of
inner secretion (i.e., hormones). The second group is surrounding factors influencing the
cell activity (osmotic pressure, temperature, pH). At the present we also include the third
group – mechanisms providing structural and functional unity of an organism. These are
heredity, regeneration, and immune reactivity.
Nowadays it is demonstrated that:
`` Homeostasis is explained by multiple levels of management systems, i.e., the same
process may be regulated by several systems due to the existence of interactions
between them. The main are neurous, endocrine and immune system.
`` Maintaining of homeostasis is based on feedback principle. The system is capable of
testing which way its variables should be adjusted (Fig. 6.23).
`` System of homeostasis regulation is ultra-stable and includes multiple levels of
regulation. The lowest level determines constancy of main physiologic indices
and is autonomic. The middle level accomplishes adaptive reactions caused by
changes of internal environment. The highest level is assured by autonomic reactions of organs along with behavior reactions towards the signals of outer environment.
A study of processes related to homeostasis is one of the main tasks of physiology.
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3 Input:
Information
sent along
afferent
pathway to
Control
center
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4 Output:
Information sent
along efferent
pathway to activate
Effector
2 Change
detected
by receptor
alan
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Produces
change
in variable
Imb
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Receptor (sensor)
Variable (in homeostasis)
Imb
5 Response ol effector
feeds back to influence
magnitude of stimulus
and returns variable to
homeostasis
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Fig. 6.23. Feedback principle of maintaing the homeostasis
Stress
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An important contribution into the understanding of homeostasis was made by Canadian endocrinologist Hans Selye who elaborated theory of stress in 1936. He defined stress
as the non-specific response of the body to any demand for change and explained it based
on physiology as general adaptation syndrome. H. Selye had noted that laboratory animals
subjected to different adverse stimuli (extreme heat or cold, noise and other) exhibited
same pathological changes of stomach ulceration, shrinkage of lymphoid tissues and enlargement of the adrenal glands. So, he described typical features of stress. They include
activation of hypothalamic-pituitary-adrenal system followed with hypertrophy of adrenal
cortex and increased production of corticosteroids. Hyperproduction of corticosteroids
in turn causes hypoplasia of lymphoid organs due to destruction of lymphocytes and ulceration with hemorrhages in the gastro-intestinal tract. According to this stress is general non-specific neuro-endocrine reaction of an organism under the conditions that
threatens homeostasis.
There are three main stages in stress development.
1. The alarm stage. It is initial reaction in which stress factor is recognized by an
organism as a danger and “fight of flight” reaction activates. It starts with stimulation of hypothalamic-pituitary system with further releasing of adrenal gland
6.6. Homeostasis. Biological rhythms
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Biological rhythms
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hormones (adrenalin, noradrenalin and corticosteroids,) and thyroid hormones
(thyroxin). As a result recourses of organism are mobilized that help to solve stress
situation.
2. The resistance stage. It is likely that the stress situation is eradicated at the alarm
stage. If not, corticosteroids continue to be produced at high level, metabolic processes are activated, level of glucose and amino acids in blood is high. Resistance of
the organism is increased.
Thus, the first two stages of stress reaction are adaptive reactions, directed to
maintaining of homeostasis in the unfavorable conditions. If stress persists for a long
period, the organism starts to lose its ability to combat the stressor.
3. The exhaustion stage is not at all obligatory in stress reaction. If stressor continues
beyond body’s capacity, organism exhausts recourses and becomes susceptible to
disease and death.
The examples of diseases that might develop at this stage are arterial hypertension, diabetes mellitus, stomach and duodenal ulcers, psychotic disorders and others. The disorders in this case can be termed as disadaptation disorders.
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Biological rhythms are cyclical phenomena in living organism. They are essential components of homeostasis. Science studying biological rhythms is termed chronobiology
(from Creek chronos – time). Biological rhythms are observed at all levels of organization of
living organisms from molecular-genetic to biospheric. There are two major categories of
biological rhythms: endogenous and exogenous.
Endogenous rhythms are regulated by the organisms itself. They include rhythms of cell
division, body temperature, secretion of endocrine glands, heartbeat, respiration and other. They can be changed by the action of environmental factors within narrow limits, and
for some processes it is impossible at all. Actually endogenous rhythms are physiological
rhythms that support the continuous vital activity of organisms – respiration, circulation,
cell division, etc. Endogenous rhythms are controlled by genotype.
Exogenous rhythms are the result of external factors like a change in the seasons,
alternation of day and night, ocean tides. Many of them are geophysical in nature
since they are related to the rotation of the Earth relative to the Sun and the Moon
relative to the Earth. Many environmental factors on our planet (the light regime, temperature, air pressure, humidity and other) are under the influence of these rotations.
In addition, such cosmic rhythms as periodic changes in solar activity affect the living
nature. Exogenous biorhythms which coincide in time with geophysical cycles (daily,
tidal, equal to the lunar month, annual) are called adaptive biological rhythms. They
arose as an adaptation of living beings to regular ecological changes in the external
environment. Thanks to them, the most important biological functions of the body,
such as nutrition, growth, reproduction, coincide with the most favorable time of the
day or year.
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Chapter 6. Human ontogenesis. Prenatal and postnatal periods of ontogenesis
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Environmental stimuli that maintain exogenous cycles are called zietgebers, which
comes from German and translates as “time givers.” Except for geophysical factors zietgebers include sunlight, noise, food, and even social interaction.
By periodicity all biorhythms can be subdivided into:
`` Circadian rhythms.
`` Ultradian rhythms.
`` Infradian rhythms.
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Circadian rhythms (from Latin circa – around and dies – day, meaning “approximately
a day”) are genetically determined endogenous rhythms with a period close to 24 hours
(can vary in different people from 24.2 h to 24.5 h). In normal conditions circadian rhythms
are synchronized to the 24 h day primarily by the light-dark cycle and social activity (after
this they can be named diurnal rhythms).
The humans have more than 300 physiological and behavioral functions with circadian
cycles including waking up/sleep cycle, changes in body temperature, blood pressure, digestive function, patterns of hormone secretion, and levels of alertness.
Circadian rhythms are regulated by neural center (the circadian clock) localized in the
hypothalamic suprachiasmatic nuclei (SCN). Main genes (clock genes and clock-controlled
genes) controlling the circadian rhythm has been discovered now. Genes are expressed
rhythmically in SCN cells. Rhythmic expression of genes is regulated at the level of transcription/translation by the principle of feedback.
The Nobel Prize in Physiology or Medicine 2017 was awarded jointly to Jeffrey C. Hall,
Michael Rosbash and Michael W. Young “for their discoveries of molecular mechanisms
controlling the circadian rhythm”.
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The activity of the center is influenced by light trough specialized photosensitive
ganglion cells of eye retina. An important role in the regulation of circadian rhythms is
performed by the pineal hormone melatonin which synthesis is controlled by the SCN.
Secretion of melatonin peaks at night (“darkness hormone”). It controls many processes
associated with the change of day and night and with seasonal changes in the duration of
dark period (seasonal rhythms).
Ultradian rhythms have a period shorter than 24 hours. Examples are rhythms of respiration and heartbeat.
Infradian rhythms are longer than 24 hours. Many cycles are coordinated with lunar
month (circalunal rhythms) which lasts 29.5 days (human menstrual cycle). There are ocean
tides cycles synchronized with the phases of the moon that affect littoral animals. Cycles
which period last for a year are termed circannual cycles (Latin annus – a year). They include the rhythms of body weight, reproduction in plants and animals, migration in birds.
For some cycles regulation is photoperiodic. Photoperiodism is the physiological reaction
of organism to the duration of day or night. Other cycles can be temperature controlled.
Most circannual cycles are endogenic, but external factors can influence them.
6.6. Homeostasis. Biological rhythms
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Desynchronosis or circadian rhythm disorders are disorders caused by alterations of
the body’s circadian rhythms. They can be caused by rapid long-distance trans-meridian
travel (Jet lag) or by frequent rotation shifts or night work (shift work disorders). Desynchronosis manifest as sleep disorders, fatigue, poor concentration, headache, irritability. It
is an important medical problem in organization of work in a number of professions such
as pilots, cosmonauts, miners and other.
`` Multiple Choice Questions (Choose one correct answer):
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1. Fetus gets nourishment and oxygen through the:
C. Placenta
A. Yolk sac
B. Allantois
D. Amnion
2. Fertilization in human female occurs in the:
A. Fallopian tube
C. Uterus
B. Vagina
D. Ovary
3. Mesoderm gives rise to:
C. Intestinal lining
A. Epidermis
B. Liver
D. Muscles
4. Embryo reaches the uterus from the fallopian tube in about:
C. 7 days
A. 24 hours
B. 4-5 days
D. 14 days
5. Germ layers are formed during:
C. Gastrulation
A. Copulation
B. Cleavage
D. Fertilization
6. At the time of ovulation in a human female, all the following are true except that:
A. Meiosis is at metaphase II stage
B. First polar body has just been expelled
C. Zona pellucida has broken down
D. Fertilization is possible
7. Cleavage of the zygote gives rise to:
A. Blastula
C. Gastrula
B. Neurula
D. Foetus
8. Heart develops from embryonic:
A. Ectoderm
C. Mesoderm
B. Endoderm
D. Both mesoderm and endoderm
9. Human eggs are:
A. Alecital
C. Microlecital
B. Mesolecital
D. Macrolecital
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Chapter 6. Human ontogenesis. Prenatal and postnatal periods of ontogenesis
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10. Amount of yolk and its distribution are changed in the egg. Which one is affected?
A. Pattern of cleavage
C. Number of
D. Fertilization
B. Formation of zygote
blastomeres
11. Which one is produced by mesoderm?
A. Striated muscles and notochord
B. Heart and brain
C. Spinal cord and notochord
D. Brain and notochord
12. When do the three germ layers differentiate?
A. Histogenesis
B. Gastrulation
C. Cleavage
D. Fertilization
13. Growth pattern is allometric in:
A. Fish
B. Locust
C. Humans
D. Insects
14. Growth is unlimited in:
C. Mammals
E. Humans
A. Insects
B. Birds
D. Fish
15. Bones enlarge by:
C. Multiplicative
D. Appositional growth
A. Auxetic growth
B. Accretionary growth
E. All these modes
growth
16. Decreased defense against pathogens in aging is due to the atrophy of:
C. Thymus
A. Thyroid gland
E. Adrenal cortex
B. Parathyroid glands
D. Pituitary gland
17. In aging, there is:
A. Decrease in calcium content of arteries and cartilage
B. Increase in calcium content of arteries and cartilage
C. Decrease in blood urea
D. Decrease in cholesterol content of cornea and lens
18. Science about death is:
A. Gerontology
C. Thanatology
B. Geriatry
D. Valeology
`` FILL IN THE BLANKS:
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1. In humans prenatal period lasts about _______ days or ___ weeks.
2. The chorionic cells secrete a hormone named ____________________ (______).
3. Formation of the neural tube is called _____________, embryo in this stage –
_______________.
4. From 9th week the embryo is called ____________.
5. The __________ is a vascular structure by which fetus is attached to the uterine wall.
6. People with ________________(________________) type of constitution have long
limbs, tall torsos, slimmer hips and shoulders, _______lungs, _____ position of diaphragm, ____________ dissimilation.
6.6. Homeostasis. Biological rhythms
153
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7. _________________ theory states that cells and tissues continuously wear out due
to internal and external stress factors.
8. _____________________ – is a natural ability of an organism to repair or replace
damaged or lost organs and tissues.
9. ________________ or ___________ age is time passed from a moment of birth.
`` TRUE OR FALSE:
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1. During the cleavage the embryo as a whole does not change in size (so the size of
blastocyst is almost the same as a zygote one) and remains enclosed in zona pellucida.
True
False
2. Gastrulation in human occurs by invagination and migration of the cells.
True
False
3. Epiboly is splitting of one layer of cells into two parallel layers.
True
False
4. The allantois connects embryo with placenta.
True
False
5. Totipotency means that cell can give rise to all types of cells, both embryonic and
extraembryonic.
True
False
6. In the direct development the larva, which is not like an adult, hatches out of the egg.
True
False
7. Congenital defects formed from 3rd to 8th weeks after fertilization are called embriopathies.
True
False
8. Allo- or homotransplantation (allografting) is the transplantation of organs and tissues between organisms of different species.
True
False
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Chapter 7.
Regularity of heredity in humans
7.1. Mono- and dihybrid cross. Mendel’s laws
Basic terms of genetics
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Genetics (from Greek genesis – origin or production) is a science studying heredity and
variation of organisms.
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Heredity – ability of organisms to transfer their traits to the next generation.
Inheritance is the way of transmission of traits through generations.
Variation – an ability of an organism to change, to get new features during its development. Heredity and variation are among the basic characteristics of living organisms.
Genotype – the genetic constitution of an individual, set of genes in diploid set of chromosomes.
Phenotype – a complex of external and internal features which appears under the control of genotype influenced by the environmental conditions; expression of the hereditary
constitution of an organism.
Allelic genes – genes located at the same locus of homologous chromosomes and determining one character (a heritable feature). One of the allelic genes is inherited from
mother, another one – from father, thus there are two allelic genes in a genotype of diploid
organism.
Each character can have different phenotypic manifestations. For example, eye color
may be brown or blue; the number of fingers on a hand may be five or six. Contrasting variants for a character are called alternative traits (Fig. 7.1). Alleles are the different variants
of the gene that control alternative traits. They are formed due to the different mutations
in same locus.
Homozygous organism has same alleles at a single locus of homologous chromosomes and produces one type of the gametes (Fig. 7.2).
Heterozygous organism has different alleles at a single locus of homologous chromosomes and produces two types of gametes (Fig. 7.3).
Dominant gene is an allele that manifests in the homozygous as well as heterozygous
state and masks the effect of recessive allele. Dominant alleles are labeled by capital letter (A).
Recessive gene is an allele that manifests in the homozygous state only. Recessive alleles are labeled by small letter (a).
Thus, there are three variants of genotype:
AA – dominant homozygote
Both have dominant phenotype
Aa – heterozygote
aa – recessive homozygote, has recessive phenotype.
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7.1. Mono- and dihybrid cross. Mendel’s laws
Fig. 7.1. Alternative traits – black and white color of hair
B
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A
Allele of the
brown eyes
Homologous chromosomes
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Homologous chromosomes
Locus that
determines
eye color
Allele of the
brown eyes
Allele of the
blue eyes
Locus that
determines
eye color
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Fig. 7.2. Homozygous organisms: A – dominant (AA); B – recessive (aa)
Allele of the
brown eyes
Fig. 7.3. Heterozygous organism (Aa)
Homologous chromosomes
Locus that
determines
eye color
Allele of the
blue eyes
Allele of the
blue eyes
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Chapter 7. Regularity of heredity in humans
For example, brown eyes is a dominant trait (A). Person with brown eyes might be homozygous (AA) or heterozygous (Aa). Blue eyes is recessive trait. Person with blue eyes is
always homozygous (aa).
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Mendel’s laws of inheritance
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An Austrian monk Gregor Mendel (1822–1884) is considered to be a father of genetics. He
was the first to explain the main laws of heredity in 1865. Significance of Mendel’s experiments
had not been realized till 1900 when three scientists – Hugo De Vries in Holland, Carl Correns in
Germany and Erich von Tschermak in Austria rediscovered Gregor Mendel's laws and began to
make use of his findings.
Gregor Mendel was successful in his experiments as he chose suitable subject for studying and elaborated a new method of genetic experiments. He carried out his work on garden pea. Garden pea was the best material for hybridization experiments because of the
following reasons:
1. Pea plants have various contrasting traits. Mendel studied inheritance of seven alternative traits: tall or dwarf stem, green or yellow seeds, round or wrinkled seeds, red
or white flowers with axial or terminal positions, inflated or constricted pod of green
or yellow color.
2. Peculiarity of flower structure. Pea plants are self-pollinated, but artificial cross-pollination can be performed easily.
3. A pea plant has a short life cycle, a great number of offspring and is convenient in
handling.
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Mendel elaborated method of experimental breeding – hybridization. The hybridization method is characterized by the following features:
1. Selection of pure lines (homozygous forms) with alternative characters. A pure line
is a population that originates trough inbreeding or self-fertilization. Organisms of a
pure line are always homozygous.
2. Analyzing the inheritance of each investigating character separately.
3. Exact calculations of an offspring with different traits in each generation.
4. Studying the character in several successive generations.
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Mendel proposed genetic symbols to write the scheme of crossing. Parents are marked
by letter P (from Latin parentes). A maternal organism is to be written down first (♀ – the
mirror of Venus). A paternal organism is marked secondly (♂ – the shield and spear of Mars).
Multiplication sign “×” means crossing. Gametes (sex cells) are marked by letter G. Gametes
are formed by meiosis, thus are haploid and carry just one gene from a pair of allelic genes.
The resulting offspring are named the first filial generation (F1, from Latin filia – children).
Next generations are marked by indices 2, 3 (grandchildren, great-grandchildren).
7.1. Mono- and dihybrid cross. Mendel’s laws
157
Monohybrid cross. Laws of dominance and segregation
♀AA × ♂aa
P:
yellow
green
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A – yellow
a – green
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Mendel started his experiments from monohybrid cross. It is a cross in which only
a pair of contrasting traits is analyzed.
For example, Mendel crossed pea plants with yellow and green seeds and got all offspring with yellow seeds.
A
a
Aa – 100 %
G:
F1:
yellow
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Mendel found that in all seven traits F generation resembled only one of the parents.
1
The form of trait expressed was called dominant and the one hidden recessive. So, the first
Mendel’s law is the law of dominance.
Law of dominance (First Mendel’s law). In crossing between homozygous organisms that differ in one pair of contrasting traits all the hybrids of first generation will
manifest just one dominant trait. All hybrids will have same phenotype and genotype.
Then Mendel allowed F1 hybrids to self-pollinate. He noticed, that the hybrids of the
second generation had 3 : 1 ratio in seeds color. Followed crossings showed the genotypic
ratio of F2 generation as 1 : 2 : 1.
F1:
G:
F2:
♀ Aa
yellow
A,a
AA, Aa,
×
♂ Aa
yellow
A,a
Aa,
aa
yellow yellow yellow
green
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Law of segregation (Second Mendel’s law). The hybrids of F1 generation produce offspring with 2 contrasting characteristics in the phenotypic ratio 3 : 1 (3 yellow : 1 green)
and the genotypic ratio 1 : 2 : 1 (1 dominant homozygote : 2 heterozygotes : 1 recessive
homozygote).
For explanation of crossing results Mendel proposed hypothesis of gametes purity,
which now is termed as the law of purity of gametes. The law of purity of gametes states
that in hybrids of F1 generation dominant and recessive genes do not mix with each other
and segregate during gametogenesis, in such a way that each gamete receives only one
gene from allelic pair.
The cytological confirmation of this law is chromosomes behavior during meiosis. In
the anaphase I homologous chromosomes, containing allele genes, move towards the opposite poles of the cell. Each gamete gets only one chromosome of a homologous pair and
thus only one allele gene.
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Chapter 7. Regularity of heredity in humans
Deviation from Mendelian ratio in a monohybrid cross
P:
♀AA × ♂aa
red
white
A
a
♀Aa × ♂Aa
F1:
pink
G:
F2:
Aa
pink
pink
A, a
A, a
AA, Aa, Aa, aa
red
pink
pink white
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G:
F1:
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In some cases, the phenotypic and genotypic ratio in F2 generation differs from that, observed by Gregor Mendel. It can be explained by incomplete dominance and lethal alleles.
Incomplete dominance is a kind of allelic gene interactions in which heterozygotes
have an intermediate phenotype, that is distinct from either homozygous parent.
For example, a cross between pure lines of red-flowered four o’clock plant (Mirabilis jalapa) (AA) and white flowered plant (aa) results in the F1 hybrids with pink flowers: The F2
offspring produce red, pink and white progeny in the ratio 1 : 2 : 1, respectively.
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The phenotypic and genotypic ratio in F2 generation is the same (1 : 2 : 1) in case of incomplete dominance. Example of incomplete dominance in humans is inheritance of wavy
hair. Dominant homozygotes have curly hair, recessive homozygotes – straight hair and
heterozygotes have wavy.
Lethal alleles are the alleles that in homozygous state cause death of an individual.
Death of the individual with certain genotype shifts the genotypic and phenotypic ratio. In
humans the dominant allele of brachydactyly (short fingers) in homozygous state causes
the gross skeletal defects which lead to the death shortly after birth.
P1:
♀Aa
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brachydactyly
Gamets:
A, a
F2:
AA, Aa,
×
♂Aa
brachydactyly
A, a
Aa, aa
Death brachydactyly normal
In case of prenatal death the phenotypic ratio in F2 is 2 : 1 instead of 3 : 1.
Dihybrid cross. Law of Independent Assortment
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The dihybrid cross is the cross in which inheritance of two pairs of alternative traits
are studied simultaneously. For example: Mendel crossed two pure lines of pea plants with
yellow (A) round (B) and green (a) wrinkled (b) seeds. All F1 offspring were diheterozygous
with yellow and round seeds (law of dominance).
7.1. Mono- and dihybrid cross. Mendel’s laws
♀AABB
P1:
♂aabb
×
yellow, round
green, wrinkled
It must be remembered that each gamete contains
one gene from each allele pair, so, it carries alleles
of both characters (A and B) (Fig. 7.4).
AB
ab
AaBb – 100 %
G:
F2:
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yellow, round
After F self-pollination:
1
P:
♀AaBb
yellow, round
×
♂AaBb
yellow, round
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G: AB, Ab, aB, ab AB, Ab, aB, ab
♀ F2
♂ AB
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Each gamete contains one gene of each allelic pair, it must have the gene A (or a) and
gene B (or b) (Fig. 7.5). Four types of gametes are formed in diheterozygote because of
random segregation of maternal and paternal chromosomes in anaphase of meiosis I.
There are 16 variants of random maternal and paternal gametes combinations.
A Punnett square helps in analysis of F2 filial generation:
Ab
aB
ab
AB
AABB
yellow round
AABb
AaBB
AaBb
Ab
AABb
AAbb
AaBb
Aabb
aB
AaBB
AaBb
aaBB
aaBb
ab
AaBb
Aabb
aaBb
aabb
yellow wrinkled
yellow round
yellow round
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yellow round
yellow round
yellow round
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yellow round
yellow round
yellow wrinkled
green round
A
A
a
B
B
B
b
A
a
B
B
B
b
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green wrinkled
A
A
Fig. 7.4. Producing of gametes in
homozygote (AABB) – one type of
gamete
yellow wrinkled
green round
green round
A
yellow round
or
a
A
B
b
Fig. 7.5. Producing of gametes in heterozygote (AaBb) –
four types totally
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Chapter 7. Regularity of heredity in humans
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The phenotypic ratio is 9 : 3 : 3 : 1 in offspring of diheterozygous parents. The phenotypic variants are:
9/16 – yellow round (A_B_);
3/16 – yellow wrinkled (A_bb);
3/16 – green round (aaB_);
1/16 – green wrinkled (aabb).
The ratio in each pair of traits taken separately is 3 : 1 (12 yellow and 4 green; 12 round
and 4 wrinkled, like in monohybrid cross), so segregation of each pair of characters occurs independently. Later genetic experiments showed that independent inheritance is
observed if genes A and B are located in different pairs of chromosomes. It is explained
by independent assortment of maternal and paternal homologous chromosomes at the
anaphase I of meiosis (see Chapter 5.3).
The genotypic ratio is: 1AABB: 2AABb: 2AaBB: 4AaBb: 1AAbb: 2Aabb: 1aaBB: 2aaBb:
1aabb. The ratio in each pair of genes taken separately is 1 : 2 : 1.
2
2
A common phenotypic ratio in dihybrid cross is: (3 : 1) ; genotypic ratio is (1 : 2 : 1) .
If the parents differ in more than two characters, the cross between them is known
as polyhybrid cross. The law of independent assortment is also applicable in this case. A
n
n
common ratio in polyhybrid cross is: (3 : 1) – by a phenotype; (1 : 2 : 1) – by a genotype,
where n is number of pairs of characteristics, in which organism is heterozygous.
Law of independent assortment (the third Mendel’s law). If parents differ in two or
more pairs of contrasting traits, the inheritance of each pair occurs independently, if
genes coding this characteristics are located in different pairs of chromosomes.
Test cross
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An experimental crossing is widely used in genetic analysis.
A test cross helps to define the genotype of individual with dominant phenotype,
which could be either a homozygous or heterozygous. It is the cross between the dominant individual and the recessive homozygote. If F1 generation is uniform, the genotype of dominant parent is AA; if the ratio is 1 : 1, the genotype of dominant parent is Aa.
♀AA × ♂aa
A
a
Aa
100 %
P:
G:
F1:
♀Aa × ♂aa
A, a
a
A, a
aa
50 %
50 %
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P:
G:
F1:
The test cross of a diheterozygous organisms yields offspring in the genotypic and phenotypic ratio 1 : 1 : 1 : 1.
P:
G:
F1:
♀AaBb
× ♂aabb
AB, Ab, aB, ab
ab
AaBb, Aabb, aaBb, aabb
7.2. Multiple alleles. Blood groups. Immunogenetics
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Mendelian characters
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Characters following Mendel’s laws are termed as Mendelian characters. Examples of
latter in humans are brown and blue eyes, freckles, ability to roll up a tongue in a pipe, free
and attached ear lobe and other. Some hereditary single gene disorders are also inherited as Mendelian traits. As dominant disorders are inherited polydactyly, brachydactyly,
achondroplasy (one of the hereditary dwarfism syndromes). Examples of recessive disorders are albinism, deaf-and-dumbness, microcephalia, phenylketonuria, cystic fibrosis and
most of other inborn errors of metabolism.
Variable expressivity and reduced penetrance
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Many Mendelian characters are characterized by variable expressivity and reduced
(incomplete) penetrance. Variable expressivity is an extent to which certain genotype
is expressed on the phenotypic level. The degree of manifestation of a gene can vary in
different individuals even in one family. Examples are congenital defects of extremities like
polydactyly or ectrodactyly (claw like hands or feet). Patient with polydactyly can have 6,
7 or even more fingers or toes. In ectrodactyly just right hand or two hands or both hands
and feet are affected.
Penetrance is the percentage of individuals with particular genotype who exhibit genotype-associated characteristics. Penetrance can be complete or incomplete. In case of complete penetrance, 100 % of individuals with certain genotype have the trait, controlled by this
genotype. If some individuals with dominant genotype (AA or Aa) do not manifest dominant
trait, penetrance is considered to be reduced (incomplete). For example, retinoblastoma (malignant tumor of retina) is inherited as dominant disease with penetrance of 90 %. It means that
only 90 % of persons with diseases associated genotype become sick, and 10 % stay healthy.
With the advancement of molecular genetics, some of the underlying mechanisms of
variable expressivity and reduced penetrance have been elucidated. These include type
of mutation, peculiarities of regulation of gene expression, modifier genes (influence of
genome as a whole), influence of environmental factors.
7.2. Multiple alleles. Blood groups. Immunogenetics
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Mendel had studied the characters, which were controlled by a pair of allele genes. But
most characters in population are determined by more than two alleles (3, 4 or more). If
there are three or more alleles responsible for a single characteristic in population, they
are known as multiple alleles. Multiple alleles are the result of subsequent mutations of
a certain gene locus. The primary normal condition of a gene is called a wild type allele, a
new one – a mutant allele.
The most important features of multiple alleles are summarized below:
`` Multiple alleles of a gene always occupy the same locus in the chromosome.
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Chapter 7. Regularity of heredity in humans
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`` Multiple alleles always influence the same character.
`` The wild type allele is nearly always dominant, while the other mutant alleles in the
series may show hierarchy of dominance.
`` Though the number of allele genes in a diploid organism is always equal to two, in
population its number is unlimited.
`` The more the number of allele genes, the more is the variety in their combinations in
the population. It is an important factor of genetic variability. Two allele genes (A and
a) give three possible combinations – AA, Aa and aa. Three alleles (A , A2, a) make six
1
possible genotypes A1A1, A2A2, aa, A1A2, A1a and A2a. In general, n alleles form n(n
+ 1) / 2 possible genotypes. Number of homozygotes is equal n (same as number of
alleles), and number of heterozygotes is calculated by formula n(n–1) / 2.
A classic example of multiple alleles is a fur color in population of rabbits. This character
is determined by four alleles (A, ach, ah, a). Rabbits’ black fur is determined by the dominant
allele A, white color is determined by recessive allele a. Allele ach controls chinchilla color
(gray) and ah is for Himalayan coat (white except for black nose, ears, feet and tail). The
genes demonstrate hierarchy of dominance. Gene A dominates over the rest, ach dominates over ah and a, ah – over a. So, dominance may be symbolized like A> ach>ah>a.
Four alleles produce 10 genotypes in population. Black rabbits could have AA, Aach, Aah
and Aa genotypes, chinchilla rabbits – achach, achah and acha, Himalayan ones – ahah and aha,
white rabbits are always homozygous aa.
Example of multiple alleles is inheritance of ABO blood groups.
Inheritance of ABO blood groups
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EC
Blood groups are characterized by certain antigens on the surface of red blood cells and
antibodies in plasma. Antigens are the molecules that challenge the immune system and
cause production of the antibodies. About 35 erythrocytic antigen systems that include
more than 300 antigens are known today (Fig. 7.6). Antigens are determined by genotype,
so blood groups do not change throughout the life. Two most important human blood
groups are AB0 system and Rh (Rhesus factor).
Blood groups of AB0 antigen system is an example of multiple alleles in humans. AB0
blood groups were discovered in 1900, when Karl Landsteiner cleared why some blood
transfusions were successful while others could be deadly. By mixing the red cells and serum of different persons Landsteiner identified three types of blood, called A, B and C (C
was later to be re-named O for the German “Ohne”, meaning “null” in English). The fourth
less frequent blood group AB, was discovered a year later.
The Nobel Prize in Physiology or Medicine 1930 was awarded to Karl Landsteiner
"for his discovery of human blood groups".
Thus, AB0 antigen system includes four blood groups–0(I), A(II), B(III), AB(IV) (Table 7.1). It
is controlled by three alleles of gene (I0, IA, IB) of chromosome 9.
7.2. Multiple alleles. Blood groups. Immunogenetics
Cromer
163
AB0
Daffy
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D
MNS
IC
Diego
Rh-factor
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Fig. 7.6. Example of antigens on the membrane of RBC
Table 7.1. Frequency of AB0 phenotypes in most populations
(cited from Blood Groups and Red Cell Antigens, Dean L. Bethesda:
National Center for Biotechnology Information; 2005)
Blood groups
Ethnic group
A(II)
B(III)
AB(IV)
44%
43%
9%
4%
Blacks
49%
27%
20%
4%
Asians
43%
27%
25%
5%
EC
Caucasians
0(I)
R
`` gene IA specifies antigen A;
`` gene IB specifies antigen B;
`` gene I0 is recessive, it doesn’t specify any antigen.
Genes IA and IB are codominant. Codominance means that both the genes are equally
dominant and expressed in the phenotype. Presence of IA and IB genes determines presence
of two antigens (A and B) of IV blood group. The dominance relationships between AB0 alleles can be symbolized as (IA = IB) > I0. Three alleles give 6 possible genotypes (Table 7.2).
Each blood group has specific antigens on erythrocytes and antibodies in blood
plasma.
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Chapter 7. Regularity of heredity in humans
Table 7.2. Characteristics of the AB0 blood group
Antigen of
erythrocytes
Antibodies
of plasma
Gene
Genotypes
None
A
B
A,B
α, β
β
α
None
I0 (recessive)
IA (dominant)
IB (dominant)
Both IA and IB
I0I0
I I , IAI0
IBIB, IBI0
IAIB
A A
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0(I)
A(II)
B(III)
AB(IV)
D
Blood
Groups
Gene H
IC
Synthesis of AB0 antigens is a multistep process. The precursors of A and B antigens is
antigen H, controlled by gene H in chromosome 19. People with gene IA have the enzyme
transforming H into antigen A, and people with IB gene – the enzyme transforming H into
B. The I0 allele encodes a non-functional enzyme, so neither A or B antigen is produced, living the H antigen unchanged (Fig. 7.7).
antigen H
Gene IA – antigen A and some H-antigen
Gene IB – antigen B and some H-antigen
Gene I0 – antigen H
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Fig. 7.7. Scheme of antigens A and B production
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EC
Antigens A and B react with α- and β-antibodies. Antibodies α cause the agglutination
of A-antigen containing erythrocytes, β-antibodies do the same to B-containing erythrocytes. That’s why person with A antigen does not have antibody α, and person with B antigen does not have antibody β.
The antibodies α and β in plasma appear at the first months after birth and their
maximum levels are reached by 3–10 years. According to the most popular theory
A-antibodies (α) and B-antibodies (β) in blood plasma are formed naturally due to the
existence of bacterial and food antigens similar to A and B antigens of erythrocytes. After birth bacteria start to inhabit the alimentary tract of a child. There is immunologic
tolerance for bacterial antigens, similar to self-antigens. So, children having A antigen
produce antibodies β against bacterial B-antigens and do not produce α, children with
B-antigen produce antibodies α against bacterial A antigen and do not produce β. Children of the 0(I) group produce both antibodies α and β, AB(IV) group children have no
antibodies at all.
Importance of ABO blood groups in medicine
1. The ABO blood groups are important in blood transfusions. If antigen A meets
antibody α or antigen B meets antibody β, it causes agglutination of donor erythrocytes. Agglutinated red blood cells block capillaries of recipient, which causes dysfunction of kidney and other organs and leads to death.
7.2. Multiple alleles. Blood groups. Immunogenetics
– universal donor has
no antigens
III (B)
IV (AB)
Fig. 7.8. Scheme of possible blood transfusion
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II (A)
D
I (0)
165
– universal recipient,
has no antibodies
EC
TR
IC
In medical practice, blood of the same group is transfused. Theoretically it is possible to transfuse blood of another group if agglutination is avoided. Group 0(I) is
considered to be universal donor (no antigens) and group AB(IV) – universal recipient (no antibodies). The scheme of possible blood transfusion is given in Fig. 7.8.
2. Studying of blood groups inheritance can help in cases of disputed parentage.
Blood groups sometimes help to decide cases of disputed parentage in criminal
courts, because a particular pair of blood groups in parents may give some and not
all blood groups in progeny. Therefore, if a child has a blood group which is not likely
to result from the blood groups of a married couple claiming parentage, it proves
that the child has a doubtful parentage (is illegitimate) or adopted. However, the
technique of DNA testing has become recently available to solve such cases.
3. AB0 blood groups are associated with some multifactorial diseases. For example:
peptic ulcer is more common in group 0 individuals, cardiovascular disorders and
gastric cancer in patients with A blood group, ankylosing spondylitis in individuals
with AB group. These associations are taken into account for calculation of chance to
be sick for relatives of affected person.
Inheritance of Rhesus factor. Rhesus conflict
R
In 1940 K. Landsteiner and A. S. Weiner found new antigen in erythrocytes of monkey
macaque-rhesus, so it was called Rhesus-factor (Rh-factor). Later similar antigen was found
in human erythrocytes. About 85 % of Caucasians have it and thus are considered to be
Rhesus-positive (Rh+), 15 % do not have it and are Rh-negative (Rh–). Nowadays it is estimated that Rhesus factor is a group of antigens encoded by two tightly linked genes (RHD
and RHCE) located next to each other on chromosome 1. Gene RHD controls synthesis of
antigen D. Dominant allele (D) specifies synthesis of this antigen and recessive one (d) is
mutant and antigen is not formed. Antigen D is the most immunogenic among all the
166
Chapter 7. Regularity of heredity in humans
D
antigens of Rh-factor system. Person with antigen D is considered to be Rh-positive. If antigen D is absent, person is Rh-negative. Gene RHCE controls synthesis of antigens C, E, c, e.
Antigens C and E are formed by alternative splicing (see Chapter 4.4). Simplistically we can
study inheritance of Rh-factor as a monogenic character (Table 7.3)
Table 7.3. Characteristics of the Rh blood group
Antigen of erythrocytes
Antibodies of plasma
Antigen D
No antigen D
Absent
Absent
Rh-positive (Rh )
Rh-negative (Rh–)
+
Gene
Genotypes
D
d
DD, Dd
dd
TE
Group
TR
IC
Medical importance of RH blood group:
1. Clinical importance has transfusion of Rh-positive blood to Rh-negative recipient. The first transfusion leads to immunization of the recipient and production of
anti-Rh antibodies. The second transfusion of Rh-positive blood results in hemolysis (destruction) of donor erythrocytes that can affect inner organs and even causes
death of the recipient.
2. Another important situation is pregnancy of Rh-negative women with Rh-positive fetus. When Rh-negative female marries Rh-positive male their children can be
Rh-positive.
P:
G:
F1:
♀dd × ♂DD
d
D
Dd
Rh+
or
P: ♀dd × ♂Dd
G:
d
D, d
F1:
Dd,
dd
Rh+
Rh–
R
EC
The first pregnancy usually ends with delivery of a healthy child. But during the labor
erythrocytes of a child get into the maternal blood and stimulate mother’s immune system
to produce antibodies against Rh+-factor. During the next pregnancy anti-Rh antibodies
pass through placenta and destroy Rh+ erythrocytes of the fetus. Hemolysis of erythrocytes
leads to jaundice of the newborn, edema, anemia and even death of a child (hemolytic
disease of the newborn or “erythroblastosis fetalis”). In severe cases mother-fetus Rh-factor
incompatibility ends with intrauterine death of the fetus.
The risk of hemolytic disease of the newborn can be reduced by giving Rh-negative
mothers anti-D antibodies to destroy fetal RBC that may pass through placenta into the
maternal blood.
The MNS blood group
One more example of erythrocyte antigens is the MNS blood group. The MNS blood
groups is determined by two completely linked genes, located on chromosome 4. One
of these genes has codominant alleles M and N, which control production of correspond-
7.2. Multiple alleles. Blood groups. Immunogenetics
167
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Concept of immunogenetics
D
ing antigens M and N. There are three possible combinations of antigens depending on
genotype of a person (MM, MN, NN). Another gene also has two codominant alleles S and
s, which control synthesis of antigens S and s. As genes are tightly linked, child gets certain
combinations of MN and Ss alleles from mother and father (as haplotypes). Analysis of combinations can be used in cases of disputed paternity. Incompatibility in MNS blood group
antigens sometimes leads to transfusion reactions and hemolytic disease of the newborn.
TR
IC
Immunogenetics is the study of genetic bases of the immune response. It includes
the study of genetically based variants of normal immune response, antibodies diversity,
inheritance of antigen systems, including the blood groups antigens, and genetic variation
that results in immune defects.
Peculiarities of immune system organization and functioning are very important in
understanding of immunogenetics. Human immune system includes central (thymus, red
bone marrow) and peripheral (tonsils, spleen, appendix, lymph nodes) specialized organs
and set of the cells that fulfill immune defense of an organism.
There are two principle types of immunity: innate and adaptive (specific acquired)
ones (Table 7.4). Both types involve humoral response that protects extracellular spaces
and cell-mediated response that fights intracellular infections.
Table 7.4. Features of innate and adaptive immunity
Characteristics
Non specific for a particular pathogen (for
molecules shared by groups of related microorganisms or molecules produced by damaged host cells)
EC
Specificity
Innate immunity
Adaptive immunity
Specific for certain antigen
Cells are active all the time since birth
Cells are normally in silent
mode and become active only
when the antigen is identified
Response
Comes immediately as soon as a foreign body
enters the human system, provide the initial
defense
Develops later (delayed immunity)
Diversity of recognized antigens
Limited
Extremely high
Components
Cellular and chemical barriers of skin and mucosal epithelium, antimicrobial and antiviral
proteins (lysozyme, interferon and other)
Phagocytes (macrophages, neutrophil leukocytes)
Lymphocytes (T cells and
B cells)
antibodies, produced by
B cells
Memory
None
Yes
R
Activity type
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Chapter 7. Regularity of heredity in humans
R
EC
TR
IC
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D
Innate immune response is not specific to a particular pathogen. This system activates
within minutes to hours after a foreign agent invades through the human body, thus innate
immune system can also be termed as immediate response of immune system. It consists
of biochemical and cellular defense mechanisms. First line of defense includes physical and
chemical barriers: skin (mainly the epidermis), epithelial lining of respiratory tract and gut and
antimicrobial molecules of their mucus, lysozyme in saliva and tears, gastric acid in the stomach and other. The second line of defense involves chemicals and cells that are quickly released
in the blood, even if the host has never been previously exposed to a particular pathogen.
The pathogen-associated molecules stimulate phagocytosis, inflammatory response and
synthesis or activation of defense proteins (for example, interferon). Phagocytosis is the most
important mechanism of cell-mediated innate immunity. Leukocytes (neutrophils and macrophages) recognize pathogen, engulf
and destroy it. Macrophages process
foreign antigens and represent them
Red bone marrow
to other immune cells for activation of
adaptive immune response. They also
release the inflammatory mediators.
Adaptive immunity is highly specific
to a particular pathogen (specific immuProcesses
Processes in the
nity). Quite often it gives long-lasting
in thymus
bone marrow
protection: for example; someone who
recovers from measles is now protected
against measles for lifetime. The main
T-lymphocyte
B-lymphocyte
components of adaptive immunity are
lymphocytes that provide humoral and
Transport with blood
cell-mediated immunity. Two classes of
Lymph node
lymphocytes participate in this process.
B lymphocytes (B cells) provide humoral and T lymphocytes (T cells) cellmediated immune reactions (Fig. 7.9).
B lymphocytes were so called as first
they were found in birds in an organ the
bursa of Fabricius. In mammals no anatomic equivalent of the bursa exists and
Antigen
Cooperation
Antigen
early differentiation of B cells occurs in
the red bone marrow (bursa-derived or
bone marrow-derived lymphocytes). T
cells also arise in the bone marrow but
Lymphoblasts
Plasma cells
migrate to thymus for differentiation
(thymus-derived lymphocytes). There
Cell immune reactions
Humoral immune reactions
are several types of T lymphocytes,
which functions are given in Table 7.5.
Fig. 7.9. Scheme of adaptive immune response
7.2. Multiple alleles. Blood groups. Immunogenetics
169
TE
D
Humoral response protects extracellular spaces. It is mediated by antibodies which
are produced by B lymphocytes. An antibody or immunoglobulin (Ig), is a large, Y-shaped
protein formed by four polypeptide chains (two ”light” and two “heavy”) (Fig. 7.10). Each
molecule has antigen-binding site that is specific to certain antigen and binds to it with
precision according to the “key-lock” principle. By binding to microorganisms antibodies
prevent invading of host cells, target bacteria for phagocytosis, neutralize bacterial toxins.
Antibodies participate in response to parasitic disorders and allergic reactions also.
The adaptive humoral response follows the chain of events. B cells identify antigens
circulating in the blood or lymph. T lymphocytes and signaling molecules of immune system (interleukins) co-stimulate B cells and initiate B cell proliferation (multiplication). Some
of the progeny of the expanded B cells differentiate into plasma cells. The plasma cells
secrete antibodies which are specific to the antigen. Other progeny cells become memory
cells that provide future immunity.
IC
Table 7.5. Functions of T lymphocytes
Types of
T lymphocytes
Move to the site of the infection and release the chemicals that destroy
cells infected with viruses or intracellular bacteria or initiate their apoptosis;
rejection of transplanted organs (allo- or xenotransplantation)
TR
Cytotoxic T cells
(T killers)
Functions
Release chemicals that activate the proliferation of T cells and B cells and
increase macrophage activity after the antigen has been recognized
Regulatory T cells
(suppressors)
Regulate immune response and suppress it when the infection has been
defeated
Memory T cells
Remain in the body to respond to the future infections by the same antigens
EC
Helper T cells
Variable region of heavy chain
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Antigen-binding site
Light chain
Fig. 7.10. Structure of antibody
Heavy chain
Variable region of light chain
Constant region of light chain
Constant region of heavy chain
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Chapter 7. Regularity of heredity in humans
TE
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One of the important questions of immunogenetics is the ability of an organism to produce specific antibodies to a huge number of different potential antigens. Great diversity of
antigen-binding site structure is explained by several genetic mechanisms. Genes for heavy
chains (chromosome 14) and light chains (chromosomes 2 and 22) expand DNA segment,
consisting of several regions. Somatic recombination of these regions and further alternative mRNA splicing is one source of the antibodies diversity. Another important mechanism
is somatic mutations that occur with high frequency in immunoglobulin genes during the
division of stimulated B lymphocytes.
The Nobel Prize in Physiology or Medicine 2011 was divided, one half jointly to Bruce A. Beutler and
Jules A. Hoffmann "for their discoveries concerning the activation of innate immunity" and the other
half to Ralph M. Steinman "for his discovery of the dendritic cell and its role in adaptive immunity".
R
EC
TR
IC
Cell-mediated response fights intracellular infections (including viruses) and any cells
(transplanted or mutant) that carry foreign antigens. It is mediated by T lymphocytes.
T lymphocytes recognizes antigen only in the complex with MHC (Major histocompatibility complex, see Chapter 6.5) molecules on the surface of special antigen-presenting
cells. The most important antigen-presenting cells are dendritic cells, which are present
in almost all tissues and organs. They ingest microorganisms or soluble proteinic antigens, digest and process them and present on their surface in complex with MHC molecules. Other cells that also can present antigens are macrophages and B lymphocytes.
Non-differentiated T lymphocyte recognize peptide-MHC complex that make it to
produce signaling molecules (cytokins), and stimulates cellular proliferation. Some T cells
become cytotoxic (effector) cells and destroy cells displaying the antigens; some T cells
become helper cells and secrete cytokins that attract other immune cells and stimulate
phagocytosis. Some activated T lymphocytes differentiate into memory cells, which survive for long periods and respond rapidly if encounter same antigen.
Important characteristic of T lymphocytes is presence of specialized T cells surface
antigen receptors that should specifically combine with antigens. Genes of T cells surface antigen receptors are located in chromosomes 7 and 14. Structure of receptors is
similar with that of antibodies and diversity of receptors is explained by similar recombination mechanisms. Somatic mutations unlike the B cells are not characteristic for
proliferating T cells; it prevents autoimmune reactions (immune response towards self
antigens).
The Major Histocompatibility Complex plays a central role in the cell-mediated immune
response. MHC of class I present peptide antigens to cytotoxic T lymphocytes. If this peptide is derivative of self protein immune response is not activated. Molecules MHC of class II
are expressed just on the surface of antigen-presenting cells, thymus epithelium and endothelial cells. They are required for initial stages of immune response activation.
MHC molecules are known as Human Leukocyte Antigens. They are very polymorphic
and play crucial role in transplant rejection (see Chapter 6.5). Genetic polymorphism of
7.2. Multiple alleles. Blood groups. Immunogenetics
171
D
HLA system and other antigen systems, like blood groups ABO, Rh and other is also a subject of immunogenetics.
The main differences between humoral and cell-mediated adaptive immunity are summarized in Table 7.6.
Table 7.6. The principle features of humoral and cell-mediated adaptive immunity
Characteristics
Humoral immunity
Cell-mediated immunity
Antibody-mediated
Cell-mediated
Cell type
B lymphocytes
Mode of action
Antibodies circulating in blood serum,
secreted or attached to cell surface
bind to bacteria and target them for
phagocytosis, neutralize bacterial
toxins
Purpose
Primary defense againt intracellular
Primary defense againt extracellular
pathogens: extracellular bacteria, circu- pathogens: viruses and fungi, intracellular bacteria, graft rejection, fighting
lating virus
tumor cells
TE
Mechanism
T lymphocytes
IC
Directed cell-to-cell contact with
releasing of substances that destroy
infected cells, secretion of signalling
molecules (cytokines), initiation of
apoptosis
R
EC
TR
Inherited immunodeficiency disorders. One more subject of immunogenetics is inherited immunodeficiency disorders. Both innate and acquired immune mechanisms can be
affected. Some examples of these are:
`` Bruton-type agammaglobulinemia. It is X-linked recessive disease caused by mutation of gene for signal molecule (tyrosine kinase) specific to B cells. B cells lose the
ability to differentiate into plasma cells producing antibodies. Mostly boys are affected. After first month of life they suffer from recurrent bacterial infections of skin,
respiratory and digestive systems because of immunoglobulin deficiency and absence of B lymphocytes.
`` Severe combined immunodeficiency is characterized by abnormal humoral and cell
mediated immunity and thus susceptibility to both bacterial and viral infections. Disease is caused by mutations of different genes that control signal molecules (interleukins and other), their receptors and other. Depending on mutant genes disease is
inherited as autosomal-recessive or X-linked recessive.
`` DiGeorge syndrome is a result of chromosomal mutation-deletion (lost) of the region
in the long arm of chromosome 22. As several genes are lost, immunodeficiency is
just one of the multiple manifestations of the disease. There is a reduced number of
T lymphocytes and failure of T cell dependent antibody production due to partial
absence of thymus gland.
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Chapter 7. Regularity of heredity in humans
7.3. Allelic and non-allelic gene interactions. Pleiotropy
Allelic Interactions
TE
D
Manifestation of characters is a result of complex interactions between different molecules, including structural proteins, enzymes, pigments and other substances. All these
substances are genetically determined, so an interaction of genes is, by the fact, interaction
of gene products.
The gene interactions are as follows:
1. Allelic (intra-allele) interactions are between the two alleles of a single gene: complete dominance, incomplete dominance, co-dominance.
2. Non-allelic (inter-allele) interactions occur between the alleles of different genes at different loci of the same or different chromosomes. Complementary interaction, epistasis and polymery (polygenic inheritance) are the types of non-allele genes interaction.
R
EC
TR
IC
`` Complete dominance takes place when one of the alleles (dominant) completely
manifests itself in both homo- and heterozygous state. Another allele (recessive one)
is not manifested in heterozygotes. Biochemical explanation of this phenomenon
may be as follows: the dominant gene is responsible for the active form of the enzyme, the recessive one is mutant and its active product is not formed. So, if a dominant gene is present in a genotype, the character is promoted. If a dominant allele is
absent, the character is not manifested.
`` Incomplete dominance is the case of the intermediate phenotypic expression in the
heterozygotes (see Chapter 7.1). Inheritance of four-o’clock plants color is an example of incomplete dominance (the crossing of red-flowered plants with white flowered ones results in pink-flowered plants in F ). Examples in humans are sickle-cell
1
anemia, anophtalmos (congenital absence of the eyeballs) and cystinuria.
Sickle cell anemia is an autosomal recessive disorder, characterized by atypical
hemoglobin molecule and sickle (crescent) shape of red blood cells. Such erythrocytes break down easily (hemolysis) that leads to anemia, fatigue, enlargement of
liver and spleen, delayed growth. Heterozygous carriers usually do not have symptoms of the diseases. In low oxygen levels, high altitudes, dehydration and some
other conditions they can demonstrate attacks of the disease caused by hemolysis of
RBCs. Disease is common in African countries, India, Mediterranean basin and African
Americans as heterozygotes are protected against malaria.
Anophtalmos is also autosomal-recessive trait. Recessive homozygotes don’t
have eyeballs, heterozygous persons have small eyeballs.
Cystinuria is one of the inborn errors of metabolism, characterized by abnormal
metabolism of amino acid cystine. Recessive homozygotes have cystine stones in the
kidneys, heterozygous carriers excrete increased amount of cystine with urine.
`` Codominance means that both the genes are equally dominant and expressed in the
phenotype. The AB (IV) and MNS blood groups are the examples (see Chapter 7.2).
7.3. Allelic and non-allelic gene interactions. Pleiotropy
173
Non-allelic gene interactions
TR
IC
TE
D
Non-allelic gene interactions give the examples of a single character controlled by two
or more pairs of genes. The expression of a particular character is the net result of a series of
enzyme mediated biochemical reactions. The production of each enzyme depends upon a
specific gene, so each metabolic pathway is controlled by several non-allele genes.
In non-allelic gene interactions the typical 9 : 3 : 3 : 1 ratio observed in dihybrid cross gets
modified.
There are several types of non-allelic gene interactions:
`` Complementary interaction of dominant genes means that they complement each
other and produce a new character while present together. This is a frequent phenomenon. A purple color of flowers in sweet pea plants depends on the presence of two
dominant genes. Gene P controls the synthesis of colorless precursor of the purple
pigment. Gene C controls the enzyme that converts precursor into purple pigment.
Presence of two dominant alleles P and C together gives purple flower color. The lack
of both or one dominant alleles (P or C) produces white flowers. In crossing of white
flowered plants with genotypes CCpp and ccPP all offspring have purple flowers.
P – colorless precursor of the purple pigment (white);
p – absence of precursor (white);
C – enzyme that converts precursor into purple pigment;
c – absence of converting enzyme.
white
P:
G:
F1:
♀CCpp
Cp
white
× ♂ccPP
cP
CcPp
Purple 100 %
R
EC
Self-pollination of F1 generation produces F2 generation with following phenotypes:
9/16 purple (C-P-) : 7/16 white (3/16 C-pp, 3/16 ccP-, 1/16 ccpp).
Examples of complementary genes in humans are inheritance of normal hearing, hemoglobin and interferon production.
Normal hearing is controlled by many non-allelic genes. Simplistically we can consider
that it depends on presence of two dominant non-allelic genes. The dominant allele D influences the development of the cochlea and the dominant allele E controls the development
of the acoustic nerve. If any of them is absent, the normal acoustic apparatus isn’t formed.
Mammal cells produce the protective protein interferon in the presence of the normal
alleles of two genes in the second and the fifth chromosomes.
Human hemoglobin of adults consists of 2α and 2β chains. These chains are controlled
by genes of chromosomes 16 and 11.
`` Epistasis is the suppression of a gene by another one at a different locus. The gene
that suppresses another one is called as an inhibiting or epistatic gene. The gene
which expression gets suppressed is termed as a hypostatic gene.
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Chapter 7. Regularity of heredity in humans
1
white
TE
white
P:
G:
F:
D
In fowls the gene C is responsible for dark feather color. Gene I is the epistatic over gene
C, so fowls with CCII genotype are white. In crossing of white fowls with genotypes CCII and
ccii all offspring are white.
C – dark color;
c – white;
I – epistatic gene (inhibitor);
i – absence of inhibition.
♀CCII
CI
× ♂ccii
ci
CcIi
white 100 %
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EC
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IC
Crossing of F1 generation produces offspring of F2 generation in following phenotypic
ratio: 13/16 white (9/16 C-I-, 3/16 ccI-, 1/16 ccii) : 3/16 dark (C-ii). So, F2 ratio is 13 : 3.
The Bombay phenomenon (after the city in which it was first discovered) is an example
of recessive epistasis in humans. A family with unusual inheritance of AB0 blood groups has
been described in Bombay (nowadays Mumbai, India). A mother with 0 blood group and a
father with B blood group had children with AB and 0 groups. Principles of the AB0 blood
group inheritance exclude birth of a child with AB group in mother with O blood group.
As maternal grandparents had 0 and A blood groups, it was supposed that the mother
A
has got I gene from parents in inactive state and gave it to a child with AB blood group.
A
Suppression of I gene in mother is explained by presence of epistatic recessive gene h. In
persons that are recessive homozygous for gene h (hh genotype), antigens A or B are not
A
B
synthesized despite presence of genes I or I in genotype. Gene H determines antigen H,
an essential precursor of antigens A and B. In persons with genotype hh antigen H is not
synthesized and subsequently antigens A and B cannot be produced.
Polygenic inheritance (polymeria) or quantitative inheritance takes place when several non-allelic genes control one and the same character enhancing it by their cooperation.
These genes are called polygenes or cumulative genes and the feature they determine is
polygenic. These genes are marked by the same letter with different indices (A1, A2, A3 and
so on). In case of cumulative polygenic inheritance the more dominant genes are in genotype the more pronounced is the feature (additive effect). Polygenic traits are also known
as quantitative or metric traits because they are measured and expressed in units of length,
weight and number. The presence of polygenes makes an organism less susceptible to mutations.
Polymeric inheritance was discovered by a Swedish geneticist Nilsson-Ehle (1908) when
he studied the inheritance of kernel color in wheat. In crossing of red- and white-kerneled
wheat F1 generation was with pink kernels. In F2 generation 15/16 of offspring were colored
with different intensity and 1/16 was white. For explanation of this result Nilsson-Ehle assumed that kernel color in wheat is controlled by two genes, each with a pair of alleles,
exhibiting cumulative effect.
7.3. Allelic and non-allelic gene interactions. Pleiotropy
♀A1A1A2A2 × ♂a1a1a2a2
P:
red
A1A2
G:
F1:
white
A1a1A2a2
a1a2
Pink
D
A1 – red;
a1 – white;
A2 – red;
а2 – white.
175
F1 Generation
F2 Generation
A1A1A2A2A3A3
(very dark)
A1a1A2a2A3a3
A1a1A2a2A3a3
1
8
1
8
Sperm
1
1
8
8
1
8
1
8
1
8
1
8
Fraction of population
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Eggs
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1
8
1
8
1
8
1
8
1
8
1
8
1
8
1
8
a1a1a2a2a3a3
(very light)
TR
P Generation
IC
TE
Crossing of F1 generation produces F2 offspring in following phenotypic ratio: 1/16 red
(A1A1A2A2) : 4/16 light red (2 A1a1A2A2, 2 A1A1A2a2) : 6/16 pink (4A1a1A2a2, 1 A1A1a2a2, 1 a1a1A2A2) :
4/16 light pink (2 A1a1a2a2, 2 a1a1A2a2) : 1/16 white (a1a1a2a2).
Additive effect in polymeria forms continuous variations of the trait in population. The
distribution of such traits often is close to a bell-shaped or normal distribution with extreme phenotypes rare and the proportion of intermediates high.
Growth intensity, speed of ripening in plants, milk yield in cattle, egg production in
poultry are the examples of polygenic signs. Human polygenic characters are skin color,
height, body weight, intelligence, blood pressure, susceptibility to diseases.
The human skin color shows a wide continuous variation explained by the differences
in amount, type and packaging of melanin in the skin cells (Fig. 7.11). There are more than
20
64
20
64
6
64
1
64
1
64
6
64
15
64
20
64
15
64
Fig. 7.11. Polymeric inheritance of skin color
6
64
1
64
Skin pigmentation
176
Chapter 7. Regularity of heredity in humans
TE
D
twenty known genes involved in control of melanin production and distribution. The effect of genes is additive, so the amount of melanin produced is always proportional to
the number of dominant genes. If suppose that skin color is controlled just by three pairs
of polygenes, people with six dominant alleles (A1A1A2A2A3A3) demonstrate maximal skin
pigmentation (black color), which is characteristic for African populations. Caucasians with
white skin color and low melanin level are recessive homozygotes (a1a1a2a2a3a3). Skin color
in children of one couple with visibly different amount of melanin (“black” or “white”) show
the gradation of colors from very pale to very dark depending on dominant alleles number.
Pleiotropy
EC
TR
IC
Pleiotropy takes place when many features depend on one gene. It is explained by
participation of gene product in a spectrum of different activities. There are two principle
types of pleiotropy: primary and secondary ones.
The primary pleiotropy means simultaneous manifestation of different characteristics
caused by primary gene product.
The Marfan disease in humans is an example of primary pleiotropy (Fig. 7.12). It is autosomal-dominant disease caused by mutation of fibrillin gene. Fibrillin is one of the proteins
of connective tissue. As connective tissue is abundant in many organs, patients have multiple affections. They are tall with long extremities and arachnodactyly (long slender fingers),
have congenital heart defects, shortsightedness, and sometimes dislocation of eye lenses.
Another example of primary pleiotropy in humans is control of red hair, freckling and
sun-sensitivity by melanocyte-stimulating hormone receptor gene.
In case of the secondary pleiotropy allele of the gene initiates a consequent chain of
various effects. Thus, patients with sickle cell anemia exhibit the following sequence of
anomalies: abnormal hemoglobin causes sickle-shaped RBC that causes hemolytic anemia
and in turn, enlargement of the liver and spleen because of active hemolysis of the erythrocytes.
7.4. Chromosomal theory of heredity
R
The main idea of Chromosomal theory is that genes are located in chromosomes.
Mendel came to the conclusion of the heredity principles without the knowledge of
genes and chromosomes. Over the next decades after Mendel’s findings cytological
bases of heredity became more understandable. In 1878 Walther Flemming described
chromatin threads in cell nucleus and behavior of chromosomes during mitosis. In 1888
Heinrich Waldeyer coined the term “chromosome” to describe the bodies in the nucleus
of cells. Meiosis has also been discovered at this time and in 1890 August Weismann described its role for reproduction and heredity. Walter Sutton and Theodor Bovery, compared the behavior of the chromosomes in meiosis with the Mendel’s laws and in 1903
proposed a theory that chromosomes were the carriers of hereditary factors (genes).
7.4. Chromosomal theory of heredity
177
Marfan syndrome
D
Eye problems
Abnormal chest, heart and lung problems
TE
Short torso
Tall, thin body frame
TR
IC
Long arms, legs and fingers
Fig. 7.12. Primary pleiotropy. Marfan syndrome
R
EC
Later an American scientist Thomas Hunt Morgan while experimenting with drosophila
flies in 1910–1916 demonstrated association of hereditary factors with chromosomes and
formulated chromosomal theory of heredity. He studied and explained the following questions:
1. Importance of chromosomes as carriers of hereditary information.
2. Linkage of genes.
3. Crossing-over and chromosome mapping.
4. Chromosomal definition of sex.
5. Sex-linked inheritance.
Linkage of genes
Each chromosome carries a number of genes. All the genes located on the same chromosome are said to be linked genes. They can be linked together on one of the autosomes
or on the sex chromosome. Such genes of one chromosome are called as linkage group.
Set of genes in homologous chromosomes is the same, so number of linkage groups is
178
Chapter 7. Regularity of heredity in humans
♀AB
AB
grey winged
G:
F:
♂ab
ab
×
AB
1
TE
P:
D
equal to the number of chromosomes in haploid set. The genes of a linkage group have a
tendency to be inherited together but independently of the genes of other linkage groups.
The Morgan’s experiment showed the main regularities of autosomal linkage (inheritance of genes of the same autosome). He crossed drosophila flies with a grey body (A),
long wings (B) and black body (a) without wings (b). F1 flies were grey with long wings
(Fig. 7.13).
black wingless
ab
AB
ab
grey winged
1
IC
The test cross of F males produced the following offspring (see Fig. 7.13):
F:
1
♀ab
ab
♂AB
ab
×
black wingless
grey winged
ab
AB
ab
AB, ab
ab
ab
grey winged 50 %
black wingless 50 %
TR
G:
F:
2
EC
According to Mendel's laws diheterozygous organism should produce four types of
gametes in equal proportion (AB, Ab, aB, ab – 25 % each). Morgan explained the results of F1
males test cross by location of A and B genes in one chromosome. Biological peculiarity of
drosophila male flies is absence of crossing-over, so males produce two types of gametes
and consequently two types of offspring. In absence of crossing-over (no recombination)
linkage of genes is called complete.
Grey winged
R
P
F1
×
Black wingless
Black wingless
P
Grey winged
Grey winged
Grey
winged
50 %
Black
wingless
50 %
F2
Fig. 7.13. The Morgan’s experiment with crossing of drosophila flies with grey body, long wings and black
body without wings (F1) and further test cross if male is diheterozygous (F2)
7.4. Chromosomal theory of heredity
179
Test cross of F females gives another result (Fig. 7.14):
1
♂ab
ab
grey winged
♂AB, Ab, aB, ab
AB,
Ab,
ab
ab
G:
F:
2
grey
winged
41.5 %
grey
wingless
8.5 %
black wingless
ab
aB,
ab
black
winged
8.5 %
D
×
ab
ab
black
wingless
41.5 %
TE
♀AB
ab
P:
EC
TR
IC
Test-cross results of drosophila flies males and females differ due to crossing-over in
females. Crossing-over leads to production of four types of gametes: two non-recombinant
(AB and ab) and two recombinant (Ab, aB). If crossing-over occurs linkage of genes is called
incomplete. Number of recombinant gametes is always less than non-recombinant. Further experiments showed that chance of recombination between two certain genes of one
chromosome is constant and directly proportional to the distance between the genes (the
more the distance between the genes, the more the percentage of crossing-over). Linked
inheritance is observed if chance of crossing over is less than 50 %. If chance of crossingover is higher than 50 %, genes are inherited independently.
Examples of complete linkage in humans are:
`` inheritance of Rh-factor genes (RHD and RHCE);
`` inheritance of MN and Ss blood groups (Chapter 7.2);
`` inheritance of HLA antigens (Chapter 6.5).
Examples of incomplete linkage in humans are:
`` inheritance of Rh-factor gene (RHD) and gene of elliptocytosis (oval shape of erythrocytes) that are in the first chromosome at the 3 % crossing-over distance;
Grey winged
R
F1
Black wingless
×
F2
Grey winged
41.5 %
Grey wingless
8.5 %
Black winged
8.5 %
Fig. 7.14. The Morgan’s experiment with test cross if female is diheterozygous (F2)
Black wingless
41.5 %
180
Chapter 7. Regularity of heredity in humans
`` inheritance of red-green color blindness and hemophilia that are in the X chromosome at the 9.8 % crossing-over distance;
D
Crossing-over and chromosome mapping
TR
IC
TE
T. H. Morgan proposed to use percentage of crossing-over for marking the distance
between genes and their order in the chromosome. Thus, distance between genes that
control color of the body and length of the wings in drosophila fly is 17 % of crossing-over.
Later, student of the T. H. Morgan, Alfred Henry Sturtevant, named the unit of distance as
centiMorgan (cM) in honor of his teacher. One cM is equal to 1 % of crossing-over or, by
other words, 1 % chance that gene at one locus on a chromosome will be separated from a
gene at another locus due to crossing over in a single generation.
Analysis of gene linkage allows composing genetic maps of chromosomes. Genetic
map is the arrangement of genes in chromosomes. Genetic mapping includes determination of linear order of genes and relative distances between them. The first genetic maps
were composed for drosophila fly, nowadays the maps of chromosomes are made for many
prokaryotic and eukaryotic organisms, including humans (Fig. 7.15). Analysis of recombination frequency (crossing-over) is used for genetic maps composing, so centiMorgan is
also known as map unit.
Modern DNA technologies permit direct identification of gene location in a chromosome and determination of distance between the genes in base pairs. Maps composed by
direct DNA studying are called physical maps.
Genetic and physical maps are similar, but non-identical. Number of base pairs corresponding to one centiMorgan varies between males and females (crossing over in females
is more frequent) and between different regions of chromosome. One centiMorgan matches to about one million base pairs in humans on average.
EC
The main principles of chromosome theory of heredity
R
Based on the results of his experiments T. H. Morgan in 1915 published “The mechanisms of Mendelian Heredity” in which formulated the main principles of chromosome
theory of heredity.
Postulates of the chromosome theory of heredity are the following:
1. Genes are situated in the chromosomes in the linear order. Each gene occupies a certain place (locus).
2. Genes of one chromosome form a group of linkage and are inherited together. The
number of linkage groups is equal to the number of the haploid set of chromosomes.
There are 23 linkage groups in human females and 24 in males, as X and Y chromosomes form different groups of linkage.
3. Linkage of genes can be interrupted by crossing-over. It is the exchange of allele
genes between homologous chromosomes.
4. The percentage of crossing-over is directly proportional to the distance between genes.
7.4. Chromosomal theory of heredity
TE
D
retinitis pigmentosa
enolase-1
6-phosphoglyceraldehyde dehydrogenase
elliptocytosis
glutamate dehydrogenase
galactose 4-epimerase
rhesus blood groups
α-L-fucosidase
scianna blood groups
adenylate kinase (mitochondrial)
uridine monophosphate kinase
phosphoglucomutase-1
amylase
duffy blood groups
cataract
antithrombin-3
UDP-glucose pyrophosphorylase-1
guanylate kinase
peptidase
fumarate hydratase
5-s RNA
TR
IC
Eno
PGD
17 27
Rh
9 32
Sc
16 14
UMK
14 24
PGM
26 34
PKU
AMY
14 circa 40
cataract duffy
circa 25 50
PEPC
181
Fig. 7.15 Genetic map of chromosome 1 of the human genome with some genes (from Fincham Genetics,
1983). Linkage group is shown with location of genes and recombination frequencies (figures on the left are
from male and those on the right from female meiosis; note higher frequencies in female). Map is based on
family studies (genealogic method) and cytogenetic approaches
EC
The Nobel Prize in Physiology or Medicine 1933 was awarded to Thomas H. Morgan
"for his discoveries concerning the role played by the chromosome in heredity".
Inheritance of sex
R
Several ways of sex determination evolved during the evolution of animals. Amount of
yolk or action of external factors can determine development of males or females in some
organisms. For example, males of the sea-worm bonnelia are small and parasite on the
body of the females. Fertilization takes place in water. The larva develops in a male organism on the surface of a female but it becomes female when develops apart.
The most common and progressive in animals is chromosomal determination of sex.
Each set of female or male chromosomes contains the pairs of similar chromosomes also
called autosomes (marked as A) and a pair of different chromosomes or heterochromosomes (sex chromosomes, marked XX and XY). Autosomes are the same in male and female organisms. Sex chromosomes determine the sex of an organism, they are partially
homologous and pair with one another during meiosis (see Chapter 3.3).
182
Chapter 7. Regularity of heredity in humans
P: ♀44A+XX
G: 22A + X
F1: 44 A + XX,
50 % females
TE
D
In humans and other mammals, a female has XX and a male has XY chromosomes. The
females produce one kind of gametes with X chromosome and are termed as homogametic. Males produce two kinds of gametes (50 % gametes contain X chromosome and 50 %
gametes – Y chromosome) and are termed as heterogametic. The sex of future child is determined at the moment of fertilization. It depends on sex chromosome in sperm cell that
fertilizes the egg. In humans there is an equal probability of an X containing egg combining
with Y or X containing sperm, so there is 50 % chance of the offspring being a female and
50 % a male.
×
♂44A + XY
22A + X, 22A + Y
44A + XY
50 % males
TR
IC
In fact, sex ratio of males to females born is 106 : 100. Possible explanation of this fact is
based on different size and weight of X and Y chromosomes (see Fig. 3.20). Chromosome Y
is smaller in size, so sperm carrying it moves faster and quite often reaches egg first.
There are other variants of chromosomal determination of sex. In birds and some reptiles
females are heterogametic (referred as ZW) and males are homogametic (referred as ZZ).
In insects sex may depend on the number of sex chromosomes. Males have only one X
chromosome (XO), and females have two X chromosomes (XX) or vice verse.
In honey bee females develop from fertilized diploid egg and males develop by parthenogenesis from non-fertilized haploid eggs.
Development of sex in humans
R
EC
Sexual traits in humans develop under the control of many genes located in autosomes
and sex chromosomes (Table 7.4). It is considered, for example, that number of genes important in development and functioning of testis and prostate is about 1200, ovaries–500,
and uterus – 1800. Many of these genes control transcription factors and thus are also involved in forming and regulation of many other organs.
Chromosome Y is crucial in human sex differentiation. The presence of Y chromosome is essential for male development and absence of Y results in female development. Early human embryo has non-differentiated primary gonads and two primitive
ducts that can give rise to either the male or the female reproductive tracts (Wolffian or mesonephric and Mullerian or paramesonephric ducts) (Fig. 7.16). Differentiation towards the male reproductive system begins on the 6 week of embryogenesis
from activation of SRY gene (Sex-determining Region of Y chromosome) located on
the short arm of chromosome Y. It controls transcription factor that stimulates the medulla of gonad to develop into a testis. By the end of week 9 Leydig cells start to produce testosterone, which stimulates development of Wolffian duct to male internal
genitalia (seminal vesicles, vas deferens, epididymis). Sertoli cells produce Mullerian
7.4. Chromosomal theory of heredity
183
Table 7.4. Examples of genes involved in development of sex in humans
Location
SRY
(Sex-determining Region of Y
chromosome)
Yp
Transcription factor, activates
genes for testis development
SRY deletion leads to infertile
females with karyotype 46, XY;
Translocation of SRY on X chromosome leads to infertile males
with karyotype 46, XX
AZF (Azoospermy Factor)
Yq
Regulates spermatogenesis
Mutations lead to failure of spermatogenesis and infertility
MIF (Mullerian Inhibitory
Factor)
19p
Activate regression of Mullerian
duct in male embryo
AR
(Androgen
receptor)
Xq
Control formation of testosterone Certain mutations cause absence
receptor
of androgen receptors and insensitivity to testosterone. Complete
insensitivity causes Morris syndrome (syndrome of testicular
feminization). Patients with 46,XY
karyotype have external female
genitalia, blindly ended vagina
and testis in abdominal cavity
Associated pathology
TE
Mutations lead to persistence of
Mullerian duct derivatives (fallopian tubes, uterus and upper
part of vagina) in phenotypically
and karyotypically males
IC
TR
WNT4
WNT7A
Function
D
Example
1p
3p
Specify secreting signaling factor
that regulates formation of Mullerian ducts in females, important in
development and maintenance of
oocytes, formation of kidneys and
some hormone-producing glands
Underdevelopment of Mullerian
duct derivatives in females
R
EC
Formation of gonads – 5 weeks
Fig. 7.16. Non-differentiated primary gonads in human embryo
Gonad
Paramesonephric duct
Mesonephros
Mesonephric duct
Urogenital sinus
Ureter
184
Chapter 7. Regularity of heredity in humans
Male
XY chromosome
with Y genes
Genetic, Gametic,
Chromosomal Sex
XX chromosome
No Sry
D
Sry (TDF)
medulla
Gonadal Sex
TE
ovary
immature
female genitalia
+
external sex
characteristics
Estradiol + Progesterone
IC
MRF (Mullerian
Regression
Testosterone (Leydig Cells)
Factor;
Sertoli
Cells)
immature male genitalia
+
5a-Dihydroexternal sex
Testosterone
characteristics
Behavioral &
Metabolic Sex
cortex
testis
Phenotypic Sex
Internal
&
External
Female
adult phenotype
adult phenotype
TR
Fig. 7.17. Sex determination in humans
EC
Inhibitory Factor (MIF), which causes regress of Mullerian duct. The development of external male genitalia is mediated by dihydrotestosterone, produced from testosterone
by 5α-reductase.
In absence of SRY gene cortex of embryonic gonad develops into an ovary which produces estradiol. In absence of MIF internal genitalia are formed from Mullerian duct (fallopian tubes, uterus and upper vagina). Wolffian duct regresses. External genitalia evolve
into female ones under the estradiol action (Fig. 7.17).
In humans determination of gender depends on both genetic and social factors. It is a
multistep process, described in Table 7.5.
Sex-linked inheritance
R
Sex-linked inheritance is inheritance of characters controlled by genes of non-homologous regions of X and Y chromosomes.
Sex-linked inheritance was discovered by T. H. Morgan who noticed that inheritance of
eyes color in drosophila flies was associated with the sex of the parents.
Morgan crossed red eyed female (normal wild type) with white-eyed male (mutant
type) and found that first generation progeny had red eyes only. So, red color of eyes is
dominant over white.
7.4. Chromosomal theory of heredity
185
Table 7.5. Genetic and social factors determining determination of gender
in humans (after В. Н. Ярыгин, 2015)
Steps of gender determination
Males
Females
XY
XX
Gonadal
Testis
Ovaries
Gametic
Sperms
Eggs
Hormonal
Androgens
Estrogens
Somatic
Male phenotype
Civilian (passport)
Man
Sexual upbringing
Man
Sexual auto-identification
(may or may not coincide with
chromosomal or somatic)
Typical male or atypical
TE
D
Chromosomal
Female phenotype
Woman
Woman
IC
Typical female or atypical
A
X – red eyes;
a
X – white eyes.
A A
♀X X
a
♂X Y
×
TR
P:
red eyes
white eyes
X
A a
XX,
X ,Y
A
XY
A
G:
F:
1
a
red eyes
EC
After that Morgan crossed males and females of F1 generation and got ratio total red to
total white 3 : 1 as in experiments of Mendel. But all females were with red eyes and males
had red and white eyes in the equal proportion.
F:
1
G:
F:
2
A a
♀X X
A
♂X Y
×
red eyes
A
a
red eyes
A
X , X X ,Y
A A
A a
A
XX,
XX,
X Y,
♀red eyes
a
♀red eyes ♂red eyes
X Y (3 : 1 ratio)
♂white eyes
R
Crossing of white-eyed female and red-eyed male exhibited another results in F1 and F2
generations. In F1 generation all females were with red eyes and all males with white eyes.
P:
G:
F:
1
a a
♀X X
white eyes
a
×
A
♂X Y
red eyes
A
X
A a
XX,
X ,Y
a
XY
♀red eyes
♂white eyes
186
Chapter 7. Regularity of heredity in humans
1
G:
F:
2
A a
♀X X
×
red eyes
A
a
♂X Y
white eyes
a
a
X ,X
A a
XX,
X ,Y
XX,
a a
♀red eyes ♀white eyes
X Y,
A
XY
a
♂red eyes
♂white eyes
(1 : 1 ratio)
TE
F:
D
So, the white-eyed females transmit their trait to males and red-eyed males to females.
Crossing of F1 hybrids produced red-eyed and white eyed females and males in equal proportion.
R
EC
TR
IC
By analyzing the results of the cross T. H. Morgan came to conclusion that gene of eye
color in drosophila fly is located in X chromosome. In drosophila fly females are homogametic (XX) and males are heterogametic (XY). Inheritance of eye color followed situation
when males inherit X chromosome from female and male gives X chromosome to females
(criss-cross inheritance).
Inheritance of genes situated in sex chromosomes was termed as sex-linked inheritance. Characters determined by genes of sex chromosomes are sex-linked characters.
There are X-linked (dominant or recessive) and Y-linked patterns of inheritance. White color
of eyes in drosophila fly is an example of X-linked recessive character.
Main features of X-linked recessive inheritance are:
1. Males have only one copy of X chromosome and so the trait manifests itself even if
it is present in a recessive form. Thus, males with XY karyotype are considered to be
hemizygotic. Most of the patients with X-linked recessive disorders are men.
2. A female has two X chromosomes so has to be homozygous to express a recessive
trait (receives recessive alleles from both her parents).
3. A male transmits his recessive X-linked alleles to his daughters (criss-cross inheritance).
4. A father cannot transmit the X-linked trait to his sons. If a son gets a recessive Xlinked disease, it is always inherited from his mother.
Examples of X-linked recessive human disorders are red-green color blindness (daltonism) and hemophilia. Mostly men are sick with these disorders. Hemophilia is a condition
of slow blood clotting, so even a minor injury can lead to profuse bleeding. The scheme of
its inheritance is given below.
If a normal woman marries a man suffering from hemophilia, all their children are
healthy, but all the daughters become carriers of the disease.
H
X – normal blood clotting;
h
X – hemophilia.
P:
G:
F:
1
H H
♀X X
healthy woman
H
X
H h
XX,
healthy daughter
(carrier)
×
h
♂X Y
man with hemophilia
h
X ,Y
H
XY
healthy son
7.4. Chromosomal theory of heredity
187
In next generation healthy daughters, who are the carriers, have a chance to give birth
to the sons with hemophilia.
H
♂X Y
×
healthy mother (carrier)
healthy father
H
h
X ,X
H H
H h
XX,
XX,
1
healthy
daughter
healthy
daughter
(carrier)
H
X ,Y
h
XY
H
X Y,
healthy
sick son
son
(50 % of sons)
TE
G:
F:
D
H h
♀X X
P:
If a mother is a carrier and a father is sick, there may be affected daughters.
H
♀X X
P:
h
healthy mother (carrier)
1
H
h
X ,X
H h
H
X X,
X Y,
sick father
h
h
h
XX,
X ,Y
h
XY
IC
G:
F:
h
♂X Y
×
healthy
daughter
(carrier)
healthy
son
sick
sick
daughter
son
(50 % of children)
TR
The main characteristics of X linked dominant inheritance:
A
1. Affected father (X Y) transfers the disease to all his daughters and to none of his sons.
A a
2. If mother is sick and heterozygous (X X ) the disease is inherited by half of her daughters and sons.
Examples of the X linked dominant traits in humans are vitamin D resistant rickets and
hypoplasia of teeth enamel (dark teeth enamel).
R
EC
The main characteristics of Y linked inheritance:
1. Only males are affected. Features determined by Y chromosome genes are called holandric (from Greek holo – whole, entire, andrikos – masculine).
2. Trait is transmitted from father to all his sons and never to the daughters.
Nowadays just about 50 genes are confined to Y chromosome. Many of them control
the differentiation of testis and spermatogenesis. Mutations of these genes are not inherited as affect reproduction. Just few examples of the Y-linked traits are suspected by pedigree analysis: hairy ears (hypertrichosis of pinna) and Y-linked type of deafness.
Incomplete (partial) sex-linkage
Chromosomes X and Y have homologous regions on their short arms. There is a chance
of crossing over and exchange of genes between homologous parts of X and Y chromosomes. If a gene is situated in this region trait is usually inherited as autosomal one (no
differences between genders), so homologous region is called pseudoautosomal. Genes of
pseudoautosomal region are said to be incompletely (or partially) sex-linked. Examples
188
Chapter 7. Regularity of heredity in humans
Sex-influenced and sex-limited characters
D
are genes of some immune receptors and short stature homeobox gene (SHOX). Mutations
of SHOX gene cause congenital defects of skeleton with autosomal dominant or autosomal-recessive patterns of inheritance.
IC
TE
Sex-influenced characters are controlled by genes of autosomes but expressed more
frequently in one sex than in another. In most of the cases it is explained by the influence
of sex hormones. For example, baldness is dominant in males, so man with genotype
Aa is bald. In females baldness is recessive and woman with same genotype has normal
hair. Another example of trait that is dominant in males and recessive in females is short
index finger.
Sex-limited characters are features manifested only in individuals of a particular sex. For
example, genes controlling production of milk and development of uterus are present in
both sexes, but expressed in females only.
TASKS & QUESTIONS
TR
`` Multiple Choice Questions (Choose one correct answer):
R
EC
1. Auricle-dental displasia is autosomal dominant disorder, which is characterized by
the lack of molars and some other defects. There is a normal child in family where the
mother is healthy and the father is ill. What is the risk of having the second child with
displasia?
A. 50 %
C. 75 %
E. 0 %
B. 100 %
D. 25 %
2. Healthy parents have a deaf child with albinism (two recessive characters). What is
the genotype of the parents?
A. AABB and AABB
C. aaBB and aaBB
E. AABb and AaBb
B. AaBb and AABB
D. AaBb and AaBb
3. A normal woman and a man suffering from aniridia (absence of iris, autosomal dominant character) have five children with aniridia. What is the chance of having a normal child in this family?
A. 0 %
C. 50 %
E. 100 %
B. 25 %
D. 75 %
4. Albinism is a recessive character. Which marriage has a 50 % risk of an affected child?
A. AA and aa
C. Aa and Aa
E. AA and AA
B. Aa and aa
D. Aa and AA
7.4. Chromosomal theory of heredity
189
R
EC
TR
IC
TE
D
5. A healthy couple has a child suffering from microcephaly (a recessive character).
What is the chance of having the next child healthy?
A. 0 %
C. 50 %
E. 100 %
B. 25 %
D. 75 %
6. Anophthalmos (the lack of eyeballs) is a recessive character. Heterozygotes have
small eyeballs (incomplete dominance). A couple is heterozygoes. What is the chance
of having a child with normal eyes?
A. 0 %
C. 50 %
E. 100 %
B. 25 %
D. 75 %
7. A father is deaf and has albinism (recessive characters). A mother is healthy and diheterozygous. Which ratio will help to calculate the chances of their children to be
healthy?
A. 3 : 1
C. 1 : 1 : 1 : 1
E. 9 : 3 : 3 : 1
B. 1 : 1
D. 9 : 7
8. Parents are healthy heterozygous carriers of recessive genes for diabetes and defect
of lenses. What ratio will help to calculate the risk of having an affected child?
A. 1 : 1
C. 9 : 3 : 3 : 1
E. 9 : 7
B. 3 : 1
D. 15 : 1
9. A man with AB(IV) Rh– blood has a wife with B(III) Rh+ blood. Her father has 0(I) Rh–
blood. There are children with B (III) Rh– and 0(I) Rh+ blood groups in this family. A
forensic expert determined that one child is illegitimate. Which character permits to
exclude the paternity?
A. AB0 blood groups
D. Plasma proteins
B. AB0 and Rh blood groups
E. Rh-factor and plasma protein
C. Rh-factor
10. Children have 0(I) and AB(IV) blood groups. Their parents should have:
D. A(II) and AB(IV)
A. 0(I) and A(II)
B. 0(I) and B(III)
E. AB(IV) and 0(I)
C. A(II) and B(III)
11. Healthy parents with A(II) and B(III) blood groups have a child sick with phenylketonuria (recessive character) and 0(I) blood group. What is the genotype of this child?
A. I0I0 aa
C. IBI0 aa
E. I0I0 AA
A
0
A
B
B. I I aa
D. I I Aa
12. Rh-factor inheritance is very important in obstetrics practice. In which situation is
there a chance of newborn hemolytic disease because of Rh-conflict?
A. First pregnancy of Rh+ woman with Rh– fetus
B. First pregnancy of Rh– woman with Rh+ fetus
C. Second pregnancy of Rh+ woman with Rh– fetus
D. Second pregnancy of Rh– woman with Rh+ fetus
E. Pregnancy of Rh– woman with Rh– fetus
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Chapter 7. Regularity of heredity in humans
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13. Deafness is caused by different recessive genes a and b situated in different homologous chromosomes. A deaf man with aaBB genotype married a deaf woman with
AAbb genotype. They have four children. How many of them are deaf?
A. Nobody
C. Half
E. All of them
B. 1/4
D. 3/4
14. A patient is sick with the Marfian’s syndrome. This syndrome is an example of the following genetic phenomenon:
A. Complementarity
C. Polymeric genes
E. Codominance
B. Epistasis
D. Pleiotropy
15. There are several types of hereditary glaucoma (high intraocular pressure). One type
is determined by a dominant gene, another one by a recessive gene. A father is sick
and diheterozygous (AaBb), a mother is sick and homozygous (aabb). What is the risk
of having an affected child in this family?
A. 0
C. 50 %
E. 100 %
B. 25 %
D. 75 %
16. Biosynthesis of an interferon molecule is controlled by two dominant non allele
genes. What type of interaction is between these genes?
A. Complementarity
D. Incomplete dominance
B. Epistasis
E. Complete dominance
C. Polymeric interaction
17. Cystinuria is an autosomal recessive disorder, characterized by formation of stones
in the kidneys. Heterozygous persons have an elevated level of cystin in urine. What
type of gene interaction is present?
A. Complete dominance
D. Epistasis
B. Incomplete dominance
E. Codominance
C. Complementarity
18. Hereditary deafness is determined by two recessive genes d and e. For normal hearing both dominant alleles (D and E) are required. Parents are heterozygous. What
phenotypic ratio can we use to calculate the risk in this family?
A. 9 : 3 : 3 : 1
C. 9 : 7
E. 15 : 1
B. 1 : 1 : 1 : 1
D. 13 : 3
19. A healthy couple has a son sick with haemophilia. The maternal grandfather suffers
from haemophilia also. What is the mode of this trait inheri­tance?
A. X-linked recessive
D. Autosomal dominant
B. Autosomal recessive
E. Y-linked
C. X-linked dominant
20. A healthy woman married a man sick with haemophilia. There were no cases of haemophilia in her family history. What is the risk for their child to be affected?
A. 0
C. 50 %
E. 100 %
B. 25 %
D. 75 %
7.4. Chromosomal theory of heredity
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21. Hypertrichosis (excessive hair growth) of auricles is determined by Y-linked gene.
What is the chance for an affected father to have an affected son?
A. 0
C. 50 %
E. 100 %
B. 25 %
D. 75 %
22. There is a recessive X-linked gene in humans that cause death of an embryo at the
early stage of development. What zygote will be eliminated?
A. Xa Y
B. XAXa
C. XAY
D. XAXA
23. Hypoplasia of dental enamel is X-linked dominant disorder. A mother has normal
teeth (XhXh), a father is affected. This feature is inherited by:
A. Daughters only
D. Half of the daughters
B. All children
E. Half of the sons
C. Sons only
24. Anhydrotic ectodermal dysplasia (absence of sweat glands, dental defects) is the Xlinked recessive character. What are expected phenotypes of the offspring if a man is
affected and a woman is healthy but has an affected father?
A. Half of the daughters and sons are affected
D. All daughters are affected
B. All children are healthy
E. All sons are affected
C. All children are affected
25. Genes situated in the same chromosome form a group of linkage. How many groups
of linkage are in a healthy man?
A. 46
C. 23
E. 2
B. 24
D. 22
26. The characters that are inherited through the sex chromosomes are termed sexlinked. Choose the sex-linked characters:
E. Polydactyly
A. Rh-factor
C. AB0 blood groups
B. Color blindness
D. Phenylketonuria
27. The genotype of an individual is BC || bc; the distance between genes B and C is 20
centiMorgans. Produced gametes are:
A. BC : Bc : bC : bc = 40 % : 10 % : 10 %: 40 %
B. Bc : BC : bc : bC = 40 % : 10 % : 10 % : 40 %
C. BC : bC : Bc : bc = 25 % : 25 % : 25 % : 25 %
D. BC : bc = 50 % : 50 %
E. Bc : BC : bc : bC = 10 % : 40 % : 10 % : 40 %
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`` FILL IN THE BLANKS:
1. Contrasting manifestations of the characters are called _______________ and are
controlled by different __________ of the gene.
2. ____________________ are the genes that in homozygous state cause death of an
individual.
3. The resulting offspring are named _________ (from Latin ________ – children).
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Chapter 7. Regularity of heredity in humans
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`` TRUE OR FALSE:
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4. The third Mendel’s law is law of ______________________ and states if parents differ
in two pairs of contrasting characteristics, the inheritance of each pair occurs independently in ratio in F2 ______________.
5. _________________ is the percentage of individuals with particular genotype who
exhibit genotype-associated characteristics.
6. The law of _________________ states that in hybrids of F1 generation dominant and
recessive genes ________ mix with each other and segregate during gametogenesis,
in such a way that each gamete receives ___________ gene from allelic pair.
7. There are two principle types of immunity: ___________ and __________.
8. _________________ is when sons inherit X chromosome from mother and father
gives X chromosome to daughters.
9. In absence of crossing-over linkage of genes is called ______________.
10. Features determined by Y chromosome genes are called __________________.
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1. According to Mendel's laws diheterozygous organism should produce four types of
gametes in equal proportion (AB, Ab, aB, ab – 25 % each).
False
True
2. The mammals females produce one kind of gametes with X chromosome and are
termed as homogametic.
True
False
3. The primary normal condition of a gene is called a mutant type allele, a new one – a
wild allele.
True
False
4. Bruton-type agammaglobulinemia is X-linked recessive disease caused by mutation
of gene for signal molecule (tyrosine kinase) specific to B cells.
True
False
5. The presence of Y chromosome is essential for male development and absence of Y
results in female development.
True
False
6. Chromosomes X and Y have homologous regions on their short arms.
True
False
7. Genes controlling production of milk and development of uterus are expressed in
females only. Such kind of characters are termed as sex-influenced.
True
False
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Chapter 8.
Variation, its forms and manifestation
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Variation is an ability of organisms to change their characters. It is one of the most important properties of living organisms. Variation provides the variety of organisms and the
unique properties of each organism.
There are two types of variation – phenotypic and genetic variation.
`` Phenotypic variation (modifications) – variation in phenotype without genotype
changes (non-hereditary).
`` Genetic variation – variation in phenotype caused by genotype changes (hereditary).
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8.1. Phenotypic variation
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This is the name for normal variants that appear due to environmental influence and
do not concern a genotype. Examples in humans are suntan, increase of the muscle volume after the high long-lasting physical exertions, increasing of erythrocytes number and
amount of hemoglobin in people who live high in the mountains. Some clinical features of
human disorders, like rising of temperature and increasing of leukocytes number during
infections are also the examples.
Modifications share several characteristics:
`` Modifications are not inheritable as do not change genotype.
`` Modifications are adaptive. For example, increasing of erythrocytes number and
amount of hemoglobin in the highland adapt to low oxygen pressure; rising of temperature and increasing of leukocytes are defense mechanisms against infections.
`` Modifications are single-vectored, which means that the same factors of environment cause the similar changes of the phenotype in organisms of a certain genotype. For example, regular trainings enhance the growth of muscle bulk, lungs capacity, and bone firmness in everybody; in summer all Caucasians get suntan under the
action of UV rays.
`` Modifications occur in a mass character – similar changes occur in all individuals of
the species.
`` Level of expression of variation due to the environmental factor depends on the intensity and duration of its action.
`` As a rule, modifications are reversible. If the environmental factors influence ceases,
modifications disappear. Thus, after the end of physical trainings muscle bulk and
lung capacity decrease again. If hazardous environmental factors act for a long time
during the period of development (embryogenesis or early postembryonic stages),
the changes can be non-adaptive and irreversible, e.g., congenital defects in a child
Chapter 8. Variation, its forms and manifestation
Modification
(non-hereditary changes)
Mutation
(hereditary changes)
Common (similar) phenotype
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Fig. 8.1. A phenocopy is an environmental condition that imitates (copies) the phenotype produced
by a gene
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with alcohol fetal syndrome if mother consumes alcohol during the pregnancy;
skeleton deformation due to deficiency of vitamin D (vitamin D-deficient rickets).
A condition of environmental etiology that mimics a condition of genetic etiology
is termed phenocopy (Fig. 8.1). For example, vitamin D-deficient rickets has similar
manifestation with vitamin-D resistant rickets (X-linked dominant hereditary disorder), thus it is its phenocopy.
Modifications are characterized by the norm of reaction. It is the genetically determined limits of the trait varieties under the action of a certain external factor. The norm of
reaction is congenital as it is determined by a genotype. For instance, in same conditions
expression of a suntan differs between individuals. Thus, any character depends on two
factors: genotype and environment.
The contribution rate of a genotype and environmental influence in manifestation of the
trait may vary. Some features, such as AB0 blood groups depend only on a genotype. These
features have a zero norm of reaction. Other signs vary insignificantly and have a narrow
norm of reaction (like height of an organism). Signs that vary considerably have a wide norm
of reaction (body weight, number of leukocytes). Such signs are not qualitative but quantitative. They depend on a great number of genes and are not inherited as Mendelian traits.
Modifications are characterized by statistic terms as mean (average), variance, standard deviation. Normal distribution of such characters in population gives a classic “bell shaped” curve:
extremes are rare and mean is common.
8.2. Genetic variation. Recombination and mutation
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Genetic variation is a variation caused by change of hereditary information. There are
two types of genetic variation – recombination and mutations. Genetic variation is hereditable, it is important in evolution as provides material for natural selection.
Recombination
Recombination is a type of variation which is created by new combinations of existing
genetic information. It is the result of sexual reproduction and provided by the following
mechanisms:
8.2. Genetic variation. Recombination and mutation
a
a
a
A
B
a
b
A
b
B
b
B
b
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A
D
A
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Fig. 8.2. The random segregation of homologous chromosomes (of maternal and paternal origin) in anaphase I of meiosis. Diheterozygous organism (AaBb) produces four types of gametes
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1. Crossing-over in prophase I of meiosis (see Chapter 5.3).
2. The random segregation of homologous chromosomes (of maternal and paternal
origin) in anaphase I of meiosis (Fig. 8.2).
3. Random fusion of gametes during fertilization.
4. Random selection of a partner in marriage.
Multiple alleles also increase number of genotypes and phenotypes in population.
These mechanisms maintain genetic diversity and phenotypes variety in populations of
sexually reproducing organism and uniqueness of each individual.
By recombination can be explained difference between children of the same parents.
Birth of a child with autosomal recessive disorder (i.e., albinism) in healthy heterozygous
parents is also an example of recombination.
Mutations
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Mutations are the alterations of hereditary material, sudden and non-directed changes
of a genotype. Characteristics of mutations are opposite to that of modifications.
Mutations are inherited by the next generations, non-adaptive and occur suddenly in a
single individual. They are usually irreversible. The same factor may cause different mutations and, vice versa, the same mutations are sometimes caused by different factors.
By the influence on organism’s viability mutations can be neutral, harmful and seldom
useful. Harmful mutations cause hereditary disorders or are lethal.
Germ-line and somatic mutations
Depending on the type of mutant cells there are two types of mutations: germ-line
(germinal) and somatic.
Germ-line mutations take place in germ cells. These mutations are inheritable and so
are of great significance in heredity and the evolution. The mutation occurs during gametogenesis and affects only individual produced by the gamete carrying the mutation.
Chapter 8. Variation, its forms and manifestation
Fig. 8.3. Somatic mutations lead to mosaicism
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Somatic mutations take place in the somatic cells, so they are not inherited during the
sexual reproduction. Somatic mutations lead to mosaicism (Fig. 8.3). Mosaicism is the existence of two or more genetically different cell lines in one individual who develops from
a single zygote. If somatic mutation takes place during the embryonic development, an
organism usually has high proportion of mutant somatic cells and mosaicim manifests
phenotypically in newborns. The examples of mosaics are individuals with eyes of different
color. Chromosomal and single gene disorders also can be caused by somatic mutations
during embryogenesis. In case of mosaicism phenotypic manifestations of disease depend
on proportion of mutant cells. In adults somatic mutations often lead to tumors.
Genome, chromosomal and gene mutations
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Depending on the impairment of genetic material mutations are subdivided into three
groups:
`` genome mutations (numerical chromosomal aberrations);
`` chromosomal mutations (structural chromosomal aberrations);
`` gene mutations.
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1. Genome mutations are the changes in the chromosome number. There are three
types of genome mutations – polyploidy, aneuploidy and haploidy.
The basic haploid set of chromosomes is n, normal diploids have 2n chromosomes. Polyploidy is the state of having more than two complete haploid sets of chromosomes. There
are several types of polyploidy: triploidy (3n), tetraploidy (4n), etc. (5n, 6n, 7n, 8n). Polyploidy
is beneficial in plants and harmful in animals. In humans triploidy (3n = 69 chromosomes)
and tetraploidy (4n = 92) has been described. Triploidy is caused by non-disjunction of all
chromosomes in meiosis in one of the parents or fertilization of an egg by two sperms. Tetraploidy is explained by non-disjunction of chromatids in mitosis after fertilization. Polyploidy
is lethal mutation, in most cases it causes spontaneous abortions or stillbirth. If born alive
polyploid children have severe congenital defects incompatible with life.
8.2. Genetic variation. Recombination and mutation
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Aneuploidy is changing of the chromosome number unequal to the haploid set. There
are nullisomy, monosomy and polysomy. These mutations arise from non-disjunction of a
single pair of chromosome.
Nullisomy is the absence of a pair of homologous chromosomes (2n – 2). In humans it
is lethal.
Monosomy is the presence of only one chromosome from a pair of homologous chromosomes (2n – 1). In humans monosomy is lethal, except for Shereshevsky – Turner syndrome (monosomy of X chromosome, karyotype 45, X).
Polysomy is the presence of extra-chromosomes. In humans it includes trisomy (2n + 1,
47 chromosomes), tetrasomy (2n + 2, 48 chromosomes) and pentasomy (2n + 3, 49 chromosomes). The most well-known chromosomal disorders caused by autosomal trisomy
are: Patau syndrome (trisomy 13, karyotype 47, XX, + 13 or 47, XY, + 13); Edwards syndrome
(trisomy 18, karyotype 47, XX, + 18 or 47, XY, + 18); Down syndrome (trisomy 21, karyotype
47, XX, + 21 or 47, XY, + 21). Examples of polysomy in the sex chromosomes are: polysomy X
or super-female syndrome (trisomy X, karyotype 47, XXX; tetrasomy X, karyotype 48, XXXX;
pentasomy X, karyotype 49, XXXXX); polysomy Y or super-male syndrome (karyotypes 47,
XYY; 48, XYYY; 49, XYYYY); Klinefelter syndrome (karyotypes 47, XXY; 48 XXXY; 49, XXXXY).
Haploidy is the state of having the haploid (n) set of chromosomes in somatic cells. It
is observed in plants and some lower invertebrates. In the majority of animals, including
humans, haploidy is lethal.
2. Chromosomal mutations (structural chromosomal aberrations) are changes of the
chromosomal structure (Fig. 8.4). Main types of chromosomal aberrations are as follows:
`` Deletion – loss of a part of chromosome.
`` Duplication – doubling of a chromosomal segment.
B
C
D
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A
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A
B
C
D
E
A. Deletion
E
A
B
C
D
A
B
D
E
E
C
A
B
C
D
E
A
B
C
D
E
A
B
C
D
E
M
N
P
Fig. 8.4. Types of chromosomal aberrations
B. Duplication
C. Inversion
D. Translocation
A
B
C
D
D
A
B
E
D
C
A
B
C
D
P
M
N
E
E
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`` Inversion – reversed position of chromosomal segment (180° rotation).
`` Translocation – transfer of chromosomal segment from one chromosome to another.
In most of cases chromosomal aberrations result from failure of crossing over. Chromosomal aberrations lead to loss or coping of certain genes and thus result in chromosomal
disorders. The most famous example is “cat cry syndrome” caused by deletion of the short
arm of the 5th chromosome (karyotype 46, XX,del5p or 46,XY,del5p). Leukemia and some
other types of cancer also can be caused by chromosomal mutations. For example, more
than 90 % of patients with chronic myeloid leukemia have Philadelphia chromosome. It is
a result of reciprocal translocation (mutual exchange) between chromosomes 9 and 22.
Philadelphia chromosome contains most part of chromosome 22 and segment of long arm
of chromosome 9. This translocation creates on chromosome 22 excessively active hybrid
oncogene through fusions of parts of two genes located in the breakpoints. Stimulation of
cell division by this gene leads to leukemia.
3. Gene mutations are changes of gene (DNA) structure (Fig. 8.5).
ATG C T ATC C G C
ATG C T ATC C G C
Duplication
Insertion
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ATG C T ATC C G C
Substitution
ATG C T ATC C G C
AT G C T ATC C G C
Deletion
Inversion
ATG C A ATC C G C
ATG C T T ATC C G C
ATG C T C ATC C G C
ATG C ATC C G C
AT T C G ATC C G C
Fig. 8.5. Types of gene mutations
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There are: substitution of nucleotides, deletion of nucleotides, insertion of nucleotides,
inversion of DNA segments within or outside the gene. Gene mutations are caused by
modification of nitrogenous bases, errors of DNA replication, repair and recombination.
DNA mutations arrest protein biosynthesis or cause the synthesis of abnormal proteins.
Substitution of nucleotide causes replacement of amino acid (missense mutations) or formation of stop codon with synthesis of truncated protein (nonsense mutations). Sometimes substitution of nucleotide does not manifest as substitution of amino acid due to
degeneracy of genetic code (silence mutations). Deletion, duplication and insertion of nucleotides not multiple three cause frame shift mutation. All codons downstream the mutation are shifted, thus all amino acids after mutation site differ. If deletion or duplication is
multiple of three, it causes loss or gain of amino acids. Gene mutations result in single gene
disorders like hemophilia, sickle cell anemia, phenylketonuria, etc.
Some hereditary disorders can be caused by mutations of different genes (i.e., hemophilia A and B). They are termed as genocopies.
According to the phenotypic manifestation gene mutations are dominant or recessive.
8.2. Genetic variation. Recombination and mutation
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Spontaneous and induced mutations
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According to the factor that causes mutation they are divided into spontaneous and induced. Spontaneous mutations occur due to natural failure of cellular processes. Most of
spontaneous mutations are the result of replication errors. Other causes are nitrogenous
bases modifications, repair errors, unequal crossing over and other. At the level of gene the
mutation rate ranges from 10–4 to 10–7 per locus per cell division. Mutation rate is determined
by size of the gene and its organization. Certain nucleotide sequences (nucleotide repeats, CG
sequences and some other) are more prone to mutations and termed mutation hot spots. Mutation rates increase with age of the parents. Non-disjunction of chromosomes occurs more
often in females after 35 and single gene mutations increase with paternal age (after 40).
Induced mutations are induced artificially by mutagenic agents: physical, chemical
and biological ones. Ionizing radiation, ultraviolet radiation (UV) and high temperature
are examples of physical mutagens. Chemical mutagens are some pharmaceuticals (i.e.,
inhalation anesthetics), industrial chemicals (phenol, formaldehyde, methyl mercury,
nitrous oxide, pesticides, etc), colchicine. A lot of chemical mutagens have been identified in tobacco smoke including polycyclic carbohydrates such as benzopyrene. Chemical mutagens and UV rays cause mostly gene mutations. Colchicine affects disjunction
of chromosomes by destroying spindle fibers, thus leads to genome mutations. Ionizing
radiation can break down the phosphodiester bonds of double strand DNA that violates
integrity of chromosomes and leads to structural chromosomal aberrations. Ionizing
radiation can also promote chemical reactions that change DNA bases.
Biological mutagens are viruses, toxins of some bacteria and molds. Some human hormones (estrogen) demonstrate mutagenic activity also. Biological mutagens cause gene
mutations.
Mutagens, that cause mutations of genes involved in carcinogenesis (development of
tumors) are named carcinogenes.
Modifiers of mutagenic activity
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There are chemical substances that can enhance (co-mutagens) or decrease (antimutagens) activity of mutagens. Quite often they are present in our food.
Co-mutagens are the non-mutagenic agents that promote activity of mutagens. For example, co-mutagenic activity has one of the substances (harman or 1-methyl-β-carboline)
that is contained in tobacco tar and some food (broiled beef, broiled sardine and other).
Food additive E110 (Sunset yellow or Orange Yellow) that is widely used to give yellow
color for soft drinks is also co-mutagen.
Antimutagens are the agents that reduce the rate of induced and spontaneous mutations. Antimutagens can be classified into desmutagens and bio-antimutagens.
Desmutagens cause chemical modification of mutagens outside the cell, thus inactivating mutagens before they attack DNA. Examples are vegetable and cereal fibers that
absorb mutagens, cabbage and other vegetables with peroxydase activity.
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Bio-antimutagens influence intracellular processes. They increase fidelity of DNA replication, stimulate processes of DNA repair, activate enzymes of detoxification of different
mutagens. Powerful mutagens that are formed in cellular metabolic processes are freeoxygen radicals, so factors that inhibit free-radical reactions are also bio-antimutagens. Examples are carotenoids, vitamins C, B2, A, E, folic acid, and other.
Edible plants contain a lot of antimutagens. These are phenolic compounds of strawberries, raspberries, grapes, etc., citrus juice flavonoids, antimutagens of green and black
tee, carotenoids in apricot, carrots, yellow-red pepper, etc., curcumin in curcuma and so on.
Some compounds demonstrate both mutagenic and anti-mutagenic effects depending on their dosage. Examples are β-carotene and vitamin C (ascorbic acid) as they are able
to both scavenge and produce free radicals.
The law of homologous series of variation
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The law of homologous series of variation was formulated by Soviet geneticist
N. I. Vavilov in 1922 based on his studies of crop diversity. It states that genetically closely related species and genera are characterized by similar series of heritable variation with such
regularity that knowing the series of forms in one species we can predict the occurrence of
similar forms in other species. The more closely related the species, the more resemblance
they demonstrate. Nowadays the law is explained by similarity of genomes and mutations
in related species. For example, polydactyly, achondroplasia, albinism is observed in many
mammalian species, hemophilia is described in humans and dogs. It permits studies of human hereditary disorders on animal models.
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TASKS & QUESTIONS
`` Multiple Choice Questions (Choose one correct answer):
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1. Endemic goiter is common in some geographical regions as a result of low iodine in
diet. This is an example of:
A. Gene mutation
D. Structural chromosomal aberration
B. Recombination
E. Numerical chromosomal aberration
C. Modification
2. A patient has chromosomal disorder, caused by extra chromosome 21 in all cells.
What is the primary underlying defect of the disease?
A. Failure of meiotic division in parents
A. Failure of mitotic division during embryogenesis
B. Congenital infection
C. Teratogenic exposure
D. Gene mutation
8.2. Genetic variation. Recombination and mutation
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3. In human DNA adenine was replaced by cytosine. What type of mutation took place?
A. Gene mutation
E. Inversion
C. Polyploidy
B. Deletion
D. Translocation
4. Replacement of nucleotides in DNA results in:
A. Single gene disorders
C. Anomaly of autosomes
B. Chromosomal disorders
D. Anomaly of sex chromosomes
5. Two nucleotides in a DNA molecule were lost after X-ray irradiation. It is an example
of the following mutation:
A. Deletion
D. Translocation
E. Replication
B. Duplication
C. Inversion
6. Talidomid intake by a pregnant women in 50-s of XX century led to the birth of thousands of children with congenital defects of skeleton (absence of limbs). This congenital defect is a result of:
A. Modification
D. Triploidy
B. Trisomy
E. Gene mutation
C. Monosomy
7. A woman suffering from toxoplasmosis during pregnancy has a child with multiple
congenital defects. It is a result of:
A. Carcinogenesis
D. Chemical mutogenesis
E. Recombination
B. Teratogenesis
C. Biological mutogenesis
8. Sickle cell anemia is a common hereditary disease in South Africa. The main symptom of the disease is a crescent shape of RBC because of replacement of glutamin by
valin in hemoglobin β-chain. The underlying hereditary defect is:
D. Numerical chromosome mutation
A. Gene mutation
B. Structural chromosomal defect
E. Recombination
C. Crossing over
9. A blue-eyed girl has a brown spot in the right iris. It is a result of:
A. Genome mutation
D. Gene mutation
B. Chromosomal aberration
E. Germinal mutation
C. Somatic mutation
10. A patient with a mosaic type of the Down’s syndrome has about 50 % of cells with a
normal karyotype and 50 % of cells with trisomy 21. The disease is a result of mistake in:
A. First meiotic division
D. Amitosis
B. Second meiotic division
E. Endomitosis
C. Mitosis
11. After X-ray irradiation the segment of a DNA molecule turns around and joins in a
reverse direction. It is:
A. Inversion
D. Translocation
B. Deletion
E. Replication
C. Duplication
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12. There are three copies of the 13th chromosome in the karyotype of a child with multiple congenital defects. The type of the mutation is:
A. Polyploidy
D. Monosomy
B. Trisomy
E. Chromosomal aberration
C. Nullesomy
13. A chromosome has the following linear order of genes ABCDEHKTM. After the mutation there is the following order of genes CDEHKTM. The type of the mutation is:
A. Inversion
D. Translocation
E. Monosomy
B. Deletion
C. Duplication
14. Cytogenetic studying of an aborted embryo showed 45 chromosomes, one copy of
the 3rd chromosome. Type of the mutation is:
A. Chromosomal aberration
D. Polysomy
B. Point mutation
E. Monosomy
C. Nullisomy
15. Gene mutation changes:
A. Number of the chromosomes in the diploid set
D. Structure of a gene
B. Number of the haploid sets
C. Structure of a chromosome
E. Number of genes
16. Polyploidy is one of the genome mutations. It is:
A. Structural changes of the chromosomes
B. Duplication of a chromosome part
C. Increase in the entire haploid sets of chromosomes
D. Decrease in the entire haploid sets of chromosomes
E. Two extra chromosomes in the diploid set
17. Factors of different nature have a mutagenic effect. The chemical mutagen is:
A. Water
D. Colchicine
B. Ethyl alcohol
E. Sodium chloride
C. Nicotine
18. Factors of different nature have mutagenic effect. The biological mutagens are:
A. Helminths
C. Viruses
B. Bacteria
D. Toxoplasma
19 An example of the disease that develops as a result of gene mutation is:
A. Haemophilia
D. Down syndrome
B. Patau syndrome
E. Klinefelter syndrome
C. Cat cry syndrome
20. An aborted embryo has 69 chromosomes. It is an example of:
A. Haploidy
D. Monosomy
B. Polyploidy
E. Duplication
C. Trisomy
8.2. Genetic variation. Recombination and mutation
203
`` FILL IN THE BLANKS:
`` TRUE OR FALSE:
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1. Increasing of the number of erythrocytes and the amount of hemoglobin in people
who live high in the mountains is an example of ______________________ .
2. If similar changes occur in all individuals of the species in same conditions it describes
___________ character of ___________________.
3. Germ-line mutations are of great significance in evolution because _______________
and occur during ______________.
4. Triploidy is caused by ________________ of _____ chromosomes in meiosis in one of
the parents or fertilization of an egg by _______________.
5. More than 90% of patients with chronic myeloid leukemia have _____________
chromosome that is a result of _____________ translocation between chromosomes
9 and _____.
6. Mutagens that cause mutations of genes involved in development of tumors are
named ________________.
7. _____________ and __________ demonstrate both mutagenic and anti-mutagenic
effects depending on their __________.
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1. Vitamin D-deficient rickets has similar manifestation with vitamin-D resistant rickets,
thus it is a genocopy.
True
False
2. Random selection of a partner in marriage is one of the mechanisms of recombination.
True
False
3. In case of mosaicism phenotypic manifestations of disease depend on proportion of
mutant cells.
True
False
4. Polyploidy is beneficial in animals and harmful in plants.
True
False
5. Substitution of nucleotide can cause replacement of amino acid (nonsense mutations) or formation of stop codon (missense mutations).
True
False
6. Co-mutagens are the non-mutagenic agents that promote activity of mutagens.
True
False
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Chapter 9.
Methods of human genetics
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The basic regularities of heredity and variation are applicable to all living organisms
including human being. The branch of genetics which deals with heredity and variation in
men is termed as human genetics. One of the human genetics founders is Francis Galton,
who in 1869 published his book “Hereditary Genius: An Inquiry into Its Laws and Consequences” where he analyzed the role of heredity and nurture in inheritance of talent. He
laid the foundations of genealogic, twins and dermatoglyphic methods of genetics, applied statistical method to biological researches.
Medical genetics is one of the human genetics branches, which deals with hereditary
disorders, works out the methods of diagnosis, treatment and prevention of hereditary
pathology.
9.1. Peculiarities of human genetics.
Notion of hereditary disorders
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Human being is a very specific subject of genetic analysis. The main problems of human genetics are explained by ethical and biological factors. First of all, experimental cross
which is the main method of classical genetics is not applicable in humans. Small number
of descendants of one couple impedes statistic analysis of traits distribution. Alternation of
generations is slow and life span of investigator is comparable with that of a person, whose
genealogy is studied. Thus investigator can examine maximally three to four generations
of one family. Humans are characterized by more complex karyotype with great number of
linkage groups and more complex genotype than classical objects of genetic experiments.
All the reasons mentioned above led to elaboration of special methods of human genetics studying. Methods of human genetics include pedigree analysis, twins method,
cytogenetic method, dermatoglyphics, biochemical method, molecular-genetic method,
population-statistic method, hybridization of somatic cells etc.
These methods allowed to determine peculiarities of genetics of normal human characters and hereditary disorders.
Hereditary disorders are the diseases, caused by mutations.
There are three main groups of hereditary disorders:
`` Chromosomal disorders. These are disorders, caused by structural and numerical
chromosomal aberrations. Examples are Down syndrome, Edwards syndrome, Turner
syndrome. Cytogenetic methods are used for diagnosis of these disorders.
`` Single gene disorders. These are disorders, caused by gene mutations. Examples are
polydactyly, Marfan syndrome, sickle cell anemia, albinism, hemophilia. Biochemical
and molecular-genetic methods are used for diagnosis of single gene disorders.
9.2. Pedigree analysis (genealogic method)
205
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`` Multifactorial disorders (disorders with hereditary predisposition). These disorders develop as the result of summary effect of both genetic and environmental
factors. Examples are congenital heart defects, arterial hypertension, schizophrenia,
diabetes mellitus.
9.2. Pedigree analysis (genealogic method)
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Pedigree analysis is one of the first methods introduced in human genetics but is still
widely used in medical practice.
The pedigree method is based on composition of the pedigree (family tree) and its analysis. It makes possible:
`` to define a pattern of inheritance of certain character in a family;
`` to define genotype of a family members;
`` to estimate expressivity and penetrance of a gene;
`` to calculate genetic risk (to predict the probability of affected child birth).
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Pedigree analysis includes following stages:
1. Collection of information about the family.
It begins with proband. Proband – is a person whose pedigree should be composed. Frequently proband is a sick person with hereditary disease, rarely – healthy
person which has affected relatives. Proband is also named propositus if male or
proposita if female. Sisters and brothers of proband are termed siblings. Important
is information about all affected relatives, abortions, stillbirths, infant death, and infertility cases.
2. Pedigree charting.
There are international rules and symbols used for pedigree charting. The main
symbols are given in Fig. 9.1. We usually start charting of pedigree from proband and
his siblings. They are situated in the middle between families of mother and father.
All members of one generation are placed on one line and are numerated from left
to right. Generations are numbered at the left by Roman numerals from up to down.
Pedigree should not include less than 3–4 generations.
3. Pedigree analysis.
Pedigree analysis includes solving of several questions. The first question is
whether the trait was inherited or it is the result of a fresh mutation. Then we should
estimate the pattern of trait inheritance in the family. Knowing the pattern of inheritance allows to determine genotypes of family members and to calculate genetic risk.
The characteristics of pedigrees with main patterns of inheritance are following:
Autosomal-dominant. The feature is equally expressed in females and males, is present
in all generations and transmitted from affected parent to his child without skipping of
generations (vertical inheritance) as shown in Fig. 9.2.
Chapter 9. Methods of human genetics
Normal male
Affected male
Normal female
Affected female
Propositus
Proposita
Marriage
Consanguineous marriage
Heterozygous for
autosomal genes
Carrier of X-linked
recessive gene
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Parents with son and daughter
(in order of birth)
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Dead
Dizygotic twins
Sex unspecified
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Monozygotic twins
4 Number of children
1
2
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I
III
2
1
II
1
2
Abortion or stillbirth
of unspecified sex
3
Identification of person in
pedigree from the generation (Roman numerals)
and the order in the
generation
?
Female with children in
two marriages
Zygosity uncertain
Divorced
Illigitimacy
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Propositus
Fig. 9.1. Symbols used for pedigree charting
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1
2
Genotype of affected person is AA or Aa, and
I
of healthy person is aa. If one of the parents is
sick and heterozygous (Aa) and another one is
II
healthy (aa) risk to have an affected child equals
1
2
3
4
5
6
7
50 %. If both parents are sick and heterozygous III
(Aa) genetic risk is 75 % (see Chapter 7.1).
1
2
Examples of hereditary diseases with autosomal-dominant pattern of inheritance are achon- Fig. 9.2. Typical pedigree with autosomaldominant inheritance
droplasia, polydactyly, Marfan syndrome.
Autosomal-recessive. The feature is equally expressed in females and males. Only few
persons in the pedigree are affected; the parents of a sick child are healthy and often con-
9.2. Pedigree analysis (genealogic method)
207
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sanguineous; as a rule disease may be seen in several
I
siblings (horizontal inheritance) as shown in Fig. 9.3.
1
2
3
4
Genotype of affected person is aa, and of healthy
person is AA or Aa. Affected children are born in hetII
erozygous parents. Such parents have 25 % risk of a
1
2
sick child birth (see Chapter 7.1).
Examples are albinism, phenylketonouria, sickle III
1
2
3
4
5
6
cell anemia.
Recessive X-linked. Mainly males are affected. Par- Fig. 9.3. Typical pedigree with autosoents of affected child are usually healthy, but mother mal-recessive inheritance
is a carrier of a recessive gene. Affected males in the
pedigree are related trough their mothers (Fig. 9.4).
Genotype of affected male is XaY. Females are affected rarely (genotype XaXa). Genotype
of a healthy male is XAY. Healthy female has genotype XAXA or XAXa (healthy carrier). If mother is healthy carrier she transmits gene of the disease to half of her daughters and sons, but
only sons will be affected (genetic risk is 50 % for sons) (see Chapter 7.5).
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II
III
IV
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Carrier female
Affected male
Fig. 9.4. Typical pedigree with X-linked recessive inheritance
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Examples of the X-linked recessive diseases are hemophilia and red-green color-blindness.
Dominant X-linked. It shares some characteristics with autosomal-dominant pedigree:
affected child has affected parent (vertical inheritance), both genders are affected, but
there are twice as many affected females as affected males (Fig. 9.5).
Genotype of affected male is XAY and genotype of affected female is XAXA or XAXa. Genotype of healthy male is XaY and genotype of healthy female is XaXa.
If father is affected the disease is transmitted to all his daughters and never to sons (no
father-to-son transmission). If mother is affected, disorder is inherited by half of her daughters and sons (see Chapter 7.5).
Chapter 9. Methods of human genetics
I
II
II
III
III
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208
IV
IV
Fig. 9.5. Typical pedigree with X-linked dominant
inheritance
Fig. 9.6. Typical pedigree with Y-linked inheritance.
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Examples of X-linked dominant diseases are vitamin D-resistant rickets, hypoplasy of
teeth enamel (dark teeth enamel).
Y-linked. Only males are affected (Fig. 9.6). Sick boy has genotype XYa.
A disorder is transmitted from affected father to all his sons (see Chapter 7.5.). Example
of Y-linked trait is hypertrichosis of pinna.
Mitochondrial inheritance. All the offspring of affected mother are affected (Fig. 9.7).
Affected father does not transmit the disease to his children (see Chapter 3.2).
Leber optic atrophy is an example of mitochondrial disease.
So, pedigree analysis is used for determining a pattern of inheritance and calculation of
genetic risk in a family who come for medical-genetic counseling.
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I
1
2
II
1
2
3
4
4
5
5
6
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III
1
2
1
2
3
6
7
8
IV
3
Fig. 9.7. Typical pedigree with mitochondrial inheritance
4
5
6
9.3. Twins method of genetics
209
9.3. Twins method of genetics
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Twins method is based on comparing of traits in pairs of identical and fraternal twins. Method allows to determine the role of heredity and environment in manifestation of characters.
Monozygotic and dizygotic twins
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Humans normally bear only one offspring at a time. Multiple birth results from simultaneous intrauterine development of two (or more) embryos. The most common form of
multiple birth is twinning – the birth of a pair of children.
Monozygotic (MZ) or identical twins originate from a single conception (single egg
is fertilized by a single sperm) (Fig. 9.8). Single zygote starts to divide and at certain moment embryo divides into two (or more) parts developing into separate individuals. Very
late division after 14 days of embryonic development can result in conjoined or Siamese
twins. Monozygotic twinning occurs in approximately 1 in 300 birth in all populations and
predisposing factors to it are still poorly understood.
As identical twins develop from a single zygote they share same genotype so are said
to be natural clones. Traits that are controlled by genotype are same in identical twins (sex,
blood groups, eye color, etc). Differences between twins of a monozygotic pair would be
expected to be attributable to environmental factors.
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One egg is fertilized
Fig. 9.8. Development of monozygotic twins
Fertilized egg
Fertilized egg divides into two.
Two parts separate and develop independently
Two babies have identical
genotypes
210
Chapter 9. Methods of human genetics
Two chorions
Amnion
Amnion
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Two eggs are fertilized
simultaneously
Dizygotic (Dichorionic, Diamniotic)
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Fig. 9.9. Development of dizygotic twins
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Dizygotic (DZ) or fraternal twins originate from two separate conceptions. Two eggs
get matured simultaneously and each is fertilized by sperm (Fig. 9.9). Two zygotes develop
into two different individuals. Incidence of dizygotic twinning varies in different populations. It is minimal in Asia countries (1 in 500 deliveries) and maximal in Africa (approximately 1 in 22 in Nigeria). In North America and Europe it is about 1 in 100 to 1 in 120
deliveries. Chance of dizygotic twinning is associated with an increased level of folliclestimulating hormone that causes multiple ovulation. In turn it is influenced by season (increases in Europe in summer), use of ovulation inducing drugs, and is higher in tall and
heavy females at age of 30 to 40 years.
As fraternal twins develop from two different zygotes they have different genotypes,
sharing 50 % of genes. Traits that are controlled by genotype can be same or not. Differences
between twins of a dizygotic pair are explained by both genetic and environmental factors.
Zygocity of twins is determined by DNA testing, comparing of morphological characteristics, analysis of blood groups, HLA antigens and some other approaches.
Twins method of human genetics
Twins method is based on assumption that if a trait is influenced by genotype, then
within-pair resemblance for that trait should be higher in MZ twins than in DZ twins.
If the trait manifests in both twins, these twins are called concordant. If only one from
a pair of twins has the trait twins are called discordant.
9.3. Twins method of genetics
211
Twins analysis allows calculation of pair concordance coefficient (K) by the following
formula:
C
100 %
C+D
(9.1),
D
K=
where: C – is the number of concordant twin pairs;
D – is the number of discordant twin pairs.
KMZ – KDZ
100 %
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H=
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For single gene disorders concordance coefficient for MZ twins is 100 %, for DZ twins
concordance is 50 % if disorders is autosomal-dominant and 25 % if autosomal-recessive. If
monozygotic twins do not show full concordance for a given condition, it can be concluded that non-genetic factors also play a part in it. If disorder is multifactorial concordance
usually varies from 40 to 60 % for MZ and from 4 to 18 % for DZ twins. The more is role of
genotype in manifestation of multifactorial trait the more is the difference in concordance
between MZ and DZ twins (Table 9.1).
There are several methods to estimate contribution of heredity and environment into
manifestation of a trait. One of the first formulas for calculation of coefficients of heredity
(H) was proposed by K. J. Holzinger in the 30th years of XX century. It is based on comparing
the concordance of identical and fraternal twins.
100 % – KDZ
(9.2),
where: H is coefficient of heredity; KMZ % coefficient of concordance of monozygotic
twins; KDZ % – coefficient of concordance of dizygotic twins.
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Table 9.1. Concordance rates in MZ and DZ twins, coefficients of heredity
and environment influence for some human disorders (in units)
Disorders
Coefficients of concordance
Coefficient of
Heritability
MZ
DZ
heredity
environment
Height
0.94
0.44
0.11
0.89
1.0
IQ
0.76
0.51
0.49
0.51
0.50
0.95
0.49
0.10
0.90
0.92
0.69
0.10
0.35
0.65
0.70
Epilepsy
0.69
0.14
0.36
0.64
>1
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Dermatoglyphics
Schizophrenia
Tuberculosis
0.53
0.21
0.59
0.41
0.64
Endemic goiter
0.71
0.70
0.03
0.97
0.02
Tumors of the same type
0.59
0.24
0.46
0.54
0.70
Appendicitis
0.29
0.16
0.12
0.88
0.26
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Chapter 9. Methods of human genetics
Coefficient of environment influence (E) is calculated by formula:
E = 100 % – H
(9.3)
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If H is more than 70 %, the character is determined by genotype mainly. If H is 70–30 %–
the feature depends on both environment and genotype. If H is less than 30 %, environment is the main factor determining the feature.
Studying of concordance allows estimation of heritability of multifactorial traits. Heritability is the proportion of population variation in a trait that is due to genetic factors.
Simple formula is used for measuring of heritability:
h = 2 (CMZ – CDZ)
(9.4)
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If heritability exceed 1.0 it indicates that shared environmental factors must be operating
(see Table 9.1).
Thus, twins method helps to estimate the extent to which a trait is influenced by genotype. On the basis of twins studies group of multifactorial disorders has been recognized.
Nowadays molecular genetic testing of twins is used to study influence of different factors
on gene expression.
9.4. Cytogenetic methods. Chromosomal disorders.
Dermatoglyphics
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The cytogenetic methods are based on karyotype studying. They allow determining
number and structure of chromosomes. In medical genetics cytogenetic methods are used
for diagnosis of chromosomal disorders. The branch of human genetics that studies human
karyotype and chromosomal disorders is termed cytogenetics.
Cytogenetic methods include:
`` karyotyping;
`` molecular-cytogenetic methods;
`` detection of sex chromatin.
Karyotyping
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Karyotyping is studying of a karyotype (diploid set of the chromosomes) of the somatic
cells. It is the main cytogenetic method for diagnosis of chromosomal disorders. Characteristics of normal human karyotype and main principles of karyotyping are described in
Chapter 3.3.
The normal number of human chromosomes was first correctly recognized by two cytogeneticists Joe Hin Tjio and Albert Levan in 1956, who improved methodic of karyotyping. Their investigations stimulated rapid development of cytogenetics and discovery of
9.4. Cytogenetic methods. Chromosomal disorders. Dermatoglyphics
213
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chromosomal disorders. In 1959 French pediatrician and geneticist Jerome Lejeune explained Down syndrome as trisomy 21 (extra chromosome 21). The karyotypes in other
common chromosomal disorders were determined during the next decade. The further
development of cytogenetics was stimulated by introduction of differential chromosome
staining (Fig. 9.10). In 1968 Swedish cytologist and geneticist T. O. Caspersson showed
that quinacrine mustard (QM) and quinacrine hydrochloride (QH) react with nucleic acid
and produce specific banding patterns on chromosomes when viewed with UV light (Qbanding).
The banding patterns differ in every chromosome pair and thus provide a means by
which each pair can be distinguished from the other. The method also helps to examine
the chromosome structure and detect chromosomal aberration.
Nowadays the most popular technique of differential staining is Giemsa banding (Gbanding or G-staining). G-banding involves trypsin treatment of the metaphase plate followed by staining with Giemsa. Trypsin denaturates histones in transcriptionally active
DNA (euchromatin). Following Giemsa staining, these regions will appear as light bands. In
genetically inert and highly condensed chromatin regions (heterochromatin) histones are
protected from the trypsin and therefore stain darkly (see Fig. 9.10). In an average metaphase preparation, approximately 400 dark and light bands can be resolved in a haploid set
1
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2
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6
13
19
7
14
20
3
8
9
10
15
21
4
16
22
5
11
12
17
18
X
Y
Fig. 9.10. Karyotype of a patient with Turner syndrome. Differential chromosome staining (G-banding)
214
Chapter 9. Methods of human genetics
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of chromosomes. If cell division is arrested at prometaphase, when chromosomes are less
condensed, 550 to 850 bands can be resolved (high resolution karyotyping).
G-banding can be used to diagnose numerical chromosomal mutations and structural
chromosomal aberrations as translocations, deletions, duplications, inversions etc. However, the resolution of G-banding is limited for the identification of very small chromosomal
aberrations like microdeletions and complex chromosome abnormalities which involve
several chromosomes. In detection of such abnormalities molecular-cytogenetic methods
are helpful.
Molecular-cytogenetic methods
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Molecular-cytogenetic methods combine cytogenetic and molecular-genetic techniques. The basic method is FISH method (Fluorescent In Situ Hybridization). Fluorescently-labeled DNA-probes are used at this method (Fig. 9.11). DNA probe is fragment of DNA
(100–1000 nucleotides) with known sequence of nucleotide bases which is complementary to the DNA of studied chromosome region. Probes are labeled with fluorescent dyes
so can be detected by fluorescent microscopy.
The method is based on hybridization (attachment) of fluorescently labeled single
strand DNA probe with complementary region of chromosomal DNA. If DNA probe finds
complementary sequence it attaches there and spot of fluorescence at this region is observed. For example, in case of trisomy probe hybridizes in three locations and three spots
of fluorescence are visualized (Fig. 9.12). If there is a deletion or monosomy, just one spot
instead of two is visible. Probes for detection of all common chromosomal rearrangements
are available now. Multiple probes can be used to give each chromosome it unique color
(spectral karyotyping or SKY method).
Fluorescent
DNA-probe
A G C C G A
18
21
Mix with singlestranded DNA
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Single-stranded
CG
DNA
AT
A
T
AT
T
CG
C
C
C
G
G
A
T
GC
TA
AG
A
C
AT
T
G
T
C
C G Base pairing
T
C
G
G
indicates the
A
AG
site of interest
Fig. 9.11. Hybridization of fluorescently-labeled DNA-probes
21
21
Fig. 9.12. Demonstration of Down syndrome (trisomy 21) using FISH analysis
with probes specific for chromosome 18
(green) and chromosome 21 (red). The
three red signals confirm trisomy 21
9.4. Cytogenetic methods. Chromosomal disorders. Dermatoglyphics
215
Molecular-cytogenetic method permits to study both metaphase and interphase chromosomes. It is much more sensitive than karyotyping.
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Detection of sex chromatin
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Detection of Barr bodies. Canadian scientists Murray L. Barr and Ewart G. Bertram in 1949
discovered that the interphase nucleus of motor neuron in cat females but not in cat males
contain a small chromatin particle near the nucleolus. They hypothesized this chromatin
particle, later called sex chromatin or Barr body, is a highly condensed X-chromosome. Similar chromatin particles were observed in the cells of other mammalian females (Fig. 9.13).
In 1961 an English geneticist Mary Lyon proposed a clear explanation of sex chromatin.
Key elements of Lyon’s hypothesis are:
1. Each cell of a female mammal has only one active X-chromosome. Another one is
inactive, highly condensed and looks like a chromatin body in interphase nucleus.
2. The inactivation occurs early in the embryonic development. Now it is shown that
in humans inactivation process takes place within approximately 7 to 10 days after
fertilization.
3. The inactivated X-chromosome of a particular cell might be either of paternal and
maternal origin. Which chromosome become inactive is determined randomly. Once
an X-chromosome is inactivated in a cell, it will remain inactive in all the progeny of
that cell (Fig. 9.14).
4. Each female has two populations of cells: with active maternal or paternal X-chromosome, thus females are mosaics for X-chromosome activity.
The mechanism of chromosome inactivation is considered to be dosage compensation.
All female cells contain XX chromosomes
while male cells contain one X and one Y. Xchromosome is larger in size and has more
genes then the Y-chromosome. However,
due to inactivation of one X-chromosome
females produce X-linked gene products
in almost same quantity as males. Some
regions of X- and Y-chromosomes are homologous (pseudoautosomal regions). On
X-chromosome they are located on the tips
of short and long arms and escape inactivation. In total about 15 % of genes of condensed X-chromosome remain active.
Inactivation is controlled by X-inactivation center located on the long arm of
X–chromosome. It contains XIST gene (XInactivation Specific Transcript) for a long Fig. 9.13. Sex chromatin or Barr body in buccal
non-translated RNA that is transcribed only epithelium (shown with the arrow)
216
Chapter 9. Methods of human genetics
Barr body
XIST gene
mat
X-inactivation
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pat mat
Xi
or
Expression of maternal alleles
X
X
XIST gene
Barr body
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pat
X-inactivation
Xi
Expression of paternal alleles
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Fig. 9.14. Random inactivation of paternal (pat) and maternal (mat) X-chromosome in females
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on the inactive X-chromosome (see Fig. 9.14). This long RNA binds to X-chromosome from
which it was produced and initiates its inactivation. Inactivation includes deacetylation
and methylation of histones and methylation of DNA and is one of the examples of epigenetic control (see Chapter 4.5). Studying of X-chromosome inactivation allows to understand some important mechanisms of gene expression regulation in mammals.
Epithelial cells of buccal mucosa are taken usually for Barr bodies examination. The
scraping from the cheek is evenly spread on the slide, fixed in alcohol, stained with any of
the basic dyes and then studied under the microscope. In buccal mucosa cells Barr body
is found under the nuclear membrane (see Fig. 9.13). Barr bodies can also be detected in
segmented neutrophil leukocytes of the blood smear. In leukocytes they look like a small
drumstick projections of the nucleus (Fig. 9.15).
The studying of sex chromatin is used for:
`` Express diagnosis of chromosomal disorders with abnormal number of X-chromosomes. The number of sex chromatin bodies (n) is one less than number of X-chromosomes (n = X – 1) (see Fig. 9.15). So, a normal male has no Barr bodies and normal
female has one Barr body.
`` Express detection of the chromosomal sex in case of ambiguous genitalia in a patient. However, karyotyping is required in both cases.
`` In past method was used in forensic medicine for definition of sex of a victim or criminal. Nowadays it is replaced with molecular-genetic methods.
Detection of Y-chromatin. Genes of the Y-chromosome are not subjected to the dosage compensation. The Y-chromosome never inactivates even if present in more than one
copy. A large portion of the long arm of Y-chromosome is heterochromatic and quinacrine
lights it up more than other chromosomes. Extensively fluorescent region of Y-chromosome is termed Y-chromatin or F-body (F from fluorescent). It is detected in epithelial cells
of buccal mucosa and blood leukocytes as a brilliant spot 0.3–1.0 μm in size.
9.4. Cytogenetic methods. Chromosomal disorders. Dermatoglyphics
I
II
III
Normal male XY or female XO (Turner
syndrome)
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1X
Chromosome
Normal XX female or XXY male (Klinefelter syndrome)
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2X
Chromosomes
3X
Chromosomes
217
XXXX female (polysomy X) or XXXXY male
(Klinefelter syndrome)
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4X
Chromosomes
XXX female (trisomy X) or XXXY male
(Klinefelter syndrome)
Fig. 9.15. The number of X-chromosomes (I) and the number of Barr bodies in buccal mucosa cells (II) and
“drumsticks” in leukocytes nuclei (III)
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The number of Y-chromatin bodies is equal to the number of Y-chromosomes. Normal
male cell contains one F-body. Method can be used as express method for detection of Ychromosomes number.
Chromosomal disorders
Chromosomal disorders are disorders caused by numerical or structural chromosomal
mutations. They include disorders caused by mutations of autosomes and mutations of
sex chromosomes. Examples of most common chromosomal disorders of both groups are
given in Table 9.1.
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Chapter 9. Methods of human genetics
Table 9.1. Examples of chromosomal disorders
Disorders
Karyotype
Incidence in
the newborns
Clinical features
D
Disorders, caused by mutations of autosomes
47,XY,+21 or
47,XX,+21
1 : 700–800
Mental retardation, muscular hypotonia, microcephaly (small head), brachicephaly, flat face, nose
with flattened bridge, mongoloid slant of palpebral
fissures, epicanthic folds of the skin in the inner
angle of the eyes, large protruding tongue, single
transverse palmar crease (“simian crease”), congenital heart defects in 50 % of the patients, congenital
defects of digestive and other systems.
About 80 % of children with Down syndrome survive
to age 10 years and average life expectancy is 50 to
60 years
Edwards
syndrome
47,XY,+18 or
47,XX,+18
1 : 6000–8000
Microcephaly (small head) with prominent occiput
(dolihocephaly), small mouth and chin, typical
overlapping of fingers (index finger over the third,
fifth finger over the fourth), severe congenital
defects of inner organs. Most infants die during the
first months of life. Mental retardation in survivors
is profound
TR
IC
TE
Down syndrome
47,XY,+13 or
47,XX,+13
1 : 7800–
14000
Microcephaly, cleft lip (cheiloschisis) and cleft palate (palatoschisis), polydactyly, multiple congenital
defects of inner organs. Most infants die during the
first months of life. In the unusual event of longterm survival there is a profound mental retardation
Cri-du-chat
(cat cry or
5 p–) syndrome
46,ХХ, del 5p–
or
46,XY, del 5p–
1 : 45000–
50000
Unusual cat-like cry in neonates caused by underdevelopment of the larynx, microcephaly, round face,
anti-mongolian slant of palpebral fissures, mental
retardation. Many patients now survive to adulthood
but are mentally retarded
EC
Patau syndrome
Disorders caused by mutations of sex chromosomes
R
Klinefelter
syndrome
47, XXY (one
Barr body)
In rare cases
48, XXXY (2
Barr bodies)
or 49, XXXXY
(3 Barr bodies)
Super male 47, XYY
(polysomy Y
syndrome)
1 : 800–1000
male newborns
Only males are affected. Patients are taller than
average with disproportionally long arms and legs,
narrow shoulders and wide hips, poor musculature,
infertility. Enlargement of breast glands (gynecomastia) and increased risk of the breast cancer in adults.
Intelligence is usually normal or mild learning difficulties. Degree of mental deficiency and physical abnormality increases with each additional X-chromosome
1 : 1000 male
newborns
Only males are affected. Patients are tall, sometimes with emotional immaturity, hyperactivity,
impulsive behavior and learning disabilities.
9.4. Cytogenetic methods. Chromosomal disorders. Dermatoglyphics
Disorders
Karyotype
Incidence in
the newborns
219
Clinical features
45,X
(no Barr
bodies)
1 : 3000–5000
female newborns
Only females are affected. Patients have short stature, “webbed neck” and congenital heart defects.
They do not develop secondary sexual characteristics
(poor development of breast), have primary amenorrhea and infertility. Intelligence is usually normal.
Super female (polysomy X
syndrome)
47,XXX (two
Barr bodies)
1 : 1000 – female newborns
Only females are affected. Most of patients have no
physical abnormalities and are fertile. Sometimes
irregular menses, infertility and mild mental retardation are observed. Degree of mental deficiency
increases with each additional X-chromosome.
Patients with pentasomy (49, XXXXX) have congenital defects.
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In rare cases
48, XXXX (3
Barr bodies)
or 49, XXXXX
(4 Barr bodies)
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Turner
(ShereshevskyTurner)
syndrome
TR
Disorders caused by numerical or structural aberrations of autosomes usually manifest
at birth by multiple congenital defects and usually lead to early death. If disorders are compatible with life, patients are mentally retarded. Main methods of diagnosis of these disorders are karyotyping and FISH-method.
Disorders caused by numerical or structural aberrations of sex chromosomes are less
severe. Patients usually have normal intelligence, normal life span and are successfully socially adapted. The main manifestations might be poorly developed secondary sexual characteristics and infertility. Quite often disorders are recognized at puberty. As an addition for
karyotyping and FISH method detection of sex-chromatin can be used.
EC
Dermatoglyphics
R
Dermatoglyphics (from Greek derma – skin and glyphe – carve) is the study of patterns
of the ridged skin of the fingers (dactyloscopy), palms (palmoscopy) and soles (plantoscopy). In fact it is a scientific study of fingerprints.
Skin ridges are formed on the third to fourth month of embryogenesis and remain same
throughout life. The ridge pattern is an individual characteristic of each person and there
are no two persons with exactly similar dermatoglyphic patterns. Formation of skin ridges
is mostly controlled by genotype of a person and patients with hereditary disorders can
have unusual ridge patterns. So, method is used in diagnosis of hereditary disorders, especially chromosomal.
The most important dermatoglyphic features of hereditary disorders are:
`` Ridges pattern on the fingers. The main patterns are arches, loops and whorls
(Fig. 9.16). The arches are the least frequent pattern in healthy individuals but meet
often in patients with chromosomal disorders.
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Chapter 9. Methods of human genetics
B
C
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D
A
Fig. 9.16. Ridges pattern on the fingers: A – whorl, B – loop, C – arch
Normal
transverse
creases
Simian crease
TR
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`` Palms creases pattern. Healthy individuals
usually have three main palmar creases:
distal transverse, proximal transverse and
thenar crease. Patients with hereditary
disorders often have a single transverse
crease known as simian crease (Fig. 9.17).
`` Skin creases on the sole of the foot. Deep
longitudinal or transverse creases are the
features of some chromosomal disorders.
Dermatoglyphics is also used in detection of
twins zygocity (monozygotic twins have not less
than seven identical fingerprints) and in forensic
medicine for identification of a person.
Thenar crease
Fig. 9.17. Palms creases pattern
EC
9.5. Single gene disorders.
Biochemical method of medical genetics. DNA diagnosis
Single gene disorders
R
Single gene disorders are disorders, caused by mutation of a single gene. More than
3000 single gene disorders have been described up to date. They are inherited like monogenic traits and demonstrate autosomal-dominant, autosomal-recessive or X-linked modes
of inheritance. The disorders can manifest as congenital defects, inborn errors of metabolism or combined states. Examples of some single gene disorders with different patterns of
inheritance are given in Table 9.2.
Biochemical methods and DNA testing are used for laboratory diagnosis of single gene
disorders.
9.5. Single gene disorders. Biochemical method of medical genetics. DNA diagnosis
221
Table 9.2. Examples of single gene disorders with different patterns of inheritance
Population rate
in Europe
Location
of gene
Main manifestations
Autosomal-dominant disorders
4p
Marfan syndrome
1 : 10000–
1 : 15000
15q
Syndactyly
(different types)
1 : 2500–
1 : 3000
2q, 6q
Polydactyly
(different types)
1 : 630–1 : 3300
7p, 7q,
19 p
Dwarfism, shortness of proximal parts of
extremities, macrocephaly (large head),
prominent lumber lordosis. Intelligence
and life span are normal
TE
1 : 100000
High stature, long and slander extremities,
arachnodactyly (long and slander or “spider” fingers), laxness of joints, deformation of chest, scoliosis, shortsightedness,
dislocation of lenses, aortic aneurysm (local
widening), cardiac valves defect
Any degree of webbing or fusion of fingers
or toes, involving soft parts only or including bones
IC
Achondroplasy
D
Single gene
disoder
The presence of more than five digits on
either hand or foot
TR
Autosomal-recessive disorders
Congenital absence of one or both eyes
1 : 42000–
1 : 250 000
3p, 14q,
18q and
other
Phenylketonuria
1 : 8000–
1 : 6000
12q
Albinism
1 : 39000
9p, 11q,
15q,
1 : 35000–
1 : 150000
9q
Disorder manifests after the newborn starts
to feed on milk. Clinical features include
hepatomegaly (enlargement of liver),
jaundice, cataract, delayed psychomotor
development. Galactose is excreted with
urine. Early administration of galactosefree diet prevents mental retardation
1 : 3600 among
Eastern European (Ashkenazi)
jews; 1 : 360 000
in other populations
15q
Psychomotor deterioration from the 4–5th
month of life, cherry-red spot in the retina
of eye. Blindness, deafness, idiocy. Death
on the 3–4th year of life. Deficiency of
enzyme hexoaminidase A in blood serum
and tissues
EC
Anophthalmia
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Galactosemia – disturbance of monosaccharide galactose
(component of milk
sugar – lactose) metabolism
Tay-Sachs disease
(GM2 gangliosidosis)
Lysosomal storage
disease caused by accumulation of gangliosides (type of lipids)
Delayed psychomotor development in children, mental retardation, seizures, “mousy
odor” of sweat and urine, depigmentation
of skin, hair and iris (child fades)
Skin and hair are depigmented, eyes are
pink or light-blue. Typical light sensitivity
and decreased visual acuity
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Chapter 9. Methods of human genetics
Location
of gene
Cystic fibrosis (mucoviscidosis) – disturbance of chloride
transport, caused by
dysfunction of transmembrane transport
protein
1 : 1600–
1 : 3000
7q
Congenital hypothyrosis – group of the
diseases with different
etiology
1 : 3500–
1 : 4000
Main manifestations
Accumulation of excessively viscid mucous
secretions leads to blockage of the airways
and of the pancreatic ducts. It causes recurrent pneumonitis and pulmonary insufficiency. Poor secretion of pancreatic enzymes
leads to malabsorbtion and an increase of
the fat content in stool. Level of sodium and
chlorides in sweat is elevated (“salty sweat”)
TE
D
Population rate
in Europe
Low level of thyroid gland hormones
causes delayed psychomotor development,
specific appearance (short neck, saddle-like
nose, edema of eyelids, large tongue, dry
hair), coarse cry, bradycardia, hypothermia.
Starting in time, replacement treatment
with hormone thyroxin is successful
IC
Single gene
disoder
X-linked recessive disorders
1 : 2500 males
Xq
Prolonged bleeding after trauma, hemorrhages into elbow, knee, ankle joints (hemarthrosis), internal hemorrhages. Activity
of clotting factor VIII is decreased
Red-green color blindness (daltonism)
About 8 % of
males and 0.6 %
females
Xq
Affected persons do not distinguish red and
green colors
TR
Hemophilia A – deficiency of blood clotting factor VIII
X-linked dominant disorders
EC
Vitamin D resistant
rickets (phosphate
diabetes)
Xp
Decreased reabsorption of phosphates in
kidney leads to the low level of P with normal
level of Ca in blood. Deformations of bones
typical for rickets appear on the 1–2 year of life
Biochemical methods
R
Biochemical genetics is the combination of genetics and biochemistry and deals with the
genetic control of metabolic pathways. Mutations of genes that control metabolic pathways
cause a group of single gene disorders termed as inborn errors of metabolism. Most of them
are autosomal-recessive or X-linked recessive disorders. More than 700 different inborn errors
of metabolism have been described to date. They can be divided into groups according to
the substances which are not metabolized or transported normally. Examples are:
`` Disturbance in amino acids metabolism (phenylketonuria, albinism).
`` Disturbance in carbohydrates metabolism (galactosemia, fructosuria).
`` Disturbance in lipids metabolism (familial hypercholesterolemia, Tay-Sachs disease).
`` Disturbance in hormone synthesis (congenital hypothyrosis).
`` Disturbance in transport of chlorides (cystic fibrosis).
9.5. Single gene disorders. Biochemical method of medical genetics. DNA diagnosis
223
Non-functional enzyme, abnormal
biochemical processes
Inborn errors of metabolism
TE
Gene mutation
D
In humans various metabolic processes usually include several consequent steps. Each
step is provided by a certain enzyme, which synthesis is, in turn, controlled by a gene.
Mutation of the gene causes defect in enzyme activity and either the alteration in metabolic process or its complete blockage (Fig. 9.18), that can be detected by biochemical
methods.
Fig. 9.18. Principle of inborn errors of metabolism development
IC
In most of the inborn errors of metabolism, problems arise due to (Fig 9.19):
`` accumulation of non-metabolized substrates of enzymatic reaction which quite often are toxic in excessive amount or interfere with normal function.
`` production of abnormal metabolites of these accumulated substrates.
`` reduced ability to synthesize normal products of reaction.
The error in the metabolic pathway is ultimately expressed in the form of the disease.
Metabolic block
A
TR
Accumulation of substrate and
its abnormal metabolites
B
Reduction of normal
product level
Fig. 9.19. General scheme of metabolic failure in inborn errors of metabolism
R
EC
Basing on the scheme of metabolic failure for diagnosis of the disease biochemically
can be detected:
`` high level of substrate of reaction (upstream of the metabolic block);
`` low level of normal product of reaction (downstream of the metabolic block);
`` accumulation of abnormal metabolites;
`` absence or reduction of the enzyme activity.
Many inborn errors of metabolism have similar clinical features and differential diagnosis is based on biochemical methods. In this case biochemical diagnosis often includes
two steps:
1. Selective screening tests – selection of the cases of inborn errors of metabolism
among the sick persons. It is done if an affected person has general manifestation
of inborn errors of metabolism. Usually it is done with the sample of urine. These
are simple qualitative biochemical tests with visual detection (change in color of
urine most often).
2. Verification of diagnosis. It is done by precise quantitative tests. We can study enzyme activity or specific metabolic products in urine, sweat, blood plasma, cerebrospinal fluid, culture of the cells.
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Chapter 9. Methods of human genetics
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A classic example of an inborn error of metabolism is phenylketonuria. This disorder
develops due to the mutation of gene coding phenylalanine-4-hydroxylase enzyme, whose
function is converting of phenylalanine into tyrosine. Tyrosine in turn is a precursor for
synthesis of melanine, thyroxine and some other substances.
Due to the deficiency of this enzyme the metabolism of phenylalanine is altered. Phenylalanine accumulates in blood plasma and is converted into abnormal metabolites (phenylpyruvic, phenylacetic acids and other) instead of converting into tyrosine. High level of
plasma phenylalanine and its abnormal metabolites damages the brain and leads to severe
mental retardation. Abnormal metabolites are excreted with urine. Excretion of phenylacetic acid with urine and sweat causes “mousy” odor of sick child. The enzyme block leads
to a deficiency of tyrosine with a consequent reduction in melanin synthesis. Affected children therefore often have blond hair and blue eyes.
Biochemically we can detect:
1. Excretion of phenylpyruvic acid with urine. It is detected by adding 10 % FeCl3 (ferric chloride) to urine sample that is known as Folling’s test (in honor of Norwegian
physician and biochemist Ivar Folling who first described phenylketonuria and detected phenylpyruvic acid in urine of affected child). In presence of phenylpyruvic
acid green color appears. This test can be used as selective screening test.
2. High level of phenylalanine in blood. This test should be used for verification of diagnosis.
Treatment of phenylketonuria is based on maintaining of normal blood phenylalanine
levels by restricting dietary intake of phenylalanine containing food. Early diagnosis and
early treatment prevents mental retardation of sick child.
With the aim of early diagnosis of the phenylketonuria mass newborn screening is performed.
R
EC
Mass newborn screening is biochemical examination of all newborns with the aim of
early diagnosis of the inborn errors of metabolism. It is done for preclinical detection of
the disease, early treatment and prevention or reduction of the clinical manifestations.
Screening programs are used for those disorders that are common in population and can
be successfully treated or prevented if detected in time, but without treatment have serious effect on health. Other important factors are availability of reliable diagnostic tests and
medical genetic counseling.
Examples of screening programs in Ukraine are screening for phenylketonuria and congenital hypothyrosis (treatment is replacement of thyroxin).
Recent progress in technology has provided the opportunity to study not only the level of
gene product by biochemical methods but directly the gene by molecular-genetic methods.
DNA diagnosis (molecular-genetic methods)
DNA diagnosis is the verification of the diagnosis of the disease by studying of the gene.
DNA diagnosis is applicable for
9.5. Single gene disorders. Biochemical method of medical genetics. DNA diagnosis
225
TE
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`` diagnosis of single gene disorders;
`` diagnosis of infectious disorders (identification of DNA or RNA of the agent);
`` detection of predisposition to multifactorial disorders, including cancer;
Molecular-genetic methods are also used in forensic science (DNA fingerprinting and
DNA profiling) for identification of a person and paternity dispute cases; in evolutionary
genetics, paleontology and anthropology.
Examples of laboratory techniques for DNA analysis are polymerase chain reaction, nucleic acid hybridization techniques and DNA sequencing.
R
EC
TR
IC
Polymerase chain reaction. Molecular genetic analysis became widely available for
practical medicine since 1983 when Kary Mullis proposed polymerase chain reaction (PCR)
for artificial coping of DNA fragments.
Polymerase chain reaction (PCR) is an approach to making million copies (amplification)
of a short specific DNA sequence for further analysis. It copies the process of DNA replication and follows similar rules (see Chapter 4.2).
The PCR process requires four main components (Fig. 9.20A):
1. Template DNA. This contains the DNA sequence to be amplified. Any nucleated cell
of an individual can be used for DNA extraction. In medical genetics leukocytes or
buccal epithelial cells are usually used. The quantity of genomic DNA can be very
small (even one copy) as PCR is very sensitive.
2. Pair of oligonucleotide primers. These are short single-strand DNA molecules (typically 20 bases) of known sequence obtained by chemical synthesis. Primers should
be complementary to DNA sequence on either strands of the target DNA fragment
and bound it. They are required for initiation of DNA replication, so if primer does not
find complementary sequence synthesis of DNA does not occur.
3. DNA polymerase (Taq-polymerase). It is a heat-resistant form of the enzyme initially
derived from bacteria Thermus aquaticus. The bacteria inhabit hot springs and thrive
at temperature about 70 °C, so have thermally stable enzymes.
4. Deoxyribonucleotide triphosphates (dATP, dGTP, dCTP, dTTP).
All components are mixed in Mix Buffer for the amplification. Amplification of target
DNA sequence occurs in a specific device thermal cycler (amplificator). It involves the repeated cycles of DNA synthesis.
Each cycle includes three stages (Fig. 9.20B):
`` Denaturation. Mixture is heated to 90–95 °C. At this temperature DNA molecules
separate into single strands.
`` Annealing. The mixture is cooled to a temperature (40–60 °C) that allows binding of
the primers to the complementary sequence of a single-strand DNA.
`` Extension (elongation). The mixture is heated to 70–75 °C which is optimal for Taqpolymerase. In the presence of a large number of free DNA nucleotides, a new DNA
strand is synthesized, extending from the primer sequences.
The heating-cooling cycle is then repeated 30–35 times. Each newly produced fragment of target DNA acts as a template for synthesis of the new copies in the next cycle, so
226
Chapter 9. Methods of human genetics
A. PCR components
B. PCR process
Taq polymerase
Primers
Nucleotides
Mix Buffer
PCR Tube
55 °C
Primers bind to template DNA strands
2. Annealing
72 °C
Taq polymerase synthesizes
new DNA strands
3. Extension
IC
PCR cycle
1. Denaturation
TE
DNA Sample
D
Heat to 95 °C
DNA strands separate
Two new
DNA molecules
Thermal Cycler
TR
Fig. 9.20. PCR components (A) and stages of PCR process (B)
R
EC
primer-bounded DNA products are amplified geometrically. The number of copies doubles
in each cycle producing millions of fragments of the original DNA (i.e., 230 from a single
DNA molecule in 30 cycles) in only a few hours.
Once DNA is amplified, it can be analyzed in a variety of ways. The simplest way is size
analysis of PCR products by gel electrophoresis. Electrophoresis is a technique which measures the rate of migration of charged molecules in a gel medium when an electrical field
is applied. Nucleic acid is negatively charged molecule and migrates towards the positive
electrode (anode). Position of nucleic acid (distance from the start point of migration) in
agarose or polyacrylamide gel depends on the size and conformation of the DNA fragment. Small molecules migrate faster and are nearer to anode than long ones in a given period of time. Position of DNA fragments in gel is visualized by staining with fluorescent dye
ethidium bromide. It joins DNA and gives orange color bands in UV illumination. Size of the
fragments is typically determined by comparison with DNA fragments of known length.
Modern modification of PCR known as real-time PCR combines amplification with automated DNA analysis, so results sometimes are available within one hour of a sample being taken.
The Nobel Prize in Chemistry 1993 was awarded "for contributions to the developments of methods
within DNA-based chemistry" to Kary B. Mullis (one half ) "for his invention of the polymerase chain
reaction (PCR) method".
9.6. Population statistic method
227
TR
IC
TE
D
Nucleic acid hybridization techniques are based on use of nucleic acid probes and nucleic acid hybridization. Hybridization is complementary pairing of DNA from two different
sources. Nucleic acid probes are single strand small DNA or RNA fragments (oligonucleotides) of known sequences labeled either with radioactive isotopes or signal fluorescent tag
(fluorescein or rhodamine). DNA probes can be obtained from genomic DNA or artificially
produced. Hybridization involves mixing of patient’s DNA and DNA probe that have been
denatured to make them single strand. The labeled probes hybridize (undergo complementary base pairing) only with the complementary sequences, so they identify such sequences
in tested DNA or RNA. Presence of radioactive labels is visualized by placing X-ray film; fluorescent labels are visualized by fluorescence. Modern approach based on the usage of DNA
probes is application of DNA microarrays (also known as DNA chips). To make a DNA microarray, oligonucleotides are robotically placed on a small glass slide (1 cm2). A single slide
contains thousands of different oligonucleotides with normal and mutant DNA sequences.
Fluorescently labeled DNA from a person is hybridized with the oligonucleotides on the
slide to determine whether the DNA hybridizes with the normal or with the mutation-containing oligonucleotides. The pattern of hybridization signals is analyzed by a computer.
DNA sequencing methods are based on direct determination of the nucleotides order
in DNA molecule. DNA sequencing permits detection of any gene mutation or detection
of several mutations simultaneously. Modern sequencing techniques are automated and
cost less than 1000 $ for whole genome analysis. In future it may be possible to analyze
the entire genome of a person and determine predisposition to multifactorial disorders,
heterozygous carrying of single gene disorders and peculiarities of drug metabolism. It will
allow medicine to be predictive, personalized and preventive.
9.6. Population statistic method
R
EC
Population genetics is the study of allele frequencies in populations and the forces
which maintain or change the frequencies of particular alleles and genotypes in populations. Population statistic method of medical genetics is based on studying frequencies
of pathologic genes (dominant or recessive) and genotypes (homo- and heterozygous) in
population which is very important for the prophylaxis of hereditary diseases.
Population is a group of individuals of one species who inhabit a certain territory for a
long period of time and are capable of interbreeding. First human populations have been
separated from each other by natural geographic barriers. Later this factor has been somewhat replaced by social, national and religious concerns. Thus modern human populations
had appeared. Human population is a group of people inhabiting a certain territory and
marrying each other. Examples are city population, country population, community population, etc.
Natural population is composed of many individuals; each one with a unique combination of genes (alleles) in the genotype. The total number of all alleles in a population
is termed as gene pool. Each allele occurs in the population’s gene pool with a certain
228
Chapter 9. Methods of human genetics
Frequency of allele A =
number of copies of allele A
total number of alleles (A + a)
D
frequency which can be expressed as a fraction of a unit or percentage. For instance, if
half the alleles is A and half is a, each allele has an allele frequency of 50 %, or 0.5. In general, if there are two alleles of a certain gene in a population (A and a) we can define allele
frequency as:
(9.4),
TE
Genotypes frequencies (AA, Aa, aa) can be also calculated in the population.
Genetic processes in large populations. Hardy-Weinberg law
TR
IC
In 1908 an English mathematician G. H. Hardy and a German physician W. Weinberg defined independently the law describing genetic processes in large populations
(Hardy-Weinberg principle or the law of genetic equilibrium). The law states that
“gene frequencies in a population remain constant from generation to generation, if no evolutionary factors such as migration, mutation, selection and drift
are operating”.
G. H. Hardy and W. Weinberg provided a simple algebraic formula to calculate expected
gene (allele) and genotype frequencies in population. If we represent the frequency of allele A in the population as p and the frequency of allele a as q, then p + q = 1. If the two
alleles in the population are in the proportions p and q, the sperms and eggs contain them
in the same proportions. If mating is random the various combinations of gametes in F1
generation can be represented as shown in Fig. 9.21.
♂
A (p)
a (q)
A (p)
AA (p2)
Aa (pq)
a (q)
Aa (pq)
aa (q2)
EC
♀
Fig. 9.21. Frequencies of gametes and of genotypes in F1 generation
R
The frequency of genotypes in offspring from this mating is:
p2 (AA) + 2 pq (Aa) + q2 (aa) = 1 (100 %)
or
(p + q)2 = p2 + 2pq + q2 = 1 (100 %)
For instance, parental population consists of heterozygous organisms Aa, thus frequencies of dominant (A) and recessive (a) alleles in this population are equal: p = q = 0.5. Crossing of the individuals with Aa genotypes gives the following results:
9.6. Population statistic method
P:
G:
F:
1
229
♀Aa × ♂Aa
A,a
A,a
AA, Aa, Aa, aa
D
Frequency of F1 genotypes is:
(0.5A + 0.5a) × (0.5A + 0.5a) = 0.25AA + 0.5Aa + 0.25aa.
TE
Actually, 0.25 organisms with AA genotype produce 0.25 gametes with gene A; 0.5 Aa
organisms produce 0.25 ga­metes with gene A and 0.25 gametes with gene a; 0.25 organisms with aa genotype give 0.25 gametes with gene a.
Thus the proportions of the various genotypes are the same in the first filial generation
as they were in the parental generation (Table 9.3).
IC
Table 9.3. Proportions of genotypes and alleles in F1 generation
Proportions of genotypes
Proportions of alleles
0.25 AA
0.25 A
0.25 a
TR
0.5 Aa
0.25 A
0.25 aa
0.25 a
Frequency of alleles in F1 generation
0.5 A
0.5 a
R
EC
F1 generation will produce sperms and eggs in proportion 0.5A and 0.5a, so frequency
of F2 genotypes will be: (0.5A + 0.5a) × (0.5A + 0.5a) = 0.25AA + 0.5Aa + 0.25aa. Frequency
of alleles will be 0.5A and 0.5a. We could continue such calculations for next generations,
but the result would always be the same: the relative proportion of the genotypes would
remain constant from one generation to another, and would occur in the proportions p2:
2pq : q2.
Hardy-Weinberg law relates to population without an influence of evolutionary factors
changing gene frequencies. Such mathematical model of population is termed as ideal
population. The characteristic features of an ideal population are as follows:
`` Large population (indefinite number of individuals).
`` Random mating (panmixis). It means that the particular genes carried by an indivi­
dual do not influence his choice of mate.
`` Absence of natural selection. Selection forces operate by increasing or decreasing
reproductive fitness of the individuals with certain genotypes. It will change proportion of these genotypes and alleles.
`` Absence of migrations which can introduce new alleles into a population or cause
exchange of alleles between different populations.
`` Absence of mutations. High rate of mutations of a particular gene increase the proportion of mutant alleles in a population.
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Chapter 9. Methods of human genetics
EC
TR
IC
TE
D
It has been found that the genetic processes in large human populations are also close
to ideal one. So the Hardy-Weinberg’s law is applicable to genetic studies of the human
populations including frequency of mutant alleles causing hereditary disorders. Natural
selection acts against disease genotype (disease can cause death or reduce fertility of an
affected individual), but new mutations of the gene occur in each generation and proportions of alleles and genotypes remain constant from generation to generation. Constant
frequency of recessive disorders in population is also maintained by heterozygous carriers.
The practical purposes of Hardy-Weinberg’s law in human genetics are:
1. Calculation of heterozygous carriers frequency. It is especially important for recessive
disease causing alleles. For example, about 1/2500 Caucasian humans are born with
cystic fibrosis (autosomal-recessive disorder). They are homozygous for nonfunctional
alleles of a gene for a chloride transport protein involved in mucous secretion. Without this function, mucus is very viscous and blocks airways and pancreatic ducts that
explain chronic pneumonitis and malabsorption. As the frequency of homozygotes
(q2) is 1/2500 or 0.0004, q (square root) equals 0.02 (1/50). Frequency of the dominant
gene (p) is 1 – q = 1 – 0.02 = 0.98. The frequency of heterozygous carriers for cystic
fibrosis is 2pq = 2 × (1 – 0.02) × 0.02 = 2 × 0.98 × 0.02 = 0.392 (approximately 1/25).
In other words one in 25 individuals in a population is a carrier of this recessive allele.
Albinisms frequency in Europe is 1/20000, frequency of heterozygous persons is
1/70 that can be calculated in same way.
Using Hardy-Weinberg principle we calculate the frequencies of all alleles and
genotypes.
2. It allows defining quantity of alleles controlling the trait. For instance, a German
mathematician Felix Bernstein has found that AB0 blood groups are specified by
a series of multiple alleles using the Hardy-Weinberg principle (modified formula for
multiple alleles).
3. It allows studying intensity of mutation processes by comparing real and expected
rates.
4. It is used to determine the relation links between populations. For instance, Gypsy
population has the same genetic makeup as the population of North India and that
allows us to suppose that they originate from this region.
Factors that can disturb Hardy-Weinberg equilibrium
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If a population is found not to be in the Hardy-Weinberg equilibrium, there are several
possible causes:
`` Selection. It affects (increases or decreases) the viability or fertility of individuals or
gametes of particular genotypes in the population. The example is sickle-cell anemia
in which heterozygotes are relatively immune to infection with Plasmodium falciparum (agent of Falciparum or malignant malaria). In the regions where this form of
malaria is endemic the proportion of heterozygous individuals is increased. It is considered that accumulation of recessive disorders in large populations is caused by
9.6. Population statistic method
increased biological fitness in heterozygotes comparing with healthy homozygotes.
Examples of recessive alleles that are maintained by natural selection are given in
Table 9.4.
Non-random mating (assortative and consanguineous mating). Assortative mating
is a tendency to choose partners with similar characteristics like intelligence, racial
origin or hereditary disorders (deafness, dwarfism and other). Such mating increases
frequency of homozygotes. Similar effect is observed in consanguineous marriage
(marriage between relatives). It explains increased risk of children with autosomalrecessive disorders if parents are related.
Migration introduces new alleles in a population as migrants mate with aborigines.
Exchange of genes between populations is termed as gene flow. Through time gene
flow between populations make them genetically more similar. Nowadays migration
factor becomes more intensive.
Mutations. Fresh mutations shift proportion of mutant alleles, especially if there is
intensive action of mutagenic factors.
Small population size. Genetic processes in small populations don’t follow the HardyWeinberg equilibrium.
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Table 9.4. Examples of increased resistance (proved or suspected)
of heterozygous carriers of recessive diseases
Hereditary disorder
Mode of inheritance
Region
Resistance
Autosomal-recessive
Tropical Africa
Falciparum malaria
α and β talassemia
(hemoglobinopathia)
Autosomal-recessive
Mediterranean basin
Southeast Asia
Falciparum malaria
Phenylketonuria
Autosomal-recessive
Western and Eastern
Europe
Spontaneous abortion
rate lower
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Sickle-cell anemia
Cystic fibrosis
Autosomal-recessive
Western and Eastern
Europe
Cholera
Tuberculosis
Tay-Sachs disease
Autosomal-recessive
Eastern European
(Ashkenazi) Jews
Tuberculosis
Genetic processes in small populations. Isolate. Deme
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The proportion of A and a alleles in the small population is much more variable from
generation to generation than in the large population. It is due to the random fluctuations of allele transmission in meiosis and fertilization. As a result in a few generations
one of the alleles might disappear and another one fixed, so population becomes homozygous (AA or aa). The random change in allele frequency in the small population
is called genetic drift. The smaller the population, the greater the role of genetic drift,
in large population its influence being negligible. Due to genetic drift rare alleles can
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be promoted and some orphan (rare) single gene disorders became frequent in small
populations.
Other factors explaining increased proportion of homozygotes in the small populations are founder effect and bottleneck effect. Founder effect occurs when new population is established by a small number of founders. Accumulation of certain alleles is explained by small mating population. For example, more than 40 rare hereditary disorders
are common in Finns (congenital nephritic syndrome, rare forms of dwarfism and other)
due to founder effect and genetic isolation. It is thought that Finland population has
been founded by a small number of individuals about 100 generations ago. It is considered that one in five individuals in this population is heterozygous carrier of at least one
of these rare disorders. Bottleneck effect occurs when certain event (earthquake, volcano eruption and other disasters) reduces population to a small handful, which do not
represents initial genetic structure of population. Famous example is accumulation of
a rare type of complete color blindness (complete achromatopsia, autosomal-recessive
disorder) in population of atoll Pingelap in the Pacific Ocean. In 1775 after a catastrophic
typhoon only about 20 aborigines survived. Just one of the survives was sick. Today the
disorder is prevalent in about 10 % of the population and about 30 % are healthy heterozygous carriers due to bottleneck and founder effects, consanguineous marriages and
rapid population growth.
Small human populations are formed as the result of isolation (geographical, ethnic,
religious or social). Small populations isolated by non-geographical reasons exist even
in modern megalopolices. There are two types of small human populations: isolate and
deme. Isolate is a small population consisting of up to 1,500 persons. The frequency of
consanguineous marriages in isolates is over 90 %. Local inbreeding population composed of 1,500 to 4,000 persons is called deme. The consanguineous marriages in deme
are up to 80–90 %. High number of dominant or recessive homozygous individuals is characteristic for these types of population due to genetic drift and other processes described
above. Examples of rare disorders that are relatively common in certain populations are
given in Table 9.5.
Congenital nephrotic syndrome
Autosomal-recessive
Finns
Albinism
Autosomal-recessive
Hopi (Arizona) and San Blas
(Panama) Indians
Cartilage-hair hypoplasia (dwarfism, light-colored and sparse hair)
Autosomal-recessive
Amish (group of traditional
Christians) in Pennsylvania
Nephropathic cystinosis
Autosomal-recessive lysosomal storage disorder
Hutterites (group of traditional
Christians) in North America
Table 9.5. Examples of rare disorders that are relatively common
in certain small populations
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Disease
Mode of inheritance
Populations
9.7. Prophylaxis of hereditary disorders. Genetic counseling. Prenatal diagnosis
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9.7. Prophylaxis of hereditary disorders.
Genetic counseling. Prenatal diagnosis
Genetic counseling
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Each family has a risk of having a child with hereditary disorder or congenital defect. It
is explained by heterozygous carrying of hereditary disorders, chance of fresh mutations
and action of teratogenic factors.
There are two steps of prophylaxis of hereditary disorders: primary and secondary.
The main aim of primary prophylaxis is to provide optimal conditions for gametogenesis,
fertilization and early stages of embryonic development. It includes healthy life style,
optimal age of child birth, avoiding of mutagenic and teratogenic factors and other. Secondary prophylaxis is aimed on reducing the risk of sick child birth or manifestations of
hereditary disease. It includes prenatal diagnosis of hereditary disorders and neonatal
screening.
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Important way of prophylaxis of hereditary disorders and congenital defects is genetic
counseling. It is a process in which patients or their relatives are informed about the dignosis and the consequences of the disorder, its mode of transmission, genetic risk and the ways
by which that risk can be prevented or reduced. Genetic counseling is recommended if:
`` there is a child or close relatives with hereditary disorder or congenital defects, cases
of stillbirth, infertility;
`` mother is older than 35 (increased risk of numerical chromosomal aberrations) or
father is older than 40 (increased risk of single gene mutations);
`` marriage is consanguineous. In such case risk that both parents are carriers of same
autosomal-recessive disorder is higher;
`` female were under the action of mutagenic or teratogenic factors during the first
trimester of pregnancy;
`` fetus is suspected to have hereditary disorder by results of prenatal diagnosis.
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The steps of medical genetic counseling include:
1. Diagnosis of hereditary disorder. It involves analysis of pedigree, clinical and laboratory investigations.
2. Calculation of genetic risk (chance to have sick child). In case of single gene disorders
recurrence risk can be calculated on the bases of Mendel’s laws. For other groups of
hereditary disorders recurrence risk is based on population studies.
3. Communication with the family. Geneticist should explain clearly the diag­nosis, genetic bases of the disease, prognosis, and ongoing management, options for reduction of genetic risk.
All this information will help family to take their own decision concerning next pregnancy.
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Chapter 9. Methods of human genetics
Prenatal diagnosis of hereditary disorders
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Centrifuge
Biochemical
analysis
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Placenta
Amniotic fluids
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Prenatal diagnosis is the diagnosis of hereditary disorders or congenital defects in fetus during the pregnancy (before birth). It is of utmost
importance for the couples who are at high risk of
having a child with hereditary disorder.
The first method of prenatal diagnosis introduced in medical practice is ultrasonography. It
allows detecting congenital defects of different
organs and is very useful for prenatal diagnosis of
chromosomal disorders.
If it is required to study karyotype of a fetus or
to detect gene mutation invasive methods are used
(Fig. 9.22). Examples of the techniques available for
invasive prenatal diagnosis are chorioncentesis
(chorionic villus sampling), amniocentesis (sampling of amniotic fluid which contains fetal cells),
placentocentesis (sampling of placenta) and cordocentesis (sampling of blood from umbilical cord).
Cells samples are aspirated through the abdominal
wall under the ultrasonographic control. Obtained
cells are used for karyotyping if chromosomal disorder is suspected. For diagnosis of single gene disorders DNA analysis or biochemical methods are used.
If fetus is affected prenatal treatment (if possible) is proposed. If disease is severe, incurable
and incompatible with social adaptation parents
should make a decision about prolongation or
termination of pregnancy.
Fetal cells
DNA
analysis
Cell culture
Karyotyping
Biochemical
analysis
Fig. 9.22. Schematic representation of prenatal diagnosis of hereditary disorders using invasive method such as amniocentesis
9.7. Prophylaxis of hereditary disorders. Genetic counseling. Prenatal diagnosis
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TASKS & QUESTIONS
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`` Multiple Choice Questions (Choose one correct answer):
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1. Autosomal-recessive pattern of inheritance is characterized by:
A. Small number of affected individuals
B. Horizontal transmission of disease
C. Healthy parents of an affected child are heterozygous carriers of the mutant gene
D. The chance of having of a healthy child for heterozygous couple is 75%
E. All of the above
2. Pedigree of a family demonstrates affected individuals of both sexes in each generation. It is typical for the following pattern of inheritance:
A. Y-linked
D. X-linked recessive
E. X-linked dominant
B. Autosomal-recessive
C. Autosomal-dominant
3. A young healthy couple has two children suffering from the Taay–Sachs disease
(a storage disorder with accumulation of lipids). It became clear that parents were
consanguineous. What is the most possible pattern of inheritance of the disease?
A. Y-linked
D. X-linked recessive
E. X-linked dominant
B. Autosomal-recessive
C. Autosomal-dominant
4. A healthy woman has affected sons with the same hereditary disorder in her two
marriages. Both of her husbands are healthy. What is the most possible pattern of
inheritance of the disease?
A. Y-linked
D. X-linked recessive
E. X-linked dominant
B. Autosomal-recessive
C. Autosomal-dominant
5. A healthy woman is the carrier of color blindness. Her husband is healthy. What is the
risk of having an affected child in this family?
A. 0 %
D. 50 % of all children
B. 50 % of daughters
E. 75 % of all children
C. 50 % of sons
6. A family is characterized by hereditary deafness transmitted in gene­rations. Which
method helps to detect the pattern of inheritance of the disease?
A. Genealogic
D. Population statistic
B. Twins method
E. Biochemical
C. Cytogenetic
7. The twins method of human genetics is the method of:
A. Diagnosis of chromosomal disorders
B. Diagnosis of inborn errors of metabolism
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C. Detection of the pattern of inheritance
D. Detection of the influence of genotype and environment on the character
E. Calculation of genes frequency in population
If H (coefficient of heredity) is 55 %, the character:
A. Equally depends on a genotype and environment
B. Depends on a genotype only
C. Depends on environment only
D. Depends on the environment but influenced by a genotype
E. Depends on a genotype but influenced by environment
What karyotype abnormality have persons with the Shereshevsky – Turner syndrome?
A. Absence of one X chromosome
B. Absence of one 21st chromosome
C. Absence of one 15th chromosome
D. Extra 21st chromosome
E. Extra 18th chromosome
The epithelial cells of a male patient have two Barr bodies. It indicates the:
A. Shereshevsky – Turner syndrome
D. “Superfemale” syndrome
B. Klinefelter syndrome
C. Patau syndrome
E. “Supermale” syndrome
Which chromosomal disease in males is characterized by one drumstick in the nucleus of the neutrophile leukocytes?
A. Shereshevsky – Turner syndrome
D. “Superfemale” syndrome
B. Down syndrome
E. “Supermale” syndrome
C. Klinefelter syndrome
Which of the following conditions is the result of abnormal number of autosomes?
A. Klinefelter syndrome
D. Shereshevsky – Turner syndrome
B. Patau syndrome
E. Haemophilia
C. “Superfemale” syndrome
A forensic expert has made a conclusion that the blood spots at the place of crime
belong to a woman. Which blood component has been studied?
D. RBC
A. Blood plasma
B. Blood serum
E. Leukocytes
C. Platelets
Diagnosis of the Edwards syndrome is made by the:
A. Twins method
D. Biochemical method
B. Pedigree analysis
E. Cytogenetic method
C. Population statistic method
Diagnosis of haemophilia, phe­nylketonuria,diabetes mellitus is made by the:
D. Biochemical method
A. Twins method
B. Pedigree analysis
E. Cytogenetic method
C. Population statistic method
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8.
Chapter 9. Methods of human genetics
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15.
9.7. Prophylaxis of hereditary disorders. Genetic counseling. Prenatal diagnosis
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16. A person has balanced translocation (no clinical manifestations) of long arm of the
21st chromosome to 22nd. What disease is of high risk in his children?
A. Shereshevsky – Turner syndrome
D. Klinefelter syndrome
E. Down syndrome
B. Edwards syndrome
C. Patau syndrome
17. Ideal population is characterized by:
A. Unlimited number of individuals
B. Random mating (panmixia)
C. Absence of mutations and migrations
D. Constant ratio between AA, Aa and aa genotypes
E. All of the above
18. Small population (1,500–4,000 individuals) with frequency of consanguineous marriages about 80–90 % is:
A. Deme
D. Ideal population
B. Isolate
E. Biocenosis
C. Pure line
19. Gene drift is characterized by:
A. Homozygocity of the population
B. High frequency of one of the alleles in population
C. Low frequency of one of the alleles in population
D. All of the above
20. Genetic structure of the population is changed by the following factors:
A. Assortative mating
D. Genetic drift
B. Migration
E. All of the above
C. Isolation
21. Frequency of the gene A is 0.6; frequency of the gene a is 0.4. What is the frequency
of Aa genotype in this population?
A. 0.6
D. 0.48
B. 0.4
E. 0.64
C. 0.24
22. DNA diagnosis is applicable for:
A. Diagnosis of single gene disorders
D. Cancer detection
B. Diagnosis of infectious disorders
E. All of the above
C. Paternity dispute cases
23. Polymerase chain reaction includes:
A. DNA denaturation
C. Extension of DNA
B. Primer annealing
D. All of the above
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Chapter 9. Methods of human genetics
`` FILL IN THE BLANKS:
`` TRUE OR FALSE:
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1. In the case of X-linked dominant pattern of inheritance genotype of affected male is
_______ and genotype of affected female is _______ or _______.
2. In the case of _________________ inheritance all the offspring of affected mother
are affected.
3. If disorder is multifactorial concordance usually varies from __________ % to MZ and
from ___________ to DZ twins.
4. Very small chromosomal aberrations like _______________ can be detected using
molecular-cytogenetic method such as ______________ method.
5. Inactivation of X–chromosome is controlled by _______________ located on the
_______ arm of ___________________.
6. Each cycle of PCR includes three stages: _____________________,
_______________________, ________________________.
7. __________ is a small population consisting of up to 1,500 persons and frequency of
consanguineous marriages in it is ___________%.
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1. Multifactorial disorders are disorders, caused by gene mutations.
True
False
2. The pedigree method makes possible to estimate expressivity and penetrance of a
gene.
True
False
3. Patients with Cri-du-chat syndrome have short stature and “webbed neck”.
True
False
4. Example of inborn errors of metabolism is disturbance in carbohydrates metabolism
such as congenital hypothyrosis.
True
False
5. Newborn screening programs are used for common in population disorders and can
be successfully treated if detected in time, but without treatment have serious effect
on health.
True
False
6. The total number of all alleles in a population is termed as gene flow.
True
False
7. Hardy-Weinberg’s law allows studying intensity of mutation processes by comparing
real and expected rates.
True
False
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Chapter 10.
General notions of parasitology.
Protists as human parasites
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10.1. General notions of parasitology
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In the process of living world evolution different kinds of interaction between species
have been formed. Close and often long-term interaction between organisms of different
species is termed symbiosis (from Greek sym – together and bios – life).
The main types of symbiosis are mutualism, commensalism and parasitism.
Mutualism is an interaction, which benefits both participants. Example is interaction
between humans and enteric bacteria Escherichia, Lactobacillus and some other species.
They provide a barrier to pathogenic bacteria, produce vitamins K and B, metabolize some
dietary fibers. In turn, bacteria get a shelter and use intestinal content for nutrition.
Commensalism (from Greek com – together and mensa – table or meal) is a kind of
interaction in which one organism is benefited and another one remains relatively unaffected. Benefited organism (commensal) lives and feeds in the host but produces neither
harm nor benefit to the host. Examples are Entamoeba coli inhabiting lumen of human
large intestine and Entamoeba gindivalis inhabiting gingival pockets.
Parasitism is an interaction in which one of the organisms (parasite) benefits from the
relationship and another one (host) is injured. Usually parasite physiologically or metabolically depends upon its host. Parasitism differs from predation. Predator attacks its victim,
kill it and devour immediately. The parasite is harmful for its host but they both have to
reach the balance as parasite that kills its host will die with it. If parasite produces sublethal
effect it can use host for repeated feeding and has an opportunity to spread to another
host. Parasites usually kill the host only in case of heavy infection.
In fact, all infectious agents including viruses, bacteria, fungi, protists, helminthes and
arthropods are parasites. However, usually we termed as parasites protists and agents of
animal nature (helminthes and arthropods). The science dealing with human parasites and
diseases caused by them is called medical parasitology. It includes medical protozoology
(studies parasitic protists), medical helminthology (studies parasitic worms – helminths)
and medical arachnoentomology (studies arthropods – agents and vectors of human diseases).
Classes of parasites and hosts
Parasites can be obligate and facultative. Obligate parasites cannot survive without
parasitic life. Some animals are obligatory parasites at one stage of life cycle and are freeliving at another stage. Facultative parasites exist in a free-living state but become para-
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sitic if they have an opportunity. Example is Negleria amoebae that live in ponds, swimming pools and other water reservoirs but can invade nasal mucosa and pass through the
olfactory plate into the meninges. In this case it becomes an agent of amoebic meningoencephalitis. Accidental parasites attack an unusual host. Dog tapeworm Dipylidium caninum usually parasites in dogs and cats. If human occasionally swallows a flea with larva of a
parasite, he also became infected. Aberrant parasites are located in unusual places where
they cannot develop or survive (i.e., ascaris in ovary).
According to the time parasite spends in/on the host, there are permanent parasites or
temporary parasites. Permanent parasites spend the whole life in the host organism or on
its surface. Examples are dysentery amoeba, ascaris, head louse. Under permanent parasitism a parasite holds on (or in) host’s organism either at certain stage of development
or a whole life. For instance, just larval stage of Wohlfarthia fly parasites on human body
(so-called larval parasitism). Trichina worm spends all life cycle stages inside a host body.
Sometimes permanent parasitism is accompanied by a change of host (malaria parasites).
Temporary parasites visit host for a short period for nutrition. Such temporal parasites live
free in nature (ticks, mosquitoes) or inhabit host dwelling place (bed bug, fleas).
Due to parasite location they are subdivided into ectoparasites and endoparasites. Ectoparasites live on the surface of the host’s body (arthropods) and endoparasites live inside the host in body cavities, organs and tissues (protists and helminthes).
Parasites adapted to one certain host are called monoxenous. If parasite has a wide
range of hosts, it is considered to be panxenous.
Hosts are classified into definitive and intermediate. Host that harbor sexually reproduced parasite is called definitive. If parasite reproduces asexually or immature larval stages are present, host is called intermediate. The Anopheles mosquito is the definitive host
for the malaria parasite as it reproduces sexually in the mosquito. Human being is an intermediate host for the malaria parasite as it reproduces asexually in man. Reservoir hosts are
infected animals in which organism parasite survives, multiplies and from where it can be
transmitted to other hosts.
The host, which is naturally infected with certain species of parasite, is a natural host.
The host, which is usually not infected with parasite, is accidental host.
Host-parasite interactions
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Host-parasite relationship demonstrates profound morphological and physiological
adaptations of parasites to their way of life. These include reduction of the limbs, presence of attachment organs in endoparasites (suckers, hooks and other), and modification of mouthparts in insects (piercing – sucking type). Body shape and size usually are
optimal for dwelling place. Organs that are not necessary for a parasitic existence are
frequently lost. For instance, Apicomplexa protists (malaria species, toxoplasma and other) have no locomotor organelles, Cestoidea worms (tapeworms) lack digestive system.
Quite often parasites lose the ability to produce necessary cellular components as they
obtain them from the host.
10.1. General notions of parasitology
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Parasites developed specialized mechanisms for entrance into the body or tissues of
the host. They have special organs for penetration (i.e., conoid and ropthria in toxoplasma,
hooklets in oncosphere of tapeworms) and can elaborate proteolytic enzymes. Important
adaptation for parasitism is evading of host immune response. It is provided by location of
parasites in relatively protected sites, changes in the surface antigen structure, production
of immune suppressors.
Another important adaptation is increased reproductive capacity of parasites comparing with free-living organisms. Multiplication of some of them occurs at larval stages
(Trematodes).
Parasites vary according to the degree of damage they inflict upon their hosts. The
harmful effect is called pathogenic effect. Non-specific pathogenic effect is explained by
releasing of different metabolic products of the parasite (toxic-allergic action), mechanical
injuring of the cells, tissues, and organs, immune suppression. Parasites absorb nutrients
and microelements required for the host, cause intestinal obstruction, give portal of entry
for other pathogens. However, in many cases clinical manifestations of parasitic diseases
are absent or are non-specific (fatigue, headache, allergy). In turn, host organism tries to
eliminate parasite via immune response.
The outcome of parasitic disease is determined by several factors. These are number of
parasites and degree of their pathogenicity, genetic constitution of a host (i.e., resistance
to malaria infection in heterozygous carriers of sickle cell anemia), peculiarity of immune
response, the diet or nutritional status.
Transmission of parasitic diseases
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Spreading of parasitic diseases involves sources of the disease and ways of transmission.
Sources of infection are infected man or infected animal. Sometimes infected humans
stay healthy but serve as a source of infection for their surroundings. Such humans are
termed as healthy carriers. For instance, it is characteristic for Entamoeba histolytica and
Giardia lamblia infections. Sometimes hosts serve as a source of infection for themselves
(autoinvasion).
Disease which circulates just in humans is termed as anthroponosis (i.e. trichomoniasis). Disease that affects both humans and animals is anthropozoonosis (i.e. tryponosomiasis). Diseases that circulate among vertebrate animals are called zoonosis. Human become infected accidently, person-to-person transmission does not normally occur.
Ways of transmission of parasitic disease are variable and influenced by location of the
parasite in human body. The main ways are:
`` fecal-oral for intestinal parasites – through dirty hands, contaminated water and
food. House flies and cockroaches can serve as mechanical vectors of agents;
`` alimentary – through the flesh of infected animals (meat, fish), if infective stage of the
parasite is located in tissues;
`` contact way – by penetration through the skin or by direct contact with the infected
organism;
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`` sexual transmission – if parasite is located in sexual organs;
`` transplacental – from mother to fetus through placenta;
`` through the bites of blood-sucking arthropods. Diseases transmitted through the
bites of ticks and insects are termed as vector-borne diseases. Blood sucking arthropods are considered to be specific vectors if parasite undergoes certain stages of development in them. For example, Anopheles mosquito is a specific vector for malaria,
as parasite undergoes sexual reproduction in its organism.
Human diseases with natural focus are the diseases that circulate in nature among
animals at certain territories. Human being is one of the potential hosts for the parasites
that cause these diseases and can be infected if get into the territory of natural focus. The
notion of human diseases with natural foci was introduced by academician Y. N. Pavlovsky.
He described the main components of natural focus that include agent of the disease, reservoir animal host, specific vector (often) and appropriate climate conditions. Examples of
diseases with natural foci are trypanosomiasis, confined to certain areas of tropical Africa
and alveococcosis in the forests of Northern Europe.
10.2. General characteristic of protists.
Parasitic amoeboid protozoa.
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Protozoans or protists (from Greek protos or protistos – first of all, zoon – animal) are
unicellular eukaryotic organisms. They may be aquatic (fresh water or marine), terrestrial
or parasitic. Parasitic forms have worldwide distribution and cause serious diseases in humans and animals.
Morphology. Protisits are usually colorless with varied shapes (spherical, oval, bellshaped, spindle-shaped, slipper-like or irregular). The cell structure is typically eukaryotic.
The body consists of uninucleate or multinucleate protoplasm bounded by a delicate
membrane or a firm pellicle. The cytoplasm often is differentiated into an outer rim of relatively homogeneous ectoplasm and a more granular inner endoplasm.
The ectoplasm participates in locomotion and engulfment of food materials. It also
functions in respiration, in discharging waste materials as well as a protective covering for
the cell.
Within the endoplasm there are the nucleus (single, double or multiple) and all eukaryotic
organelles. Some protists have contractile vacuoles for osmoregulation, discharging of liquid
metabolic products and respiration. Several food vacuoles also may be seen in the cytoplasm.
Protozoans move with the help of finger-like pseudopodia, whip-like flagella or short
and hairy cilia. Some parasitic forms lack organelles of locomotion.
Metabolic activities. Parasitic protists are heterotrophic. The cell gets nourishment
from the environment by diffusion or by active transport across the plasma membrane
(phagocytosis or pinocytosis). Some protozoa have specialized digestive organelles such
as cytostome (cell mouth) and a cytopharynx.
Respiration takes place through the body surface of the organisms.
10.2. General characteristic of protists. Parasitic amoeboid protozoa.
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Excretion of waste material is carried out through the body surface, contractile vacuoles, and by exocytosis.
Reproduction is mostly asexual. The commonest way is binary fission. Other ways of
asexual reproduction are multiple fission (schizogony) and budding (endodyogony).
Sexual reproduction occurs by syngamy (male and female gametes are produced, following by fusion and formation of zygote) and conjugation in which two organisms join
together and reciprocally exchange nuclear material.
Encystation. The active feeding and growing stage of the protozoa is called the trophozoite (from Greek trophos – nourishment) or vegetative stage. Some species form inactive
or dormant stage under unfavorable conditions called cyst. This stage serves for protection, survival and dispersal. The cyst stage may also involve reproduction by the nucleus
dividing once or more to give rise to daughter trophozoites. The cyst if present is an infective stage for the host.
Classification of protists. Unicellular eukaryotes are referred to the Kingdom Protozoa
(Protista). The classification of Protozoa is problematic question as this group includes different, often evolutionary non-closely related organisms. Nowadays it is under revisement
on the basis of molecular-genetic data. The simplest and one of the older classifications is
based on the means of locomotion of an organism. It includes Ameboids (Sarcodina), Flagellates, Sporozoans and Ciliates. According to the one of the modern approaches most of
the parasites of medical importance belong to the Phylums Sarcomastigophora (Ameboids
and Flagellates), Apicomplexa (Sporozoans) and Ciliophora (Ciliates).
Parasitic protists are studied by medical protozoology. Disorders caused by protists are
called protozoan diseases.
Parasitic amoeboid protozoa
Classification
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Kingdom: Zoa
Subkingdom: Protozoa
Phylum: Sarcomastigophora
Subphylum: Sarcodina
Class: Rhizopoda
Order: Amoebina
Species: Entamoeba histolytica
E. coli
E. gingivalis
General characteristics of ameboid protozoa (Sarcodina)
Typical features of Sarcodina are the following ones (Fig. 10.1):
`` Absence of pellicle; the body is covered by a cell membrane.
`` The body shape is inconstant.
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Pseudopodium
Contractile vacuole
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Food vacuole
Membrane
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Nucleus
Endoplasm
Ectoplasm
Fig. 10.1. Typical features of Ameboid protozoa (Sarcodina)
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`` Organelles for locomotion are pseudopodia that are used for food capturing also.
`` They are uninucleate as a rule. Differentiation into ectoplasm and endoplasm is well
expressed. There are many food vacuoles and contractile vacuole (in fresh water
forms) in endoplasm.
`` Asexual reproduction occurs by binary fission. Sexual reproduction has not been reported in many species, in some other occurs by syngamy.
`` Cyst formation takes place under unfavorable conditions.
`` Amoebae may be free-living or parasitic. A few of free-living forms can on occasion
act as human pathogens.
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Entamoeba Histolytica
Entamoeba histolytica is an agent of amoebic dysentery or amoebiasis.
Geographical distribution. It is worldwide, but much more common in tropical regions.
Location. Parasites inhabit the large intestine of human. Extraintestinal location is the
liver, brain, lungs, and other organs.
Morphology. E. histolytica occurs in trophozoit and cyst forms (Fig. 10.2). Trophozoit
exists in two variants:
`` magna form or large vegetative stage is a pathogenic form;
`` minuta form or small vegetative stage is the main form of existence;
`` cystic form or cyst stage is an infective stage.
The magna form measures 20–40 µm. The cell is covered by membrane, cytoplasm is
differentiated into ectoplasm and endoplasm. It is an erythrophage, so it has phagocytized erythrocytes in endoplasm. This feature is of diagnostic importance, as RBCs are not
found in other intestinal amoebae. There is one nucleus usually slightly visible in unstained
parasite. The specific feature of the nucleus is a small compact karyosome (several granules
of chromatin) located centrally. In freshly passed specimens amoeba demonstrates directional movement by one large, fingerlike pseudopodium at a time. The magna form lives in
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10.2. General characteristic of protists. Parasitic amoeboid protozoa.
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Fig. 10.2. Entamoeba histolytica: A – large vegetative stage; B – small vegetative stage; C – cyst stage;
1 – erytrocytes in endoplasm; 2 – nucleus; 3 – food vacuoles
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the wall of the large intestine. It produces proteolytic enzymes, which may cause formation
of the ulcers. This form is revealed at the acute stage of amebiasis.
The minuta form is located in the lumen of the large intestine and feeds on bacteria of
intestinal contents. Its size is 15–20 µm, phagocytozed erythrocytes in cytoplasm are absent. The minuta form is present in the human stool during the recovering.
The cysts are spherical, 10–15 µm in size; mature cysts possess 4 nuclei (immature ones
have 1–2). Cysts are found in stool of the patients in the recovering period or in healthy
cyst carriers.
Life cycle. Infection occurs by ingestion of mature cyst with contaminated water
or food. In the lower part of the small intestine each nucleus of a cyst divides into two
ones (Fig. 10.3). It gives 8 minuta forms. They inhabit the lumen of the large intestine,
feed on bacteria, leukocytes and are nonpathogenic. In the lower part of the large intestine they turn into cysts which are excreted with stool and preserved for a long time
in the soil.
As minuta form is nonpathogenic commensal, a person with this form is considered to
be a healthy cyst carrier (asymptomatic cyst passer).
Under the influence of some predisposing factors (changing of intestinal microflora,
dehydration, pH changing, immunosuppression because of different factors) minuta form
turns into magna form. It starts to produce proteolytic enzymes, penetrates mucosa of
large intestine, causes necrosis and formation of ulcers (intestinal amoebiasis). Magna form
can get into blood vessels and with blood reaches the liver, lungs, brain and other organs
causing amoebic abscesses (extraintestinal amoebiasis).
Epidemiology. Ameboiasis is an anthroponosis. The main source of infection is a healthy
cyst carrier or a patient with chronic amebiasis in the period of remission. People who excrete vegetative forms only are not epidemically dangerous, as the vegetative form dies in
15–30 min after having been discharged.
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Fig. 10.3. Life cycle of Entamoeba histolytica: 1 – cyst stage in digestive tract; 2 – small vegetative stage;
3 – large vegetative stage; 4 – cyst stage in stool
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Mode of transmission is fecal-oral. Food, water, fruit, vegetables, items of everyday usage and dirty hands are considered to be transfer factors of the disease. Flies and cockroaches serve as mechanical vectors.
Pathogenicity. If only minuta form is present, infection is asymptomatic. The trophozoits of magna form produce necrosis, abscesses and finally amoebic ulcers in the colon.
This clinically manifests as abdominal pain, nausea, vomiting, and diarrhea. Stool is usually
loose and flecked with blood. Intestinal bleeding, peritonitis because of ulcer penetration
are possible complications of amoebic dysentery. Extraintestinal amoebic abscesses develop when trophozoites enter the portal circulation and reach different organs of the body.
Amoebic abscesses of the liver, lungs, muscles are mostly common.
Diagnosis. The diagnosis of intestinal amoebiasis is demonstration of the magna form
in stool. Microscopic examination of wet mounts is used. Small amount of fecal material is
emulsified in a drop of normal saline solution and also separately in 2 % iodine solution.
The saline mount serves to detect vegetative forms, while iodine preparation shows the
morphological details of trophozoits and cysts.
The diagnosis of extraintestinal amoebiasis (amoebic abscess of the liver, lungs, etc) is
difficult. It requires parasitologic examination of abscess contents got during the operation or by diagnostic aspiration or serologic tests (immunological test – demonstration of
antibodies in blood serum).
The non-pathogenic species E.dispar is morphologically very similar with minuta form
of E.histolytica. Differentiation of these species is possible by molecular-genetic analysis.
Prophylaxis. Personal prophylaxis is to keep the rules of personal hygiene (to boil the
water, wash vegetables, fruit, and hands before meals).
10.2. General characteristic of protists. Parasitic amoeboid protozoa.
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Control of the disease includes treatment of the patients and examination of close contacts. Carriers should be removed from the food handling occupations and treated properly. Health education, hygiene of the environment and provision of safe water is very important.
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Entamoeba Coli
Entamoeba coli is a nonpathogenic commensal intestinal amoeba. It is worldwide in
distribution.
Location. Lumen of the large intestine.
Morphology. It exists in two forms: trophpzoit (vegetative stage) and cyst. Trophozoit
has a size of 20–30 µm. There are a lot of food vacuoles with ingested bacteria, but it does
not phagocytize the erythrocytes (Fig. 10.4). Cysts are spherical or oval in shape, 15–35 µm
in diameter. A mature cyst has 8 nuclei. Number of nuclei is a key sign in discrimination
with cysts of E. hystolytica.
Modes of transmission are the same, as for E. histolytica.
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Fig. 10.4. Entamoeba coli: A – vegetative stage; B – cyst stage; 1 – nucleus; 2 – food vacuole
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Entamoeba Gingivalis
Entamoeba gingivalis is nonpathogenic commensal.
Location. In the gingival pockets, in carious teeth.
Morphology. Trophozoit is 8–30 µm in size, the cytoplasm is differentiated into two layers and contains phagocytized bacteria, leukocytes, epithelial cells. It does not form cysts
(Fig. 10.5).
Epidemiology. Infection occurs as a result of using common spoons, forks, cups, by direct oral contact or through droplets of saliva.
Diagnosis. Examination of the wet mounts from dental deposit, gingival pockets.
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Fig. 10.5. Entamoeba gingivalis: vegetative stage; 1 – nucleus
Pathogenic free living amoebae
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Among the free-living amoebae found in water and soil a few are potentially pathogenic.
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Naegleria Fowleri
Naegleria fowleri is worldwide in warm fresh water. It may cause primary amoebic meningitis in young adults and children. Human infection occurs from water while swimming
or diving in ponds. The amoebae invade the nasal mucosa, pass through the olfactory
nerve branches into the meninges and brain and cause acute purulent meningitis and encephalitis. The diagnosis is by demonstration of the trophozoites in the cerebrospinal fluid.
The disease almost always ends fatally.
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Acanthamoeba (Hartmanella) Culbertsoni
Acanthamoeba causes chronic amoebic keratitis. Infection can be acquired through
abrasions of the cornea. Often the disease is associated with the use of contact lenses. The diagnosis is by demonstration of the cysts in corneal scraping or by culture. In
persons with immunodeficiency infection can manifests as granulomatous amoebic encephalitis.
Classification
Phylum: Ciliophora
Class: Ciliata
Species: Balantidium coli
10.3. Parasitic Ciliates
10.3. Parasitic Ciliates
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General characteristics of Ciliates
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Ciliates are characterized by the following features:
`` Constant shape of the body and presence of pellicle.
`` Large number of locomotion organelles – cilia on the whole body surface.
`` High degree of morphological and physiological specialization.
`` Organelles of the digestive system are oral groove (peristome) leading to the cell
mouth (cytostome), cytopharynx, food vacuoles, cytopyge (anal pore or cytoproct).
`` Two contractile vacuoles are the organelles for osmoregulation and excretion of liquid metabolic products.
`` The ciliates have two different types of nuclei, which are called macronucleus and
micronucleus. Macronucleus is polyploid, it controls all metabolic activities, growth,
and asexual reproduction. Micronucleus is always diploid, provides storage of hereditary information and sexual reproduction by conjugation.
`` Reproduction occurs in two ways: asexually (transverse binary fission) and sexually
(conjugation). During the conjugation two mating individuals fuse at their oral region. Polyploid macronucleus dissolves; diploid micronucleus of each individual divides by meiosis to form four haploid nuclei. Three nuclei disappear, last one divides
into two nuclei and reciprocal exchange by one of them occurs. It results in recombination of genes, which is needed for variation and better adaptation to environmental conditions.
`` Under unfavorable condition ciliates form cysts.
`` Many ciliates are free living fresh water or marine forms, only few are parasitic and
pathogenic.
Balantidium Coli
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Balantidium coli is a causative agent of balantidiasis.
Geographical distribution. Worldwide.
Location. The large intestine.
Morphology. The vegetative form is egg-shaped (ovoid) (Fig. 10.6). It measures 40–
120 µm in length, 30–80 µm in width. Morphology is typical for ciliates. Cysts are shaped
spherically, 40–60 µm in diameter. Cysts have thick cell wall, macronucleus is visible inside.
Life cycle. Humans become infected by ingestion of the cysts with contaminated food
or water. Cysts in the small intestine turn into the vegetative forms (trophozoites), which
feed and multiply in the lumen of the large intestine. The parasite may be excreted in the
faeces as cysts or trophozoites, but in human intestine encystation is rare.
Epidemiology. Natural hosts are pigs, man is incidental host. B. coli has also been detected in dogs, monkeys and rats. The main source of infection is pig, rarely healthy cystcarrier or patient with balantidiasis. Mode of infection is fecal-oral. Flies and cockroaches
may serve as mechanical vectors.
Pathogenicity. Infection is mostly asymptomatic. Human disease occurs only when the
resistance of the host is suppressed by one or more predisposing factors (malnutrition, in-
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Fig. 10.6. Balantidium coli: A – vegetative form; B – cyst form; 1 – cell mouth; 2 – cilia; 3 – food vacuole;
4 – micronucleus; 5 – macronucleus, 6 – contractile vacuole
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fection by bacterial or other parasites). Balantidium starts to produce proteolytic enzymes,
causing the ulcers on the mucous membrane of the large intestine. The caecum and sigmoidal bowels are affected more often. Patients suffer from abdominal ache, vomiting,
loose stool with mucous and blood. Clinical manifestations resemble amoebic dysentery
because of similar pathogenic effects.
Balantidiasis often becomes chronic. It is rare but possible for healthy person to be
a cyst carrier. In this case a small number of cysts are excreted with faeces.
Diagnosis. Demonstration of throphozoites and cysts (rarely) in stool. Diagnostic methods are the same as for amoebiasis.
Prophylaxis. Personal prevention is to follow the rules of personal hygiene, especially at
pig farms. Control of the disease is the same as for amoebiasis.
10.4. Parasitic Flagellates
Classification
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Kingdom: Zoa
Subkingdom: Protozoa
Phylum: Sarcomastigophora
Subphylum: Mastigophora
Class: Zoomastigophorea
Order: Diplomonadida
Species: Giardia lamblia (Lamblia intestinalis)
Order: Trichomonadida
10.4. Parasitic Flagellates
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Species: Trichomonas vaginalis
T. hominis
T. tenax
Order: Kinetoplastida
Species: Leishmania donovani
Trypanosoma brucei gambiense
L. infantum
T. b. rhodesiense
L. major
T. cruzi
L. tropica
L. mexicana and L. braziliensis
General characteristics of flagellates
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Flagellates are characterized by the following features:
`` permanent shape of the body;
`` cell is covered by pellicle;
`` one or two nuclei are the same in structure and function;
`` the body possesses one to several flagella (whip-like appendages) for locomotion.
Flagella arise from the basal body (kinetoplast), which is derived from centrioles.
Parabasal body is located near kinetosome in some flagellates. It is similar with Golgi
apparatus and considered to contain reserve materials for energy supply. In some
species the flagellum runs parallel to the body surface, to which it is connected by a
membrane called the undulating membrane;
`` asexual reproduction occurs by longitudinal binary fission. Sexual reproduction has
been reported in a few species only.
Depending on their habitat, flagellates can be considered under two groups:
1. Intestinal and genital flagellates.
They bear multiple flagella and are found in the alimentary or urogenital tracts. Most
luminal flagellates are nonpathogenic commensals. Two of them cause clinical diseases: Giardia lamblia or Lamblia intestinalis and Trichomonas vaginalis.
2. Haemoflagellates (blood and tissue flagellates).
They possess a kinetoplast from which a single flagellum arises. They are transmitted
by blood sucking insects and found in blood and tissues. The most important haemoflagellates are species of leishmania and trypanosoma.
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Intestinal and genital flagellates
Giardia Lamblia (Lamblia Intestinalis)
Infection may be asymptomatic or cause the disease – giardiasis (lambliasis).
Geographical distribution. Worldwide, it is the most common intestinal protozoan
pathogen, especially in children.
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Fig. 10.7. Lamblia intestinalis: (A – ventral view; B – lamblia is tightly attached to the epithelial cell; C – dorsal
view; D – cyst): 1 – flagella; 2 – basal body; 3 – sucking discs; 4 – nucleus; 5 – parabasal body; 6 – axostyle
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Location. It lives in the duodenum and upper jejunum and is the only protozoan parasite found in the lumen of the human small intestine.
Morphology. Lamblia occurs in the trophozoite and cyst forms (Fig. 10.7).
The trophozoite has a pear-shaped body 10–18 µm in length, with 4 pairs of flagella, 2
nuclei, 2 axostyles running along the midline. Parasite is bilaterally symmetrical. Dorsally
it is convex and ventrally it has a concave sucking disc, which occupies almost the entire
anterior half of the body.
The cyst is ovoid, about 12 µm by 8 µm in size and is surrounded by a tough hyaline cyst
wall. The mature cyst contains four nuclei situated at one end.
Life cycle. The infective stage is a cyst, which gets into the human body through water,
food or dirty hands. The cyst hatches out into two trophozoites, which multiply then by
binary fission in the duodenum. The trophozoite attaches by means of the sucking disc to
the epithelial cells of the intestinal villi and crypts, feeding by pinocytosis. Reproduction is
asexual (binary fission). Encystation occurs in the colon. The trophozoite retracts its flagella,
which remain as curved bristles in the cyst. Cysts are passed in stool and remain viable in
soil and water for several weeks. There may be up to 2 000 000 cysts per gram of faeces.
Epidemiology. The disease is anthroponotic. The main source of infection is a human
being. The transmission mechanism is fecal-oral. Infection is acquired by the ingestion of
cysts in the contaminated food and water, through the dirty hands, toys.
Pathogenicity. G. lamblia does not invade tissues, but remains tightly attached to the
epithelial surface in the duodenum and jejunum. This may cause abnormalities of villous
architecture, parietal digestion and absorption of nutrients in the small intestine. In children it may cause epigastric pain, abdominal discomfort, and diarrhea. In adults infection
10.4. Parasitic Flagellates
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Trichomonas Vaginalis
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is mostly asymptomatic. Such infected persons are considered to be healthy cyst carriers
and may serve as a source of infection.
Diagnosis. Faeces and duodenal contents are examined. The cysts, rarely trophozoites
can be found in stool; in duodenal contents only trophozoits are present.
Prophylaxis. Man should keep the rules of personal hygiene (washing hands before
meals, washing vegetables, fruit, boiling drinking water).
Control of the disease is improvement of sanitary conditions, revealing of asymptomatic cyst carriers among the food staff, destruction of mechanical vectors of the disease (flies,
cockroaches).
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Trichomonas vaginalis causes the disease – urogenital trichomoniasis.
Geographical distribution. Parasite is cosmopolitan (worldwide) in distribution.
Location. It lives in the vagina of the females and urethra and prostate of the males.
Morphology. Trichomonas vaginalis exists only as the trophozoite (Fig. 10.8A). Cysts are
not formed. The trophozoite is ovoid or pear-shaped about 10 to 40 µm long with a short
undulating membrane reaching up to the middle of the body. It has 4 free anterior flagella
and a fifth one running along the outer margin of the undulating membrane, which is supported at its base by a flexible rod, the costa. A prominent axostyle runs throughout the
length of the body and projects posteriorly. There is a small cytostome at the anterior side.
The cytoplasm shows prominent granules. Parasite is motile, with a characteristic wobbling
or rotatory movement.
Life cycle. Sexual transmission is the usual mode of infection. The trophozoite is infective form. Parasites live and multiply by binary fission in the urogenital tract of the
patient.
Epidemiology. The disease is anthroponotic. Infected humans are the main source
of the infection. In the absence of cystic stage, transmission is possible mainly from
direct person to person contact. Although the parasites died rapidly out of the host
(e.g., for 35–40 min in water) transmission may occur where is a lack of proper toilets
or bathing facilities. Children may get infection through towels or sponges shared with
an infected parent. Infection by contaminated gynecologic and urologic instruments is
possible too.
Pathogenicity. Infection is often asymptomatic, particularly in the males. In females it
may produce severe pruritic vaginitis with an offensive, yellowish, often frothy discharge.
These may be complaints of local irritation or a burning and itching sensation in the vagina.
Diagnosis. Microscopic examination of vaginal or urethral discharge. Either wet mount
or stained smear examination is used. Sometimes parasite can be found in urine. Culture
method may be employed to increase the chance of identification. DNA testing is also
available in nowadays.
Prophylaxis. Personal prevention is to avoid occasional sexual contacts and to use
condoms. Control of the disease is sterilization of gynecologic and urologic instruments,
health education.
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Fig. 10.8. Trichomonas species: A – T. vaginalis; B – T. hominis; C – T. tenax; 1 – nucleus; 2 – axostyle; 3 – flagella; 4 – undulating membrane
Trichomonas Hominis
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It is a common commensal of the large intestine. There is a little evidence that it is
pathogenic for humans. T. hominis exists only as the trophozoite, which can survive outside the host body for a few hours or even days. Trophozoit measures 8 to 12 µm and
carries 3-5 free flagella and an undulating membrane that extends the full length of the
body (Fig. 10.8B). It is important to distinguish it from T. vaginalis as urine can frequently
contaminate faeces.
Trichomonas Tenax
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T. tenax measures 5–10 µm (Fig. 10.8C). It is a harmless commensal, which lives in the
mouth, in the periodontal pockets, carious teeth cavities and less often in tonsil crypts. It
doesn’t form cysts. About 30% of healthy adults are infected by T. tenax. Transmission is by
kissing or salivary droplets.
Haemoflagellates (Blood and Tissue Flagellates)
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Some common features of these parasites are:
1. All haemoflagellates have similar life cycles. They all require an insect vector for transmission of the disease and don’t form cysts.
2. Parasites metamorphose during development, a number of development stages and
tissue tropism are different for each species.
3. They live in the blood and tissues of man and other vertebrate hosts, and in the gut
of the insect vectors.
4. The specific morphological structure of haemoflagellates is kinetoplast. It is DNAcontaining part of a specialized large mitochondrion adjacent to the basal body.
These parasites have one nucleus and single flagellum. The portion of the flagellum,
which is inside the body of the parasite, is called an axoneme or axial filament.
10.4. Parasitic Flagellates
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Leishmania species
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Across the tropics a few important disease are caused by different species of Leishmania.
Leishmania donovani and Leishmania infantum are causative agents of visceral leishmaniasis.
Leishmania major and Leishmania tropica are causative agents of cutaneous leishmaniasis or Old World cutaneous leishmaniasis.
Leishmania brasiliensis and Leishmania mexicana – are causative agents of mucocutaneous leishmaniasis or New World cutaneous leishmaniasis.
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The life cycle of leishmania involves an alternate existence in a vertebrate and insect
host sand fly (Phlebotomus). Development of all leishmania species passes through two
stages (Fig. 10.9A):
Aflagellate stage (amastigote or leishmanial form). It is of an oval shape, 2–3 µm in
length, and has a large nucleus, occupying 1/3 of a cell. There is a short rod-shaped kinetoplast close to the nucleus. It is an intracellular parasite, which is present in the organism of
vertebrate animals and humans.
Flagellate stage (promastigote or leptomonade form). Its body is 10–20 µm long, with
one nucleus and one long flagellum. It is an extracellular parasite, which is present in a gut
of the biological vector sand fly (Phlebotomus).
Leishmania major and Leishmania tropica are causative agents of cutaneous leishmaniasis.
Geographical distribution. Countries with tropical and subtropical climate (Mediterranean countries, Middle East, India).
Location. Amastigote stage is present in the skin cells of the humans.
Morphology is typical for all leishmania.
Life cycle (Fig. 10.9B). Parasites are ingested by sand flies feeding at the site of skin lesions. In the midgut of the sand fly flagellate forms develop and replicate. In a week parasites become infective and concentrate in the forgut and proboscis of the sandfly. They are
in turn transmitted to the skin of persons bitten by the sand flies. Parasites remain confined
to skin, without being transported to the internal organs.
Pathogenicity. Developing of the ulcers at the place of bite.
Epidemiology. Infection occurs through the sand fly bite (vector born disease).
Leishmania tropica is the agent of anthroponotic (urban) type of the disease (Oriental
sore). The main source of the disease is a patient with leishmaniasis. Epidemic chain is as
follows: human being → sand fly → human being. The anthroponotic urban type ulcers
are painless, dry, often single, leading to disfiguring scars. This is seen mainly in children in
epidemic areas. The dry ulcers usually heal spontaneously in about a year.
Leishmania major (see Fig. 10.9B) is the agent of anthropozoonotic (rural) type of the
disease. The main source of the disease (reservoir) is rodents (rats, gerbils and others). Rural
type of the disease is a natural foci disorder.
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Kinetoplast
Basal body
Axoneme
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Kinetoplast
Basal body
Axoneme
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Flagellum
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Fig. 10.9. Leishmania: A – Amastigote; B – Promastigote; C – Life cycle of Leishmania major – a causative
agent of cutaneous leishmaniasis: 1 – promastigote forms of leishmania; 2 – biological vector sand fly
(Phlebotomus); 3 – amastigote forms in the body of the reservoir host
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Epidemic chain is as follows: rodents → sand fly → human being. The zoonotic rural
type ulcers are moist, inflamed and often multiple. The ulcers heal in 2 to 6 months.
Diagnosis. Demonstration of intracellular aflagellate forms in the skin cells from the
edge of the ulcer. If smear is negative, the material can be cultured on nutritive medium
and flagellate stages can be demonstrated.
Leishmania brasiliensis and Leishmania mexicana are causative agents of mucocutaneous leishmaniasis.
It is distributed in the regions of South and Central America with tropical and subtropical climate (Brasilia, Panama, Venezuela and other). Life cycle is similar with those
of L. major. Peculiarity of the disease is involvement of mucous membranes of the oral
cavity, pharynx, larynx and nose sometimes accompanied with destruction of the nose
cartilage.
Leishmania donovani and Leishmania infantum are causative agents of visceral leishmaniasis.
Geographical distribution. Regions with tropical and subtropical climate (Mediterranean countries, India, Sudan, China, Tropical Africa).
Location. Liver, spleen, red bone marrow, lymph nodes.
Morphology and life cycle are similar to other leishmania species. After the bite of infected sand fly parasites from skin migrate to the sites of location with bloodstream and
proliferate inside the cells of the lymphatic nodes, liver, spleen, red bone marrow.
Epidemiology. Infection occurs through the sand fly bite, in which gut promastigotes
multiply.
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Fig. 10.10. Life cycle of Leishmania infantum – a causative agent of visceral leishmaniasis: 1 – leptomonade
form of leishmania; 2 – sand fly (Phlebotomus); 3 – dogs, jackals – natural reservoirs for leishmania; 4 – leishmanial form in the bone marrow smear.
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Fig. 10.10. Life cycle of Leishmania infantum – a causative agent of visceral leishmaniasis: 1 – promastigote form of leishmania; 2 – sand fly (Phlebotomus); 3 – dogs, jackals – natural reservoirs for leishmania;
4 – amastigote form in the bone marrow smear
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L. donovani causes anthroponotic Indian visceral leishmaniasis (kala-azar). Human being is the only host and reservoir of the disease.
L. infantum causes anthropozoonotic Mediterranean (infant) leishmaniasis (Fig. 10.10).
Reservoir and source of infection are dogs or wild canines such as jackals, foxes and wolves.
The disease affects mostly young children. Infant leishmaniasis belongs to the group of
natural foci disorders.
Pathogenicity. The clinical symptoms begin with fever. Enlargement of spleen (splenomegaly) and liver (hepatomegaly) occurs. Splenomegaly starts early and is progressive and
massive. Enlargement of the liver and lymph nodes is not so prominent. Anemia occurs as
a result of the red bone marrow affection.
Diagnosis:
1. Direct methods: demonstration of the parasite in the red bone marrow or lymph
nodes aspirate. Specimens are got by puncturing. Culture method and animal inoculation (injection of aspirate to laboratory animals, like hamsters and microscopic
examination of their organs) are applicable also.
2. Indirect method: immunological tests (serodiagnosis – demonstration of antibodies
to leishmania in the blood serum).
3. Leishmania can be detected in affected tissues by DNA testing.
Prophylaxis. Prevention of cutaneous and visceral leishmaniasis is principally same.
Personal prophylaxis is usage of anti-sand fly measures: repellents, protective nets, bed curtains, mesh doors. Vaccination is effective measure for cutaneous leishmniasis prevention.
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Control of parasite and vector includes diagnosis and treatment of an affected individual, eradication of reservoir rodents; reducing the sand fly population by insecticides
spraying. Health education is also important.
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Trypanosoma species
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Trypanosoma brucei gambiense and Trypanosoma brucei rhodesiense are the agents
of African trypanosomiasis (sleeping sickness).
Geographical distribution. Western and central parts of the equatorial Africa.
Location. Blood plasma, lymph, lymph nodes, cerebrospinal fluid, brain, spinal cord,
kidneys and serous cavities.
Morphology. Body is extended, 17–28 µm long, uninucleated. It bears one flagellum
and undulating membrane (Fig. 10.11).
Life cycle . The life cycle of Trypanosoma involves an alternate existence in a vertebrate
and insect host tsetse fly (Glossina sp.). Vertebrate hosts are humans, domestic and wild
animals (mostly antelopes) (see Fig. 10.11).
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Fig. 10.11. The life cycle of Trypanosoma species (A – Trypanosoma brucei rhodesiense; B – Trypanosoma
brucei gambiense; С – trypanosome in the host organism): 1 – tsetse fly (Glossina morsitans) – biological
vector for agent of Rhodesian sleeping sickness; 2 – Trypanosomes in the organism of vector; 3 – antelopes –
reservoir hosts for trypanosome; 4 – tsetse fly (Glossina palpalis) – biological vector for agent of Gambian
sleeping sickness; 5 – Trypanosomes in the organism of vector; 6 – pigs – chronic asymptomatic carriers for
trypanosome; 7 – flagellum; 8 – nucleus; 9 – basal body; 10 – kinetoplast; 11 – undulating membrane; 12 – red
blood cells
10.4. Parasitic Flagellates
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Human infection is acquired by the bite of the tsetse fly, which is a biological vector of
the disease. On introduction into the skin, parasites proliferate initially and afterwards enter the blood stream and lymph nodes through the lymph. Invasion of the central nervous
system occurs after several months.
Epidemiology. The disease is anthropozoonotic. A human-being is considered to be a
reservoir host and source of infection for T. gambiense (Gambian sleeping sickness), though
pigs and other domestic animals can act as chronic asymptomatic carriers of the parasite.
Antelopes are main reservoirs for T. rhodesiense (Rhodesian sleeping sickness).
Pathogenicity. The central nervous system and internal organs are affected. The early clinical features are fever, enlargement of the lymph nodes, liver and spleen. Chronic meningoencephalitis develops after several months or even years. It manifests with increasing headache,
mental dullness, apathy and sleepiness. The patient falls into coma followed by death.
Diagnosis. Demonstration of parasite in blood smear, aspiration material from the
lymph nodes or cerebrospinal fluid. Sometimes cultivation or animal inoculation (rats) are
used. Serological tests and molecular-genetic tests have been also developed.
Prophylaxis. Prevention measures depend mainly on control of the vector. Contacts
between humans and tsetse flies need to be broken.
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Trypanosome cruzi is the agent of American trypanosomiasis (Chagas’ disease).
Geographical distribution is South and Central America.
Location: myocardium, brain, lymph nodes, liver and other internal organs.
Morphology. T. cruzi exists as promastigote (flagellate) and amastigote (aflagellate)
forms. Promastigote one is very much similar to T. brucei, and amastigote is similar to leishmania amastigote (Fig. 10.12).
Life cycle of T. cruzi passes in two hosts (see Fig. 10.12).
Vertebrate hosts are humans, and a variety of wild and domestic animals, such as opossums, armadillos, raccoons, wood rats, dogs and cats. Invertebrate host is triatomine (Reduviid or kissing) bug.
At night the bugs emerge from the cracks in the walls and painlessly extract a blood
meal from the sleeping people. Bugs defecate while feeding, and infection is acquired
when faeces of infected bug are rubbed into the bite wound or mucosal surfaces (conjunctiva). The parasite spreads through the lymphatic system and transforms into amastigote
form inside the cells of skeletal and cardiac muscles, neuroglia and other. At this stage intracellular multiplication of the parasite takes place. Then parasites turn into flagellate form
and releases into blood stream. These forms are infective for the triatomine bugs.
Pathogenicity. The most affected organ is the heart. Other commonly affected sites are
skeletal muscles and nervous system. Affection occurs as a result of intracellular multiplication of the parasite. Damage to the autonomic nerve cells often leads to “megadisease” –
dilatation of the esophagus, colon, and ureter.
Diagnosis is demonstration of the parasite in blood smears or tissues specimens or
serological tests. Animal (Guinea pig) inoculation may be done by blood, cerebrospinal
fluid or lymph node aspirate. Xenodiagnosis is possible. It is feeding of laboratory tri-
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Fig. 10.12. A – the life cycle of Trypanosoma cruzi: 1 – kissing bug (Triatoma infestans) – biological vector of trypanosomiasis; 2 – Trypanosomes in the organism of vector; 3 – armadillo – a natural reservoir of
American trypanosomiasis; 4 – Trypanosomes promastigote in blood of vertebrate host; 5 – red blood cells;
B – Trypanosoma form; C – Leishmanial form
atomine bug on the patient and demonstration of the parasite in intestinal contents of
the bug.
Prophylaxis. Control and elimination of vector bugs; provision of better housing as
most human infections are transmitted by bugs living in cracks and crannies in the walls.
Vaccination against the disease is at the stage of the field trials.
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10.5. Apicomplexa parasites
Classification
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Phylum: Apicomplexa
Class: Sporozoea
Order: Haemosporina
Species: Plasmodium malariae
Pl. vivax
Pl. ovale
Pl. falciparum
Order: Coccidia
Suborder: Eimeriina
Species: Toxoplasma gondii
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General characteristics of Apicomplexa (Sporozoa)
Malaria parasites
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Sporozoa are characterized by the following features:
`` All are pathogenic endoparasites.
`` The body has single nucleus and elastic pellicle or cuticle. They do not possess organelles of locomotion (i.e., flagella, pseudopodia, cilia) and digestion due to parasitic
way of life. The mode of nutrition is absorptive.
`` Specific feature is the presence of an apical complex (conoid and rhoptries) for entering the host cell.
`` The parasite requires two hosts and alternation of sexual and asexual reproduction
to complete its life cycle. Asexual reproduction occurs by multiple fission (schizogony). The sexual reproduction takes place by fusion of gametes resulting in the formation of zygote. It is followed by the formation of haploid spores. Thus life cycle of the
parasites includes stages of schizogony, gametogony, and sporogony.
`` An organism where parasite completes its sexual cycle is considered to be the definitive (primary) host. The intermediate (secondary) host is the one where parasite
multiplies asexually.
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Four species of malaria parasites (Plasmodium sp.) are known to infect man (Fig. 10.13):
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Fig. 10.13. Types of malaria parasites (Plasmodium sp.). A – Plasmodium vivax; B – Plasmodium malariae; C – Plasmodium ovale; D – Plasmodium falciparum: 1 – intact red blood cells; 2 – “ring” trophozoite;
3-5 – “amoeboid” trophozoite; 6 – “mature” trophozoite; 7 – schizont; 8 – morula; 9 – female gametocyte;
10 – male gametocyte
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Plasmodium vivax – causes benign tertian malaria or vivax malaria.
P. malaria – causes quartan malaria.
P. falciparum – causes malignant tertian malaria or falciparum malaria.
P. ovale – causes ovale-malaria. It is similar with benign tertian malaria.
Geographical distribution is from 40° S to 60° N in countries with different climate.
P. vivax has the widest geographical distribution and is the most common species of
malaria. It is prevalent in tropical, subtropical and temperate climate.
P. falciparum is responsible for the largest number of malaria cases. It is limited to tropical Africa, and some parts of Asia including India, because at temperatures below 20 °C its
development in mosquito is greatly retarded.
P. malariae occurs in tropical Africa, Sri Lanka and parts of India.
P. ovale is the rarest species and is seen mostly in tropical Africa.
Location. Hepatic cells, then erythrocytes (RBCs).
Morphology and life cycle. All species of Plasmodium have the life cycle involving two
hosts: man and various species of anopheline mosquitoes (Fig. 10.14).
In a human being parasites undergo asexual reproduction in the liver (tissue schizogony) and in the RBCs (blood schizogony). Therefore a man is an intermediate host. Sexual
forms of the parasites complete development in female anopheline mosquitoes (gametogony and sporogony), so mosquito acts as a definitive host.
Sporozoite is the infective stage of Plasmodium. It has an uninucliate, spindle-shaped
or crescent-shaped body covered by an elastic pellicle, 11–15 µm in length and 1.5 µm in
width.
An infected anopheline mosquito female bites a man and injects several hundred
sporozoites along with saliva into the blood. In 15–45 minute all sporozoites penetrate
into the liver cells where they grow and turn into tissue trophozoites. They undergo asexual reproduction by multiple fission or schizogony (tissue schizont stage). Daughter cells
are called tissue merozoits. This stage of development is called the tissue (hepatic or preerythrocytic) schizogony. Duration of this stage is about 8 days (Plasmodium vivax), 18 days
(P. malariae); 9 days (P. ovale) and 6 days (P. falciparum). After completing the tissue schizogony the infected liver cells burst open releasing thousands of merozoites (500–40.000)
which pass into the blood stream and attack the red blood cells.
Some of tissue sporozoites (hypnozoites) of Pl. vivax and Pl. ovale may stay in the liver
cells without the development, forming a reservoir of parasites which can prolong the disease in a latent form and cause late relapses of the disease.
After entering the erythrocytes each merozoite becomes trophozoite. There are a few
stages in this process, which have been given names because of their morphology (“ring”,
“amoeboid”, “mature” trophozoite). Stained by Giemsa, the early trophozoite appears to
consist of a blue ring of cytoplasm around the colorless vacuole and a dot-like red nucleus.
Trophozoit grows and forms pseudopodia (“ameboid” stage). “Mature” trophozoite is oval
and occupies almost all RBC. Then the nucleus of the trophozoite undergoes multiple division (schizogony), forming a schizont stage. Portions of cytoplasm segregate around the
daughter nuclei so that up to 24 small erythrocytic merozoites are formed. Development
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Fig. 10.14. Lyfe cycle of malaria parasites species: A – tissue schizogony (1 – sporozoite is inoculated in blood
and penetrates liver cells; 2 – tissue schizonts; 3 – tissue merozoites); B – erythrocytic schizogony (4 – erythrocytic trophozoites and schizonts; 5 – morula; 6 – erythrocytic merozoites); C – starting of gametogony in
human (7 – microgametocyte; 8 – macrogametocyte); D – completing of gametogony in mosquito (9 –
microgametes; 10 – fertilization of macrogamete; 11 – ookinete); E – sporogony (12 – oocyst; 13 – oocyst
with sporozoites)
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of the parasite inside the RBCs is called erythrocytic (blood) schizogony and continues for
48 hours (P. vivax, P. ovale, P. falciparum) or 72 hours (P.malaria). Then the exhausted erythrocytes burst out, the merozoites (1.5 µm by 1.0 µm in size) are released and invasion of
new RBCs takes place.
After several cycles of erythrocytic schizogony in some erythrocytes merozoites form
micro-(male) and macro-(female) gametocytes (beginning of gametogony). In four days
gametocytes become infective for mosquitoes. Further stages of the Plasmodium life cycle
occur just in mosquito.
Anopheles mosquito female takes up some male and female gametocytes with the
blood while feeding on infected person. The gametocytes release in the stomach of
mosquito where male gametocytes divide to form 6 to 8 long motile male gametes and
female gametocytes directly become female gametes (completing of gametogony).
Male gamete fuses with the female gamete to form zygote. A zygote elongates to become a worm-like motile organism called ookinete. The latter penetrates the stomach
wall. It becomes immobile and gets encysted (oocyst stage). About 200 to 5,000 such
oocysts may be seen on the outer surface of the stomach. The nucleus of the oocyst
(sporont) divides by meiosis and then by mitosis to form a large number of haploid cells
(sporogony). Finally up to 10,000 of uninucleate haploid sporozoites are formed in each
oocyst.
The oocyst ruptures and sporozoites emerge into the haemocoel (body cavity) of the
mosquito. Many of them penetrate the salivary glands of mosquito and from there enter
the human body with each bite.
The duration of the development of Plasmodium in mosquito is 7–45 days and depends
on the species of parasite and temperature of the environment.
Epidemiology. Malaria is an anthroponotic vector-born disease. The source of infection
is a man. There are three modes of transmission:
`` through the bite of infected mosquito, which is the biological vector of the disease.
Infective stage is sporozoit;
`` through placenta, from mother to fetus;
`` through blood transfusion.
In last two cases infective are the stages of erythrocytic schizogony.
Pathogenicity. The main clinical features are fever peaks followed by anemia and splenomegaly.
The typical malarial attack has three distinct stages: the cold stage with chill and shivering, the hot stage with hot sensation and high temperature; the sweating stage with
profuse sweating and rapid dropping of the temperature. Fever paroxysm usually lasts for
8 to 12 hours.
Malaria attacks follow the completion of erythrocytic schisogony and are due to releasing of merozoites, red cell fragments, malarial pigment and other parasitic debris. The periodicity of the attacks varies with the species of the parasite. It is approximately 48 hours
(each third day) in tertian malaria and 72 hours (each forth day) in quartan malaria. Anemia
with hepatosplenomegaly develops gradually.
10.5. Apicomplexa parasites
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Duration of untreated infection for falciparum malaria is 6 to 17 months, for vivax malaria is 5–8 years, for ovale malaria – 12–20 months. For quartan malaria late relapses of the
disease has been described in up to 50 years from initial infection. It is explained by constant low level of erythrocytic schisogony in such patients. The most severe is falciparum
malaria, which is usually fatal in non-immune individuals without treatment.
Diagnosis. The most important method is the demonstration of the parasites in blood.
The parasites are most abundant in the peripheral blood late in the febrile paroxysm, a few
hours after the peak of the fever. Therefore, blood smears should be collected at this period. In practice, it is advisable to obtain blood smear when a patient is first seen, and then
a few hours after the height of the fever.
Two types of blood films are prepared for examination: thick and thin films. The drop
of blood from the finger top is touched with a clean dry slide near one end. The blood is
spread on the slide with the corner of another slide to produce a square or circular patch of
moderate thickness. This is a thick film.
For a thin film preparing a small drop of blood is collected on the slide. The blood is
spread evenly and thinly with the edge of a spreader slide to make thin unicellular layer.
Thick blood smears are generally more sensitive for the detection of parasites, whereas
thin smears are preferable for species identification.
Repeated blood smears have to be examined before a negative result is given as blood
parasites may be scarce.
Prophylaxis. Personal prophylaxis is avoiding mosquitos bites by suitable clothing, using bed curtains (particularly nets impregnated with permethrin) or application of repellents on the exposed skin.
For travelers visiting endemic areas, chemoprophylaxis (intake of anti-malaria medicines) provides effective protection. Prophylaxis should begin on the day of arrival and to
be continued for 4 to 6 weeks after departure.
Control of the disease must be directed at breaking the human-mosquito life cycle.
It includes: 1) treatment of malaria cases; 2) vector control measures like environmental
modification, usage of chemical larvicides and insecticides, biological methods; 3) health
education.
The 1902 Nobel Prize in Physiology or Medicine was awarded to Ronald Ross "for his work on
malaria, by which he has shown how it enters the organism and thereby has laid the foundation
for successful research on this disease and methods of combating it”.
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The 1907 Nobel Prize in Physiology or Medicine was awarded to Charles Laveran "in recognition
of his work on the role played by protozoa (of the Plasmodium family) in causing diseases”.
Toxoplasma gondii
Toxoplasma gondii is a causative agent of toxoplasmosis.
Geographical distribution. It is worldwide in distribution and causes natural infection
in over 200 species of the birds, reptiles and mammals, including man that serves as an in-
Chapter 10. General notions of parasitology. Protists as human parasites
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termediate host. About one third of the human race is
believed to be infected with the parasite though clinical disease results rarely.
Location. It is an intracellular parasite, which may
develop in the liver, spleen, brain, lymphatic nodes,
eyes, muscles and other organs.
Morphology. Toxoplasma gondii is an intracellular parasite. Stage which develops in the cells of the
host is trophozoite (endozoite). The endozoite is crescent shaped with one end pointed and the other end
rounded (Fig. 10.15). It measures approximately 3 µm
up to 7 µm. The nucleus is ovoid and situated nearer
to the blunt end of the parasite. Electron microscopy
reveals an apical complex, consisting of conoid and
rhoptries, at the pointed end.
Like in other Apicomplexa life cycle includes stages
of asexual reproduction (endodyogeny), sexual reproduction (gametogony) and sporogony which occurs in
outer environment.
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Life cycle
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Toxoplasma completes its life cycle in two kinds of Fig. 10.15. Trophozoite toxoplasma
hosts (Figs. 10.16, 10.17).
under electronic microscope:
Definitive host is a cat or any other felines, which 1 – conoid; 2 – rhoptries;
3 – pellicle; 4 – nucleus
also serves as intermediate host.
Intermediate hosts are men, mice and other mammals (more than 200 species), birds (more than 100 species), and even reptiles.
Life cycle of the toxoplasma includes:
`` endodyogeny in an intermediate host;
`` endodyogeny, schizogony and gametogony in definitive host;
`` sporogony in soil or water.
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Development in Man
Infection usually occurs after the ingestion of oocysts (through dirty hands or contaminated food and water) or by eating improperly cooked meat of infected animals. In man
and other intermediate hosts asexual development of the parasite occurs. From the site
of entry parasites with blood and lymph flow get to such organs as the liver, spleen, brain,
lymph nodes, eyes and muscles. Trophozoites can invade any nucleated cell and replicate
by a process called endodyogeny or internal budding (two daughter trophozoites being
formed within the parent cell). When the host cell becomes distended with the parasites, it
disintegrates releasing the trophozoites which infect other cells. Actively multiplying parasites are called tachyzoites. During acute infection, the proliferating trophozoites within a
10.5. Apicomplexa parasites
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Fig. 10.16. Toxoplasma life cycle: 1–6 – schizogony in cat's epithelial cells of small intestine; 7 – penetration of
merozoites into the epithelial cells of the small intestine; 8 – formation of macrogametocytes; 9 – formation
of microgametocytes; 10 – a macro- and microgamete; 11 – zygote (oocyst) shedding with the cat feces,
sporogony; 12 – oocyst maturation in soil; 13 – mature oocysts containing two sporocysts with 4 sporozoites in each (sporulation in the outer environment); 14–22 – endodyogeny in tissues of the definitive and
intermediate hosts (14–16 – formation of pseudocysts; 17 – pseudocyst ruptures, endozoites infect other
cells; 18–22 – formation of tissue cysts); 23 – cyst gets to the intestine of cat with meat
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host cell may appear rounded and enclosed by the host cell membrane. This structure is
called the “pseudocyst” or “colony” (see Fig. 10.17).
Formation of pseudocysts in cells of internal organs is characteristic for the acute period
of the disease. With the immune response parasites start to form tissue cyst. Parasites multiplying slowly within the host cell produce a tough cyst wall. Such a cyst contains thousands
of parasites (bradizoites) and remains viable for several years. A tissue cyst is formed during
the chronic phase of the infection and can be found in the muscles and other tissues and
organs, including the brain. In immunocompetent persons formation of tissue cysts starts
very soon so they don’t manifest the disease. In normal immune response the cysts remain
silent, but in a immunocompromised person they may get reactivated, leading to clinical
disease.
Development in Cat
Infection occurs after the ingestion of oocysts or by eating meat of infected animals.
Sexual development of the parasites undergoes in the epithelial cells of the small intestine.
They grow within the host cells and asexual form of division (schizogony) occurs first lead-
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Endodyogeny in the inner organs
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Cat serves as definitive and
intermediate host
Schysogony and
gametogony in small
intestine
Sporogony in soil
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Transplacental
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B
Endodyogeny in intermediate hosts
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Fig. 10.17. Life cycle and circulation of toxoplasma: A – endozoite; B – pseudocyst; C – tissue cyst
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ing to the formation of merozoites. Some merozoites enter extra-intestinal tissues and multiply by endodyogeny (asexual development as in intermediate hosts). Some merozoites
invade intestinal epithelial cell and initiate gametogony. A macrogamete is fertilized by a
motile microgamete resulting in the formation of the immature oocyst.
The oocyst is spherical or ovoid, about 10 to 12 µm in size and contains a sporoblast. Cats
shed millions of oocysts per day in faeces for about two weeks during the primary infection.
Development in the outer environment
A freshly passed oocyst becomes infectious only after undergoing sporogony in soil or
water. It lasts from 2 days to three weeks depending on the environmental conditions. Dur-
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ing the sporogony sporoblast divides into two sporocysts followed by development of four
sporozoites inside each. The mature oocyst with eight sporozoites is the infective form. It is
very resistant to environmental conditions and can remain infective in soil for about a year.
When the infective oocyst is ingested, it releases sporozoites in the intestine of the host,
which initiate infection.
Epidemiology. Human toxoplasmosis may be acquired as follows:
`` ingesting food containing parasites (raw or half-raw meat or force-meat). Infective
stage is pseudocyst or tissue cyst with endozoites;
`` through dirty hands or food contaminated with oocysts (vegetables, berries, fruit,
non-boiled water);
`` transplacental transmission from mother to fetus;
`` occupational transmission to laboratory personnel, veterinarians and slaughterhouse workers through the broken skin (scratches);
`` organs transplantation and granulocytes transfusion;
`` blood transfusion (rare).
A human being is a blind alley for toxoplasma as a rule and doesn’t serve as a source of
infection for other hosts.
Pathogenicity. Clinical toxoplasmosis may be congenital or acquired.
Congenital toxoplasmosis results when infection is transmitted transplacentally from
mother to fetus. This occurs only when the mother gets primary toxoplasma infection, either clinical or asymptomatic, during the pregnancy. Mothers with chronic or latent toxoplasmosis acquired earlier do not infect their babies.
Severity of fetal damage is higher in early pregnancy. Spontaneous abortion or congenital defects occur at this period. Children infected in the middle of the pregnancy may develop clinical manifestations of toxoplasmosis in weeks, months or even years after birth.
Children have cerebral calcifications, hydrocephalus, microcephaly, affection of retina. In
future there can be strabismus, blindness, deafness, epilepsy, mental retardation. If infection occurs in late pregnancy, children are born with manifestations of acute toxoplasmosis, like fever, jaundice, diarrhea, petechial rashes.
Infection acquired in the postnatal period is mostly asymptomatic. In immunocompetent persons tissue cysts are formed quickly and person becomes a healthy carrier of the
parasite. Prevalence of asymptomatic infection vary from 10 to 90 % from place to place.
Chronic toxoplasmosis can develop in some infected persons. The commonest manifestations in this case are lymphadenopathy, chorioretinitis, headache, fatigue. Approximately,
35 % of cases of chorioretinitis in the USA and Europe have been reported to be due to
toxoplasmosis.
Toxoplasmosis is severe in the immunocompromised persons, particularly in AIDS patients, either it is due to reactivation of latent infection or to new acquisition of infection.
Acute toxoplasmosis in adults is one of the AIDS-associated diseases.
Diagnosis:
1. Serodiagnosis. Various serological tests are available for the serological diagnosis of
toxoplasmosis. It is demonstration of antibodies to toxoplasma in blood serum.
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2. Demonstration of trophozoites in lymph nodes aspirate, bone marrow aspirate, cerebrospinal fluid establishes the diagnosis of acute toxoplasmosis. Examination of
amniotic fluid, placenta or tissues of the newborn establishes the diagnosis of congenital infection.
3. Isolation of T. gondii. The organism can be isolated by inoculating body fluids, leukocytes, or tissue specimens into the peritoneal cavity of mice, or into tissue cultures.
Mice should be examined for Toxoplasma in peritoneal fluid at 6–10 days after inoculation or earlier if they die (biological method of diagnosis).
4. Intra-skin allergic test with toxoplasmin. Presence of toxoplasma is marked by swelling and redness at the place of antigen injection.
5. Molecular-genetic diagnosis (DNA testing).
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Prophylaxis. The measures recommended for prevention and control of toxoplasmosis
include:
`` proper hand washing, washing of fruit and vegetables, boiling of water;
`` proper cooking of meat. Cysts in meat can be killed by either heating up to 60 °C for
30 min or freezing to -20 °C;
`` prevention of human-cat contact. Pregnant women are advised to avoid exposure
to cats.
TASKS & QUESTIONS
`` Multiple Choice Questions (Choose one correct answer):
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1. The following form of Entamoeba histolytica is pathogenic for humans:
C. Cyst
A. Forma magna
B. Forma minuta
D. Pre-cystic form
2. Which material is used for balantidiasis laboratory tests?
A. Duodenum content
D. Urine
B. Blood
E. Vaginal discharges
C. Faeces
3. Number of nuclei in cyst of amoeba is an important criterion in discrimination between Entamoeba histolytica and:
D. Entamoeba gingivalis
A. Trichomonas hominis
B. Giardia lamblia
E. Balantidium coli
C. Entamoeba coli
4. The rounded cysts with two unequal nuclei, covered with thick envelope were discovered in water samples from the pig farm sewage. They are cysts of:
A. Giardia lamblia
D. Entamoeba coli
B. Entamoeba histolytica
E. Trichomonas hominis
C. Balantidium coli
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5. Direct infection from a sick person is possible in:
A. Amoebiasis
C. Leishmaniasis
E. Toxoplasmosis
B. Malaria
D. Trypanosomiasis
6. Keeping personal hygiene rules is particularly significant for prevention of:
A. Amoebiasis
C. Leishmaniasis
E. Chagas’ disease
B. Malaria
D. Trichomoniasis
7. Toxoplasma gondii may develop in the following intermediate hosts, EXCEPT:
A. Humans
C. Birds
E. Fish
B. Cattle
D. Pigs
8. Which of the following Protozoans may affect brain and eyes in human?
A. Leishmania tropica
C. Plasmodium vivax
E. Entamoeba gingiB. Giardia lamblia
D. Toxoplasma gondii
valis
9. Which of the following infections during pregnancy may be manifested as congenital disorders and mental retardation in the newborn?
A. Toxoplasmosis
C. Trichomoniasis
E. Leishmaniasis
B. Trypanosomiasis
D. Malaria
10. Toxoplasma is characterized by ALL mentioned below, except for:
A. Have a wide range of hosts
B. Cat is a definitive host
C. Sick person is a main source of infection
D. Spread widely
E. Endozoites are crescent-shaped:
11. Cats are definitive hosts for Toxoplasma, because in its organism ... occurs.
C. Gametogony
A. Endodyogeny
B. Schizogony
D. Sporogony
12. A person has preliminary diagnosis of toxoplasmosis. What material should be used
for laboratory diagnosis of the disease?
A. Feces
C. Blood
B. Sputum
D. Urine
13. Serological tests are used for the diagnosis of:
A. Giardiasis
C. Amoebiasis
E. Balantidiasis
B. Toxoplasmosis
D. Trichomoniasis
14. Life cycle of Malaria parasite in human organism finishes at the following stage:
A. Gametocytes
C. Ookinete
E. Schizonts
B. Gametes
D. Sporozoites
15. Plasmodium malariae is the agent of:
A. Benign tertian malaria
C. Benign quartan malaria
B. Malignant tertian malaria
D. Ovale malaria
16. Infective stage of Plasmodium for humans is:
A. Sporozoites
C. Schizonts
E. Gametes
B. Merozoites
D. Gametocytes
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Chapter 10. General notions of parasitology. Protists as human parasites
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17. Incubation period of malaria corresponds to the following stage of malaria parasite
in human organism:
A. Sporogony
D. Schizogony in RBC
B. Tissue schizogony
E. Endodyogeny
C. Gametogony
18. Individual preventive measures against malaria include:
A. Protection from mosquitos
B. Identification and treatment of sick persons
C. Follow rules of personal hygiene
D. Flies and cockroaches control
19. Malaria fever attack starts along with the following stage of malaria parasite:
A. Tissue schizogony
D. Merozoites penetrate into RBC
B. Gametocytes formation
E. Mature schizonts formation
C. Merozoites release from RBC
20. 48-hour duration of RBC schizo­gony is characteristic for ALL species of malaria parasites EXCEPT:
C. Plasmodium falciparum
A. Plasmodium malariae
B. Plasmodium ovale
D. Plasmodium vivax
21. Which parasites from mentioned below inhabit the human small intestine?
A. Balantidium coli
D. Leishmania donovani
B. Giardia lamblia
E. Entamoeba histolytica
C. Trichomonas vaginalis
22. An ability of parasites to produce harmful effect and to cause a disease is:
A. Pathogenicity
D. Preying
B. Mutualism
E. Commensalism
C. Parasitism
23. Sexual transmission is possible in:
A. Giardiasis
D. Leishmaniasis
B. Toxoplasmosis
E. Trypanosomiasis
C. Trichomoniasis
24. Parasites inhabiting inner organs of the host are:
A. Ectoparasites
D. Obligatory parasites
B. Endoparasites
E. True parasites
C. Optional parasites
25. Preventive measures against giardiasis include:
A. Washing hands
D. Treatment of the patients
B. Washing fruits and vegetables
E. All of the above
C. Boiling of water
26. Trophozoits of which protozoans are infective for human:
A. Trichomonas vaginalis
D. Balantidium coli
B. Giardia lamblia
E. Entamoeba coli
C. Entamoeba histolytica
10.5. Apicomplexa parasites
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27. Laboratory diagnosis of giardiasis is done using:
A. Microscopy of duodenum content
D. Microscopy of blood smear
B. Serologic tests
E. Sputum microscopy
C. Infection of laboratory animals
28. Diseases that affect both humans and animals are termed as:
A. Zoonosis
E. Nature foci
C. Anthropozoonosis
B. Anthroponosis
D. Vector-born
29. Nature foci diseases:
A. Exist in certain biogeocenosis independently on human presence
B. Agents circulate among wild animals
C. Exist on territories with certain geographic conditions
D. Leishmaniasis is an example
E. All of the above
30. Control of leishmaniasis includes all EXEPT for:
A. Extermination of sand flies
D. Extermination of street dogs
E. Treatment of sick persons
B. Extermination of rodents
C. Control of mosquitoes
31. Blood sucking insects are vectors for ALL diseases EXCEPT for:
A. Cutaneus leishmaniasis
D. African trypanosomiasis
B. Visceral leishmaniasis
E. American trypanosomiasis
C. Giardiasis
32. African sleeping sickness is caused by:
A. Leishmania tropica
D. Trypanosoma cruzi
B. Giardia lamblia
E. Trypanosoma gambiense
C. Leishmania donovani
33. South American trypanosomiasis vector is:
A. Sand fly
C. Mosquito
E. Flea
B. Tsetse fly
D. Triatomine bug
`` FILL IN THE BLANKS:
R
1. _______________ is types of symbiosis which benefits both participants.
2. __________ parasites become parasitic if they have an opportunity, otherwise they
exist in free living state.
3. Parasites adapted to one certain host are called ___________________.
4. Healthy cyst carriers serve as a source of infection for their surroundings and it is
characteristic for following disorders __________, __________, __________.
5. The simplest classification of Protozoa is based on the means of their locomotion and
includes______________, ____________, __________ and __________.
6. Schizogony and gametogony of toxoplasma occurs in __________ of cat.
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Chapter 10. General notions of parasitology. Protists as human parasites
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7. Kinetoplast is a specific morphological feature characteristic for species of
___________ and ___________.
8. Some of tissue sporozoites (_______________) of Pl. _______ and Pl._______ may
stay in the liver cells without the development, forming a reservoir of parasites.
`` TRUE OR FALSE:
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1. Commensalism is an interaction in which one of the organisms benefits from the
relationship and another one is injured.
True
False
2. Temporary parasites spend the whole life in the host organism or on its surface.
True
False
3. Example of disease with natural foci is trypanosomiasis in certain area of tropical Africa.
True
False
4. Diseases that affects both humans and animals are called zoonosis.
True
False
5. In the lower part of the small intestine each nucleus of injected Entamoeba hystolytica cyst divides and gives 8 minuta forms.
True
False
6. Trichomonas Tenax is pathogenic and causes trichomoniasis.
True
False
7. In the case of transplacental infection by toxoplasmosis the invasive stage is oocyst.
True
False
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CHAPTER 11.
Helminths. Flat and round worms
as human parasites
IC
TE
Parasitic worms are termed helminths (from Greek helmins – worm), so diseases they
cause are called helminthoses.
Helminths belong to two phylums: Plathelminthes and Nemathelminthes. Phylum
Plathelminthes includes parasitic classes Trematodes and Cestoidea while Nemathelminthes
has only one parasitic class Nematoda.
According to the peculiarities of their development helminths are divided into two
groups: bio- and geohelminths. Biohelminths are worms with alternation of definitive and
intermediate hosts in their life cycle (Fig. 11.1). Definitive host is the one, in which adult
worms multiply sexually. Development of larvae occurs in the organism of intermediate
host. If intermediate host is absent and larval stage maturates in an environment (usually
in soil) parasitic worms are considered as geohelminths (Fig. 11.2).
infected
human
Factors of transmission
TR
Source of invasion
animals
the
environment
intermediate
host
elements of the
environment
susceptible
person
Fig. 11.1. Transmission of biohelminths
EC
Source of invasion
infected
human
animals
factors of transmission
elements of the environment
susceptible
person
R
Fig. 11.2. Transmission of geohelminths
11.1. General characteristics of flat worms.
Flukes (Trematodes)
General features of phylum Plathelminthes (Flat worms):
1. Bilateral symmetry of body which is flattened dorsoventrally.
2. They are triploblastic animals, i.e., arise from three germ layers: ecto-, endo- and mesoderm.
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CHAPTER 11. Helminths. Flat and round worms as human parasites
Classification
IC
Trematodes (flukes)
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3. Body cavity is absent, inter-organic space is filled with parenchyma (loose connective
tissue).
4. The body is enclosed by a single layer epidermis or by firm tegument and three muscle layers (circular, longitudinal and oblique).
5. The digestive tract, if present, is incomplete, i.e., consists of for- and midgut, which
ends blindly.
6. Circulatory and respiratory systems are absent.
7. Excretory system is of protonephridial type. It consists of flame cells, leading into
tubules that open out by one or more excretory pores.
8. The nervous system comprises cerebral ganglia and two main nervous trunks connected at intervals by transverse commissures.
9. The reproductive system is well developed. Mostly are hermaphrodites.
10. All of them are biohelminths.
TR
Phylum: Plathelminthes
Class: Trematodes
Species: Fasciola hepatica (liver fluke)
Opisthorchis felineus (cat fluke)
Clonorchis sinensis (Chinese liver fluke)
Paragonimus westermani (lung fluke)
Schistosoma haematobium
S. japonicum, S. mansoni (blood flukes)
Dicrocoelium lanceatum
Nanophyetus salmincola
Metagonimus yokogawai
Morphology of Trematodes
R
EC
Trematodes (from Greek trema – hole, eidos – appearance) are characterized by:
1. Flat leaf-like unsegmented body (Fig. 11.3). Typical external feature is presence of
two prominent suckers (oral and ventral) for fixation. A ventral sucker is also known
as the acetabulum.
2. The wall of the body consists of a thick noncellular layer of cuticle, followed by a thin
base membrane and underlying muscles. A tough resistant cuticle made of scleroprotein, protects the fluke from the juices of the host. It bears small spines, spinules
or scales. The spinules anchor the fluke, provide protection and facilitate locomotion.
3. The digestive system consists of the mouth cavity, muscular pharynx, oesophagus
and intestine. The last one divides into two lateral branches running on either sides
of the body to the posterior end and ending blindly. There is no anus. Indigestible
remains of food are passed out through the mouth.
4. Excretory and nervous systems have typical for flat worms structure.
11.1. General characteristics of flat worms. Flukes (Trematodes)
1
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2
3
19
18
6
7
8
9
10
11
12
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17
5
TE
23
22
21
20
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4
13
14
TR
15
16
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Fig. 11.3. Morphology of flukes: 1 – mouth and oral sucker; 2 – pharynx; 3 – esophagus; 4 – intestine; 5 – female genital pore; 6 – male genital pore; 7 – uterus; 8 – vitellaria; 9 – ootype; 10 – vitelline duct; 11 – ovary;
12 – sperm duct (vas efference); 13 – testis; 14 – blind ends of intestine; 15 – excretory bladder; 16 – excretory
pore; 17 – Layrer's canal; 18 – Mehlis' gland; 19 – seminal receptacle; 20 – ejaculatory duct (vas defference);
21 – seminal vesicle; 22 – ventral sucker; 23 – cirrus sac with cirrus
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5. The majority of flukes are hermaphrodites. Fertilization is internal. The anatomy of
the reproductive system encourages cross-fertilization, though self-fertilization may
take place. The reproductive organs are complex and occupy most of the body.
The male reproductive system consists of testes (usually two), sperm ducts (vas efference), seminal vesicles, ejaculatory duct (vas defference) and cirrus. The cirrus opens by
male genital aperture in a common genital atrium.
The female reproductive system consists of one ovary with oviduct, seminal receptacle,
uterus, yolk bodies or vitellaria, Mehlis’ gland (produce shell of the eggs), Laurer’s canal (may
serve as a vagina or as a reservoir of excess shell material) and ootype. Ootype is a central
organ of female reproductive system. It is a small sac-like organ in which all other organs
enter, the parts of an egg are assembled and the eggs are shaped. The eggs pass from the
ootype into the uterus. It is the largest organ of the body and contains thousands of eggs. It
opens in the common genital atrium.
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CHAPTER 11. Helminths. Flat and round worms as human parasites
6. Eggs are yellow or yellow brown, oval in shape. There is an operculum on anterior
end and a small knob on posterior end, except those of schistosomes.
Life cycle of Trematodes
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All flukes are biohelminths. They have complicated life cycles with alternation of the
hosts and generations. Presence of polyembryogenesis (multiplication of larvae) provides
progressive increasing of parasite number during the development.
Sexual reproduction of Trematodes occurs in an organism of definitive host. Trematodes
are oviparous (lay eggs). The life cycle of Trematodes is as follows:
1. The eggs in most of species develop in water. The first stage larva, motile ciliated
miracidium, escape into water and penetrates the intermediate host – a freshwater
snail.
2. Inside the snail the miracidium turns into the sac-like sporocyst. In the sporocyst
germ cells give the origin for maternal and daughter rediae stages, which in turn
produce cercariae. The asexual multiplication during larval development is of great
magnitude and in some species a single miracidium may give rise to over a half million cercariae.
3. Cercariae are the tailed larvae, they escape from the snail into water. In some species cercariae encyst on water vegetation to form adolescariae (infective stage). In
other species they invade second intermediate host (fish, crabs or others) to form the
metacercariae, which are infective stages. Infection is acquired by ingesting adolescariae from aquatic plants or by metacercariae from second intermediate host.
Diseases brought with trematodes are called trematodoses. The liver fluke, the cat fluke,
the lung fluke, the blood fluke are examples of trematodes, which infect man.
Fasciola Hepatica (liver fluke)
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EC
Fasciola hepatica or the liver fluke is an agent of fascioliasis (Fig. 11.4).
Geographical distribution. Sheep and cattle-rearing areas.
Morphology. The adult worm is leaf-shaped, 30 mm long and 15 mm broad, grayish
brown in color. It has a conical projection anteriorly and is rounded posteriorly.
The eggs are large, ovoid, operculated, yellow and about 130–150 µm × 80 µm in size.
Location. The adult worm inhabits the bile ducts and gallbladder of the definitive host.
Life cycle. The definitive hosts are herbivorous animals – sheep (main reservoir host),
cattle, pigs, horses and sometimes humans.
The intermediate hosts are snails of the genus Lymnea.
In the definitive host eggs are laid in the bile ducts and are passed out in the faeces.
The embryo matures in water in about 10 days and the miracidium hatches out. It
should penetrate the snails of the genus Lymnea (Lymnea truncatula) within eight hours.
In snail the miracidium progress through the sporocyst, redia and cercaria stages in about
1 or 2 months. The cercariae escape into the water and encyst on aquatic vegetations to
become adolescaria (metacercaria) which can survive for a long period.
11.1. General characteristics of flat worms. Flukes (Trematodes)
Suckers
279
Uterus
Ovary
D
2
3
Testis
11
10
5
6
7
9
IC
1
TE
Vitellaria
4
TR
8
Fig. 11.4. Morphology and life cycle of the liver fluke (Fasciola hepatica): 1 – adult worm (marita); 2 – definitive hosts; 3 – the egg; 4 – miracidium; 5 – intermediate host (snails of the genus Lymnea); 6 – sporocyst;
7 – maternal redia; 8 – daughter redia; 9 – cercaria; 10 – adolescaria (metacercaria); 11 – adolescaria on the
grass
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Sheep, cattle or man become infected while eating water vegetation or drinking water
with adolescaria, which is the infective stage for the definitive host. The infective larva excysts in the duodenum and migrates through the intestinal wall, liver capsule, liver parenchyma and reaches the bile ducts. Parasites become mature in 3–4 months and live in the
host organism for 5 years or even more.
Pathogenicity. Fasciola causes mechanical injury of the liver parenchyma and obstruction of the bile ducts. Metabolic products of the helminths cause toxic-allergic
reactions. Patients present initially with loss of appetite, fever, epigastric pain, hepatomegaly. At the chronic stage inflammation of the gall bladder, liver, and mechanical
jaundice are common. Mechanical irritation of the tissues may provoke liver cirrhosis
and even cancer.
Diagnosis. Demonstration of the eggs (ovoscopy) in aspirated bile or feces. There might
be a misdiagnosis if person consumes liver of animals sick with fascioliasis. The fasciola
eggs in this case pass through the intestinal tract and can be demonstrated in feces (transitory eggs). To avoid spurious diagnosis patients are recommended to exclude liver from
the diet 3–5 days before testing. Serodiagnosis is applicable.
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CHAPTER 11. Helminths. Flat and round worms as human parasites
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Prophylaxis:
Personal prevention: to boil water and to wash vegetables.
Control of the disease:
1. Health education.
2. Prevention of fecal contamination of water used for plant watering.
3. Veterinary control and treatment of affected sheep and cattle and changing of the
pastures if highly contaminated. Contaminated water reservoirs are treated with
molluskicides for killing the intermediate host.
Opisthorchis felineus (cat fluke)
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EC
TR
IC
Opisthorchis felineus (cat fluke) is the agent of opisthorchiasis (Fig. 11.5).
Geographical distribution. Opisthorchis felineus is common in Europe and Russia, especially in Siberia where raw fish is consumed traditionally. In Ukraine it is spread in the basins
of large rivers.
Location in the organism of definitive host is the bile ducts, gallbladder, pancreatic
ducts.
Morphology. The body is lancet-shaped and measures 8–13 mm long and 1.2–2.2 mm
broad. Usually there is a reverse dependence between number and size of parasites in the
infected individual. The body is semi-transparent and internal organs can be easily seen. The
intestine is shaped as two nonbranched tubes. Two testis with 4 to 5 lobes are present in the
posterior part of the body. Excretory bladder is S-shaped and lies between testis. The uterus
filled with eggs lies in the middle. Yolk sacks are located laterally. The ovaries shaped as compact slightly lobed bodies lie between uterus and testis. The ejaculation tube is behind them.
Eggs are oval, operculated, yellowish brown and measure 25–30 µm × 10–15 µm.
Life cycle. Development takes place with alternation of three hosts – one definitive and
two intermediate hosts.
The definitive hosts are humans, cats, dogs and other fish eating canines, rats, pigs. Two
intermediate hosts are required to complete life cycle. The first intermediate host is fresh
water snail, the second one – fish.
The eggs are excreted with faeces, miracidium does not hatch in water, but only when
ingested by the first intermediate host (snail of genus Bithynia). In about three weeks cercariae emerge from the mollusk's body and swims attaching itself to a body of the second
intermediate host – Cyprinid fish (at least 80 species). Metacercariae develop in the muscles of the fish within next 6 weeks.
Infection occurs when such fish is eaten raw or inadequately processed. Infective stage
for definitive host is metacercarium. Life span of the parasite is 1 to 20 years.
Opisthorchiasis belongs to the group of nature foci disorders.
Pathogenicity. Parasites cause mechanic and toxic allergic damage of the liver and
pancreas. Clinical manifestations resemble one of fascioliasis. One of the key symptoms is
inflammation of the pancreas. Chronic infection may cause cirrhosis or cancer of the liver
and pancreas.
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11.1. General characteristics of flat worms. Flukes (Trematodes)
Uterus
Testis
Intestine
D
Suckers
TE
1
Excretory
bladder
TR
IC
2
9
EC
10
3
4
5
8
7
6
8а
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Fig. 11.5. Morphology and life cycle of the cat fluke (Opisthorchis felineus): 1 – adult worm (marita); 2 – definitive hosts; 3 – the egg; 4 – first intermediate host (snail Bythinia); 5 – miracidium; 6 – sporocyst; 7 – redia;
8 – cercaria; 8a – cercaria living the snail; 9 – second intermediate host (Cyprinidae fish); 10 – metacercaria
Diagnosis is the same as for fascioliasis. The eggs may be demonstrated in faeces (ovoscopy) or aspirated bile. Serologic tests at early stage of infection.
Prophylaxis. Personal: to process fish properly. Fish should be heated for 15–20 min or
dried in the sun for at least 14 days for destruction of the larval stages.
Control of the disease includes health education, treatment of the cases.
CHAPTER 11. Helminths. Flat and round worms as human parasites
Uterus
Two testis
B
TE
A
D
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Fig. 11.6. Clonorchis sinensis (Chinese liver fluke): A – adult worm (marita); B – egg
Clonorchis sinensis (Chinese liver fluke)
IC
Clonorchis sinensis (Chinese liver fluke) is the agents of clonorchiasis.
C. sinensis (Fig. 11.6) resembles cat fluke by size, shape, life cycle and medical aspects,
but has different geographical distribution and some morphological peculiarities. It is
common in Vietnam, Korea, China, Japan, also has been reported from India. Distinct morphological feature is the deeply branched testes lie in tandem at the posterior end of the
body.
TR
Dicrocoelium lanceatum or dendriticum (lancet fluke)
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Dicrocoelium lanceatum (lancet fluke) is the agent of dicrocoeliasis (Fig. 11.7).
Geographical distribution. Dicrocoelium lanceatum is worldwide among the herbivorous mammals. In humans disease is sporadic and reported rarely.
Location in the organism of definitive host is the bile ducts and gallbladder.
Morphology. The body is lancet-shaped and measures 5–15 mm long and 1.5–2.5 mm
broad. The characteristic feature is presence of two slightly lobed testis anterior to the ovary. The voluminous uterus occupies the posterior two-thirds of the worm.
Eggs are thick shelled, dark brown, operculated, and measure 38–45 µm × 25–30 µm.
Life cycle. Development takes place with alternation of three hosts – one definitive and
two intermediate hosts.
The principle definitive hosts are sheep, sometimes other herbivorous animals and humans. The first intermediate hosts are the land snails of the genera Abida, Hellicela and
other. The second host is an ant.
The eggs of fluke with fully developed miracidium are excreted with faeces of definitive
hosts. Snails ingest eggs. When cercarias are formed they agglomerate in groups of 200
to 300 in slime balls of secreted material at respiratory chamber of the snail. The crawling
snails shed this slime balls on vegetation, where they are eaten by ants. Metacercaria develop in the ant. Sheep get the parasite by eating grass with infected ants. Humans acquire
the disease by occasional swallowing of the ants with food.
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11.1. General characteristics of flat worms. Flukes (Trematodes)
TR
IC
2
Testis
TE
1
D
Uterus
EC
10
9
3
4
9
5
8
11
7
6
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Fig. 11.7. Morphology and life cycle of the lancet fluke (Dicrocoelium lanceatum): 1 – adult worm (marita);
2 – definitive hosts; 3 – the egg; 4 – first intermediate host (land snails of the genera Abida, Hellicela etc.);
5 – miracidium; 6 – primary sporocyst; 7 – secondary sporocyst; 8 – cercaria; 9 – slime balls; 10 – second
intermediate host (ants of the genus Formica); 11 – metacercaria
Pathogenicity and diagnosis are similar to those of Fasciola hepatica.
Prophylaxis. Personal: to be attentive and not to eat food with ants. Control of the disease is of low efficacy and includes veterinary measures and health education.
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CHAPTER 11. Helminths. Flat and round worms as human parasites
Paragonimus westermani or ringeri (lung fluke)
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Ovary
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Paragonimus westermani (ringeri) or the lung fluke is the agent of paragonimiasis
(Fig. 11.8).
Geographical distribution. The parasite is endemic in the Far East, China, Japan, SouthEast Asia, India.
Location. Typical location in the definitive host is the lungs; atypical location is the liver,
spleen, mesentery, muscles, brain, etc.
Morphology. An adult worm is reddish brown in color, very thick bodied and resemble
coffee bean by the shape. Its size is about 7.5–12 by 4–6 mm. Two testes are present in the
posterior end of the body.
The eggs are operculated, 80–110 by 50–60 µm in size and yellow brown in color.
Life cycle. It passes its life cycle in 3 hosts: one definitive and two intermediate hosts.
Definitive hosts are humans, dogs, cats, pigs and rodents. Tigers and leopards in Asia are
usual hosts. The first intermediate host is fresh water snail of the genus Melania. The second
one is fresh water crayfish or crab.
Eggs are excreted with sputum and faeces. Miracidium hatches out of egg in water and
penetrates into the snail.
Testis
2
3
5
10
9
8
Uterus
11
6
7
4
1
Fig. 11.8. Morphology and life cycle of the lung fluke (Paragonimus westermani (ringeri)): 1 – adult worm
(marita); 2 – definitive hosts; 3 – the egg; 4 – miracidium; 5 – first intermediate host (snail of the genus Melania); 6 – sporocyst; 7 – maternal redia; 8 – daughter redia; 9 – cercaria; 10 – second intermediate host (fresh
water crayfish or crab); 11 – metacercaria
11.1. General characteristics of flat worms. Flukes (Trematodes)
285
IC
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Cercaria emerges from the snail after about three months and should invade second
intermediate host within 24–48 hours. Metacercariae develop in muscles of crabs and crayfish. The definitive host gets the disease by ingestion of raw or undercooked intermediate
hosts with metacercariae, which is the infective stage. Metacercariae hatch in the duodenum, penetrate through the gut wall, migrate through the diaphragm into the pleural cavity and enter the lungs. Adult worms develop in 2 to 3 months. Sometimes the migrating
larvae lose their way and reach ectopic sites such as the brain, mesentery, liver or others.
Life span of the parasites is up to 20 years.
Paragonimiasis belongs to the group of nature foci disorders.
Pathogenicity. Paragonimus causes pulmonary lesions. In the lungs, pair of parasites lie
in cystic spaces with a fibrous capsule. This causes cystic dilatation of the bronchi, abscesses and pneumonitis. A patient has cough with blood streaked sputum, chest pain. A clinical and radiological picture of chronic infection resembles tuberculosis, which frequently
coexists with paragonimiasis.
Diagnosis. Demonstration of the eggs in sputum or faeces (ovoscopy). Serologic tests
at early stage of the disease.
Prophylaxis. Personal prevention is adequate cooking of crabs and crayfish. Control of
the disease includes treatment of the cases and sanitary education.
TR
Schistosoma (Bilharzia) species (blood flukes)
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Schistosoma (Bilharzia) species (blood flukes) have some important morphological
features, which distinguish them from other trematodes.
1. Blood flukes are dioecious organisms (have separate sexes). The female worm has a
cylindrical body and the male – a canoe shaped body with gynaecophoric canal, in
which the adult female spends most of its time.
2. No muscular pharynx. Formation of single canal by the union of bifurcated intestinal
caecae.
3. Eggs are not operculated and possess spine.
4. They have one definitive and one intermediate hosts. Redia stage is absent. Forktailed cercariae develop in the sporocyst, and are infective for definitive host. Infection occurs by penetrating the unbroken skin of the definitive host.
The most important are three species of blood flukes: Schistosoma haematobium, Schistosoma mansoni, Schistosoma japonicum.
Schistosoma haematobium
Schistosoma haematobium is an agent of urogenital schistosomiasis.
Geographical distribution. Most parts of Africa, especially the Nile valley and SouthWest Asia (Syria, Libya, Sudan, Saudi Arabia, Oman, Israel, Iran, Iraq, India).
Location. Veins of the urinary bladder, uterus, prostate.
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CHAPTER 11. Helminths. Flat and round worms as human parasites
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Morphology. A male is 10–14 mm by
0.9 mm, a female is 16–20 mm by 0.25 mm
in size. The eggs are ovoid, about 150 µm by
62 µm, with terminal spine (Fig. 11.9).
Life cycle. Man is the only natural definitive
host (Fig. 11.10). The intermediate host is snail
of genus Bulinus. Eggs are laid in small venules
of the urinary bladder. They pass through the
walls of blood vessels and bladder by piercing
action of the spine and are excreted with urine
to water reservoirs. Miracidium hatches almost Fig. 11.9. Egg of Schistosoma haematobium
immediately and enters specific intermediate
host. Miracidium progresses to mother sporocyst, daughter sporocyst and then to final larval stage – cercaria. One miracidium can give rise to thousands of cercariae, all of the same
sex (after 5–6 weeks). The principal stimulation for emergence is light.
When a man enters the water the cercariae penetrate the skin, often between the hair
follicles, by means of the anterior spines and cytolytic secretions. The adult worm pairs
migrate to the venules of vesicle plexus.
Pathogenicity. At the beginning of the disease toxic and allergic symptoms are most
important, such as itching lesions at the site of entry, fever, headache, urticaria. At the
chronic stage there is an inflammation and fibrosis of vesical mucosa at the sites of deposition of the eggs. Chronic cystitis, pyelonephritis develop as well as infection of the prostate,
and perineum.
Diagnosis. Demonstration of the eggs (ovoscopy) by microscopic examination of centrifuged deposits of urine or seminal fluid.
Prophylaxis. Personal prevention is to avoid bathing in water reservoirs in endemic regions (prevention of water contact).
Control of the disease includes treatment of infected persons, protection of water contamination and its periodic purification (environmental sanitation), destruction of intermediate hosts by molluskicides, sanitary education of people.
Schistosoma Mansoni
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Schistosoma Mansoni is an agent of intestinal schistosomiasis.
Geographical distribution. The disease is spread in Egypt and South America.
Location is in portal or inferior mesenteric veins. Eggs penetrate the gut wall, reach its
lumen and are shed in faeces.
Morphology. The male is 6–14 mm by 1.1 µm, the female is 10–20 mm by 0.16 mm in
size. The eggs are 140 µm by 60 µm, with lateral spine (Fig. 11.11).
Life cycle is similar to the one of S. haematobium (see Fig. 11.10).
The definitive host is man, monkeys serve as the reservoir host.
The intermediate hosts are the snails of genus Biomphalaria.
11.1. General characteristics of flat worms. Flukes (Trematodes)
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Fig. 11.10. Morphology and life cycle of the blood flukes (Schistosoma (Bilharzia) species): 1 – adult worms
(male and female); 2 – definitive host; 3 – the eggs; 4 – miracidia; 5 – intermediate host (a – snail of genus
Bulinus, b – snail of genus Biomphalaria); 6–8 – generation of sporocysts; 9 – cercaria
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Pathogenicity. The parasite affects the large intestine and causes colic abdominal pain
with bloody diarrhea. Hepatomegaly, portal hypertension and cirrhosis may occur as a result of severe chronic infection.
Diagnosis is by demonstration of eggs in faeces.
Prophylaxis is the same as above.
Schistosoma japonicum
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Schistosoma japonicum is an agent of Japanese schistosomiasis (Oriental schistosomiasis or Katayama disease).
Geographical distribution. The parasite is found in the Far East, China, Japan and the
Philippines.
Location is in portal veins, superior mesenteric and rectal veins.
Morphology. A male is 12–20 mm by 0.5 mm, a female is 20–30 mm by 0.3 mm in size.
Eggs are more spherical than those of other schistosomes, 85 µm by 60 µm with a minute
lateral spine (sometimes invisible) (Fig. 11.12). Eggs are laid in the mesenteric veins, pass
through the gut wall and excreted with faeces.
CHAPTER 11. Helminths. Flat and round worms as human parasites
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Fig. 11.11. Egg of Schistosoma Mansoni
Fig. 11.12. Egg of Schistosoma japonicum
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Life cycle is similar to that in other schistosoma species. The definitive hosts are humans, cattle, pigs, horses and rats. Intermediate host is snail of genus Oncomelania.
Pathogenicity, diagnosis and prevention are the same as for S. Mansoni. Clinical manifestations are more severe, probably because of higher egg output (3,500 eggs daily comparing with 100–300 in S. Mansoni).
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Uncommon Trematode parasites of humans
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Nanophyetus (Troglotrema) salmincola is an agent of nanophietiasis (salmon poisoning).
Geographical distribution. The parasite is found in the Siberia and Pacific northwest
coast of North America.
Location is at the upper part of small intestine.
Morphology. A small almost round trematode, 0.52–0.58 mm by 0.35–0.47 mm. Eggs
are light brown, ovoid, 64–72 µm by 43–48 µm with a small blunt projection at the aboperculate end (Fig. 11.13).
B
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Fig. 11.13. Nanophyetus (Troglotrema) salmincola: A – marita; B – egg
11.2. Tapeworms (Cestodes) as human parasites
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Fig. 11.14. Metagonimus yokogawai: A – marita; B – egg
10 µm
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Life cycle. The definitive hosts are numerous fish-eating mammals, including humans
and some fish-eating birds. First intermediate host is mollusk, the second one is salmonid fish. Definitive host become infected by eating inadequately processed fish. Disease
manifests as gastrointestinal complaints only in case of heavy infection (more than 500
parasites in an organism). Life span of the parasite in human organism is from 35 days to
two months.
Laboratory diagnosis is demonstration of eggs in stool.
Prophylaxis of the disease is similar with opisthorchiasis.
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Metagonimus yokogawai is an agent of metagonimiasis.
Geographical distribution. The parasite is found in the Far East, the Philippines, China,
Japan, Korea, Siberia, the Balkans, Greece, and Spain.
Location is at the small intestine and cecum. Parasites are embedded in the mucus or
in the folds of mucosa.
Morphology. Parasite is small, 1.4 by 0.6 mm, and has pyriform shape with a rounded
posterior and a tapering anterior end (Fig. 11.14). A cuticle is covered with minute scale-like
spines more numerous at the anterior end. Eggs are light yellow brown, ovoid, 28 µm by 17
µm and contain mature miracidium.
The life span of the parasite in human organism is about one year.
The life cycle, pathogenesis, laboratory diagnosis and prevention are similar with
those of Nanophyetus salmincola.
11.2. Tapeworms (Cestodes) as human parasites
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Classification
Phylum: Plathelminthes
Class: Cestoidea
Subclass: Cestoda
Species: Taenia solium (Armed tapeworm or pork tapeworm)
Taeniarhynchus saginatus (Taenia saginatus)
(Unarmed tapeworm or beef tapeworm)
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CHAPTER 11. Helminths. Flat and round worms as human parasites
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Fig. 11.15. General morphology and life cycle of Cestodes: A – adult worm: 1 – scolex; 2 – neck; 3 – immature
proglottids; 4 – mature proglottids; 5 – gravid proglottids; B – scolex; C – egg; D – oncosphere; E – scheme of
the reproductive system structure of Taeniarynchus saginatus (1 – uterus; 2 – ovary; 3 – oviduct; 4 – vagina;
5 – ootype; 6 – yolk bodies; 7 – Mehlis' body; 8 – cirrus sac; 9 – cirrus; 10 – sperm ducts; 11 – testis)
Hymenolepis nana (dwarf tapeworm)
Echinococcus granulosus (dog tapeworm)
Alveococcus multilocularis
Diphyllobothrium latum (broad or fish tapeworm)
Morphology of Cestodes
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Cestodes (from Greek kestos – ribbon or girdle) are characterized by the following specific features:
1. Segmented tape – like body.
2. The body of the adult worm consists of a small head or scolex, a short neck and trunk
or strobila composed of a chain of segments (proglottids) (Fig. 11.15).
Scolex is the organ of attachment through the cup-like suckers, rostellum with
crown of hooklets, or grooves (bothria). The neck is a nonsegmented region of
11.2. Tapeworms (Cestodes) as human parasites
IV
3
2
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I
4
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12 10
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10 13 12
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Fig. 11.16. Cestodes: I – scolices; II – hermaphrodite segments; III – gravid segments; IV – transverse section of
the broad tapeworm scolex. A – broad tapeworm (Diphyllobothrium latum); B – armed tapeworm (Taenia
solium); C – unarmed tapeworm (Taeniarhynchus saginatus); D – dwarf tapeworm (Hymenolepis nana):
1 – bothria; 2 – row of hooks; 3 – suckers; 4 – neck; 5 – testis; 6 – sperm ducts; 7 – cirrus pouch; 8 – vagina;
9 –uterus; 10 – vitellaria; 11 – ovary; 12 – Mehlis' gland; 13 – ootype; 14 – uterus filled with eggs
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growth, where the segments of the body are constantly generated. Strobila is composed of different types of proglottids: immature, mature, and gravid. The anterior
part of strobila contains immature segments, in which male and female organs are
undifferentiated. Middle part of the body consists of mature (hermaphrodite) segments, in which male and female organs are identifiable and fertilization occurs.
Gravid proglottids, which contain uterus with eggs form a caudal part of the strobila.
3. The alimentary canal is absent. They consume nutrients by endosmosis through the
body surface.
4. The reproductive system of Cestodes is hermaphrodite (see Fig. 11.15). The male reproductive system consists of numerous testes, small seminal ducts, a common ejaculatory duct and a copulative organ (cirrus). The female reproductive system consists
of the ovary, oviduct, ootype, vitelline glands, Mehlis’ gland, uterus and vagina. Both
the cirrus and vagina open to a common genital atrium where self-fertilization occurs, the sperm travels through the vagina to the seminal receptacle, from which
it moves to the ootype. The oviduct of ovaries, yolk glands and Mehlis’ gland all are
opened into ootype, where the eggs are formed. Cross-fertilization may also occur
between segments of the same or two worms.
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CHAPTER 11. Helminths. Flat and round worms as human parasites
Life cycle of Cestodes
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Adult worms reside in the small intestine of man and animals; man is the definitive host
for most tapeworms that cause human infection.
All tapeworms require one or more intermediate hosts for completion of their life cycle
thus are biohelminths. Development proceeds as follows.
The eggs of Cestodes contain the first stage larva – oncosphere. Oncospheres of human tapeworms typically have three pairs of hooklets and are called hexacanth embryos.
Egg with oncosphere is an infective stage for the intermediate host. In the organism of the
intermediate host oncosphere develops into the second stage larva – larvocyst or phynn.
There are several types of the phynn (Fig. 11.17):
`` Cysticercus is a spherically shaped cyst with inverted scolex and neck (Taenia solium,
Taeniarhynchus saginatus).
`` Cysticercoid is a pyriform cyst with inverted scolex and neck and conical tail-like posterior end (Hymenolepis nana).
`` Echinococcus cyst or a hydatid cyst is a thick walled bladder with fluid and numerous
daughter cysts and scolices (Echinococcus granulosus).
`` Alveolar echinococcus cyst demonstrates external budding (Alveococcus multilocularis).
2
4
3
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а
b
7
6
5
а
Fig. 11.17. Several types of the phynn of cestodes: 1 – plerocercoid; 2 – cysticercus; 3 – cysticercoid; 4 – coenurus; 5 – alveolar echinococcus cyst (section); 6 – echinococcus (hydatid) cyst (a – endogenic growth); 7 – a
fragment of echinococcus cyst (a – brood capsules; b – daughter cyst containing protoskolices)
11.2. Tapeworms (Cestodes) as human parasites
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Taenia solium (Armed or Pork Tapeworm)
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`` Coenurus is a spherical bladder bearing multiple invaginated scolices (Taenia multiceps).
`` Plerocercoid is a flattened vermicule with rudimentary scolex and two bothria
(Diphyllobothrium latum).
Phynn is the infective stage for the definitive host. Both the adult worm and the larval
form can cause disease. The diseases caused by tapeworms have a common name cestodiasis.
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Armed or pork tapeworm (Taenia solium) is an agent of taeniasis (adult worm) and cysticercosis (larva).
Geographical distribution. It is worldwide, except for the countries and communities,
where pork is traditionally prohibited.
Location. The adult worm lives in the human small intestine. Cysticerci are localized in
muscles, brain, eyes and other organs of human body.
Morphology. The adult worm is usually 2 to 3 m long (sometimes 6–8 m). Scolex is
shaped as a ball, 1-2 mm in diameter, equipped with four suckers (see Fig. 11.16B). It also
carries a rostellum, armed with double row of hooks (25–30). Due to presence of hooks the
parasite got name armed tapeworm. The neck is narrow, approximately 5–10 mm in length.
The mature segment is almost square in shape. It contains the well-developed male
and female reproductive system. Most of testes occupy lateral zones of the segment. The
ejaculatory duct runs across the segment. The ovary is situated in the caudal part of each
segment and consists of 3 lobes. The yolk bodies are located behind the ovary. The oviduct
is widened and forms the ootype. The uterus is poorly developed in mature segment and
runs along the middle axis of a segment.
The size of gravid segment is 12 by 6–7 mm. A mature uterus in the gravid segments
consists of the central stem with 7–12 lateral branches and lacks opening. Gravid segments
passively leave the strobile.
The eggs of Taenia solium are spherical, transparent and colorless with the size 31–
43 µm in diameter. There is the oncosphere with 3 pairs of hooklets inside the egg. It is
surrounded by double contoured striped coat.
The phynn is of a cysticercus type.
Life cycle. The definitive host is human being. The intermediate hosts are pigs, sometimes human, wild and domestic dogs, cats (Fig. 11.18).
Gravid segments pass out passively as short chains. Segments contain eggs with oncospheres, which are indistinguishable from those of T. saginata.
Intermediate hosts (pigs) are infected while eating gravid proglottids. In the stomach
oncospheres liberate, get into the blood vessels and are carried with blood to the different
parts of the body. 24–74 hours later they penetrate into intermuscular connective tissue
and turn into phynns (Cysticercus cellulosae) in about 2–2.5 months. Cysticercus is a milkywhite bladder with an inverted scolex and the neck. Its shape reminds a grain of rice, and
measures usually about 5 mm up to 15 mm, but can be much larger in brain. The pork con-
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CHAPTER 11. Helminths. Flat and round worms as human parasites
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9
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5
4
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1
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Fig. 11.18. External structure and life cycle of armed tapeworm (Taenia solium): 1 – adult worm; 2 – definitive
host; 3 – gravid segments; 4 – egg; 5 – intermediate host; 6 – oncosphere; 7 – phynn (cysticercus); 8 – “measly
pork”; 9 – brain affected with cysticercosis
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taining Cysticercus cellulosae is usually referred to as “measly pork”.
Human can be infected through inadequately cooked measly pork. The head evaginates out in the small intestine and anchors the mucous membranes. The parasite reaches
maturity 67–72 days later. T. solium has a long life-span of about 25 years or more.
Man can also be an intermediate host for a pork tapeworm.
Infection is acquired in following cases:
`` most commonly by the accidental ingestion of eggs with water or vegetables;
`` by autoinfection, if person is sick with teniasis. By retrograde peristalsis the gravid
segments may be regurgitated in the stomach. They are digested and thousands of
eggs released. External reinfection occurring from anus to fingers and to mouth is
also possible.
Cysticerci could be localized in one organ or may be disseminated. The common sites
are striated muscles of the tongue, neck, shoulders, cardiac muscle, subcutaneous tissue,
brain, and eyes. Cysticerci can survive for about 5 years.
Pathogenicity. An adult worm causes taeniasis. The parasite affects the host by mechanical injuring of the intestinal mucosa, absorption of nutrients and formation of pathologic intestinal reflexes. The disease manifests as abdominal discomfort, alternating diarrhea and constipation, anemia, weakness, loss of weight, fatigue.
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A
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11.2. Tapeworms (Cestodes) as human parasites
B
Fig. 11.19. Cysticerci: A – in the eye; B –brain containing cysticerci
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Cysticercus larvae in humans cause cysticercosis (Fig. 11.19). Clinical symptoms depend
on the site affected. Ocular cysticercosis may cause blindness. Epilepsy, behavioral disorders, hydrocephalus and pareses manifest in cysticercosis of the brain.
Laboratory diagnosis. Infection with the adult worm is diagnosed by demonstration
of proglottids in faeces (helminthoscopy). Demonstration of eggs is also used but it isn’t
informative for differentiating T. solium from T. saginata.
Demonstration of the scolex, mature and gravid segments of the parasite after treatment (dehelminthization) is most reliable feature to identify T. solium.
The diagnosis of cysticercosis is done by biopsy of the lesion, X-rays or computer tomography scanning and immunodiagnosis (serologic tests).
Prophylaxis. Personal prevention is not to eat raw or undercooked pork.
Control of the disease includes prevention of contamination of water and soil with human faeces; adequate inspection of pork in slaughterhouses and markets; revealing and
treatment of infected persons; health education.
Taeniarhynchus saginatus (Unarmed Tapeworm or Beef Tapeworm)
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Unarmed tapeworm or beef tapeworm (Taeniarhynchus saginatus) is the agent of taeniarhynchiasis.
Geographical distribution. Worldwide.
Location. The adult worm lives in the human’s small intestine.
Morphology. The adult worm usually measures about 5–12 m. The scolex is 1.5–
2 mm in diameter, equipped with 4 suckers, no hooks are present (unarmed tape worm)
(see Fig. 11.16C). Mature segments differ from the ones of the armed tapeworm in size
(they are larger than the ones of T. solium). The ovary is composed of two lobes. The gravid
segment is 16–20 by 5–7 mm in size; uterus has 17–35 lateral branches and lacks opening.
The gravid segments are expelled singly and can crawl out of the anus, so the eggs are
present in the perianal skin. Eggs are morphologically similar to that of T. solium.
Life cycle. The definitive host is human, intermediate host is cattle (cow, zebu, buffalo).
A mature helminth is located in the small intestine of human being (Fig. 11.20).
CHAPTER 11. Helminths. Flat and round worms as human parasites
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6
8
7
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2
3
5
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1
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Fig. 11.20. External structure and life cycle of unarmed tapeworm (Taeniarhynchus saginatus): 1 – adult
worm; 2 – definitive host; 3 – gravid segment; 4 – egg; 5 – intermediate host; 6 – phynn (cysticercus); 7 – cysticercus development; 8 – “measly beef”
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The eggs or gravid segments are passed out with the feces on the ground. Eggs are not
infective for man. Animals ingest the eggs while grazing. In the stomach of an intermediate
host oncospheres are liberated, with blood reach the muscles where turn into the second
larva stage (Cysticercus bovi) in about 2 months. Shape of the Cysticercus bovi is much alike
the one of the pork tapeworm but it is pinkish and smaller (5–9 mm).
Humans are infected while eating undercooked beef with cysticerci (“measly beef”).
Unarmed tapeworm reaches maturity within 4 months after infecting human being. The
disease doesn’t complicate with cysticercosis.
Pathogenicity is the same as for teniasis.
Diagnosis. Demonstration of proglottids in faeces (helminthoscopy) or eggs in perianal
scraping, which gives a much higher recovery of eggs than examining the feces.
Prevention is the same as in case of T. solium infection.
Hymenolepis Nana (Dwarf Tapeworm)
Hymenolepis nana (dwarf tapeworm) is the agent of hymenolepiasis.
11.2. Tapeworms (Cestodes) as human parasites
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Geographical distribution. It is cosmopolitan and more common in the warm than in
cold climates.
Location The adult worms live in the human intestine, phynn occupies intestinal villi.
Morphology. It is the smallest tapeworm found in the human intestine. An adult worm
is 20 to 40 mm long, 0.5–0.7 mm in width and looks like mucus thread (see Fig. 11.16D). The
body wall of these tapeworms is thin and easy to be torn. The scolex bears 4 suckers and a
small retractable rostellum with a single row of 20–30 hooklets. Its neck is long and slender,
strobila consists of 200 or more proglottids. The width of mature proglottids exceeds their
length. They have a single genital pore on the same side of the strobila. The gravid uterus
forms a sack filled with 80–200 eggs.
Eggs of dwarf tapeworm are spherical or oval, 30–45 µm, transparent and colorless.
Each egg contains the onchosphere and filaments inside. Filaments are thread-like bodies
around the onchosphere. The phynn is of a cysticercoid type. It is shaped as a vesicle with
an invaginated scolex and a short conical tail-like projection.
Life cycle. The dwarf tapeworm is a biohelminth (Fig. 11.21). This is the only tapeworm
for which man acts as an intermediate and then as a definitive host during its life cycle. Infection occurs by ingestion of the eggs. In the human intestine the onchosphere hatches out of
the egg and penetrates actively into the villi of the small intestine or into the lymphoid follicle. It develops into the cysticercoid in about 4–6 days. At this period human being serves
as an intermediate host. When parasites re-enter the lumen of the small intestine the scolex
screws out and attaches to the mucous membrane. At this period human being serves as a
definitive host. The parasite reaches maturity in 14–15 days. Eggs are passed in the faeces.
The life span of the dwarf tapeworm is about 2 months, but the disease can last much
longer. It can be explained by autoinfection. As body wall is thin, it ruptures in the intestine,
eggs are released and some of them start to develop. Oncosheres directly invade the intestinal villi, producing new generation (internal autoinfection). External autoinfection occurs
by fecal-oral transmission in the same individual.
Hymenolepiasis is a contact anthroponotic disease (Fig. 11.22). It usually affects children (aged 3 to 12–14). Mode of infection is fecal-oral. Flies are mechanical carriers of this
disease. Eggs stay infective on dirty hands for 3–4 hours (in water up to 4 weeks).
Pathogenicity. The parasite causes mechanical irritation of the intestinal mucosa and
destruction of intestinal villi. Major clinical features are abdominal pain, diarrhea, weight
loss, headache, allergic rash.
Diagnosis is made by demonstration of the eggs in faeces (ovoscopy). Fresh specimens
only should be examined, as eggs are unstable in outer environment.
Prophylaxis. Personal prevention is to keep the rules of personal hygiene, to wash vegetables and fruit, to boil water. Control is to reveal and treat the patients; close household
contacts should be treated also.
Echinococcus Granulosus (hydatid worm)
Echinococcus granulosus is the causative agent of echinococcosis (hydatid disease)
(Fig. 11.23). The disease in humans is caused by the larval stage of the parasite.
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CHAPTER 11. Helminths. Flat and round worms as human parasites
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b
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а
Fig. 11.21. External structure and life cycle of dwarf tapeworm (Hymenolepis nana): 1 – adult worm; 2 – human is a definitive and intermediate host; 3 – egg; 4 – phynn (cysticercoid); 5 – life cycle of dwarf tapeworm
in human intestine with internal autoinfection (a – adult, b – oncosphere, c – phynn)
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Source of invasion
infected human
hands
houseware
susceptible person
Fig. 11.22. Transmission of contact helminthoses
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Geographical distribution. Worldwide. It is more prevalent in sheep and cattle raising
regions with temperate climate.
Location. The phynn (hydatid cyst) develops in various organs of man, more often in
the liver and lungs, which acts as the first and second filters for the oncospheres. It can also
present in the brain, kidneys, pancreas, heart and other organs.
The adult worm inhabits the small intestine of the dogs.
Morphology. The adult worm is 2–7 mm long. It consists of the scolex, the neck and
3–4 segments. The scolex is equipped with four suckers and a rostellum with two rows of
11.2. Tapeworms (Cestodes) as human parasites
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2
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5
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Fig. 11.23. External structure and life cycle of hydatid worm (Echinococcus granulosus): 1 – adult worm; 2 –
definitive host (2a – hydatid worm in the intestine of definitive host); 3 – gravid segment; 4 – egg; 5 – oncosphere; 6 – fragment of hydatid cyst; 7 – intermediate hosts; 8 – hydatid cysts in organs of intermediate hosts
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hooklets. The first one or two segments are immature, penultimate is sexually mature and
the last one is gravid. The gravid uterus is shaped like a sack with lateral branches and lack
uterine opening.
Eggs are spherical, 30–40 µm in diameter, have typical for tapeworms structure.
The phynn of echinococcus type (hydatid cyst) is shaped like a bladder varying from few
millimeters up to the size of a child’s head in diameter or even more. The cyst is filled with
colorless fluid. Its wall consists of two layers: the outer one is laminated cuticular (chitinous), the inner layer is germinal (parenchimatous). The germinal epithelium produces the
brood capsules with scolices and next generation of cyst (daughter cysts) into the cavity
of the maternal cyst. Daughter cysts in turn produce new generation of brood capsules
and granddaughter cysts. Small daughter cysts and scolices form the hydatid “sand” at the
bottom of the maternal cyst. It can be seen without any optical instruments. The fibrous
capsule is formed outside the echinococcus cyst as a result of cellular reaction of the host.
The phynn grows in a man very slowly. At the end of a year it is about 5 cm in diameter, but
it can survive and grow for a few decades.
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CHAPTER 11. Helminths. Flat and round worms as human parasites
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Life cycle. The life cycle is completed in two hosts. The definitive host is dog and other
canines (a wolf, a jackal, a dingo dog and other).
The intermediate hosts are most of mammals including man, sheep, cattle, and other
herbivorous mammals.
The gravid proglottids disintegrate in the intestine of dogs and the eggs are passed
out with the feces of the dog. Gravid segments are able to crawl actively from the anus
and disseminate the eggs over the hair of the dog. Human beings, sheep, cattle and other
mammals get the infection on ingestion of the eggs from contaminated food or water. Man
often acquires the disease through dirty hands after stroking an infected dog. Eggs can be
spread on grass and then be transmitted onto the sheep wool, so infection may occur after
cutting the wool or its processing.
In the human intestine eggs shell is destroyed and onchospheres penetrate the mucous
layer of the intestine. Then they are transported with blood to the liver, lungs, heart and
other organs and turn into echinococcus cysts. Human being is the blind alley in the life
cycle of echinococcus.
The definitive hosts (dogs, wolves and others) become infected while consuming the
organs of animals with echinococcus cysts. Each scolex of the cyst turns into the mature
worm in the small intestine of a definitive host, causing multiple infection.
Pathogenicity. The echinococcus cyst compresses healthy tissue (pressure effect), its
metabolic products are toxic and cause allergy. Clinical symptoms depend on the size and
location of the cyst.
The damage of the echinicoccus cyst is especially dangerous. Rupturing of the cyst
through trauma or during the surgical removing may lead to the anaphylactic shock
and spreading of the infection through seeding the peritoneal cavity with hydatid
sand.
Diagnosis is done by complex examination of the ill person using X-ray, ultrasound,
computer tomography methods. Confirmation of the diagnosis is done by immunologic
methods (serologic tests).
Aspiration of the hydatid cyst can be taken during the surgery. Scolices and hooks are
found in the sediment of aspiration material after centrifugation.
The Casoni’s allergic test has a historical significance. The test is based on the principle
of immediate hypersensitivity (intradermal injection of antigen and appreciation of skin
reaction).
Prophylaxis. Personal prevention is to wash hands after having touched dogs or taking care after sheep and other animals; to wash vegetables and fruit, boil water. Periodical
deworming of guard and pet dogs is useful.
Prevention of dogs from eating infected organs of animals and proper disposal of dog’s
feces reduces worm load.
Alveococcus Multilocularis (Echinococcus multilocularis)
Alveococcus multilocularis is the agent of alveococcosis (alveolar hydatid disease)
(Fig. 11.24). The disease in human is caused by larval stage of the parasite.
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11.2. Tapeworms (Cestodes) as human parasites
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Uretus
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Fig. 11.24. External structure and life cycle of Alveococcus multilocularis (Echinococcus multilocularis): 1 – adult
worm; 2 – definitive hosts; 3 – gravid segment; 4 – egg; 5 – intermediate hosts; 6 – alveococcus hydatid cyst
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Geographical distribution. The disease is prevalent in northern parts of the world from
Siberia to Canada and is characterized by presence of natural foci.
Location in human organism is the same as for echinococcus cyst.
Morphology. Alveococcus resembles echinococcus in morphology, but is smaller in size
(1.2–3.27 mm) and has spherical uterus without lateral branches in gravid segments.
The phynn type is an alveococcus (alveolar) hydatid cyst. It consists of a great number of
small cysts forming a dense body. The cyst contains little of dark yellow liquid with scolices.
It demonstrates expansive growth with outside production of daughter cysts, so is often
confused with malignant tumor.
Life cycle. The definitive hosts are foxes, dogs, wolves, polar dogs, cats. The intermediate hosts are mice and other rodents, sometimes human being.
Man acquires the disease by ingestion of eggs of alveococcus through dirty hands (after
touching dogs, processing skins of polar dogs, foxes) or while eating contaminated berries
and vegetables.
In general the life cycle is similar to that of E. granulosus.
Pathogenicity. Symptoms depend on the location of the cyst. The liver is the most common site to be affected. Clinically it manifests as an infiltrative process of the liver. The al-
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CHAPTER 11. Helminths. Flat and round worms as human parasites
Diphyllobothrium Latum (Fish or Broad Tapeworm)
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veolar cyst may give metastases into the lungs, central nervous system, lymph glands, and
almost always causes lethal outcome.
Diagnosis and prophylaxis. Methods used for the diagnosis and prevention of echinococcosis are also used for alveococcosis.
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Diphyllobothrium latum (fish or broad tapeworm) is an agent of diphyllobothriasis.
Geographical distribution. The disease occurs in central and northern Europe, North
America, Siberia, Japan and Central Africa.
Location. The adult worm inhabits the small intestine of man and other definitive
hosts.
Morphology. It is the largest worm inhabiting the small intestine of man. It measures 2 to 20 m (usually 2–9 m) in length and may have up to 40.000 proglottids. The
scolex is elongated, spoon-shaped, 5 mm in size (see Fig. 11.16A). It has two longitudinal grooves (bothria) on the dorsal and ventral surfaces. There are no rostellum and
hooklets.
A mature segment contains an ovary, loop-like uterus, yolk bodies and testes. The genital pore is situated on the abdominal side of the segment near the frontal edge. Width of
the segment exceeds its length.
The mature segment is about 1.5 cm in width, the uterus is coiled in the center of each
segment in the form of a rosette. The uterus is of an open type (opens on the abdominal
side).
Eggs resemble the eggs of trematodes in morphology. They are widely oval, operculated, yellowish brown, 60–70 by 45–50 µm.
The phynn is of a plerocercoid type. It is worm-shaped, 1–5 cm in length. The scolex
possesses two bothria.
Life cycle. The worm passes its life cycle in one definitive and two intermediate hosts
(Fig. 11.25).
The definitive hosts are man, cat, dog, pig, fox, bear and other animals.
The first intermediate host is a fresh water minor crustacean – cyclop, the second intermediate host is fresh water fish (pike, perch, trout and others).
The worm lives in the small intestine of the definitive host. Eggs are passed in feces
about 1 million a day and should get into water for the further development. First larval
stage coracidium escapes from the egg in two to three weeks at a favorable temperature.
The coracidium is covered with cilia and contains an onchosphere. It swims actively and
must be ingested by a cyclop for further development. In its body larva turns into a procercoid. If a cyclop is ingested by fish, plerocercoid phynn develops in its muscles, liver and
ovary. Such fish can be eaten up by the fish of prey. Plerocercoids in this case stay safe and
accumulate in the muscles and reproductive organs of the fish of prey, which serves as
a reservoir host.
Human being becomes infected through undercooked fish or fresh caviar. Plerocercoid
larva is infective stage. The phynn turns into the mature worm in the small intestine of a
11.2. Tapeworms (Cestodes) as human parasites
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Fig. 11.25. External structure and life cycle of fish (broad) tapeworm (Diphyllobothrium latum): 1 – adult
worm; 2 – definitive hosts; 3 – egg; 4 – coracidium; 5 – first intermediate host – cyclop; 6 – procercoid larva;
7 – second intermediate host – fish; 8 – plerocercoid; 9 – plerocercoid in fish flesh
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definitive host 2 months later. Life span of the broad tapeworm is about 10–20 years or
even more.
Diphyllobothriasis is a natural foci disease. It is common in areas with great number of
rivers and lakes.
Pathogenicity. In the majority of cases infection is mostly asymptomatic. An infected
person may suffer from abdominal pain, diarrhea, fatigue, headache and constant loss of
weight. Intestinal obstruction has been reported.
Diphyllobothrium latum consumes a lot of the vitamin B12, folic acid and other vitamins.
It causes diphyllobothric anemia that is much alike B12 deficient anemia.
Diagnosis is done by demonstration of segments (helminthoscopy) and eggs (ovoscopy) in stool.
Prophylaxis. Personal prevention is to avoid eating raw or undercooked fish. Revealing
and deworming of infected persons, purification of waste water, proper sewage disposal
and health education are important in control of the disease.
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CHAPTER 11. Helminths. Flat and round worms as human parasites
11.3. General characteristics of Roundworms (Nematodes).
Roundworms – geohelminthes
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General features of phylum Nemathelminthes (Round worms) (Fig. 11.26):
1. Triploblastic, bilaterally symmetric animals.
2. They are unsegmented, cylindrical and tapering at both ends of the body.
3. The body is covered with tough multilayered cuticle. Underlying tissues are hypoderma and four strips of longitudinal muscles.
4. The body cavity is pseudocelome filled with fluid. The body fluid serves as a hydroskeleton and participates in metabolism.
5. The digestive system is complete and shaped as a tube. The digestive tube consists
of buccal cavity, esophagus, intestine, and opened by anus.
6. The excretory system is of modified protonephridial type.
7. The nervous system consists of a nerve ring and nervous trunks on dorsal and ventral
sides with transverse commissures.
8. The circulatory and respiratory systems are absent.
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5
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Fig. 11.26. Elements of the morphology of round worms: (A – external structure; B – transverse section of ascaris: 1 – body cavity – pseudocelome; 2 – muscles; 3 – dorsal nerve; 4 – ventral nerve; 5 – intestine; 6 – uterus;
7 – ovary; C – internal structure of ascaris: 1 – nerve ring; 2– pharynx; 3 – esophagus; 4 – intestine; 5 – vagina;
6 – uterus; 7 – ovary; 8 – oviducts; 9 – testis; 10 – sperm duct; 11 – ejaculatory duct
11.3. General characteristics of Roundworms (Nematodes). Roundworms – geohelminthes
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Classification
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9. Sexes are separate (diecious worms). In both sexes, the reproductive system is tubular. Females have double ovary, oviduct, uterus and one vagina. Males have single
testis, vas deferens, the seminal vesicle and the ejaculatory duct. Sexual dimorphism
(difference in the external structure of males and females) is present. Male worms are
smaller than female and have ventrally curved posterior end.
Some of round worms are geohelminths, eggs and larvae develop in outer environment (mostly in soil). Some species are biohelminths, developing with alternation of
hosts.
Diseases caused by the round worms are called nematodiasis.
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Phylum: Nemathelminthes
Class: Nematoda
Species: Ascaris lumbricoides
Enterobius vermicularis (pinworm)
Trichocephalus trichiurus (whipworm)
Ancylostoma duodenale (hookworm)
Necator Americanus (American hookworm)
Strongyloides stercoralis (threadworm)
Trichinella spiralis (trichina worm)
Dracunculus medinensis (Guinea worm)
Superfamily: Filariidae (filariae)
Species: Wuchereria bancrofti
Brugia malayi
Loa loa (eye worm)
Onchocerca volvulus
Dirofilaria immitis
Dirofilaria repens
Ascaris Lumbricoides
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Ascaris lumbricoides is the agent of ascariasis.
Geographical distribution. Worldwide.
Morphology. The female is about 20–40 cm in length. The male is 15–25 cm. The
body is cylindrical tapering at both ends. When freshly passed in the stool the adult
worm is slight cream or pink in color. The mouth opens at the anterior end and possesses three lips – one dorsal and two ventral. The posterior end of the male worm is
curved ventrally. Morphology is typical for round worms (see Fig. 11.26).
The female produces fertilized and unfertilized eggs of the oval shape 60–75/40–50
µm in size. It has a thick multilayer shell. The external coat is albuminous, thick, golden
brown in color, coarsely mammillated. The middle one has a glossy proteinous layer. The
inner membrane is lipoid, fibrous. The membranes protect embryo from chemical and
physical damage. The fertilized egg contains a large unsegmeneted ovum with clear
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space at each pole. The unfertilized egg is elliptical in shape, its size is 80/55 µm. It is filled
with yolk cells (see Fig. 11.46).
Location. The adult worm parasites in the small intestine. Larvae migrate with blood
into lungs for maturation.
Life cycle. Ascaris is a geohelminth (eggs passed in feces undergo maturation in the
soil). The worm passes its life in one host only (human being) (Fig. 11.27). Female produces
about 240.000 eggs per day. Eggs are passed with feces and become mature in the soil. The
eggs require moisture, temperature about +12 to +37 °C and oxygen for development. At
the temperature +24 to +37 °C the development lasts for 12 to 24 days (three weeks in average), below +24 °C – for several months. Infective eggs contain mature larva. Resistance
of eggs is very high, so they can survive in the soil for up to 10 years.
Man gets the infection by the ingestion of infective eggs with food, water, raw vegetables or from hands contaminated with soil.
Larvae hatch from the eggs in the small intestine, penetrate into blood vessels and are
carried by circulation into the liver and via right heart into lungs. In the lungs the larvae penetrate into alveoli and moult twice. Then larvae crawl up to bronchi, trachea, larynx, pharynx
and then are swallowed again. The migration lasts for 14–15 days. Larvae become mature in
the small intestine in 2–3 months. The life span of the mature worm is about a year. Several
dozens of ascaris can sometimes
be present inside one host.
Larvae in
A
C
Epidemiology. Ascariasis is
lungs
anthroponosis. The source of
infection is human being. HowAdult worm in the
small intestine
ever, infection can not occur in
Adult
direct contacts, as eggs are not
worms
infective when freshly passed.
Flies and cockroaches are mechanical vectors of the disease.
Pathogenicity. Ascaris causes
toxic and mechanical injury and
1
2
allergy. During the first pulmonary stage (migration of larvae)
B
clinical symptoms are pain in the
chest, cough, urticarial rush.
During the intestinal stage
Development of the
clinical symptoms include vomegg in soil
iting, stomachache, diarrhea,
headache, insomnia. Possible
Immature egg
Mature egg
(non-invasive)
complications of the disease are
(invasive)
intestinal obstruction, perforation of the intestine, mechani- Fig. 11.27. Life cycle of ascaris (Ascaris lumbricoides): A – adult
cal jaundice because of block- worms; B – mature egg (1 – tuberous shell; 2 – larva); C – life cycle
11.3. General characteristics of Roundworms (Nematodes). Roundworms – geohelminthes
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age of the bile ducts, abscess of the liver. Migration of adult worms to the respiratory
tract can cause asphyxia.
Diagnosis. As a rule detection of the pulmonary stage is a casual situation. At this stage
of ascariasis demonstration of larvae in phlegm (larvoscopy of the phlegm) is possible. The
ovoscopy of feces is carried out to diagnose the intestinal stage of ascariasis. When only
males are present in the organism of the host, eggs in the faeces are absent.
Prophylaxis. Personal prevention is washing hands, vegetables, fruit, boiling water.
Control of the disease includes treatment of affected individuals, proper disposal of human feces, struggle with flies and cockroaches, health education.
Thrichocephalus Trichiurus or Trichiurus Trichiura (Whipworm)
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Thrichocephalus trichiurus or Trichiurus trichiura (whipworm) is the agent of thrichocephaliasis (trichuriasis).
Geographical distribution. Worldwide.
Morphology. A mature female is 3–5 cm and the male is 3–4.5 cm in length (Fig. 11.28).
Both sexes have a narrow anterior portion (3/5th) and much wider posterior end (2/5th).
The anterior end contains esophagus, the posterior end contains intestine and reproductive organs. In males the posterior end is tightly coiled. The thin anterior part of this worm
is embedded into the intestinal mucosa. Whip worm is hemathophage, it consumes blood
and tissue liquid.
Eggs of thrichocephalus are yellow and brown, shaped as a lemon (or a barrel) with
mucus plugs at each pole (Fig. 11.29). The size of an egg is 50 by 25 µm.
Location. The large intestine of man, especially the caecum and appendix.
Life cycle. Whipworm is geohelminth (Fig. 11.30). Eggs are excreted with feces. When
freshly passed they are not infective for human beings. It takes about 25–30 days for the
egg to develop in the moist soil in optimal conditions (the temperature is 25–40 °C, oxygen,
moist). In the temperate climate it may take much longer (about 10–12 months) and in dry
conditions embryonation may be prevented. When infective eggs are ingested by human
A
B
Fig. 11.28. Whipworm (Trichocephalus trichiurus):
A – male; B – female
Fig. 11.29. Egg of whipworm
CHAPTER 11. Helminths. Flat and round worms as human parasites
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Fig. 11.30. Life cycle of a whipworm: 1 – adult worm in the organism of the host, 2 – fertilized egg, 3 – invasive
egg containing larva, 4 – contaminated vegetables
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with food and water, larvae penetrate into the villi of the small intestine. Development
takes place without migration. In 3–10 days larvae leave villi and inhabit the large intestine.
30–45 days later thrichocephalus reaches maturity. The life span is about 3–5 years.
Epidemiology. Thrichocephaliasis is anthroponosis. The main source of the disease is an
affected person. The way of transmission is similar with that of ascariasis. One gets infection through the dirty hands, fruit, vegetables, berries, or water contaminated with eggs.
Eggs can survive in the soil for 3 years. Flies are mechanical carriers of thrichocephaliasis.
Pathogenicity. Whipworm causes mechanical injuring of the intestinal mucosa and
toxic-allergic reactions. It predisposes the patient to get infection with bacteria. The lumen
of the appendix can be filled with worms; that leads to appendicitis. Severe infection may
cause anemia.
Diagnosis. Demonstration of eggs in stool (ovoscopy of faeces).
Prophylaxis. The same as in case of ascariasis.
Enterobius Vermicularis (Pinworm)
Enterobius vermicularis (pinworm) is the agent of enterobiasis.
Geographical distribution Worldwide.
11.3. General characteristics of Roundworms (Nematodes). Roundworms – geohelminthes
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Morphology. Pinworm is a small worm of
white color. Female is 9–12 mm in length and
0.6 mm in width, male is 2–5 mm in length and
0.2 mm in width. The anterior end has a bladder like expansion of the cuticle called vesicle
(Fig. 11.31). The mouth is bordered by three
B
small lips. The ball-like widening of the esophagus (bulbus) can be seen through the cuticle.
The posterior end of the female is sharpened;
the one of the male is ventrally curved. In females one can see the uterus, filled with eggs.
A
Eggs are transparent and colorless. They are
covered with a thin smooth double-contoured
shell.Eggs are asymmetric in shape, planeconC
vex. Larvae of different stages can be seen inside. The size of eggs is 50–60 by 30–32 µm.
Fig. 11.31. Pinworm (Enterobius vermicularis):
Location. The lower part of the small intes- A – female; B – male; C – eggs
tine, the upper part of the large intestine.
Life cycle. The pinworm is a geohelminth, parasites in humans only (Fig. 11.32). One
can get the disease by ingestion of eggs with infective larvae. In the human intestine
larvae escape and reach maturity in 12–14 days. Pinworms consume the contents of the
intestine. After fertilization males die. The gravid females migrate from the small intestine
down to the caecum and remain there. Helminthes keep themselves attached to the mucous membrane by the vesicle and sucking actions of the bulbus. Females with mature
eggs migrate to the rectum, creep out of the anus at night and lay eggs on the skin of the
perineal region.
4–6 hours after having been laid eggs reach the infective stage. The eggs require high
moisture (optimal 90–100 %), oxygen and 36–37 °C (the body temperature) for development of the larva. The eggs do not develop in outer environment.
Females laying eggs cause severe itching. Patients scratch the itching regions while
sleeping. Thus the eggs get on fingers of the patient, under the nails, on bed linen and
then on food, toys, dishes. If the patient neglects the hygienic rules he gets infection again.
So, enterobiasis is characterized by repeated self infection – autoreinfection.
The life span of the pinworm is about a month but the disease can last for many months
or even years due to autoreinfection.
Epidemiology. Enterobiasis is a contact anthroponotic disease. It is primarily the disease of children. The only source of enterobiasis is an infected person. Humans are usually
infected by direct transfer of the eggs from anus to the mouth by contaminated fingers
(fecal-oral transmission). Transmission can also occur through contaminated night clothes,
bed linen, etc., where eggs remain viable and infective for 2–3 weeks. Airborn transmission
is possible.
Intrafamilial transmission is very common, so all members of the family should be treated.
CHAPTER 11. Helminths. Flat and round worms as human parasites
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Fig. 11.32. Life cycle of pinworm: 1 – adult female in the host's organism; 2 – fertilized egg; 3 – mature egg;
4 – factor of transmission
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Pathogenicity. The pinworms affect human being in mechanic and toxic-allergic ways.
The main symptoms of enterobiasis are itching and skin inflammation in the perineal region. Attachment of the worms to the intestinal mucosa causes inflammation, abdominal
pain, appendicitis.
Diagnosis. Demonstration of pinworms in stool and eggs in perianal scrapings taken
in the morning (before the patient takes a bath). Samples are taken with a special swab.
The Graham’s method (adhesive skin test) is more effective. Sticky cellulose tape is pressed
firmly against the perianal area and then spread on a glass and examined under the low
magnification.
Patients or their parents can find small white worms on the skin of the perianal region
at night.
Prophylaxis. Personal prevention includes proper personal hygiene (frequent hand washing before meals and after defecation). Fingers should not be put in the mouth as a habit.
To prevent autoinfection a patient has to take a bath every morning and wash his hands
carefully. Nightwear and bedlinen should be ironed every morning. Fingernails should be
cut short.
Control of the disease includes treatment of the infected case and all members of the
family and keeping the personal hygiene in kindergartens and food handling occupations.
11.3. General characteristics of Roundworms (Nematodes). Roundworms – geohelminthes
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Hookworms: Ancylostoma duodenale and Necator Americanus
Ancylostoma duodenale (Hookworm)
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Hookworms (Ancylostoma duodenale and Necator Americanus) are very closely related
to each other and are often called by a common name Ancylostomatides. They are causative agents of ancylostomatidosis or hookworm disease.
Geographical distribution: all the continents from 45° N to 30° S (along the Mediterranean coast of Europe and Africa, west coast of South America, in Northern India, China
and other). The geographical distribution of these parasites overlaps, though ancylostoma infection is more common in Asia and Europe (Old World hookworm). Necator
is prevalent in Western Hemisphere (New World hookworm). In recent time migration
of infected persons has blurred the geographical differences in distribution of the two
species.
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Ancylostoma duodenale is the causative agent of ancylostomiasis or hookworm disease.
Morphology. Adult worms are small, grayish white or reddish in color (due to ingested
blood). The anterior end has a slight bend in relation to the rest of the body – hence the
name hook worm. The female is 9–15 mm, the male is 7–10 mm in size.
The buccal capsule is provided with 4 hook-like teeth on the ventral surface and 2 knoblike teeth on the dorsal surface (Fig. 11.33A). Anticoagulant substance is secreted by glands
associated with the digestive system.
Females are tapering at the posterior end. In males the posterior end is expanded in an
umbrella like fashion.
Eggs are 65 µm long and 40 µm wide, oval, colorless, surrounded by thick transparent
shell membrane. The eggs, when passed in the feces, usually contain 2 to 4 blastomeres.
Location. The adult worm lives in the small intestine, particularly in the jejunum, less
often in the duodenum.
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2
B
Fig. 11.33. Buccal capsule of Ancylostomatides: A – Ancylostoma duodenale; B – Necator Americanus:
1 – hook-like chitinous teeth; 2 – chitinous cutting plates
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CHAPTER 11. Helminths. Flat and round worms as human parasites
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Life cycle. Ancylostoma is geohelminth (Fig. 11.34). It does not require an intermediate
host but needs certain environmental conditions to develop. The female lays about 25.000
eggs per day. Eggs are passed out in the feces of the human host. In shaded moist and
warm soil (28–30 °C) rhabditiform larvae (Fig. 11.35A) hatch from the eggs in 24–48 hours.
The larva contains a large esophagus that can be divided into 3 parts – anterior bulbus, the
narrow medial part and posterior bulbus. The larva is 0.2–0.3 mm in length. It feeds on the
organic matter and bacteria in the soil. The larva moults twice to become the infective filariform larva (Fig. 11.35B). This stage is 0.5–0.8 mm in length, with a cylindrical esophagus
that occupies one fourth of the total body length. Under the optimal conditions its development continues for 7–10 days. The filariform larvae are nonfeeding. They can survive in
the soil for several weeks depending on the temperature. Direct sunlight, salt water or cold
can kill the larvae.
The disease is anthroponotic. The source of infection is a patient with ancylostomiasis.
Infective stage is filariform larva. One can get the disease in two main ways:
1. Through penetration of the skin by filariform larvae (most common mode). A 5–10
minute contact with the contaminated soil is usually required for larvae to penetrate
the skin. The most frequent sites of entry are feet and hands (areas that normally
contact with soil).
2. By accidental ingestion of filariform larvae with vegetables, fruit or water.
Oral mode
of transmission
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Larvae in pharynx
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Migration of larvae
through the lungs
Adult worm in
small intestine
Egg
Penetration of larva
Development of larvae in soil
Fig. 11.34. Life cycle of Ancylostomatides
Anterior bulbus
Posterior bulbus
A
B
Cylindrical
esophagus
Fig. 11.35. Larvae of Ancylostomatides:
A – rhabditiform, B –filariform
11.3. General characteristics of Roundworms (Nematodes). Roundworms – geohelminthes
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The larvae migrate through the epidermis into the blood and lymph vessels, are carried to the heart and then to the lungs. There larvae break into the alveoli, migrate up the
respiratory tree to the pharynx, are swallowed and pass to the small intestine. Ancylostoma
becomes mature about 4–5 weeks after the infection. If infection occurs by ingestion of the
larvae they usually migrate through lungs, but direct development in the digestive tract
without migration is probable.
The life span of the worm is 2–5 years. There may be as many as 100–1000 worms in the
intestine of the infected person.
Pathogenicity. Ancylostoma is haematophage. One worm consumes to 0.3 ml of blood
per day and it causes anemia in case of severe infection. Apart from the amount of blood
sucked by the worm, greater amount of blood is lost by bleeding at the site of hookworm
attachment because of anticoagulant substance released by the worms.
The worm also damages the mucous membrane of the intestine that causes infections
at the sites of lesions (portal of entry for bacteria).
During the various stages of development parasite causes toxic-allergic and mechanical
damage. Migration of larvae causes rash and intensive pruritus of the skin.
Diagnosis. Demonstration of the eggs in feces (ovoscopy). Eggs of ancylostoma and
necator are similar, so differentiation of the two genera by ovoscopy is impossible. Microscopic identification of larvae (rhabditiform and occasionally filariform) by cultivation of
the stool samples on the filter paper allows to differentiate two species (larvascopy, Harada-Mori filter paper strip technique). Adult hookworms may sometimes be seen in feces as
small reddish worms.
Prophylaxis. Personal prevention is not to walk barefoot and avoid consuming fruit and
vegetables without washing. Control of the disease includes prevention of fecal-soil contact by proper sewage disposal, treatment of patients, health education.
Necator Americanus (American Hookworm)
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Necator Americanus (American hookworm) is the agent of necatoroiasis or hookworm
disease.
Morphology. Necator is smaller in size than ancylostoma. The female is about 8–13.5 mm
and male is 5–10 mm in length. The anterior end is bent dorsally. The buccal capsule is
equipped with two large ventral and two dorsal cutting plates (see Fig. 11.33B).
The life cycle, pathogenicity, diagnosis, prevention are almost the same as described
for Ancylostoma. Transmission through the skin is prevalent. Life span of the parasite is up
to 15 years. The eggs of Necator Americanus and Ancylostoma duodenale are indistinguishable. Differential diagnosis is possible by comparing of larvae.
Strongyloides stercoralis (Threadworm)
Strongyloides stercoralis is the agent of strongyloidiasis.
Geographical distribution. It is similar to that of the hookworms but is met also in more
Northern regions.
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Location. The adult worms live in the human small intestine, larvae migrate with blood
through lungs.
Morphology. Strongyloides stercoralis is one of the smallest parasites known to infect
humans (Fig. 11.36, 1–4). Males are about 0.9 mm in length, and females can grow from 2.0
to 2.5 mm. They resemble hookworms, but they have a tiny buccal capsule and cylindrical
esophagus without a posterior bulb.
Eggs are similar to the hookworm eggs. They are oval, thin-shelled, 50-58 µm by 3034µm in size. The eggs hatch in the mucosa and liberate rhabditiform larvae with a double
bulb esophagus. It is about 30 µm in diameter and between 250-300 µm in length.
Filariform larvae (infective third-stage larvae) measure up to 600 µm in length and have
a pharynx with a long fine oesophagus for sucking fluids after penetrating host tissues.
Life cycle. Strongyloides stercoralis has a very unique and complex life cycle
(Fig. 11.36, 5). It alternates between free-living and parasitic cycles and has the potential
to cause autoinfection and multiply within the host (a characteristic other nematodes do
not possess). Free living life cycle involves both males and females. Parasitic phase includes adult worms that first develop male reproductive organs, subsequently replaced
by female ones. This gives impression of parthenogenetic reproduction.
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Penetration through the skin
with further migration
2
Filariform
larvae
Eggs
Rhabditiform
larvae
Filariform
larvae
Rhabditiform
larvae
Eggs
Adults
Free-living life cycle
Soil
4
1
Adult worms
Autinfection
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Human host
(intestine)
5
3
Fig. 11.36. Morphology and life cycle of threadworm (Strongyloides stercoralis): 1 – parasitic female; 2 – parasitic male; 3 – rhabditiform larva; 4 – the filariform larva; 5 – life cycle of threadworm
11.4. Roundworms – biohelminthes
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Adult female worms in the human small intestine lay eggs in the intestinal mucosa
where they hatch to form rhabditiform larvae. The further development occurs by one of
the three potential ways.
1. In the lumen of intestine rhabditiform larvae metamorphose into filariaform one,
which penetrate the wall of the lower ileum or colon or the skin of the perianal
region, enter the circulation again, travel to the lungs, and then to the small intestine, thus repeating the cycle (autoinfection). Due to this the infection can last for
30–40 years.
2. Rhabditiform larvae exit host body with faeces. In the soil they molt into infective
filariform larvae. Humans are generally infected transcutaneously, although infection has also been experimentally induced by drinking of water contaminated with
filariform larvae. After dermal penetration, the filariform larvae are carried to the
lungs, ascend the tracheobronchial tree to enter the digestive system (small intestine).
3. Rhabditiform larvae exit host body with faeces. In the soil, under warm moist conditions, they develop into free-living males and females. Fertilized females lay eggs
which release next generations of rhabditiform larvae. They may repeat the life cycle or develop into infective filariform larvae. Harsh environmental conditions are
thought to be a stimulus towards development into parasitic stages.
Pathogenicity. Dermatitis, swelling, itching, and mild hemorrhage at the site where the
skin has been penetrated. Wheezing and coughing, along with pneumonia-like symptoms
develop at the periods of migration of larvae. Intestinal symptoms appear when females
become embedded into intestinal mucosa. Main features at the intestinal stage are chronic
diarrhea or constipation, abdominal pain, and vomiting. Light infections remain asymptomatic. In immunodeficient patients due to constant autoinfection number of parasite is
extremely high, massive invasion of the tissues with larvae may be fatal. Strongilodiasis is
considered to be AIDS associated disease.
Diagnosis. Demonstration of rhabditiform or filariform larvae in stool (larvascopy). Diagnosis can be difficult because of the day-to-day variation in larvae excretion. Serological
tests are used also.
Prophylaxis. Personal prevention includes protection of skin from contact with contaminated soil (to wear slippers, shoes, etc), and to avoid contact with faecal matter or
sewage. Proper sanitary sewage and human excrements disposal are keys to prevention.
11.4. Roundworms – biohelminthes
Trichinella Spiralis (Trichina Worm)
Trichinella spiralis (trichina worm) is the agent of trichinellosis (trichinosis).
Geographical distribution. World wide with the exception of Australia. Endemic regions include Ukraine, Belarus, Russia. In contrast to most parasitic diseases this infection is
seen much less frequently in tropical countries than in Europe and America.
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CHAPTER 11. Helminths. Flat and round worms as human parasites
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Fig. 11.37. Morphology and life cycle of trichina worm (Trichinella spiralis): A – morphology of trichina worm
(1 – male, 2 – larva, 3 – female); B – circulation of trichinella (1 – wild animals, 2 – trichina worm larvae in
muscles, 3 – synanthropic animal hosts)
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Morphology. It is one of the smallest Nematoda which infects man. The female measures 2.2–3.6 mm and male 1.4–1.6 mm in length. The anterior end of the body is narrow
(Fig. 11.37A).
Location. Adult worms live in the small intestine of the host, larvae are situated in striated muscles.
Life cycle. Trichina worm is biohelminth. The life cycle is passed in one host only
(Fig. 11.37B). The same organism serves as a definitive and intermediate host of the parasite consequently.
The trichina worm is found in many mammals: humans, cats, dogs, bears, pigs, rats,
wolves, rodents and other. Man gets the parasite mainly by eating infected pork. A rare
source of the infection is the meat of wild animals like boar, bear, polar bear etc.
Infective stage for the host is larvae. After ingesting infected meat the capsule of encysted larva is digested by gastric juice and the larva releases in the small intestine, where
it moults within 24–30 hours and becomes adult worm. The female is ovoviviparous. After
mating, the male worm dies and the female worm begins to deliver the larvae on the 4th–7th
day after the infection. At this stage humans or other hosts serve as definitive ones.
11.4. Roundworms – biohelminthes
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The life span of the female parasite in the
1
human intestine is up to 45–50 days and it produces about 2.500 larvae during this period. The
larvae penetrate the intestinal wall and migrate
through the lymph vessels to the bloodstream
which carries them to the skeletal muscles
(Fig. 11.38). The most heavily affected muscles are the tongue, chewing muscles, deltoid
muscles, intercostal muscles, pectoral muscles,
diaphragm, and muscles of the calf. The larvae
leave capillaries and penetrate into the muscle
2
fibers. After 17–20 days the larvae undergo
spiralization and become infectious. A capsule
around each larva is formed within four weeks. Fig. 11.38. Trichina worm larvae in muscles:
It is about 0.26-0.4 mm long and contains lar- 1 – capsules with spiral larvae, 2 – muscles
va coiled in 2.5 turns. The capsule consists of a
double layered wall of the connective tissue and hyaline tissue; it is calcified after 14–18
months. The larvae in the muscles can survive at least for 25 years. At the period of larvae
existing humans or other hosts are intermediate ones.
For further development the larvae are to get in the intestine of another host. So, the
human host is a dead end in circulation of the infection. Circulation of the disease in nature
is maintained by the following links: pig to pig, rat to rat, rat to pig, wild rodents to various
carnivores.
Pathogenicity. The trichinella infection is asymptomatic in the majority of cases
in humans. Manifestation depends upon the number of parasites. Symptoms of the
intestinal invasion stage during the first week of infection are nausea, vomiting, diarrhea, abdominal cramps. Symptoms of the muscle invasion stage on the second week
of infection are severe headache, muscle ache, high temperature, edema of the face
and especially eyelids, allergic rash. Symptoms are caused by the organism’s sensibility
to the toxic substances produced by Trichina worm. Allergic vasculites and infiltration
of inner organs develop. Massive invasion causes multiple toxic-allergic affection of
the internal organs (pneumonia, meningoencephalites, myocardites) which may result
in death of the patient. Clinical recovery takes place after encapsulation of the larvae
and occurs during the 3rd week of infection in mild and to 2 to 3 months in severe
infection.
Diagnosis. Demonstration of trichinella larvae in a specimen of biopsied muscle (usually from the deltoid or gastrocnemius muscle). Serodiagnosis is the mainstay of laboratory
diagnosis. Serological tests give positive results after 2–3 weeks. X-ray examination may
show the presence of calcified cysts in the muscles.
Prophylaxis. Larvae in pork are killed by heating of sliced meat 2.5 cm thick for 10 hours
above 70 °C or by deep freezing at –15 °C for 20 days, that’s why personal prevention is low
effective.
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CHAPTER 11. Helminths. Flat and round worms as human parasites
Dracunculus Medinensis (Guinea Worm)
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Basic precautions include checking pork in slaughter houses and markets. According to
the standards if in any of 24 meat samples from one animal trichinella larvae are present,
the meat is not edible.
Extermination of rats from pig farms limits the spread of the infection.
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Dracunculus medinensis (Guinea worm) is the agent of dracunculiasis.
Geographical distribution. The worm is present in tropical Africa, Middle East, Arabia,
Iraq, Iran, Pakistan, India.
Morphology. The female is 30–120 cm in length and 0.9–0.7 mm in width (Fig. 11.39, 1–2).
In a mature female the uterus occupies almost the whole body and the intestine atrophies.
The male is 12–29 mm (very small in comparison with the female) and 0.4 mm in width.
Location. The adult females are usually located in the subcutaneous tissue especially of
the legs, arms and back. Sometimes it may be located in the joints, pericardium, pleura. The
breast, buttocks or genitalia may also be affected.
Life cycle. The parasite is biogelminth, the life cycle is completed in two hosts (Fig. 11.39, 3–7).
Man is the definitive host. There is no significant animal reservoir, though dogs, monkeys, cattle, horses may be affected. The intermediate hosts are minute fresh water crusta-
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Fig. 11.39. Morphology and life cycle of Guinea worm (Dracunculus medinensis): 1 – male; 2 – female; 3 – localization of female in the subcutaneous tissue; 4 – female releases larvae by contact of the blister with water;
5 – larva in the water; 6 – invasive larva (microfilaria) in the cyclop (intermediate host); 7 – definitive hosts
11.4. Roundworms – biohelminthes
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ceans cyclops. Man gets infected by drinking unfiltered water containing infective cyclops.
While the cyclop is being digested in the stomach of the primary host the larva of microfilaria type gets released. It migrates to the connective tissue. Here larvae develop into male
and female adults in about 3 to 4 months and mate. After mating the male dies. The gravid
female grows in size, migrates within the connective tissue and after 6 months reaches
a site where it is likely to come into contact with water (usually feet).
The female is viviparious. When the anterior end of the gravid female worm comes beneath the skin surface, it secrets a toxin which causes a blister. The blister breaks, forming
an ulcer with a protruded head of the worm in the base. If the ulcer comes into contact
with water, the anterior end of the worm ruptures, releasing thousands of larvae in water.
Discharging of larvae continues for 2–3 weeks. One female worm delivers about three million larvae in its life span.
For further development the larvae should be swallowed by cyclops and turn into microfilaria 2 to 4 weeks later.
Pathogenicity. Common symptoms are arthritis, fibrosed joints, secondary bacterial infection at the sites of skin lesions. Allergic manifestations are intense pruritus and urticarial
rush, nausea, vomiting.
Diagnosis depends upon the clinical symptoms of the disease – presence of the worm
under the skin. Calcified worms can be seen by radiography. In case of unusual location
serodiagnosis is helpful.
Extraction of the worm from ulcerated lesion by rolling it on small stick a few centimeters per day is the age old remedy, which is still in practice.
Prophylaxis. Personal prevention is to drink boiled and filtered water. Control of the disease includes isolation and treatment of the infected persons, destruction of the cyclops,
chemical treatment of water reservoirs.
Eradication of the Guinea worm has been successfully done in Asia, great progress for
eradication made in Africa.
Filariidae (Filariae)
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Filariidae or filariae (from Latin filum – thread) is a group of tropical parasites. General
features of filariae are as follows:
`` These are slender thread-like worms.
`` They inhabit blood vessels, lymphatic system, connective tissues and serous cavities
of man and animals.
`` The female worms are viviparous.
`` The life cycle is passed in 2 hosts – man or some other vertebrates (definitive hosts)
and a blood sucking insect (intermediate host).
`` Infection is a vector-born disease (transmitted to man by the bite of the insect).
`` Adult worms are rarely found, the specific diagnosis is usually based on the demonstration of larvae.
Several species of the filariae infect man. They cause a number of diseases having one
common name filariasis.
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CHAPTER 11. Helminths. Flat and round worms as human parasites
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Life cycle. Human being is the definitive host for all filariae. Females of parasite are viviparous and produce a great number of microfillariae which eventually get into the blood
stream. The vectors for the fillariae comprise many species of blood sucking insects, like
mosquitoes, flies and midges. While sucking the blood, vector consumes microfillariae,
that migrate from the gut to thoracic muscles of the insect. After moulting larvae becomes
infective and migrate to the mouth parts of the vector. They enter the body of the human
host through a wound at the place of bite.
Laboratory tests include demonstration of microfilaria in the peripheral blood and serological tests. Blood for the parasitologic examination is collected at the daytime or in
the evening depending on the biology of the vector (the highest number of microfilaria in
blood is at the time of vector’s feeding).
The most common species of the filariae are the following:
1. Wuchereria bancrofti causes wuchereriasis (filaria worm infection or Bancroftial filariasis). Geographical distribution is tropics and subtropics of Asia, Africa and South America. The vectors are Culex, Anopheles and Aedes mosquitoes.
The female worm measures 80–100 mm by 0.25 mm in size, while the male worm
measures 40 mm by 0.1 mm (Fig. 11.40). In human the parasites locate in lymph vessels
and nodes. Female produces larvae into the lymph from where they pass into the blood
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Fig. 11.40. Life cycle of Wuchereria bancrofti: 1, 2 – adult male and female; 3 – definitive host is a man; 4–6 –
the stage of microfilariae development in the human body; 7 – microfilaria in peripheral blood; 8 – mosquitoes Culex, Anopheles, Aedes (intermediate hosts); 9 – invasive larva in proboscis of intermediate host
11.4. Roundworms – biohelminthes
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stream. The characteristic manifestations of the disease are due to the blockage of lymph
passage – lymphedema and elephantiasis. The life span of the worm is about 20 years.
2. Brugia malayi causes Malayan filariasis or Brugian elephantiasis. The geographical
distribution is much more restricted than that of Wuchereria and includes India, Indonesia,
Phillipines, Malaysia and nearby regions. The morphology, life cycle, clinical manifestation
and diagnosis are similar to that of Wuchereria. Vectors of Brugia are Anopheles and Mansonia mosquitoes. In case of wuchereriasis and Brugian elephantiasis the larvae usually
present in blood at night.
3. Loa-loa (eye worm) causes loaiasis. Geographical distribution is West and Central
Africa. Location in man is the subconjunctival tissue (in the eye) and subcutaneous tissue,
through which they wander (Fig. 11.41). Wanderings of the worms in tissues set up temporary swellings (calabar swelling). The vector is day biting fly of the genus Chrysops (deer
fly). Diagnosis is demonstration of microfilaria in blood and adult worms removed from the
skin or conjunctiva.
4. Onchocerca volvulus causes onchocerciasis (“river blindness”). Geographical distribution is mainly tropical Africa, but also in Central and South America. The parasite lives in
the subcutaneous tissues causing formation of nodules (Fig. 11.42). It often affects the eyes
and leads to blindness. The vector is a day-biting black fly of genus Simulium. Simulium fly
species breed in fast-flowing rivers, so disease is more common along the stream of rivers.
Diagnosis is demonstration of microfilaria in the skin samples.
Prophylaxis. Personal prevention is avoiding the vector’s bites. Control of the disease
includes treatment of infected persons and eradication of vectors.
The Nobel Prize in Physiology or Medicine 2015 was divided, one half jointly to William C. Campbell
and Satoshi Ōmura "for their discoveries concerning a novel therapy against infections caused
by roundworm parasites" and the other half to Youyou Tu "for her discoveries concerning a novel
therapy against Malaria".
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Dirofilaria
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Dirofilaria worms cause dirofilariasis. Dirofilaria mostly affect animals (zoonotic infection), in humans disease is rare. The human infection is mainly caused by the Dirofilaria
immitis (heart worm) and Dirofilaria repens.
Dirofilaria immitis affects pulmonary blood vessels and heart.
Dirofilaria repens is an agent of subcutaneous dirofilariasis. Parasite is located in the subcutaneous or submucosal tissues.
Geographical distribution. Human cases have been reported from the USA, Southeast
Asia, the Middle East, Australia, Korea, Japan, European countries, including Ukraine.
Morphology. Dirophilaria are cylindrical, slender, white worms. Dirofilaria repens females are 135–170 mm, males – 50 to 70 mm in length, and maximal width is 1.2 mm.
Dirofilaria immitis females reach 350 mm, and males – 180 mm in length.
Life cycle. Dirophilaria are biohelminthes. Definitive hosts commonly are canine (dogs) but
the parasites can also infect cats and ferrets, sporadically affect man. Dirophilaria releas mi-
CHAPTER 11. Helminths. Flat and round worms as human parasites
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Fig. 11.41. Life Cycle of Loa Loa: 1 – invasive larvae develop in deer fly body; 2 – a person is infected with bite
of deer fly; 3 – adult filariae parasite in subcutaneous connective tissue; 4 – microfilaria get into the bloodstream; 5 – day; 6 – night; 7 – deer fly sucks blood with microfilariae; 8 – calabar swelling; 9 – adult worm
under the conjunctiva
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11.4. Roundworms – biohelminthes
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Fig. 11.42. Life cycle of Onchocerca volvulus: 1 – Simulium fly species feed on blood and get larvae; 2 – invasive larvae mature in the body of fly; 3 – fly repeatedly feeds on blood; 4 – larvae crawl into the bite wound
5 – larvae develop in subcutaneous tissues and adult worms form; 6 – microfilaria migrate in subcutaneous
tissues; 7 – normal eye; 8 – affected eye
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CHAPTER 11. Helminths. Flat and round worms as human parasites
Larva migrans
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crophilaria larvae into bloodstream, where latter are ingested by feeding mosquitoes. Mosquitoes of different species are intermediate hosts. Once larvae become infective, they migrate to
the mouth parts of the mosquito. Man and other vertebrate hosts acquire infection by the bite
of infected mosquito. In human organism parasite doesn’t reach sexual maturity.
Pathogenesis. D. immitis infection can be asymptomatic. Depending on number and
location of the parasites there may be coughing, weakness, hypertension, heart failure.
In case of D. repens infection patients notice a single painful subcutaneous tumor in
the affected area which can migrate under the skin. The most affected areas are face and
eyelids, chest wall, upper arms, thighs, abdominal wall, male genitalia. The worm can be
directly visualized in the conjunctiva of eye.
Diagnosis is based on serological reactions. Quit often true nature of the lesions is discovered after surgery.
Prevention is based on the avoiding mosquito bites in areas where mosquitoes may be
infected by dirofilaria larvae. This can be done by exposing as little skin as possible by wearing protective clothing, use of mosquito nets and use of insect repellents.
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Larva migrans is a human infection with helminth larvae, which are not adapted to human
beings (helminthes of dogs, cats, pigs and some other). Humans become accidental hosts,
helminths do not reach sexual maturation and symptoms are caused by migration of larvae.
Visceral larvae migrans is caused by nonhuman ascarids such as Toxocara canis (parasite
of the dogs) and T. cati (parasite of the cats) and T. leonina, that affects both. Humans become infected by ingestion of eggs with food or water. Larvae are liberated in the intestine
and migrate with blood to the liver, lungs and other organs. They don’t complete migration
and encyst in tissues, causing hemorrhage, necrosis and severe allergic reactions. Visceral
larvae migrans mainly affect children as they are more likely to have contact with contaminated soil. Diagnosis is based on serological tests.
Cutaneous larvae migrans is caused by larvae of dog and cat hookworms (Ancylostoma
braziliense and A.caninum). Infective larvae penetrate the skin but are unable to complete
the life cycle and migrate through the subcutaneous tissue. Reddish itchy papules develop
at the points of larvae invasions. In several days serpiginous reddish intercutaneous tunnels produced by the migratory larvae become visible (creeping eruption). Migration is
accompanied with itching, allergic reactions and secondary infection. The larvae infection
may persist for weeks or even months.
11.5. Methods of laboratory diagnosis of helminthoses
All the methods of laboratory diagnosis of helminthoses are divided into two groups
(Fig. 11.43):
`` parasitological (direct);
`` immunological (indirect).
11.5. Methods of laboratory diagnosis of helminthoses
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METHODS OF LABORATORY DIAGNOSIS OT HELMITHOSES
Microscopic
Sedimentation method
Ovoscopy
Flotation methods
(eggs are
concentrated
at the surface
of salt solution)
Sedimentation
methods
(egs are
concentrated
in sediment)
Skin allergic tests
Larvoscopy
Scrape from
perianal region
and
Graham's test
Harada-Mori
Test
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Wet mount method
and its modifications
Serologic tests
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Macroscopic (helminthoscopy)
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Immunological (indirect)
Parasitological (direct)
Trichinelloscopy
and muscle
digestion method
for diagnosis of
trichinellosis
Fig. 11.43. Methods of laboratory diagnosis of helminthoses
Parasitological methods
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Parasitological methods are based on detecting helminths, larvae and eggs in the
examined material. Demonstration of the parasite or its fragments (segments, scolex) is
called helminthoscopy, of the eggs – ovoscopy, of the larvae – larvoscopy.
Morphological diagnosis of helminthoses includes two steps – detection of the parasites or their parts and identification. Results of laboratory examination strongly depend
on collection of the appropriate sample and its examination by suitable techniques.
Material for examination is to be chosen according to the location of helminths. It can
be feces, bile, sputum, urine, muscles, blood, etc. Examination of feces occupies an important place in diagnostic methods, as most of helminths live in the human intestine and
eggs are excreted with feces.
Feces for the analysis should be studied within 24 hours after defecation. Parasitological
methods can be divided into two groups:
`` macroscopic examination;
`` microscopic examination.
Macroscopic Methods
The macroscopic methods are used for revealing of roundworms, scoleces and segments of tapeworms visible with the naked eye or magnifying lens.
Small portions of feces are to be mixed with water in a test tube or Petri dish. The mixture is examined on dark background using good illumination. All suspicious elements are
to be taken out. Magnifying glass can be used if needed.
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CHAPTER 11. Helminths. Flat and round worms as human parasites
Microscopic Methods of ovoscopy
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The macroscopic examination can also be performed by the sedimentation method.
The portion of feces is mixed with water in a test tube. After a certain period of sedimentation the liquid over the sediment is to be withdrawn. The procedure is repeated several
times until the over-sediment liquid becomes transparent. Then the liquid is removed and
the sediment is studied in small portions in a tube or Petri dish.
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Microscopy is studying the samples using a microscope.
The microscopic methods include examination of wet mounts, thick smears and permanent stained preparations. Various concentration methods can be used to increase the
sensitivity of the microscopic examination.
Microscopic methods are divided into quantitative and qualitative. The qualitative
methods are used for the recognizing of the parasites and diagnosis of the disease, the
quantitative methods serve for evaluation of the parasitic load (severity of the infection).
1. Qualitative methods include:
`` Wet mount and its modification.
`` Concentration techniques:
`` methods of flotation;
`` methods of sedimentation.
`` Demonstration of eggs in a scratch from perianal region.
Wet mount method. Temporary wet mount is the simplest and easiest technique. It
can be prepared directly from fecal material. The unstained wet film is made by emulsifying small quantity (equivalent to the size of a match head) of feces in a drop of glycerin
on a slide. The smear is covered by a coverslip and examined under the microscope. This
method has low efficacy in case of small number of the parasites.
The Kato thick smear technique is more efficient modification of the wet mount method (Fig. 11.44). About 50 mg feces is taken on a slide and covered with a special wettable
cellophane coverslip soaked in glycerin containing aqueous malachite green and phenol.
The preparation is left for about an hour at the room temperature, in which period the
glycerin clears the feces and malachite green stains the eggs in green color. The eggs of
helminths stained green are seen distinctly under low power magnification.
Despite this method is more sensitive than the
wet mount method, eggs of the dwarf tapeworm,
hookworms and cat fluke are not detected. This
method is not useful for diagnosis of larvae too.
Concentration techniques. If the number
of eggs in the stool specimens is low, examination of a direct wet mount may not detect parasites hence the stool should be concentrated.
The concentration methods fall into two
main classes:
Fig. 11.44. Kato thick smear technique
11.5. Methods of laboratory diagnosis of helminthoses
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1. Flotation methods. In this method the feces is suspended in a solution of high specific gravity so that parasitic eggs float up and get concentrated at the surface.
2. Sedimentation methods. In this method the feces are suspended in a solution with
low specific gravity so that the eggs get sedimented at the bottom either spontaneously or by centrifugation.
Flotation method. Most common flotation method is the Fulleborn’s method. Flotation
of the eggs of helminths takes place in a saturated solution of salt.
The saturated solution is prepared by solving of 400 g of NaCl in one liter of boiling
water (specific gravity 1.18). The solution is to be filtered and cooled. About 2 ml of the
salt solution is taken in a flat bottomed tube and 1 g of feces is emulsified in it. Then the
container filled completely to the rim with the salt solution and a slide is placed on the
container to be in contact with the surface of the solution. After standing for 30–40 min
the slide is removed without shaking, reversed to bring the wet surface up and is examined
under the microscope.
As unfertilized eggs of ascaris, eggs of beef and pork tapeworms, and eggs of trematodes do not float in the salt solution the sediment is to be microscoped as well.
Other flotation techniques use flotation of helminths eggs in a saturated solution of
sodium nitrate, zinc sulfate or suger. The specific gravity of the solutions is over 1.38, that is
why the eggs of most helminths float and can be found in the film on the surface. There is
no need to study the sediment.
Sedimentation methods. The most simple is gravity sedimentation technique. A sufficient amount of feces is thoroughly shaken with 15–20 ml of tap water and allowed to
settle in a cone-shaped flask for an hour or two. This process is repeated several times till
the supernatant fluid is clear. Finally the sediment at the bottom is examined under the
microscope.
The Krasilnikov’s method is based on the usage of saturated solution of washing powder. 2–2.5 g of feces are mixed with 20–30 ml of solution. The mixture is sedimented for
24 h or centrifuged for 1 min (1,000 turns per minute). Three layers of sediment are formed.
The eggs are concentrated in the middle layer. 2–3 films from this level are examined under
the microscope. Eggs of all helminths can be detected.
Demonstration of eggs in a scrape from perianal region is used for diagnosis of enterobiasis and taeniarinchiasis.
This method is based on studying of the perianal and rectal mucous. A scrape from
perianal region is taken with a cottonwool swab, tightly reeled on a wooden stick, smeared
and microscoped.
Another way (Graham’s test) for collection of specimens is carried out with a Scotch
tape (an adhesive transparent cellophane tape). A strip of sticky Scotch tape is applied to
the perianal region, removed and then attached onto a glass slide for microscopic examination.
Perianal scrapings are to be taken early in the morning before the patient goes to the
toilet or takes a bath as helminths crawl out of anus to lay eggs at night. Children may undergo this procedure after their midday sleep.
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2. Quantitative methods help to estimate parasitic load. Eggs counts are not usually
done in a clinical laboratory for routine diagnosis. It is done in cases of ascariasis, the whipworm and hookworm infection for two purposes:
`` epidemiological surveys;
`` therapeutic monitoring.
In Stoll’s Dilution Egg Count Technique 4 g of faeces are mixed with 56 ml of 0.1 M NaOH
in a glass tube. Using a pipette exactly 0.75 ml of the sample is transferred to a slide and
covered by a coverglass. All the eggs present are counted. The number multiplied by 200
gives the number of eggs per gram of feces.
Microscopic larvoscopy methods
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Finding of larvae in examined material is used for diagnosis of trichinellosis, ancylostomiasis, strongyloidiasis, and different species of filarial worms. Examples are:
`` Harada-Mori test was suggested by Japanese scientists for diagnosis of hookworm
infection (Fig. 11.45). It is based on the fact that larvae hatch from eggs if the environment is warm and damp.
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Fig. 11.45. Harada-Mori culture method for diagnosis of hookworm infections: A – test tube with culture
material: 1 – cork that fixes the paper strip; 2 – paper strip; 3 – smeared feces; 4 – water. B – filariform larvae
of Ancylostomides: 1 – Ancylostoma duodenale; 2 – Necator americanus
11.5. Methods of laboratory diagnosis of helminthoses
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The Harada-Mori culture method uses strips of filter paper on which feces is smeared
in the middle third. The paper strip is kept in a conical centrifuge tube with water at the
bottom, in which the strips dip. The tubes are placed in the dark for 5–6 days at 28 °C in
an upright position to allow the larvae to molt and swim down to the water, from which
they can be collected. Method permits to distinguish larvae of Ancylostoma duodenale and
Necator Americanus.
Before microscoping larvae should be killed by rising the temperature up to 60 °C.
A laboratory assistant has to wear protective rubber gloves as larvae are infectious.
`` Trichinelloscopy and the muscle digestion method are the methods of larvae demonstration in muscles for diagnosis of trichinellosis. To perform trichinelloscopy the
muscles are to be cut into small pieces and put into the compressorium (two wide
thick blocks of glass fastened with two screws in a press type). While being pressed
muscle fibers form a thin layer and get more transparent. Then specimens should be
examined under the low power magnification.
According to Muscle Digestion Method muscle sample is digested for 30 min in solution of pepsin and hydrochloric acid at 37 °C. The larvae accumulate in solution, which is
examined under the microscope. This method is also used for epidemiological surveys of
prevalence in animals.
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Immunological methods
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Immunological methods of diagnosis are indirect methods, which are used when direct
parasitologic methods are non-informative. Methods are applicable:
`` in case of tissue location of helminths, when any stage of parasite is not excreted
outside (echinococcosis, alveococcosis, trichinelliasis, cysticercosis, etc);
`` during the period of larvae migration in the host body (ascariasis, trichinellosis);
`` when the parasiting helminths are only males or reproduction of helminths has not
begun yet.
Immunological methods include serologic tests and skin allergic tests. Serologic tests
are detection of antibodies to parasites in blood serum. Skin allergic tests have mostly
historic significance and were used for diagnosis of echinococcosis and alveococcosis (see
page 300).
Morphology of the Eggs of Helminthes
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Eggs of Trematodes (Flukes) (Fig. 11.46).
Eggs of majority of trematodes resemble conventional eggs in appearance. They vary from
30 µm to 175 µm in size and have smooth hard shell, which is transparent and is generally of
yellow brown or brown color. Most of the eggs have an operculum which is like an escape
hatch, through which the miracidium escapes. Many species have small knob on posterior
end.
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CHAPTER 11. Helminths. Flat and round worms as human parasites
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Fig. 11.46. Morphology of eggs of helminthes (arranged according to size): 1 – cat fluke; 2 – oncosphere of
the Taeniides; 3 – lancet fluke; 4 – dwarf tapeworm; 5 – pinworm; 6 – whipworm; 7 – ascaris (fertilized egg);
8 – hookworms; 9 – broad tapeworm; 10 – ascaris (unfertilized egg); 11 – Schistosoma japonicum; 12 –
Schistosoma haematobium; 13 – Schistosoma mansoni; 14 – liver fluke
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Eggs of Cestodes (Tapeworms)
The eggs of the tapeworms are divided into two groups: operculated eggs (nonembryonated when laid) and hexacanth eggs (have two layers and contain a mature embryo
(oncosphere) with 6 hooklets). The latter are spherical in shape, with thin, transparent and
colorless outer shell.
Among the above discussed Cestodes, the broad tapeworm has operculated eggs,
others have hexacanth ones. In armed and unarmed tapeworm eggs outer shell destroys quickly and usually oncosphere are found. Oncosphere of that worms have similar structure, differentiation is impossible, so in this case disease is recognized as taeniidiasis.
Eggs of Nematodes (Roundworms)
Most of the roundworms are geohelminths, that is why their eggs are usually equipped
with thick shell and shaped differently. Eggs of Nemathodes contain a fertilized ova or larvae of different stages.
The main characteristics of eggs are summarized in Table 11.1.
11.5. Methods of laboratory diagnosis of helminthoses
331
Table 11.1. Characteristics of eggs of helminthes
Species
Size of the eggs
Morphological peculiarities
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Eggs of Trematodes
Fasciola hepatica
130–150 by 80 µm
Opisthorchis felineus
Opisthorchis Sinensis
25–30 by 10–15 µm The eggs are very small, operculated, yellowish
brown. Shape is ovoid, narrowing a little posteriorly into the operculum. Contains miracidium
Dicrocoelium
lanceatum
38–45 by 25–30 µm The eggs are thick shelled, dark brown, operculated
Paragonimus ringeri
80–110 by
50–60 µm
The eggs are operculated yellow brown
Schistosoma haematobium
150 by 62 µm
The eggs are large, oval, terminally spined. Contain miracidium
Schistosoma mansoni
140 by 60 µm
The eggs have lateral spine. Contain miracidium
Schistosoma Japonicum
85 by 60 µm
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The eggs are large, ovoid, operculated, yellow
The eggs are round with a minute lateral spine.
Contain miracidium
Eggs of Cestodes
oncosphere
31 by 43 µm
The eggs are spherical, transparent and colorless.
Oncosphere is surrounded by double contoured
striped coat
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Taenia solium
31 by 43 µm
Eggs are similar to that of T. solium, but have two
lateral filaments. Oncospheres are same to T. solium
Hymenolepis nana
30 by 45 µm
The eggs are spherical or oval, transparent, colorless. Each egg contains the onchosphere with
filaments (thread-like bodies) located around it
Diphyllobothrium latum
60–70 by 45–50 µm The eggs resemble the eggs of trematodes in morphology. They are widely oval, operculated, yellowish brown, with a small hillock on an opposite pole
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Taeniarhynchus saginatus
Ascaris lumbricoides
fertilized
unfertilized
Eggs of Nematodes
The external coat is coarsely mammilated (is
covered with hillocks)
60–75 by 40–50 µm The egg contains a large round ovum with clear
spaces at each pole
The egg is elliptical, inner space is completely
80 by 50 µm
filled with yolk
50 by 25 µm
Enterobius
vermicularis
50–60 by 30–32 µm The eggs are colorless, transparent, asymmetrical
(planeconvex). Coiled larvae can be seen inside
Ancylostoma
duodenale
Necator americanus
65 by 30 µm
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Trichocephalus trichirius
The eggs are yellow brown, shaped as a lemon (barrel) with two transparent mucus plugs at each pole
The eggs of the species are similar, have oval or
elliptical shape, colorless. Freshly excreted eggs
contain 2 to 4 blastomeres
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CHAPTER 11. Helminths. Flat and round worms as human parasites
TASKS & QUESTIONS
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`` MULTIPLE CHOICE QUESTIONS (CHOOSE ONE CORRECT ANSWER):
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1. The armed tapeworm larvae are agents of:
A. Taeniasis
C. Paragonimiasis
E. Hymenolepiasis
B. Taeniarhynchiasis
D. Cysticercosis
2. Laboratory diagnosis of taeniasis is based on:
A. Demonstration of eggs in perianal mucus
B. Demonstration of proglottides in faeces
C. Serodiagnosis
D. Larvoscopy of blood
E. Biopsy of striated muscles
3. White proglottides 20 × 7 mm in size, with a large number of uterus branches (20 to
34 branches) were discovered in faeces. These may be proglottides of:
A. Fasciola hepatica
D. Taeniarhynchus saginatus
B. Opisthorchis felineus
E. Hymenolepis nana
C. Taenia solium
4. Cysticercosis in human may result from:
A. Echinococcosis
D. Taeniarhynchiasis
B. Hymenolepiasis
E. Fascioliasis
C. Taeniasis
5. Which of the following larvae may inhabit the brain?
A. Beef tapeworm
C. Dwarf tapeworm
E. Cat fluke
D. Liver fluke
B. Pork tapeworm
6. It is possible to get infected with diphyllobotriasis by eating:
A. Crabs and crawfish
D. Improperly cooked fish
B. Unwashed vegetables
E. Contaminated water
C. Improperly cooked meat
7. Human being may get infected with hymenolepiasis through:
A. Fish
B. Dirty hands, contaminated vegetables and fruit
C. Mosquito bites
D. Crabs and crawfish
E. Insufficiently roasted beef
8. What is the pathogenic action of the dwarf tapeworm?
A. Liver, lungs and brain affection
B. Malignant anemia
C. Intestine villi destruction, intoxication
D. Anemia, neurological disorders, vermiform appendix inflammation
E. Eyelids and face edema, fever and muscle pain
11.5. Methods of laboratory diagnosis of helminthoses
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9. Laboratory diagnosis of echinococcosis includes:
A. Immunological tests
C. Muscle biopsy
D. Urine ovoscopy
B. Faeces examination
10. Anemia due to the lack of the vitamin B12 is a symptom of:
A. Taeniasis
E. Diphyllobothriasis
C. Hymenolepiasis
B. Taeniarhynchiasis
D. Echinococcosis
11. Human being is a definitive host only in case of?
A. Taeniasis
C. Hymenolepiasis
E. Diphyllobothriasis
B. Alveococcosis
D. Echinococcosis
12. From the diseases listed below choose cestodosis with a natural focus:
A. Fascioliasis
D. Diphyllobothriasis
B. Hymenolepiasis
E. Taeniasis
C. Opisthorchiasis
13. Examination of FRESH faeces is essential for laboratory diagnosis of:
A. Diphyllobothriasis
D. Hymenolepiasis
B. Fascioliasis
E. Taeniarhynchiasis
C. Opisthorchiasis
14. Migration via lungs is typical for:
A. Enterobius vermicularis
D. Echinococcus granulosus
B. Trichocephalus trichiurus
E. Taenia solium
C. Ascaris lumbricoides
15. Intestinal obstruction is a possible complication of:
C. Opisthorchiasis
E. Enterobiasis
A. Hymenolepiasis
B. Fascioliasis
D. Ascariasis
16. Whipworm eggs get matured in:
A. Three weeks
C. One week
E. 25 to 30 days
B. 4 to 6 hours
D. One day
17. Which of the following refers to enterobiasis preventive measures?
A. Keeping personal hygiene rules
D. Veterinary examination of beef
B. Veterinary examination of pork
E. Consuming properly cooked meat
C. Consuming properly cooked fish
18. Lemon-shaped eggs 50 × 25 µm in size with corks on the both poles were revealed in
human faeces. Clinical manifestations include appendix inflammation. The possible
agent is:
A. Cat fluke
C. Pinworm
E. Echinococcus
B. Ascaris
D. Whipworm
19. Through the skin it is possible to get:
A. Ascariasis
C. Entetrobiasis
E. Ancylostomiasis
B. Teniasis
D. Opistorchiasis
20. A natural reservoir of trichina worms is:
A. Cattle
C. Boars
E. Crabs
B. Fish
D. Birds
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CHAPTER 11. Helminths. Flat and round worms as human parasites
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21. The infective stage in ancylostomiasis is:
A. Phynn
D. Oncosphere
B. Plerocercoid
E. Filariform larva
C. Metacercaria
22. Main manifestations of trichina worm infection are:
A. Affection of the liver, lungs, brain
B. Malignant B12 deficient anemia
C. Anemia, inflammation of appendix
D. Destruction of the intestinal villi, intoxication
E. Swelling of the face and eyelids, pain in the muscles, high temperature
23. A patient has been admitted to the hospital with complains of pain and swelling of
the right foot. A thread-like thickening with a blister at its end is seen under the skin.
The patient is two weeks from Yemen where he sometimes drank unboiled water.
Which disease can be suspected?
A. Schistosomiasis
C. Paragonimiasis
E. Dracunculiasis
B. Trichinellosis
D. Hymenolepiasis
24. Main manifestations of ancylostoma infection are:
A. Affection of the liver, lungs, brain
B. Malignant B12 deficient anemia
C. Anemia, abdominal pain, failure of digestion
D. Destruction of the intestinal villi, intoxication
E. Swelling of the face and eyelids, pain in the muscles, high temperature
25. Laboratory diagnosis of fascioliasis is:
A. Muscle biopsy
D. Immunologic tests
B. Ovoscopy of faeces
E. Ovoscopy of sputum
C. Larvoscopy of faeces
26. Laboratory diagnosis of hymenolepiasis is:
A. Ovoscopy of faeces
D. Demonstration of larvae in blood
B. Ovoscopy of sputum
E. Serodiagnosis
C. Muscle biopsy
27. Laboratory diagnosis of trichinellosis is:
A. Ovoscopy of faeces
D. Ovoscopy of urine
B. Muscle biopsy
E. Ovoscopy of perianal scrape
C. Demonstration of eggs in faeces
28. Laboratory diagnosis of echinococcosis is:
A. Immunological tests
D. Ovoscopy of urine
B. Demonstration of larvae in muscles
E. Ovoscopy of perianal scrape
C. Demonstration of larvae in faeces
29. Laboratory diagnosis of diphyllobothriasis is:
A. Ovoscopy of faeces
D. Ovoscopy of urine
B. Larvoscopy of muscles
E. Ovoscopy of perianal scrape
C. Larvoscopy of faeces
11.5. Methods of laboratory diagnosis of helminthoses
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`` FILL IN THE BLANKS:
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30. Diagnosis of dracunculiasis is:
A. Larvoscopy of faeces
D. Ovoscopy of urine
B. Larvoscopy of muscles
E. Presence of visible threads under the
C. Demonstration of eggs in faeces
skin
31. Immunological tests are the method of diagnosis for:
A. Taeniasis
C. Taeniarynchiasis
E. Enterobiasis
B. Cycticercosis
D. Opisthorchiasis
32. Oval colorless transparent eggs have been detected during the laboratory examination of faeces. There are 4 dark blastomeres inside the eggs. What is the species of
helminths?
A. Fasciola hepatica
D. Ancylostoma duodenale
E. Hymenolepis nana
B. Opisthorchis felineus
C. Diphyllobothrium latum
33. During the laboratory examination of faeces grayish widely oval operculated eggs
have been detected. The size of the eggs is about 70–75 µm. What is the species of
helminths?
A. Fasciola hepatica
D. Ancylostoma duodenale
E. Hymenolepis nana
B. Opisthorchis felineus
C. Diphyllobothrium latum
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1. _______________ are worms with alternation of definitive and intermediate hosts in
their life cycle.
2. In snail the miracidium of Flukes as a rule progress through the __________,
____________ and ___________ stages in about several months.
3. The second intermediate hosts for Dicrocoelium lanceatum are _______ in which
____________ (the last larval stage) develop.
4. The infection by schistosomiasis occurs when a man enters the _______ where the
_____________ penetrate the skin.
5. By eating inadequately processed fish a man mainly can be infected by
________________ and sometimes by _____________ and _____________.
6. Egg of ____________ contains oncosphere which in the organism of an intermediate
host (pig) develop into phynn ______________.
7. Plerocercoid is a phynn stage of _____________________ that developes in muscles
of ______________________.
8. Ancylostoma causes anemia in case of severe infection, as it is _________. Its location
in human body is __________________.
9. Adult trichina worms inhabit _______________, and larvae are located in
_________________.
10. For diagnosis of ___________________ and strongiloid infections ____________
(demonstration of larvae) is used.
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CHAPTER 11. Helminths. Flat and round worms as human parasites
`` TRUE OR FALSE:
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1. Personal prevention of fascioliasis is to process fish properly.
True
False
2. The majority of fish intermediate hosts for cat fluke are confined to Cyprinidae.
True
False
3. Body cavity in Nematodes is absent, inter-organic space is filled with parenchyma.
False
True
4. Metacercariae of lung fluke develop in muscles of crabs and crayfish.
True
False
5. Eggs of Schistosoma sp. are not operculated and possess spine.
True
False
6. Echinococcus cyst or a hydatid cyst demonstrates external budding.
True
False
7. Hymenolepiasis is a contact anthroponotic disease.
True
False
8. The characteristic manifestations of wuchereriasis are lymphedema and elephantiasis.
True
False
9. Cutaneous larvae migrans is caused by nonhuman ascarids such as Toxocara canis
(parasite of the dogs).
True
False
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CHAPTER 12.
Arthropodes as poisonous animals, vectors
and agents of human diseases
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12.1. General characteristics of Arthropods
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Arthropods is the largest phylum of the animal kingdom, which includes about 1 mln
of species.
General characteristics of Arthropods:
1. Bilateral symmetry.
2. Triploblastic (develops from three germ layers).
3. A tough, jointed chitinous exoskeleton. It has protective function and preserves the
body from drying.
4. The body is segmented. The segments are grouped in the cephalothorax and abdomen or into the head, thorax and abdomen.
5. Jointed appendages modified for a variety of functions (feeding, walking, jumping,
swimming).
6. Striated muscles, which arranged into bundles and provide independent movements
of a particular segment of the body.
7. The body cavity around the viscera is mixocoel (haemocoel). It contains the haemolymph.
8. The digestive tract is complete and has three parts: fore-, mid- and hindgut. The
mouth is provided with movable appendages (the mouth parts). These are adapted
for chewing, sucking, sponging, etc.
9. Respiration takes place by gills, trachea or lungs.
10. The circulatory system is of open type. The blood (haemolymph) flows in haemocoel
instead of blood vessels. The heart is situated on the dorsal side.
11. The excretory system may consist of green glands, opening directly to the exterior, or
Malpigian tubules opening into the gut.
12. The nervous system comprises a circumetric ring and a double midventral nerve cord
bearing a pair of ganglia per segment, or less due to fusion of adjacent ganglia.
13. The sense organs are present. The eyes are compound in most of forms, arachids
have simple ones.
14. The endocrine system is present and regulates metamorphosis.
15. Reproduction is sexual. Sexes are separate. The gonads have ducts. Fertilization is
internal in the majority of species.
16. The postembryonic development is direct or indirect with larval forms. Incomplete
metamorphosis includes stages of the ovum, larva, imago. Complete metamorphosis
includes stages of the egg, larva, pupa (chrysalis) and imago.
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CHAPTER 12. Arthropodes as poisonous animals, vectors and agents of human diseases
There are several subphylums of phylum Arthropoda, but the following ones are mostly
important for medicine: Crustaceans, Chelicerates (arachnids) and Hexapods (insects).
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Crustaceans
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12.2. Medical importance of Crustaceans and Arachnida.
Spiders and ticks
They are inhabitants of marine and fresh water reservoirs. The lower crustaceans (Cyclopes) are the intermediate hosts for broad tapeworm and Guinea worm. Crabs and crawfishes are the second intermediate hosts of the lung fluke.
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Subphylum Chelicerates. Class Arachnida
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The Arachnids have the following characteristics (Fig. 12.1B):
1. The body has two regions: cephalothorax and abdomen.
2. Cephalothorax bears two pairs of the mouth parts called chelicerae and pedipalps
for feeding and four pairs of walking legs (six pairs in general). The antennae are absent. The abdomen has no appendages.
3. Respiration occurs by trachea or book-lungs or both. The book-lungs (derivatives of
gills) are present in scorpions and spiders. Many spiders have also the tracheae.
4. Development is chiefly direct.
The major orders of Arachnida are Araneae, Solifugae, Scorpiones, Parasitiformes (ticks)
and Acariformes (mites).
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Classification
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Phylum: Arthropoda
Subphylum: Chelicerata
Class: Arachnida
Order: Araneae
Species: Latrodectus tredecimguttatus (in different regions known as karakurt, Mediterranean black widow, European black widow, steppe spider)
Lycosa singoriensis (tarantula or wolf spider)
Order: Parasitiformes
Family: Ixodidae
Family: Gamasoidae
Species: Ixodes ricinus (dog tick)
Species: Dermanyssus gallinae (chicken mite)
Ixodes persulcatus (taiga tick)
Liponyssoides saguineus (house mouse mite)
Dermacentor pictus (meadow tick)
Family: Argasidae
Species: Ornithodoros papillipes
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12.2. Medical importance of Crustaceans and Arachnida. Spiders and ticks
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4
3
9
8
10
7
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6
1
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A
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15
14
13
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Fig. 12.1. Venomous spiders: A – karakurt (Lathrodectus tredecimguttatus); B – diagram of the internal structure of the spider (1 – pedipalps; 2 – the duct of the venomous gland; 3 – venomous gland; 4 – eyes; 5 – the
main nervous ganglion; 6 – gut ceca; 7 – sucking stomach; 8 – heart; 9 – liver; 10 – the midgut; 11 – Malpigian tubules; 12 – anus; 13 – silk glands; 14 – system of trachea; 15 – ovary; 16 – genital opening; 17 – booklungs; 18 – chelicerae); C – tarantula (Lycosa singoriensis); D – Scorpion (Euscorpius tauricus)
Superorder: Acariformes
Species: Sarcoptes scabiei (itch mite)
Demodex folliculorum (follicle mite)
Order Araneae (spiders)
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The spiders are nocturnal animals, which feed on different insects, killing them with
poison.
A specific morphological feature is unsegmented body distinguishable into two regions: the anterior small cephalothorax and the posterior large swollen abdomen joined
by a narrow pedicel. The venomous glands are found near the base of chelicerae, trough
the tips of which venom is discharged.
The abdomen bears 3 or 4 pairs of tubercules that contain spinnerets (silk-producing organs containing silk glands) to spin silk thread for making web. Most of spiders trap insects
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in the web, paralyze them with venom, inject the digestive enzymes and suck the body
juices. The digestive system is adapted for feeding on semi-liquid food.
Eggs are laid in a cocoon. The spiderlings pass through 8–9 molts to become adult.
The venomous species in South Ukraine are karakurt (Latrodectus tredecimguttatus)
(one of the black-widow spider species) and tarantula or wolf spider (Lycosa singoriensis).
Karakurt (Latrodectus tredecimguttatus) is a small spider also known as the European
black widow or the steppe spider (see Fig. 12.1A). The male is 1 cm and female is 1.5–2 cm
in length. Characteristic feature of the females is dark brown or black body and legs and red
spot on the dorsal side of abdomen. Karakurt lives in the holes of rodents, sheds, garages,
toilets, rail fences, stumps, among the stones in the beaches. It avoids strong light and
bites only when disturbed. Natural biological enemies of the spiders are wasps, hedgehogs, sheep, which trample them down.
Medical importance. The venom of karakurt may be lethal for humans and animals as
it is neurotoxic and blocks neuromuscular impulse transmission. The bite is accompanied
by a sharp smarting pain, muscle and chest pain or tightness. The other symptoms may be
laboured breathing and speech, nausea, vomiting, tachycardia, bronchial spasm, depression, delirium. Most deaths from black widow bites are the result of respiratory paralysis.
The first aid is injection of anti-karakurt serum, containing antibodies to the poison. With
the purpose of prevention it is necessary to mow weed down on the places, where karakurts hide.
Tarantula (Lycosa singoriensis) is a large spider, about 35 mm in length, covered with
brown, gray, black or sometimes red hair (see Fig. 12.1C). Various stripe-like markings on
the dorsal side is typical. Tarantula is not associated with webs, it lives in the holes in the
soil and is active night hunter.
Medical importance. The bite of a tarantula spider is painful and may cause allergic reaction – hyperemia, local swelling and numbness, tachycardia, sleeplessness. Unprovoked
bites are uncommon because tarantulas are usually docile; patients usually are able to tell
what has inflicted their injury.
Order Solifugae
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It is an order of non-venomous, spiderlike
predatory arachnids (Fig. 12.2). Solifugae inhabit desert, semi-desert, tropical, and warmtemperate regions.
Solifugae (phalanges) have a segmented
cephalothorax and abdomen. The most distinctive feature of Solifugae is their large clawlike chelicerae that are used for holding and
crushing prey. Long pedipalpae function as
sense organs similar to insects’ antennae and
give the appearance of the two extra legs.
Fig. 12.2. Solifugae
12.2. Medical importance of Crustaceans and Arachnida. Spiders and ticks
341
Medical importance. Solifugae are not venomous. The greatest threat they pose to humans, is their bite in self-defense. They can produce a large, ragged wound that is prone to
infection.
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Order Scorpions
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Scorpions are elongated arachnids with large pedipalpae terminating in stout claws
(see Fig. 12.1D). Size varies from 13 mm to 20 cm. The cephalothorax is nonsegmented. The
abdomen is elongated, segmented and shows two regions: anterior broad flat preabdomen and posterior narrow cylindrical postabdomen with poison hooked sting at the end.
The poisonous glands are present in the last abdominal segment, their ducts are opened
at the end of the sting.
Scorpions are nocturnal animals, lie under rocks, boards and other protective coverings.
They are viviparous, young are carried for some time on the back of the female.
Medical importance. Clinical features of scorpion sting depend on species of the animal
and individual sensitivity of a victim. Scorpion sting causes immediate pain or burning,
very little swelling, sensitivity to touch, and a numbness sensation, that can be accompanied with sleepiness and fever. The poison of large tropical species sometimes can lead to
the death, especially in children. The first aid in patients with severe symptoms is an injection of antiscorpion serum.
Order Parasitiformes (ticks)
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The body of a tick is termed as idiosoma. It is flat, nonsegmented, with fused cephalothorax and abdomen (Fig. 12.3). Anterior (head) region is called the capitulum or gnathosoma. It carries a mouth parts comprising hypostome, chelicerae and pedipalps (Fig. 12.4).
The respiration occurs by trachea, but in some small-sized species respiration is through
the body surface.
Sexes are separate. Males are smaller than females. Development occurs with incomplete metamorphosis (egg – larva – one or several nymph stages – imago).
There are about 300 species of ticks.
Order Parasitiformes includes Ixodidae or hard ticks, Argasidae or soft ticks and Gamasoidae mites. The Ixododae ticks are more specialized, produce more progeny and infest the
host itself. The Argasidae ticks are more primitive, produce less progeny and infest the habitat of the host. Gamasoidae are mostly small ectoparasites of birds and rodents.
Family Ixodidae (hard ticks)
Ixodidae ticks are a large group of a widely spread bloodsucking arachnids. The sizes
vary from 2–5 mm up the 3 cm (see Fig. 12.3). They got name hard ticks as have a spinal
horny shield (scutum). It covers the entire dorsal surface in males and only the anterior part
(about of 1/3 of the length) in the females. Such difference is explained by more significant
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CHAPTER 12. Arthropodes as poisonous animals, vectors and agents of human diseases
Scutum
Hypostome
1
Eye
6
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Gnatosoma
Genital
aperture
5
Anal groove 2
A
4
Scutum
Palp
Anus
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4 pairs of legs
1
Idiosoma
B
2
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3
4
5
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Fig. 12.3. Ixodidae ticks (A – dog tick; B – a section of the female dog tick): 1 – female, dorsal view; 2 – female,
ventral view; 3 – male, dorsal view; 4 – larva; 5 – nymph; 6 – hypostome; 7 – Malpigian tubules; 8 – diverticula
of midgut; 9 – midgut; 10 – tracheae; 11 – salivary glands
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1
3
2
5
8
6
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4
A
1
5
B
C
3
4
Fig. 12.4. Capitulum of a tick: A – dorsal view; B – ventral view shows hypostome and lateral palps; 1 – cheliceral shaft; 2 – cheliceral digits; 3 – palp; 4-7 – articles of palp; 8 – hypostome; C – gnathosoma, imbedded
into the skin of the host: 1 – palps; 2 – cheliceral shaft; 3 – cheliceral digits; 4 – hypostome; 5 – blood vessels;
6 – intracellular cavity with inflammatory infiltrate
12.2. Medical importance of Crustaceans and Arachnida. Spiders and ticks
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enlargement of females after getting blood as they need more food for development of
eggs.
The capitulum in hungry tick is usually visible dorsally at the anterior end of the body.
Ticks are spread in each landscape zone, they are parasites of mammals, birds, reptiles.
Larvae suck blood of small rodents, birds, lizards. Nymphs feed on mammals (rabbits, hares,
squirrels), and birds. A sexually matured female feeds primarily on the cattle blood. Nymph
and imago can feed on humans.
Ticks wait for host animals from the tips of grasses and shrubs and can detect emitted
heat (by thermoreceptors), carbon dioxide expired from a nearby host (by chemoreceptors) or vibration of the soil (by vibroreceptors). The duration of bloodsucking varies from
a few hours up to a few days. Salivary secretion contains anticoagulants and anesthetics.
Several distensible diverticula of the gut accumulate the blood. When a female tick is well
fed it will swell to about 200 times its original size.
Ticks generally drop off the animal when full. Female deposits 2.000 to 8.000 eggs into
the cracks of the soil, deciduous leaves and dies after oviposition. The larva hatched from
the egg has 3 pairs of appendages (see Fig 12.3). After a few months and feeding it turns
into the nymph stage. Nymph has no sexual system and bears 4 pairs of appendages. After
about 1–3 months and feeding nymph becomes imago (adult stage). The life cycle is usually completed in 1, 2 or 3 years.
Medical importance. The ticks are temporary ectoparasites. They are biological vectors
of tick-born virus encephalitis, Lyme borreliosis, Rocky mountain spotted fever, tularemia.
A great role of the ticks as vectors is explained by broad range of hosts even distant from
each other ecologically. It is also important that Ixodidae female can transmit virus of encephalitis through the eggs (transovarial transmission) to next generation. Then virus is
transmitted to larva, nymph and imago (transphase transmission).
Ixodes ricinus (dog tick or castor bean tick) is a temporary parasite of wild and domestic
animals, sometimes can attack human being. It has a wide geographic distribution, including Europe and North Africa where prefers deciduous woodland, pastures, urban parks.
The size of a male is 2.5 mm, the size of a hungry female is 4 mm and of the female after
bloodsucking is about 11 mm. Females lay the 10.000–12.000 eggs once a life-time into
the soil. The canine tick is a vector of the tick-borne virus encephalitis (Central European
encephalitis), Lyme borreliosis, tularemia.
Ixodes persulcatus (taiga tick) is a temporary parasite of wild and domestic animals,
sometimes can attack human being. It is distributed from Europe to China and Japan inhabiting the forest regions. Taiga is the typical place of its dwelling. It is the main vector
of tick-borne virus encephalitis (taiga or Russian spring-summer encephalitis). The taiga
encephalitis is the disease which affects the central nervous system (mortality is 20–30 %).
The natural reservoirs of the taiga encephalitis virus are many wild animals including mice,
hedgehogs and chipmunks from which the disease is transmitted to the humans. Transovarial and transphase transmission of the virus is important for circulation of the virus in nature.
The agent of tick-borne encephalitis has been discovered by a virologist L. O. Zilber.
The theory of natural foci of vector-borne encephalities was created by E. N. Pavlovsky. He
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CHAPTER 12. Arthropodes as poisonous animals, vectors and agents of human diseases
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also worked out the preventive measures from tick bites and now the special Pavlovsky’s
protective nets are used. Pavlovsky proposed the system of destruction of the ticks in biogeocenosis with the help of acaricides (chemicals killing the ticks).
Dermacentor pictus (meadow tick). Specific morphological feature is light coloured shield
area behind the head. Dermacentor pictus is the inhabitant of the steppe zone and is a vector of tick-borne encephalitis, tularemia, North Asian tick typhus (tick-born rickettsiosis of the
Eastern Hemisphere), Lyme disease, Q-fever, Rocky mountain spotted fever and other.
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Family Argasidae (soft ticks)
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Argasidae ticks differ from Ixodidae ones by their morphology and life cycle.
Argasids do not have a dorsal shield, so are termed as soft ticks (Fig. 12.5). The body is
gray, long and narrow in front. It has a beak-like projection, hanging down, the edges of
the body is symmetrically mounted by rant. The mouth parts are on the ventral side and are
not visible from above. They lack eyes. Sexes are similar.
Argasidae ticks can be found throughout the world, though the distribution of each
particular species is more limited. These are ticks of shelter places. They inhabit caves, burrows, holes, and clay-walled human settlements.
These ticks are nocturnal feeders and seldom travel from the local habitat. The duration
of bloodsucking is 3–30 min. Female lays 100 to 200 eggs in several batches following successive blood meals. There are several nymphal stages in the life cycle. As period of hunger
may extend to 10–11 years, life cycle sometimes continues for 20–28 years.
An example of argasids is Ornithodoros papillipes, which is widely distributed in Central
Asia. The size of this tick is 5–8 mm, female is bit bigger in size than male.
The bites of Argasidae ticks produce hard red wheals that remain painful for about 24
hours. They are the vectors of tick-borne or endemic relapsing fever (agents of the disease
are certain species of Borrelia spirochetes).
A
B
Fig. 12.5. Argasidae ticks. Ornithodorus papillipes: A – dorsal view; B – ventral view
12.2. Medical importance of Crustaceans and Arachnida. Spiders and ticks
345
Family Gamasoidae
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Gamasoidae mites is vast group of very small mites (0.3–0.4 mm), which are ectoparasites of various mammals and birds. Examples are chicken mite (Dermanyssus gallinae) and
house mouse mite (Liponyssoides saguineus).
Rodents and birds mites prefer to suck the blood of animals, but also bite people. Their
bites often cause dermatitis (skin irritation and itching around the bite). Some species are
vectors of tick-borne encephalitis, tularemia, Q-fever.
Prevention of the tick bites. Man should close as much of body as possible when
working in tick infested areas for prevention of tick bites (wear a hat, a long-sleeved shirt
and long pants with the legs tucked into the socks). Open parts of the body should be
treated with repellents. After coming in from outdoors search for ticks on the body should
be made. All found ticks must be carefully removed with a fine-tipped tweezers. It is important to grasp the tick as close to the skin surface as possible and to pull it with even
pressure, otherwise mouth parts can break off.
Control of ticks. Ticks are best combated by treating of their habitats with acaricides.
Superorder Acariformes
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Acariform mites are small arachnids. This superoder includes constant human parasites
as itch mite and follicle mite and house dust mites.
Order Sarcoptiformes
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Sarcoptes scabiei (itch mite) causes scabies.
Morphology. The female is 0.35–0.45 mm and
the male is about 0.2 mm in length (Fig. 12.6).
The body is oval or rounded and dorso-ventrally
flattened with transverse striations and bears
spines and bristles. The first two pairs of legs
are provided with terminal stalked suckers and
claws. The posterior two pairs of legs are shorter,
situated more ventrally and carry long bristles.
The mouth parts are adopted for burrowing into
the skin.
Location. The itch mite is a constant human
intracutaneous parasite. It lives mainly in the
epidermis of the soft skin regions: between the
fingers, in armpits, lower part of the abdomen,
buttocks, popliteal fossae.
Life cycle. Mating occurs on the skin surface
(Fig. 12.7). After copulation the females bore
Fig. 12.6. Itch mite (Sarcoptes scabiei)
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CHAPTER 12. Arthropodes as poisonous animals, vectors and agents of human diseases
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4
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down into the skin and make tunnels in
the epidermis. During the life period (50
days) it lays 20–30 eggs. The development
occurs with incomplete metamorphosis
(egg, larva, nymph I, nymph II) and takes
9–14 days. Wandering of the mites in skin
causes severe itch. Scratching the mites’
tunnels the host disseminates the parasites all over the body.
Epidemiology. Man-to-man transmission occurs during the contact with
the patient (handshake) or through the
clothes and bed linen. The female can survive off the host for 2 to 3 days at room
temperature.
Laboratory diagnosis is based on
the microscope examination of the skin
scrapes, taken at the ends of the tunnels
(demonstration of the parasites).
Prophylaxis is based on personal and
social hygiene, isolation and treatment of
patients.
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Fig. 12.7. Itch mite in human skin: 1 – epidermis;
2 – nymph of itch mite; 3 – egg; 4 – itch mite female
making tunnels
Order Trombidiformes
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Demodex folliculorum and Demodex brevis (the follicle or eyelash mites) are the
agents of demodicosis.
Morphology. Demodex folliculorum is a vermiform mite 0.3–0.4 mm in length with females somewhat shorter and rounder than males (Fig. 12.8). They have eight short and
stubby legs and long tapering abdomen. The mite has pin-like mouth parts for eating skin
cells and secretion of sebaceous glands accumulating in the hair follicles. D. brevis has similar structure, but is slightly shorter (0.15–0.2 mm).
Location. It lives in the hair follicles and sebaceous glands on the face, especially on the
nose and eyelids (Fig. 12.9).
Life cycle. The life cycle is usually complete in 18–24 days. The adult females lay about
20 eggs in the hair follicle. The development occurs with the metamorphosis, six-legged
larvae hatch after 3–4 days, and the larvae develop into adults in about 7 days. The total
lifespan of a Demodex mite is several weeks.
The disease manifests by loss of eyelashes, blackheads, non specific facial dermatitis.
Most infected people do not develop clinical symptoms.
Epidemiology. The invasion takes place by contacts with a sick person, through the
towels, pillows.
12.3. General characteristics of Insecta. Insects as vectors and agents of human diseases
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3
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2
Fig. 12.9. Follicle mite in the ducts of sebaceous glands in
hair follicle: 1 – hair; 2 – follicle mite; 3 – sebaceous gland;
4 – hair follicle
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Fig. 12.8. Follicle mite (Demodex folliculorum)
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1
The house dust mites
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The diagnosis is based on microscoping of the purulent contents of the pimples or
removed hair (eyelash).
Prophylaxis is based on personal and social hygiene, and treatment of patients.
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The microscopic house dust mites of Pyroglyphidae family are responsible for house
dust allergy. The most common species of the house dust mites are Dermatophagoides
pteronyssinus and D. farinea.
Mites live in bedding, carpets, soft furnishings and clothing. They feed on human skin
scales which have been partially digested by moulds and thrive in humid environments.
House dust mite allergy (to mites by itself and proteins in their droppings) is very common and associated with asthma, eczema and allergic rhinitis.
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12.3. General characteristics of Insecta. Insects as vectors
and agents of human diseases
General characteristics of class Insecta (Insects)
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Insects are referred to subphylum Hexapoda, class Insecta. The body consists of three
regions: the head, thorax and abdomen (Fig. 12.10A). The thorax and abdomen are segmented: there are 3 thoracic segments and 9–11 abdominal ones.
The head bears a single pair of antennae, a pair of compound or simple eyes and mouth
parts adapted for the various modes of feeding. The mouth parts include the upper lip (labrum), a pair of mandibles and pair of maxillae, and the lower lip (labium). There are chewing (cockroaches), piercing-sucking (mosquitoes), sponging (flies) types of mouth parts
and other. All types of the insects’ mouth parts originate from the chewing one.
The thorax bears three pairs of legs and usually one or two pairs of wings (on the 2nd
and 3rd segments). Appendages may be adjusted for walking, running, jumping, digging
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CHAPTER 12. Arthropodes as poisonous animals, vectors and agents of human diseases
Abdomen
Thorax
Head
Wings
A
Mouthparts
Proventriculus
Heart
Aorta
Esophagus
Crop
Ostia Ovary
Colon
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Brain
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Appendages
D
Antenna
Anus
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Vagina
Salivary
Rectum
Gastric
Oviduct
gland
Malpighian
Mouth
Labrum
ceca
Labium
Seminal receptacle
tubules
Thoracic
Midgut
Subesophageal ganglion
Abdominal ganglion
ganglion
Ovipositor
B
Fig. 12.10. Morphology of insects: external (A) and internal (B)
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and swimming that depends on environmental conditions. The abdomen lacks appendages.
The digestive system consists of fore-, mid- and hindgut (Fig. 12.10B). The salivary glands
are well developed. Respiration occurs by trachea. The blood circulation system is of open
type; the heart is on the dorsal side of the abdomen. Excretion takes place by the Malpigian
tubules, which open into the hindgut. The nervous system consists of the nervous circle
with supraesophageal and subesophageal ganglia and the chain of ventral ganglia. The
supraesophageal ganglion is well-developed. It is also called the “brain” (“encephalon”) of
an insect. The sensory organs are olfactorial, taste, hearing, vision, and tactile. The eyes are
usually compound, in some parasites they are simple.
Reproduction is sexual. The development occurs with complete metamorphosis (egg –
larva – pupa – imago) or incomplete (egg – larvae – imago) metamorphosis.
Medical importance of insects. Insects are the agents of human diseases (lice), mechanical vectors of intestinal diseases (flies, cockroaches), specific (biological) vectors of infectious diseases (lice, fleas, mosquitoes, tsetse flies).
12.3. General characteristics of Insecta. Insects as vectors and agents of human diseases
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Phylum: Arthropoda
Subphylum: Hexapoda
Class: Insecta
Order: Diptera
Family: Culicidae
Genus: Anopheles, Culex, Aedes
Species: Anopheles maculipennis
Culex pipiens
Family: Muscidae
Species: Musca domestica (House fly)
Wohlfartia magnifica (Wohlfahrtia fly)
Stomoxys calcitrans (Stable fly)
Glossina palpalis (Tsetse fly)
Order: Anoplura
Sp.: Pediculus humanus capitis (Head louse)
Pediculus humanus humanus (Body louse)
Phthirus pubis (Pubic or crab louse)
Order: Aphaniptera (Fleas)
Sp.: Pulex irritans (Human flea)
Xenopsilla cheopis (Rat flea)
Order: Heteroptera
Sp.: Cimex lectularius (Bed bug)
Triatoma infestans (Reduviid or kissing bug)
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Classification
Order Diptera
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They are characterized by one pair of wings, which arise from the second segment of
the thorax. The posterior pair of the wings is reduced to form a pair of small halters (equilibrium organs). The life cycle occurs with complete metamorphosis (egg, larva, pupa, imago).
This order includes families Culicidae, Muscidae and Phlebotomus.
Family Culicidae (Mosquitoes)
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Mosquitoes (Culicidae) are bloodsucking temporary ectoparasites. The important genera of mosquitoes are Anopheles, Culex and Aedes.
Medical importance. Several species of Anopheles are vectors and definitive hosts of
malaria parasites. Some species of Anopheles serve as intermediate hosts as well as vectors
of filaria worms (Wuchereria and Brugia) in tropical countries.
Culex species are vectors of Japanese encephalitis, tularemia, filariasis.
Aedes species are the vectors of Japanese encephalitis, yellow fever, Dengue fever, tularemia, filariasis.
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CHAPTER 12. Arthropodes as poisonous animals, vectors and agents of human diseases
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2
A
B
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D
3
C
4
D
Fig. 12.11. Heads of the Anopheles (Anopheles maculipennis) and Culex (Culex pipiens) mosquitoes:
A – female Culex; B – male Culex; C – female Anopheles; D – male Anopheles; 1 – proboscis; 2 – maxillary palps;
3 – antennae; 4 – compound eyes
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Morphology. Mosquitoes possess an elongated and slender body (9–11 mm), long
slender legs, long segmented antennae and elongated proboscis (Fig. 12.11). The normal food of both sexes is nectar of flowers and juice of plants, but the females after
fertilization begin to consume blood of vertebrates. Females have piercing and sucking
mouth parts. The proboscis is a straight long tube formed by a fleshy ventral labium,
which has a deep groove on its upper side. The labrum covers labial groove dorsally. In
females the labial groove contains five needle-like stylets (two mandibles, two maxillae
and a hypopharynx). The hypopharynx possesses salivary duct which opens at the tip.
Males have sucking mouth parts for feeding on nectar and plant juices.
The head bears a pair of large compound eyes and two antennae with many bristles,
laying in a ring. The bristles are longer and much more numerous on the antennae of males
giving them a bushy appearance. In the females the antennae have rings of a few short
bristles, thus, sexes can be distinguished readily by the antennae. The head bears two maxillary palps. The maxillary palps are stiff and have many bristles. The palps in the female are
short and three-jointed, but in the male they are five-jointed and as long, or even longer as
the proboscis. The length of the palps is important in differentiation of Anopheles and Culex
(Table 12.1) mosquitoes.
The life cycle. Mosquitoes develop with complete metamorphosis: egg, larva, pupa,
imago. After mating the females lay eggs on still water. The eggs hatch in 1 or 3 days and
the larvae emerge from the lower end of each egg.
The larva is called a wriggler because of its wriggling movements. The larval life includes
several stages and lasts from 3 to 14 days each according to temperature. It has a mouth
over which there is a pair of rotary feeding brushes, formed of stiff bristles. The brushes
cause a current of water by which small organic particles and algae are wafted into the
mouth. After the fourth moult the larva changes into the pupa.
The pupa is comma-shaped, has respiratory trumpet and is called a tumbler. The pupa
is a resting stage, during this period it doesn’t feed, but the pupae of the mosquitoes are
12.3. General characteristics of Insecta. Insects as vectors and agents of human diseases
351
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peculiar in not being quiescent, they are active and can swim about. The pupa period lasts
from two to seven days depending upon the temperature.
Development of all stages in water lasts for 15 days minimally. Optimal temperature for
development is 22–25 °C, minimal temperature is 10 °C. The imago can start laying eggs in
a week’s time repeating the life history.
The period of a female life cycle from the beginning of the feeding till the moment of
laying eggs is called the gonotrophic cycle. It includes 3 stages:
1. Searching for a prey and bloodsucking.
2. Blood digestion and maturation of the eggs.
3. Flying to water and laying the eggs.
The duration of gonotrophic cycle depends on environmental temperature, in optimal
conditions it lasts for 2–5 days (in the South) and for 5–10 days in temperate climate.
Duration of the female life is 1–2 months (sometimes 3 months). Through its life a female may pass from 1–2 gonotrophic cycles (in northern regions) and up to 5–10 in the
South.
Males live for 10–15 days. All males die in autumn. Anopheles and Culex females are wintering. They suck blood and hide in covers, unoccupied rooms, cattle sheds, barns, entering
the condition of winter diapause. In spring females fly out, suck blood and start the first
gonotrophic cycle. In Aedes mosquitoes wintering are eggs.
The differences between Anopheles and Culex mosquitoes are given in Table 12.1 and
in Fig. 12.12.
Table 12.1. Comparative characteristics of Culex and Anopheles mosquitoes
Culex
Anopheles
Oviposition
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1. It lays usually 200–400 eggs on the surface of
dirty stagnant water sources.
2. It lays eggs in clusters which are glued to form
rafts.
Eggs
3. The eggs are cigar-shaped.
4. The eggs remain vertically placed in the rafts,
enclosing air between their spaces which help in
floating on the water surface. Floats are not found.
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1. It lays usually 40-100 eggs on the surface of
clean and sunny fresh water.
2. It lays eggs singly.
3. The eggs are boat-shaped.
4. The eggs remain horizontal to the water
surface and bear air-filled floats which help in
floating in the water.
Larva
5. It lies inclined obliquely at an angle with the
water surface.
6. On the 8th abdominal segment it has a long conical respiratory siphon which projects out of the
surface of the water.
7. It is bottom feeder.
5. It lies parallel to the water surface.
6. On the 8th abdominal segment the respiratory siphon is reduced.
7. It is surface feeder.
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CHAPTER 12. Arthropodes as poisonous animals, vectors and agents of human diseases
Culex
Anopheles
Pupa
8. Abdominal segments are very much curved.
9. Respiratory trumpets are short and conical.
D
8. Abdominal segments are not much curved.
9. Respiratory trumpets are long and cylindrical.
Adult
Aedes
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Anopheles
1
10. At rest it keeps its body at an angle 45 to the
surface and its proboscis remains in straight line
to the longitudinal axis of the body.
11. Wings appear spotted.
12. Maxillary palps in females are equal in
length to proboscis. In males maxillary palps
are longer than proboscis and are thickened in
a last segment
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10. At rest it keeps its body parallel to the surface
and its proboscis never lies in straight line to the
longitudinal axis of the body.
11. Wings with uniform coloration.
12. Maxillary palps in females are shorter than
proboscis. In males maxillary palps are longer than
proboscis. Last segments of palps are thin
A
4
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3
B
5
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2
Culex
5
C
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6
D
6
Fig. 12.12. Main differences between Anopheles and Culex mosquitoes: A – eggs; B – larvae; C – pupae;
D – imago; 1 – floating belts; 2 – egg raft; 3 – rudimentary respiratory siphon;4 – respiratory siphon; 5 – respiratory trumpet; 6 – abdomen
12.3. General characteristics of Insecta. Insects as vectors and agents of human diseases
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Personal protection of mosquito bites is usage of window anti-mosquito nets and repellents.
Control of mosquitoes:
1. Destruction of adults:
`` killing the mosquitoes by spraying insecticides;
`` fumigation of dwellings;
`` genetic methods (imploring of sterile males into the population, releasing of insects carrying a dominant lethal gene).
2. Destruction of larvae:
`` oiling the water reservoirs, that blocks larvae and pupa respiration;
`` spreading the insecticides over the water surface;
`` biological methods – introduction of natural enemies (minnows and gambusia
fish) in a breeding place;
`` usage of viral and bacterial agents of mosquitoes diseases.
3. Elimination of breeding places:
`` emptying of small water reservoirs like cisterns and containers;
`` water reservoirs shores are to be protected by shady trees because Anopheles larvae do not like shady places.
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Family Muscidae (Flies)
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Medical Importance:
1. Flies (house fly) are mechanical vectors of intestinal diseases, eggs of helminths and
cysts of protists.
2. Blood sucking flies are specific vectors of vector-born diseases (tsetse fly is a vector
of African trypanosomiasis). Stable fly is a vector of anthrax, tularemia, brucellosis.
3. Larvae of some flies are the causative agents of tissue and intestinal myiasis. Myiasis is the infestation of human with fly larvae, which, at least for a certain period, feed
on human tissue or ingested food of the host.
Tissue myiasis is caused by larvae of wohlfartia fly (spotted flesh fly). Intestinal myiasis
may be caused by the larvae of house fly, flesh fly, blow flies (greenbottle and bluebottle),
and drosophila fly larvae. Urinary myiasis (urethra and urinary bladder affection) may be
caused by larvae of same species.
Musca domestica (house fly).
Morphology. The body is dark, 6–8 mm in length (Fig. 12.13). There are 4 longitudinal
stripes on the thorax. The head is large and mobile. It bears two large redish-brown compound eyes.
Flies are polyphages. They feed on human food, excrements, wound discharge, etc. The
mouth parts are of sponging type, i.e., adapted to suck the liquid food. All solid food products have to be saturated with fly saliva before.
Their legs are equipped with claws and sticky pulvilli on the last segment that allows the
fly to move on any kind of a surface. Legs and body are covered with bristles. Cysts, eggs of
CHAPTER 12. Arthropodes as poisonous animals, vectors and agents of human diseases
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C
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A
D
D
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E
Fig. 12.13. Musca domestica (House fly): A – imago; B – eggs; C – larva (maggot); D – pupa; E – newly
hatched fly
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helminths, bacteria get stick to the pulvilli and bristles. A single fly can carry up to 6 millions
of bacteria upon its body and to 28 millions in its intestine.
Life cycle. Flies develop with complete metamorphosis. A female lays about 100–
150 eggs at one time and repeats oviposition 3–6 times. Eggs are laid into garbage, human feces, decomposing animals and plant matter. High temperature and high humidity
accompanying the decay of organic substances are the conditions needed for eggs development. The larva hatches from the egg 1–2 days later. The larvae are called maggots,
shaped as worms and feed on decaying garbage and feces. Larvae moult twice and turn
into pupae. For that the larva moves to cool and dry places (usually into the soil). Period
of development from the egg to imago varies depending on temperature (at 25 °C takes
about 16 days). The life span of the house fly is about 1 month.
Medical importance of flies is closely related with their nutrition habits. They consume
human and animal feces and products of surface wounds. Then they carry on agents of the
diseases on the food products. Flies are mechanical vectors of various agents of infectious
diseases like dysentery, typhoid, cholera, poliomyelitis, diphtheria, tuberculosis, etc. They
can transmit eggs of helminths and cysts of protists on their bodies.
Occasional swallowing of house fly larvae leads to intestinal myiasis (accidental myiasis). Larvae can survive in the gastrointestinal tract and cause abdominal pain, vomiting,
and diarrhea. As flies are attracted to feces and urine, accidental myasis of genitourinary
tract is known to occur.
Protection of food from flies by usage of window nets, hermetic saucepans, drawers and
glass covers prevents intestinal disorders potentially transmitted by flies.
Control of house flies:
1. Control of breeding – removal of trash in time, isolation of garbage.
2. Killing adult flies – usage of glue stripes, insecticides. Destroying of larvae with insecticides. Genetic methods – imploring of sterile males.
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Fig. 12.14. Stomoxys calcitrans (stable fly)
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Stomoxys calcitrans (stable fly) (Fig. 12.14)
is similar with house fly in size (5–7 mm in
length) and coloration. It can be differentiated
from house fly by circular dark spots in a checkerboard pattern on the abdomen. The mouth
parts are of piercing-sucking types. The proboscis is hard and sticks out. They feed on animal
blood and primarily attack livestock. In the absence of these animal hosts, they bite people,
especially in autumn.
Females lay eggs into manure around cattle.
Development is with complete metamorphosis.
Medical importance. Their stings hurt. The
injured spot starts itching and burning and can
become secondary infected. The fly is a mechanical vector (on the mouthparts) of bloodborn zoonotic and antropozoonotic diseases
like anthrax and tularemia.
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12.3. General characteristics of Insecta. Insects as vectors and agents of human diseases
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Wohlfahrtia magnifica (wohlfahrtia fly or
spotted flesh fly) (Fig. 12.15).
Morphology and life cycle. These are large
flies (9–13 mm) colored light-gray with three
dark stripes on the thorax. These flies consume
flowers’ nectar.
The females are larviparous, they deposit
alive larvae on tiny skin lesions, wounds and
mucous membranes of natural openings of a Fig. 12.15. Wohlfahrtia magnifica
host (mammals, including human being). So (wohlfahrtia fly or spotted flesh fly)
120–160 larvae at one time are being born on
scratches, into eyes, nose, and ears. Larvae are worm-shaped about 1 mm in length. They
feed on tissues and cause cavernous lesions, devour bones, destroy blood vessels. Having
spent 3–5 days in the wound larvae fall down into the soil, turn into pupae and become
imago in 11–23 days.
Medical importance. Larvae of wohlfahrtia fly parasite in animal and human tissues can
cause obligatory tissue myiasis. In severe cases larvae destroy large areas consuming the
skin, soft tissues and affecting eyes.
Larvae of some other flies in different geographical regions can cause tissue myiasis.
Maggot therapy. The artificially breeded sterile living maggots of greenbottle, bluebottle and blackbottle flies are used in the treatment of non-healing ulcers (traumatic,
diabetic, neuropathic and others). Maggots consume necrotic tissues, clearing the wound.
Secretions of maggots disinfect and promote healing.
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Tsetse flies include all the species in the genus Glossina
(Fig. 12.16) (i.e., G. palpalis and G. morsitans).
Tsetse fly is 8 to 17 mm in size. It resembles house fly but two
morphological features make it easily distinguishable. Tsetse fly
has a long proboscis which extends directly forward and while
resting folds it wings completely so that one wing is directly on top
of the other over its abdomen (in a sissors-like manner).
Medical importance. Tsetse flies are the specific vectors of African trypanosomiasis (African sleeping sickness).
Fig. 12.16. Glossina sp.
(Tsetse fly)
Order Anoplura
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Order Anoplura (lice) is represented by small wingless insects. There are about 500 species of lice. All species are parasites of different hosts. Parasites of human being are the head
louse (Pediculus humanus capitis), the body louse (Pediculus humanus humanus) and pubic
or crab louse (Phthirus pubis).
Pediculus Humanus Capitis (head louse).
Morphology. The body is light-gray with dark pigmented spots on the thorax and abdomen (Fig. 12.17A, B, E, F). Females are 3–4 mm and males are 2–3 mm in length. The body
is somewhat flattened along the dorsoventral axis and consists of the three segments: the
head, the thorax, the abdomen. The head is equipped with two short and thick anten-
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Fig. 12.17. Lice (Anoplura) and their eggs (nits): a – head louse (Pediculus humanus capitis) (male); b – head
louse (female); c – body louse (Pediculus humanus humanus) (male); d – pubic louse (Phthirus pubis); e, f –
egg of head louse; g – egg of the body louse; h – egg of the pubic louse; 1 – egg (nit); 2 – hair, 3 – sticky mass
12.3. General characteristics of Insecta. Insects as vectors and agents of human diseases
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nae (olfactory organs), two simple eyes and mouth apparatus of a piercing-sucking type. It
feeds on human blood.
The thorax is shaped as trapezium and consists of 3 merged segments. The abdomen
consists of 9 segments. There are clearly visible incisures between the abdominal segments, called festoons. The posterior end of the female bodies is split, the one of males is
curved. Females have two falcate gonopodes clearly visible through the chitinous cover.
The copulative organ of males looks like a triangle.
A louse has 3 pairs of appendages. There is one mobile claw on the last segment of each
leg. That occurs due to the extreme growth of the last segment that looks rather like a nipper. Using this apparatus lice can hold firmly on hair.
Location is head hear and scalp. One can get infection through combs, brushes, hats
of an affected person. Negligence to personal hygienic rules helps the transmission of the
parasites.
Life cycle. Eggs (nits) are being posted to the hair (3–4 eggs are being laid per day and
up to 150 eggs are produced by a female during its life). Development occurs with incomplete metamorphoses (egg, larvae I, II and III, imago). Larvae and imago feed on blood. The
development from an egg to imago lasts about 16 days. The life span of the head lice is
about 27–38 days.
Medical importance. The head lice are obligate ectoparasites, agents of pediculosis
capitis (head lice infestation). Affected people suffer from severe head itching, their hair
stick together and turns hard to brush. If pediculosis lasts for a long time bacteria inhabit
the itching scratches and purulent inflammation develops.
The head lice are vectors of vector-borne diseases – epidemic typhus and lice-borne
relapsing fever.
Transmission mechanism of lice-borne relapsing fever and epidemic typhus:
Rickettsia prowazeki is the agent of epidemic typhus. Bacteria get into the stomach of
the louse with the blood of an infected person. They penetrate into epithelial cells of the
intestine and start to reproduce. 4–7 days later infected cells burst releasing large numbers
of the bacteria into the louse’s gut. Bacteria discharge with feces. Human being becomes
infected while rubbing feces of lice with Rickettsia into the itching scratches.
The agent of lice-born relapsing fever is spirochaete (Borrelia recurrentis). The lice get
infected with blood of a sick person. Spirochaete from the intestine enter the louse’s body
cavity (hemocoel) and start to reproduce in hemolymph. The person gets relapsing fever
while crushing louse and rubbing hemolymph into the scratches that itch.
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Pediculus humanus humanus or Pediculus humanus corporis (body louse).
Morphology. Females measure up to 4.75 mm, males are up to 3.75 mm (Fig. 12.17C, G).
Their antennae are longer and thinner than in the head lice. Segmentation of the abdomen
is less distinct and the incisures are not so deep.
Location. They live in folds of underwear.
Life cycle. Development proceeds with incomplete metamorphosis. Eggs (nits) are laid
into clothes folds and are stick to the clothes. The female lays up to 14 eggs per day and
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300 per life. Development from an egg to imago lasts for 16 days at the temperature of
25 °C. The larva and imago feed on blood. The life span is 32–46 days.
Medical importance. The body lice are obligate human ectoparasites, agents of pediculosis corporis (body louse infestation). Basic symptoms are skin itching, pigmented spots
on bites points. Scratches from itching cover the body. A person gets infected through
contacts with an affected person or his clothes.
Body louse is a vector of epidemic typhus and lice-borne relapsing fever. Transmission
mechanisms of these diseases are the same as for the head louse.
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Phthirus pubis (pubic or crab louse)
Morphology. The body is short, wide and pear-shaped (Fig. 12.17D, H). The female is
1.5 mm, the male is 1 mm in length. The posterior appendages are longer than anterior
ones.
Location. On pubic hair, eyelashes, eyebrows, in armpits hair, moustache and beard. In
case of severe infection parasites are present all over the body hair.
Life cycle. Development is with incomplete metamorphosis. A female lays up to 3 eggs
per day and up to 50 eggs per life. Development from an egg to imago takes 22–27 days.
The life span is 17–22 days.
Medical importance. The pubic lice are the agents of phthiriasis. The main symptom
is itching. Places of bites are marked by bluish spots surrounded with pale skin that looks
somewhat like marble skin. Phthiriasis can be transmitted during sexual contacts and seldom through underwear of an affected person.
The pubic lice do not transmit agents of any disease.
Diagnosis of pediculosis and phthiriasis is based on demonstration of insects and nits
on the appropriate area.
Treatment is based on destroying of lice:
1. Mechanical way – brushing out the insects with a special brush, hair cutting or shaving.
2. Chemical way – washing hair and body with special shampoos and soaps that contain insecticides, processing of clothes with insecticides.
3. Physical way – clothes of an infected person are to be processed in a special disinfecting camera with steam or hot ironing.
Preventive means include:
`` hygienic rules (regular bathing, taking shower, washing of bed linen);
`` regular inspection of children in kindergarten, school, etc. Treating of affected individuals;
`` health education.
Order Aphaniptera (Fleas)
Fleas are blood sucking insects, obligate ectoparasites, vectors of infectious diseases.
They are cosmopolitan and have a wide host spectrum. Examples of fleas are human flea
(Pulex irritans) (Fig. 12.18) and rat flea (Xenopsylla cheopis).
12.3. General characteristics of Insecta. Insects as vectors and agents of human diseases
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Morphology of fleas. The body is laterally flattened, light-yellow or dark-brown in color. The body
length is 0.5–5 mm. The mouth apparatus is of piercing-sucking type. They feed on blood of different
hosts. The head is equipped with two simple eyes and
short bristles. Fleas are wingless insects. The last pair
of legs is longer than other ones and is adjusted for
jumping. The body is covered with chitinous scales.
Life cycle (Fig. 12.19). Development occurs by way
of complete metamorphosis (egg, larva, pupa, imago). Eggs are laid in cracks and fissures, dry garbage, Fig. 12.18. Human flea
rodents’ caves, etc. A worm-like larva hatches from the (Pulex irritans)
egg. It is white in color and consumes decaying organic matter and excrements. The larval
period varies from 9 to 200 days, depending on the temperature and humidity. The larvae
turn into chrysalis (pupa). Duration of the pupation period depends on the environment
conditions, varying from 7 days to a year. A mature flea lives for 1.5 years and a female lays
up to 450 eggs per life.
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Fig. 12.19. Stage of development and morphology of human flea: (A – egg; b – larva; c – pupa; d – imago; e –
morphology of flea’s appendage; f – flea; infected with plague bacteria, drinking human blood; h – block of
the foregut of the flea with plague bacteria: 1 – maxillary palps; 2 – labial palps; 3 – eye; 4 – antenna; 5 – head;
6 – thorax; 7 – abdomen; 8 – esophagus; 9 – proventriculus of foregut, blocked by bacteria; 10 – ventriculus
of midgut
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Medical importance. There are many species of fleas depending on preference to a certain host but can feed on wide range of hosts. That feature explains the medical importance of fleas as vectors of nature foci vector-borne diseases – plague, tularemia, endemic
(murine) typhus and others.
Xenopsylla cheopis (rat flea) is the most important vector of plague. Plague is an extremely dangerous nature-foci disease. Its agent is plague bacilli (Yersinia pestis). Natural
reservoirs of plague are various rodents. Plague bacilli multiply in the flea’s digestive tract
blocking the foregut (see Fig. 12.19H). An infected flea attempts to suck the blood, its gut
widens and consumed blood regurgitates into the bite wound carrying agents of plague.
Bacilli of plague are also discharged with feces of flea.
Plague is transmitted by several ways. Humans may also be infected while skinning the
animals or by air-born way when contacting sick people.
Pulex irritans (human flea) is an ectoparasite of human being. Hosts of this species are
generally mammals, especially large, including dogs and humans. When not feeding, P. irritans can be found in nests of host animals or nearly anywhere within the human house.
Bites of fleas cause local inflammation of skin and itching.
Order Heteroptera (bugs)
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Bugs is a wide group of insects. Blood sucking bugs (bed bug, kissing bug) have medical
importance.
Cimex lectularius (bed bug) (Fig. 12.20A). It has world-wide distribution.
Morphology. The body is oval shaped and dark-brown in color. A female is 4.8–8.4 mm,
male – 4.9–6.4 mm in length. The head bears compound eyes, 4-segmented antennae, and
mouth apparatus of piercing-sucking type. Bugs are wingless insects.
Life cycle. The bed bugs inhabit old houses, beds, furniture, live under wall-paper, etc.
The females lay eggs in the places they inhabit, up to 250 in a life time. Development
is with incomplete metamorphosis. The larva called nymph feeds on blood and molts 5
times to become imago. Development lasts for 28–56 days. The life span of a bed bug is
up to 14 monthes, in low temperature imago can survive without food for a year or even
longer.
Medical importance. The bed bug (Cimex lectularius) is a temporary human ectoparasite. Bed bugs are most active at night feeding on their victims while they sleep. Duration of blood sucking is from 3 to 15 minutes. Bites are usually painless but may cause
allergic reactions (red swollen itching spots). The bed bugs don’t transmit any infectious
diseases.
Preventive measures include inspecting the sleeping area for any evidence of bed
bugs, inspecting used furniture and bedding items before bringing it into the home. In
case of bed bug infestation insecticides are used.
Triatoma infestans (Reduviid, triatomine or “kissing” bug) is a blood sucking bug, distributed in Central and South America (Fig. 12.20B).
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12.3. General characteristics of Insecta. Insects as vectors and agents of human diseases
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Fig. 12.20. Bugs (Heteroptera): A – bed bug (Cimex lectularius); B – triatomine or “kissing” bug (Triatoma
infestans)
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Morphology. It is a relatively large insect, 1 to 4 cm in length. It has elongated head with
extended mouth parts of sucking-piercing type. Body is dark brown or black with orange
marking around the abdomen.
Life cycle. Triatomine bugs live in the burrows and nests of wild animals, hollow trees,
etc., but can live in or near the houses (in chicken coops, dog houses and other peridomestic habitats). Development is with incomplete metamorphosis. Duration of the life cycle
depend on the environmental conditions and varies from 4 months to two years.
Medical importance. Triatomine bugs are temporary ectoparasites of many animals
and human being and specific vectors of Trypanosoma cruzi (an agent of the Chagas’ disease or South American trypanosomiasis).
Triatomine bug feeds on blood during the night. Usually it sucks the blood from lips,
corners of the eye (that gives the name – “kissing bug”). Feeding takes 10–25 minutes,
biting is usually painless. Bugs get Trypanosoma cruzi with the blood of infected organism, parasites reproduce in the gut of the bug. Transmission of the trypanosomiasis occurs
when the infected bug defecates in the wound after blood sucking. Scratching helps the
parasites to enter the body through the bite wound.
Preventive measures include inspection and improvement of human dwelling places,
using of insecticides.
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CHAPTER 12. Arthropodes as poisonous animals, vectors and agents of human diseases
TASKS & QUESTIONS
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`` MULTIPLE CHOICE QUESTIONS (CHOOSE ONE CORRECT ANSWER):
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1. A spider is about 2 cm, round black with two rows of red spots on dorsal side of the
abdomen, covered with tiny black hairs. Identify this animal:
A. Karakurt spider
C. Solifugae
E. Tarantula
B. Scorpion
D. Mite
2. The patient who went to Carpathians was diagnosed with spring-summer encephalitis. Through the bite of which arthropod agent this disease can be transmitted?
A. Mosquito
B. Taiga tick
C. Argasid tick (Ornithodorus papillipes)
D. Itch mite
E. Dog-tick
3. A 35-year-old man found in the crevices of the apartment of adobe house arthropods with four pairs of walking legs, dark gray oval body and slightly pointed anterior
end. Define this arthropod:
A. Ornithodorus papillipes
D. Sarcoptes scabiei
E. Dermacentor nuttalli
B. Ixodes persulcatus
C. Ixodes ricinus
4. A patient is sick with tick-borne relapsing fever. Through the bite of which tick could
he become infected?
C. Ixodidae ticks
E. Dermacentor ticks
A. Argasidae ticks
B. Sarcoptes scabies
D. Gamasidae mites
5. 14-year-old boy complains of itching of the skin between the fingers which increases
at night. During the skin examination were discovered gray thin strips and rash looking as small dots. What parasite most likely causes this disease?
C. Ornithodorus papilD. Dermacentor pictus
A. Ixodes ricinus
B. Sarcoptes scabiei
lipes
E. Ixodes persulcatus
6. A patient has inflammatory alteration of facial skin. Microscopic examination of lesions has revealed arthropodes 0.2-0.5 mm in size. They have vermiform body with
four pairs of short appendages in the middle part of the body. These arthropods
cause:
A. Demodicosis
C. Myiasis
E. Phthiriasis
B. Scabies
D. Pediculosis
7. Which organism is a mechanical vector of cysts of Protozoa and agents of gastrointestinal disorders?
A. Fleas
C. Bed bugs
E. Wohlfahrtia fly
B. House flies
D. Sand-flies
8. Sand flies are specific vectors of:
A. Japanese encephalitis
C. Anthrax
E. Leishmaniasis
B. Taiga encephalitis
D. Spotted fever
12.3. General characteristics of Insecta. Insects as vectors and agents of human diseases
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9. Medical importance of Wohlfahrtia fly is a:
A. Specific vector of leishmaniasis
C. Vector of plague
D. Larva is an agent of myiasis
B. Mechanical vector of intestinal
disorders
E. Vector of trypanosomiasis.
10. Aedes mosquitoes are the vectors of:
D. Leishmaniasis
A. Malaria
B. Japanese encephalitis
E. Trypanosomiasis.
C. Anthrax
11. Which of the following is an agent of accidental myiasis?
A. Dermacentor
D. House fly larva
B. Wohlfahrtia fly larva
E. Demodex
C. Itch mite
12. House flies are vectors of:
A. Trypanosomiasis
D. Relapsing fever
B. Intestinal infections
E. Plague
C. Leishmaniasis
13. Which of the following insects is a South American trypanosomiasis vector?
A. Tsetse fly
C. House fly
E. Kissing bug
B. Wohlfahrtia fly
D. Bed bug
14. Which of the following insects is a vector of malaria?
A. Anopheles mosquito
C. Aedes mosquito
E. Sand flies.
B. Culex mosquito
D. All mosquito species
15. Head louse feeds on:
A. Epidermis
D. Human blood
B. Contents of the sebaceous glands
E. Lymph
C. Hair
16. Medical importance of the head louse is:
D. Vector of encephalitis
A. Endoparasite
B. Causative agent of phthiriasis
E. Causative agent of myiasis
C. Vector of relapsing fever
17. Causative agents of epidemic typhus in an organism of the louse are present in:
A. Hemolymph
B. Gut
C. Saliva
E. Mouth parts
D. On the surface of the body
18. Transmission mechanism of epidemic typhus is:
A. Through saliva of the lice while biting
B. Through the inoculation of lice excrements in the wound
C. By crashing the lice and inoculation of hemolymph
D. With contaminated food
19. The head and body lice are causative agents of:
A. Relapsing fever
C. Myiasis
E. Pediculosis
B. Epidemic typhus
D. Phthiriasis
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20. The pubic louse is the causative agent of:
A. Scabies
C. Pediculosis
E. Relapsing fever
B. Phthiriasis
D. Typhus
21. Transmission mechanism of lice-borne relapsing fever is:
A. Through the bite of the head louse
B. Through the bite of the body louse
C. Through the bite of the pubic louse
D. By crashing louse and inoculating of its hemolymph
E. Through the bite of the Wohlfahrtia fly
22. The bed bug is:
C. Causative agent of pediculosis
A. Ectoparasite
B. Vector of tularemia
D. Vector of plague
E. Mechanical vector of intestinal infections
23. Medical importance of the body louse is:
D. Vector of typhoid
A. Endoparasite
E. Causative agent of phthiriasis
B. Vector of plague
C. Vector of epidemic typhus
24. Causative agents of lice-borne relapsing fever in organism of the lice are present in:
A. Hemolymph
D. On the surface of the body
B. Gut
E. Mouth parts
C. Saliva
25. Medical importance of fleas:
D. Vectors of Chagas' disease
A. Agents of phthiriasis
B. Vectors of plague
E. Agents of pediculosis
C. Vectors of intestinal disorders
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`` FILL IN THE BLANKS:
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1. The body cavity of Arthropods around the viscera is ____________, and internal organs are bathed with ______________ .
2. Solifugae bite in self-defense and are not ______________ . On the place of bite
_______________ can be produced because of infection.
3. The cephalothorax and abdomen of a tick are ________ and a body is termed as
__________.
4. In scorpions the abdomen is elongated, segmented and shows two regions:
__________________ and ________________.
5. The itch mite is a human __________________ parasite and transmission occurs during _______________________ or through the __________________.
6. The _______________ nerve ganglion is well-developed in Insecta and is also called
the __________.
12.3. General characteristics of Insecta. Insects as vectors and agents of human diseases
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`` TRUE OR FALSE:
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7. At rest Culex keeps its body ___________ to the surface. It is a vector of
_________________, _______________, _________________.
8. __________ is the infestation of human with Wohlfahrtia fly larvae, which can feed
on human __________.
9. Body louse (Pediculus ______________) is obligate human ____________ and lives in
__________________.
10. Head louse is an agent of ________________ and is a vector of ________________
and ___________________.
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1. Cyclopes (the lower crustaceans) are the intermediate hosts of broad tapeworm and
Guinea worm.
True
False
2. Life cycle of ticks includes pupa stage and occurs with complete metamorphosis.
True
False
3. The venom of karakurt may be lethal for humans and animals as it is neurotoxic.
True
False
4. Demodex folliculorum lives in the hair follicles and sebaceous glands on the face.
True
False
5. All Anopheles and Culex females die in autumn and males are wintering.
True
False
6. Wohlfahrtia fly imago parasites in animal and human tissues and cause obligatory
tissue myiasis.
True
False
7. Rickettsia prowazeki is the agent of lice-borne relapsing fever.
True
False
8. Xenopsylla cheopis (rat flea) is the most important vector of plague.
True
False
9. The bed bugs are vectors of leishmaniasis and tularemia.
True
False
10. Kissing bug is an agent of the Chagas’ disease or South American trypanosomiasis.
True
False
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Chapter 13.
Evolution theory. Phylogenesis of organ
systems in vertebrates
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Evolution (from Latin: e – from; volvere – unrolling or unfolding) is a process of the irreversible changes in the structure and the functions of living organisms during their historic
existence.
13.1. Evolution theory
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The term evolution was first used by British biologist and philosopher Herbert Spencer.
Continuous evolution over many generations can result in the development of new varieties and species. Likewise, failure to evolve in response to environmental changes can, and
often does, lead to extinction. The acceptance of biological evolution is an essential part of
the modern scientific explanation of the natural world.
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Pre-Darwinian view on evolution
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The question of origins has always fascinated the human mind. From the ancient period, the existence of life has mostly been attributed to supernatural intervention. However,
naturalistic models of origins based on logic and philosophy can be traced to about the
fifth century BC in Greece. Plato (428–348 BC) and Aristotle (384–322 BC) were the philosophers that probably had the greatest impact on western thought. Their idealistic view
of striving for perfection laid the foundations for a naturalistic view of origins.
Plato’s idealistic views had a profound effect on biology. To him, the structure and
form of organisms could be understood from their function which in turn was designed to
achieve ultimate goodness and harmony imposed by an external creator.
Aristotle, the father of biology, expanded this idea to include the development of organisms and the origins of groups of organisms. To Aristotle, the adult form represented
the final goal or “telos”, and the changes occurring in embryogenesis represent a striving
towards the “telos” and are dictated by it.
Aristotle used this idea to develop a “scale of nature” in which he arranged the natural
world on a ladder commencing with inanimate matter to plants, invertebrates, and vertebrates. Among the vertebrates, he placed the fish at the lowest rung of the ladder and
humans on the highest rung. This “scale of nature” represents a progression from the most
imperfect to the most perfect.
The concepts developed by the Greek philosophers retained their influence well into
the 18th century and were nurtured by prominent thinkers such as Goethe (1749–1832),
who believed that the origin of each level of organism was based on a fundamental primi-
13.1. Evolution theory
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century French naturalist
Jean Baptiste Lamarck created the first integral theory
of evolutionary evolvement
of the organic world. He is
also significant by dividing
the animals onto vertebrates
and invertebrates with detailed classification of invertebrates, and introduction of
the term “biology”.
According to Lamarck
two main forces drive evolution: an initial tendency of
organisms to become more
complex and adaptation of
organisms to their local environment. A more frequent
and continuous use of any
organ strengths and enlarges
it, organs that are not used
reduce (exercising and nonexercising of organs). Beneficial changes are inherited
by next generations (inheritance of acquired characteristics) (Fig. 13.1A).
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tive plan – an archetype – from which the more complex features and organisms developed.
In the middle of XVIII century the great contribution into the evolution theory was
made by Swedish botanist
B
and zoologist Carl Linnaeus. A
He proposed system of naming organisms (binominal
nomenclature),
described
around 8000 plant species
and introduced the principle
of hierarchy in systematic of
nature. He started from kingdoms (the highest rank), that
were divided into classes, or- The giraffes in the early stages of
The giraffes in the early stages of
ders, genera and species.
evolution probably had necks of
evolution probably had a short neck
various lengths
At the beginning of XIX that they were stretching to reach food
Natural selection through competition led to the survival of giraffes
with long neck and their offspring
Apparently the neck stretching
continued, as is evident from the
present giraffes
Apparently only giraffes with long
neck survived through struggle for
existence
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Their offspring had longer necks to
reach food easier
Fig 13.1. Comparative characteristics of Lamarck and Darwin evolutionary hypothesis: A – Lamarck’s theory; B – Darwin’s theory
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Chapter 13. Evolution theory. Phylogenesis of organ systems in vertebrates
Darwinism
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B
C
D
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Darwinism – the theory of origin of species by means of natural selection. The British
naturalist Charles Darwin is considered to be a father of evolution theory. In the mid19th century, Charles Darwin formulated the scientific theory of evolution by natural
selection, published in his book “On the Origin of Species” (1859). At this time both scientific and social premises of Darwinism existed. Development of cytology (cell theory),
paleontology (comparative anatomy and catastrophism in geology by George Cuvier),
biogeography and biochemistry gave a new data for analysis of world evolution. Thomas
Malthus proposed a theory of excessive growth of human population and struggle for
existence in human society due to insufficient food supply. Industrial Revolution stimulated selection and occupation of new territories with unknown before species of plants
and animals.
Five-year trip around the world on brig Beagle enriched Darwin’s notion about diversity
of living organisms.
According to Darwin evolution is the continuous adaptive changes of species. The main
facts on which Darwin based his theory were as follows:
`` More offspring are produced than can possibly survive. Despite high reproductive
potential the population size remains relatively constant, that is explained by struggle for existence. It occurs between organisms of the same species (the most intense),
of different species or with unfavorable external conditions.
`` Traits vary among organisms. Morphological, physiological and behavior variation
can be passed from generation to generation (inherited variability).
`` Different traits confer different rates of survival and reproduction (differential fitness). The organisms whose variation best fit them for their environment will be the
most likely to reproduce (Fig. 13.1B).
So, main force that drives evolution is natural selection based on struggle for existence and hereditary variation.
Fig. 13.2. Scheme of directed selection: A, B, C – variation curves (norm of reaction) in populations of ancestors; D – variation curve in the current population. Arrows indicate the direction of selection
13.1. Evolution theory
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Natural selection is defined as differB
ential survival and reproduction of individuals due to different characteristics.
There are three types of natural selection.
A
1. Directed selection favors one of the
extreme phenotypes and another
extreme phenotype experiences
selection against it. The result is that
an average norm shifts towards the
more beneficial extreme (Fig. 13.2). Fig 13.3. Scheme of stabilizing selection. Norm of reDirected selection acts in chang- action in the ancestral population (A) was wider than
ing environmental conditions and the current one (B). Narrowing the norm of reaction
causes changes of traits and forma- occurred due to the extinction of individuals with extreme phenotypes.
tion of new species.
2. Stabilizing selection helps to susC
A
D
tain an average, previously estimated trait. Extreme phenotypes
with time become more rare or lost
(Fig. 13.3). It acts in stable environmental conditions. Due to stabilizing selection some species remain
unchanged for million years.
B
3. Disruptive selection supports both
extreme variants of a trait and act Fig 13.4. Scheme of disruptive selection: A – the preagainst the intermediate variants. vious norm of reaction; B – the organisms become
As a result organisms with inter- extinct; C, D – new norms of reaction. The arrow indicates the direction of the selection
mediate variant disappear and two
new species are formed (Fig. 13.4).
Darwin’s theory of natural selection explained adaptations, formation of new species,
and diversity of living organisms.
Synthetic theory of evolution
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Development of genetics permitted to explain variation and driving forces of evolution more deeply. Synthetic theory of evolution combines Darwinism and genetics. It
was introduced by several evolutionary biologists (T. Dobzhansky, R. A. Fisher, S. Wright,
G. L. Stebbins and other) in the years 1930–1940. This theory focuses on the basic processes
of gene mutation and recombination, changes in structure and number of chromosomes,
natural selection, and reproductive isolation.
According to the synthetic theory of evolution:
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`` Mutations are the source of genetic variation, that gives material for natural selection.
`` An elementary unit of evolution is a population. A population is a group of individuals of one species, which occupy a certain territory (area) and interbreed freely.
Basic properties of a population that make it a unit of evolution are: а) genetic polymorphism; b) ability to exchange the genes with other populations (population is
a genetically open system). Genetic makeup of population is termed as gene pool.
`` The basic driving factor of evolution is natural selection on a basis of struggle for
existence. It is the only directed factor of evolution.
`` There are undirected elementary evolutionary factors that shift genetic structure
of a population. These are gene drift, gene flow (see Chapter 9.6.) and waves of life
(fluctuations in number of individuals due to periodic intensive reproduction, natural
disasters and other).
`` Isolation fixes the differences that have arisen. Isolation might be of several types
(see Fig 13.5).
`` There is a microevolution (new populations, subspecies and species arise) processes
and a macroevolution processes (formation of systematic ranks above the species).
The basic regularities of both processes are principally the same and macroevolution
is a result of microevolution.
`` Evolution has a divergent nature (one systematic unit gives several other ones). Any
taxon (systematic rank) has monophyletic origin (in other words comes from a single
common ancestor).
`` Evolution is of continuous, irreversible and undirected nature.
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Modern point of view on evolution driving forces combines synthetic theory of evolution with ecology. For instance, neocatastrophism theory states that the evolution of living
organisms has been influenced to a great extent by sudden and powerful natural events
occurring at intervals. Interrupted ecological equilibrium in ecosystem causes extinction
of some species and active evolution of other ones. The intensity and speed of evolution
processes is irregular: it is very slow in stable ecological systems and becomes very fast
during ecological crises (punctuated equilibrium theory, N. Eldredge and S. J. Gould, 1972).
Isolation
Fig. 13.5. Types of isolation
Geographic
Ecological
Trophic, Seasonal, Ethological (behavioral)
Genetic
(Inability to interbreed or produce fertile offspring)
13.1. Evolution theory
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Microevolution and Macroevolution
Divergent evolution
Spieces B
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Parallel evolution
B Spieces A Spieces B
Time
Spieces A
Time
A
Convergent evolution
C
Spieces A Spieces B
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Microevolution is a complex of evolutionary processes which refers to small evolutionary changes of allele frequency within a species or population. It causes the emergence of
new populations, subspecies, and species.
Species is a group of interbreeding natural populations members of which have similar structure, habitat (area and ecological niche), interbreed freely, and produce fertile offspring. It is the only systematic unit, which really exists in nature. Organisms are corresponded to a certain species according to several criteria: same morphology (anatomic criterion),
physiological and biochemical similarity, same geographic area and ecological niche, similar
behavioral reactions (ethological criterion), same karyotype and genome (genetic criterion).
The main mechanisms of species evolution has been described above. Genetic variation and natural selection produces differences in a population or between populations of
same species that become fixed by isolation. As a result divergence with emergence of new
species occurs. There are several ways of microevolution:
1. Geographic (allopatric, organisms of same species migrate to other geographical regions with different environmental conditions) – due to geographic isolation.
2. Ecological (sympatric, organisms inhabit the same territory) – due to ecological isolation (place of nutrition, breeding, marital behavior, etc).
3. Genetic by polyploidy or cross-species interbreeding.
4. Symbiotic (examples are lichens).
Macroevolution is a process of formation of systematic ranks above the species (genus, order, class, phylum, etc). The main variants of macroevolution are divergence, convergence and parallelism (Fig. 13.6).
Divergence is a variance of features and separations onto groups (new genera, orders,
families, etc.) as an aftermath of adaptation to various conditions. Adaptive radiation as
Spieces A
Norm of variation
Norm of variation
Norm of variation
Fig. 13.6. Models of evolutionary changes: A – divergent evolution: one species forms two; B – convergent
evolution: unrelated species get similar characteristics as the result of the selection; C – parallel evolution:
two related species remain similar for a long time
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a diversity of features due to adaptation to certain conditions of the environment follows
divergence. For example mole, horse, cat, dolphin, human being that are mammals have a
different adaptive types of limbs.
Convergence is acquisition of similar features within the various, unrelated groups due
to adaptation to similar environment. Example is similar body shape of sharks (fish), ichthyosaurs (reptiles), and dolphins (mammals) (Fig. 13.7).
Parallelism – genetically close groups independently acquire similar features under
the same conditions (similar morphology in two mammals – seal and walrus). Parallelism
is widely spread among various groups of organisms during their historic development
(phylogenesis).
The main directions of macroevolution are biological progress and biological regress
(A. N. Severtsov, 1925). Biological progress includes increase in number of organisms, enlargement of geographical area they inhabit and arising of new systematic units. Biological regress is characterized by opposite processes (decrease of quantity, area, number of
systematic groups).
Biological progress is reached by arogenesis, allogenesis and catagenesis (Fig. 13.8).
Arogenesis is a way of macroevolution in which biological progress is provided by aromorphosis. Aromorphosis (morpho-physiological progress) is a general increase in degree
of organization without a marked degree of specialization so is useful in any environmental
condition. Arogenesis have led to formation kingdoms, phylums, and classes. Examples in
mammals are intrauterine carrying of a child, breast feeding, four chambered hart, alveolar
lungs, progressive development of cortex etc.
Penguin
Seal
Dolphin
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Ichthyosaurus
Ancestral reptile
Ancestral bird
Ancestral mammal
Ancestral mammal
Fig. 13.7. Convergence. These aquatic animals derive from different ancestors. They all have elongated bodies and paddle-like forelimbs as adaptation for life in the water
13.1. Evolution theory
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Allomorphosis
Allomorphosis
Aromorphosis
Allomorphosis
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Aromorphosis
Degeneration
Fig. 13.8. Ways of biological progress (according to A. N. Severtsov)
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Allogenesis is a way of macroevolution in which biological progress is provided by allomorphosis (idioadaptation). It is a rapid increase in specialization to certain environmental conditions and cause formation of new orders, genera, species. A different shape of
limbs in mammalian species is an example of allomorphosis.
Catagenesis is a way of macroevolution in which biological progress is reached by general degeneration (simplification of structure and function). It is confined to adaptation for
parasitism (i.e., absence of digestive system in tapeworms).
Evidences of evolution
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Evidences of evolution available in XIX century were based on comparative anatomy,
embryology, paleontology and biogeography. The comparative-anatomic evidences of
evolution include analogous and homologous organs, vestigial organs (rudiments) and
atavisms. Analogous organs are organs in different species that have similar function, but
different origin (eyes of crawfish and human, a wing of a fly and a wing of a bird)
(Fig. 13.9). Homologous organs are organs
in different species that have a fundamental similarity of structure as they have
been inherited from a common ancestor
(Fig. 13.10). Functionally they can be similar
or dissimilar (limbs of horse, seal’s flippers,
human hands are mammalian limbs). Vestigial organs (rudiments) are incompletely
developed organs that have lost all or most
A
B
of the original functions in evolution. These
organs were more fully developed in an- Fig. 13.9. Analogous organs:
cestors. Examples of vestigial organs in hu- A – a wing of a butterfly; B – a wing of a bird
Chapter 13. Evolution theory. Phylogenesis of organ systems in vertebrates
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B
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Fig. 13.10. Homologous organs – upper (anterior) limb: A – human; B – frog; C – bat; D – seal’s flippers;
E – horse
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mans are wisdom teeth, muscles that move auricle, coccyx (tail bone). Atavism is an evolutionary throwback when traits disappeared a generations before appear again (presence
of the ancestral features). Some congenital defects in humans are atavisms – tail, hypertrichosis (abnormal amount of hair growth over the body), supplementary mammary glands
or nipples (see Chapter 13.2).
Paleontological evidences are based on fossils studies that permitted to compare organisms living today with their ancestors. Some “missing links” were described by studies
of fossil records (i.e. archaeopteryx that combines some features of a reptile and a bird).
Embryological evidences are based on remarkable similarities of embryonic development of all vertebrates. This regularity was formulated by Ernst Haeckel in 1866
(biogenetic low): ontogeny (individual development) recapitulates phylogeny (the genealogy of the species). For example, human embryo has paired branchial grooves and
gill porches in the neck region, tail, two chambered heart on the certain stages of development. The idea that embryonic development repeats that of ancestors is called recapitulation. In fact, embryo passes through some embryonic but not adult stages that
ancestors passed through.
Biogeographic evidences are based on flora and fauna distribution, existence of endemic (confined to certain restricted small territory) and relict species (retained since ancient times, like coelacanth fish or gingko tree).
In XX and XXI centuries development of cytology, molecular biology, molecular genetics provided new evidences of evolution. They are based on similarity of energy metabolism, biochemical processes, universality of genetic code, analysis of karyotypes. The best
evidences of evolution are based on molecular-genetic studies. Comparing of genomes of
different species permits to estimate degree of relationship and period passed from separation of different lines (molecular clock). By analysis of genomes it was suspected that
13.2. Phylogenesis of organ systems in chordates
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the most recent population of organisms from which all current life on Earth evolved (last
universal common ancestor, LUCA) lived some 3.5 to 3.8 billion years ago.
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Evolution of the Skin
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Phylum Chordata has several subphylums, including Subphylum Cephalochordata
(Acrania) and Vertebrata (Craniata). The lancelet (Branchyostoma Lanceolatum) is an example of Cephalochordates. These are small fish-like marine animals that are an important
object for biological studies as demonstrate how vertebrates evolve (Fig. 13.11).
The following classes belong to vertebrates: Cyclostomata (e.g. lamprey), Pisces (Chondrichthyes or cartilaginous and Osteichthyes or bony fishes), Amphibia, Reptilia, Aves, Mammalia. These classes fall into two categories: Anamniota and Amniota. Anamniota are primary aquatic lower vertebrates. They lack amnion, so embryonic development occurs in
water environment only. Amniota are primary terrestrial higher vertebrates. The amnion
protects the embryo and permits terrestrial development.
Knowledge of morphological evolutionary changes is important for understanding of
some congenital defects in humans. Congenital defects that repeat normal state of previous evolutionary groups are termed as ontophylogenic (ancestral) defects.
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The skin of all chordates shows two layers: the outer epidermis (epithelium) of ectodermal origin and the inner dermis (connective tissue) of mesodermal origin.
The lancelet has very thin epidermis formed by single layered stratified epithelium with
unicellular mucous glands, dermis is thin and gelatinous.
The skin of all vertebrates also has two layers. The outer one is multilayered epidermis,
the inner one is the thick dermis from connective tissue.
Myomeres
Dorsal tubular nerve cord
Notochord
Dorsal fin
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Caudal fin
Postanal tail
Anus
Hindgut
Atriopore
Ileocolonic ring
Midgut
Fig. 13.11. Lancelet morphology
Hepatic cecum
Esophagus
Ocellus
Pharyngeal slit
Oral hood
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Fish have scales and contain mucous glands, which secretion reduces water friction.
There are various types of scales in fish. Placoid scales are characteristic for cartilaginous
fish (stingrays, sharks and other). Bony fish has mesodermal bony scales. Placoid scale has
a basal plate embedded in the dermis and a spine that projects out through the epidermis
(Fig. 13.12A). It consists of pulp and dentine covered by enamel, so it is homologous with
teeth. The basal plate and the dentine originate from the mesoderm while enamel is from
the ectoderm.
The skin of amphibians is naked, smooth, moist and slimy, having a thin film of mucus
secreted by multicellular mucous glands (Fig. 13.12B). Amphibians have also poisonous
glands that are more developed in toads than in frogs. The skin is abundant with blood
capillaries and functions as a respiratory organ.
The skin of reptiles (Fig. 13.12C) is rough and dry (without glands). They are first to have
stratified squamous epithelium. Epidermis consists of external corneal (stratum corneum)
and inner malpighian (stratum germinativum) layers. The stratum corneum is sloughed off
from time to time (moulting). Corneal keratin scales prevent losses of water thus enabling
reptiles to live on dry land. The bony dermal plates may locate below the scales (i.e. crocodiles). Claws appear.
In birds the skin is thin and dry, glands are absent, except an oil gland on the tail. The
stratum corneum is keratinized. It gives rise to scales and claws on the feet, horney sheath
on the jaws to form a beak and feathers of various sorts.
In mammals the skin is thick and glandular (Fig. 13.13). Epidermis has several layers or
stratums (four or five in palms and soles). The external corneal layer (stratum corneum) is
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Fig. 13.12. Evolution of skin: A – placoid scales of fish: 1 – enamel (vitrodentine); 2 – dentine; 3 – pulp; 4 – epidermis; 5 – dermis; 6 – basal plate; 7 – enamel (vitrodentine); B – skin of amphibians: 1 – epidermis; 2 – dermis;
3 – cutaneous glands (mucous and poisonous); C – skin of reptiles: 1 – epidermis; 2 – dermis; 3 – keratin scale
13.2. Phylogenesis of organ systems in chordates
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Fig. 13.13. Skin of mammals: 1 – hair; 2 – sebaceous gland; 3 – arrector pili muscle of the hair; 4 – nerve fiber;
5 – artery; 6 -vein; 7 – sweat gland; 8 – hair follicle; 9 – hair bulb; 10 – subcutaneous layer; 11 – dermis; 12 –
epidermis; 13 – touch receptor; 14 – sweat gland pore
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composed of thin scale-like keratinized dead cells without nuclei. Below it there are zones
were epithelial cells transform into corneal ones. The basal layer consists of actively proliferating epithelial nucleated cells and pigmented cells. Epidermis gives rise to skin derivatives: hair, claws, nails, hoofs and horns, sweat, sebaceous and mammary glands.
Dermis is the internal thick layer consisting of the connective tissue. Its surface stretches
into epidermis forming the so called dermal papillae. Numerous blood vessels and nerve
fibers are situated in dermis.
Fat accumulates below dermis. It occupies the subcutaneous tissue and smoothens the
body surface.
The following structures are skin derivatives in humans: sweat, sebaceous and mammary glands, hair and nails. The mammary glands of mammals originate from the sweat
glands.
The skin in mammals provides protection, thermoregulation, excretion, accumulation
of fat, synthesis of vitamin D and tactile sensitivity.
Basic directions of the skin evolution are:
`` differentiation and progressive development of the skin layers: replacement of single
layered epithelium by multilayered and thickening of dermis;
`` development and increasing of the skin derivatives number (glands, scales, feathers,
hair, etc);
`` increasing of the skin functions.
Chapter 13. Evolution theory. Phylogenesis of organ systems in vertebrates
Congenital ontophylogenic defects of the skin in humans
are hypertrichosis (excessive skin hear) (Fig. 13.14), atrichosis
(absence of hair), ichtiosis (hyperkeratinized skin), polymastia
(more than a pair of mammary glands), polytelia (more than a
pair of nipples) and other.
Evolution of the Skeleton
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The skeleton plays a very important role in the life of the
vertebrates. It forms a rigid framework, which gives support
and a proper shape to the body. It encloses and protects the
vital organs of the body and gives a hard surface for the at- Fig. 13.14. Hypertrichosis
(excessive skin hear)
tachment of muscles.
The skeleton includes two main parts: axial and appendicular.
The axial skeleton in the lancelet (see Fig. 13.11) is notochord. In higher chordates the
notochord is present during the embryonic stage only and then is partially or completely
replaced by a vertebral column.
In fish vertebral column may be cartilaginous as in chondrichthyes or bony as in osteichthyes. The skull has many small bones. The vertebrae are numerous. In fishes the notochord is persistent but reduced. The vertebral column is divided into a trunk part with ribs
and a caudal part. Fish have unpaired (dorsal, anal, caudal) and paired (pectoral and pelvic)
fins that form appendicular skeleton. Crossopterygian bony fishes (subclass Crossopterygii)
that appeared in Devonian are considered to be ancestors of all terrestrial vertebrates (tetrapodes) as the skeletal structure of their paired fins is homologous to arm and leg bones of
land-dwelling vertebrates (Fig. 13.15). Such limbs permit locomotion both on solid ground
and water result in the evolution of amphibians. Only two species of Crossopterygian fishes
(Latimeria) survived up to today.
In amphibians the endoskeleton is mostly bony but much cartilage persists in the skull.
The part of the skull containing the brain is cranium, the rest is called the viscerocranium.
The notochord is present only during the embryonic period. In amphibians the vertebral column consists of four parts: cervical (one vertebra), trunk, sacral (one vertebra) and
caudal. Chest is absent. In anurans (frog) tail vertebrae fuse forming a long, slender, tapering bone – urostyle.
The principle structure of the appendicular skeleton is the same in all vertebrates starting
from amphibians. It consists of forelimbs and hindlimbs along with pectoral and the pelvic
limb girdles. The pectoral girdle consists of the sternum, paired scapula, clavicle and coracoid. The pelvic girdle is of a V-shaped structure containing two identical halves. It occupies
the posterior end of the trunk and is connected with the vertebral column and urostyle. Each
half of the pelvis girdle contains three bones – ilium, ischium and pubis fused into one.
The skeleton of the fore-limbs is divided into three parts – humerus, radio-ulnar group
and bones of the hand (carpals, metacarpals and phalanges). The skeleton of hind-limbs consists of femur, tibio-fibula group and foot (tarsals with calcar, metatarsal parts and phalanges).
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13.2. Phylogenesis of organ systems in chordates
Bones are not attached to the backbone
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Coelacanth's fin
Coelacanth
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Ichthyostega
Ichthyostega’s feet
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Bones are attached to the backbone
Fig. 13.15. The forelimb of Devonian Crossopterygian bony fish (Coelacanth) and Ichtyostega – first terrestrial
Tetrapodes: 1 – element homologous to humerus, 2 – element homologous to radius, 3 – element homologous to ulna
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The skeleton of reptiles has the same general plan as in amphibians, but a more complicated one. The endoskeleton is completely ossified. The vertebral column is divided into
the cervical, thoracic, lumbar, sacral and caudal parts. The first and second cervical vertebrae are specially modified to support the head (atlas and axis). Thoracic vertebrae have
ribs. Most reptiles have cervical ribs and some have also lumbar ones. The ribs, sternum
and thoracic vertebrae form the chest. It surrounds and protects the heart and lungs, and
participates in respiration.
In birds the bones are light and delicate due to the presence of air cavities and air sacks
in them. The skeleton is very strong because of multiple bone fusion. The vertebral column
is divided into five parts (same as in reptiles). The sternum has keel or carina which the flying muscles are attached to. Fusion of clavicles formed interclavicle or “wish-bone”.
In mammals the skull has a large cranial cavity. The skull bones are firmly united with
sutures. A secondary palate is formed to separate airways from the alimentary tract. The
vertebral column has five regions as in reptiles. There are seven cervical vertebrae in the
neck region. Caudal part of the vertebra column is reduced to form coccyx. The scapula is
well-developed in the pectoral girdle; the coracoid is reduced up to a small process.
The basic directions of the skeletal system evolution are:
`` replacement of notochord by vertebral column;
`` replacement of the cartilage skeleton by the ossified one;
`` differentiation of the vertebral column (from two parts in fish to five ones);
`` formation of the chest;
`` development of the appendages of a terrestrial type.
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Chapter 13. Evolution theory. Phylogenesis of organ systems in vertebrates
Vertebral foramen
Transverse
process
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Normal human vertebra
A
No fusion
(exposed foramen)
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Spinous process
"Spina bifida" of vertebra
C
Fig. 13.16. Congenital defects of the skeleton: A – normal human vertebra; B – “spina bifida”; C – excessive
cervical ribs (indicated by the arrows)
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Examples of congenital defects of the skeleton are: osteogenesis imperfectum (failure
in skeleton ossification); “spina bifida” – a gap between two halves of the vertebral arch;
excessive cervical and lumbar ribs (Fig. 13.16); the cleft lip and the cleft palate; tail (long
coccyx); polydactyly – more than five fingers; syndactyly – fusion of fingers (Fig. 13.17).
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Evolution of the Digestive System
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The digestive tract (alimentary canal) is one of the axial organs of vertebrates. It originates mostly from endoderm and is situated below the nervous tube. The digestive tract is
differentiated into fore-, mid- and hindgut and contains digestive glands.
The alimentary canal of a lancelet is straight and simple (see Fig. 13.11). Anteriorly there
is an oral hood (frill-like membrane) surrounded by oral cirri which are fleshly and delicate.
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Fig. 13.17. Congenital defects of the skeleton: A – syndactyly (fusion of fingers); B – polydactyly (more than
five fingers)
13.2. Phylogenesis of organ systems in chordates
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They help in straining the food. The oral hood encloses a cavity called vestibule. The mouth
is situated at the posterior end of the vestibule. It leads into a laterally compressed pharynx
that occupies more than half of the total length of the body. The digestive and respiratory
systems are associated with one another. The pharynx contains gill slits. The food particles
are filtered from the water current that passes through the gill slits. The oesophagus is
short. The intestine shaped as straight tube opens to the exterior by the anus. A slender
hepatic cecum, that secrets digestive enzymes is situated ventral to the intestine.
In vertebrates digestive tract is more differentiated. The digestive glands present as
separate organs (liver, pancreas, salivary glands) and also are located in the mucous lining
of the alimentary canal.
In fish (Fig. 13.18A) alimentary canal is divided into the mouth, buccopharynx, esophagus, stomach and intestine (midgut and hindgut) that ends with anus. Mouth lies between
the two jaws equipped with teeth. The teeth are all alike in shape and structure (homodontous system). The tongue occupies the basement of the cavity. The salivary glands are
absent. The wall of the pharynx has gill-slits. The gill-slits are paired and open in the lateral
sides of the body. They have liver and pancreas opened into the intestine.
In amphibians (Fig. 13.18B) the mouth has usually a large gap. There are many small
teeth in upper or both the jaws. The teeth system is homodontous. The tongue is usually
protrusible and is used for catching prey. The buccopharyngeal cavity is not large. The salivary glands develop as adaptation to terrestrial life, saliva doesn’t contain enzymes. Due to
the absence of the neck esophagus is short but wide. It leads to stomach. Intestine is divided into small and short large intestine. Intestine opens into the cloaca (common chamber
into which intestinal, urinary and genital tracts open).
In reptiles the mouth is large and usually equipped with teeth on both jaws. The teeth
system is homodontous. Poisonous snakes have fangs. The buccopharyngeal cavity is divided into the buccal cavity and pharynx. One pair of salivary glands in some is transformed
into the poisonous glands. Saliva contains enzymes. The intestine becomes longer and is
well differentiated into parts. The rectum opens into the cloaca.
Birds (Fig. 13.18C) have jaws covered with corneal sheaths and forming a beak. The
teeth are absent. The esophagus is dilated into a crop for storing food grains. Beyond
the crop it leads into a thin-walled glandular chamber called proventriculus, with gastric
glands. The proventriculus is followed by a thick-walled chamber called gizzard. The gizzard is provided with pebbles used grinding the food. Some birds keep stones in gizzard
to crush grains. The bile ducts and pancreatic ducts open separately into the duodenum.
The large intestine is short. The rectum leads into the cloaca. Adaptation to flying explains shortening of alimentary canal length accompanied with high activity of digestive
enzymes.
Mammals (Fig. 13.18E) have the mouth surrounded with lips which are movable. The
buccal cavity has soft and hard palate. The number of teeth is fixed and they are produced
in two sets: milk and permanent. The milk teeth appear early in life. They are shed after
some time and are replaced by the permanent teeth. The teeth are of four types (incisors,
canines, premolars and molars) and form heterodontous system. The tongue has many
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Fig 13.18. Comparative structure of digestive system of vertebrates: (A – bony fish; B – frog; C – lizard; D – pigeon; E – rabbit; F – human): 1 – esophagus; 2 – crop; 3 – liver; 4 – gall bladder; 5 – stomach; 6 – duodenum;
7 – pancreas; 8 – midgut; 9 – small intestine; 10 – rectum; 11 – anus; 12 – large intestine; 13 – pyloric caeca;
14 – urinary bladder; 15 – caecum; 16 – appendix
functions – it is the organ of taste, helps in chewing and food swallowing, articulation
(in humans). Saliva contains digestive enzymes. There are usually four pairs (in humans –
three pairs) of salivary glands, which are opened into the buccal cavity (parotid, sublingual, submandibular or submaxillary, infraorbital). The esophagus and intestine are long.
The caecum on the border of the small and large intestines is well developed in the herbivorous animals. The liver is lobed. The cloaca is absent, so the rectum opens with anus.
13.2. Phylogenesis of organ systems in chordates
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Fig. 13.19. Diagram of various types of esophageal atresia and/or tracheoesophageal fistula (A – most of
cases (90 %) anomaly occurs in the upper part of the esophagus that ends with a blind pouch, and its lower
segment forms tracheoesophageal fistula; B – isolated esophageal atresia (4 % of cases); C – H-type (due
to its resemblance to the letter “H”) tracheoesophageal fistula (4 % of cases); D, E – other variants occur in
about 1 % of cases): 1 – bronchi; 2 – bifurcation; 3 – trachea; 4 – proximal part of the esophagus with blind
end; 5 – tracheoesophageal fistula; 6 – distal part of the esophagus
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The digestive system in mammals exhibits some modifications according to the feeding
habits. It concerns the teeth formula, the stomach structure, the length of the caecum. For
instance, the ruminant animals like cow have a four chambered compound stomach, the
caecum and appendix are well developed in mammals like rabbits (Fig. 13.18D).
The basic directions of the digestive system evolution are:
`` differentiation of the alimentary tract into parts;
`` elongation of the digestive tract and increasing of adsorption surface;
`` progressive development of the digestive glands;
`` differentiation of teeth in mammals;
`` separation of terminal parts of digestive, excretory and genital tracts.
Ontophylogenic congenital defects of the digestive tract are tracheoesophageal fistulas (openings between esophagus and trachea) (Fig. 13.19); anodontia (absence of teeth);
double row of teeth; persistence of cloaca (urogenital sinus).
Evolution of Respiratory system
Respiratory system is tightly connected with the digestive system in its origin. A common entodermal primitive gut is formed in all terrestrial vertebrates. When a human embryo is approximately 4 weeks old the esophagotracheal septum gradually partitions the
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lung bud and dorsal esophageal portion, giving the origin to the respiratory and digestive
systems.
In lancelet exchange of gases occurs mostly through the skin, but some takes place in
the 100–150 pairs of pharyngeal (gill) slits on either side of the pharynx (see Fig. 13.11).
The water passes from the pharynx into the atrial cavity through the pharyngeal slits and
then to the exterior through atriopore.
The respiratory system of fish (Fig. 13.20A) consists of four pairs of gills on bony gill
arches. They are situated on either side of the pharynx in a common chamber covered by
an operculum. There are gill petals on the gill arches where exchange of gases occurs in
capillaries, so respiratory surface is increased comparatively with lancelet.
The respiratory apparatus of amphibians are the skin and lungs that are similar to the
swim bladder of fish. The lungs have the shape of thin-walled sacks (Fig. 13.20B); the respiration tract consists of buccopharyngeal cavity and laryngo-tracheal chamber. The chest
is absent, so muscles of buccopharyngeal cavity provide ventilation of lungs. The highly
vascular skin acts as an accessory respiratory organ both in water and on land. The gills are
always present in the larval stages.
Laryngo-tracheal chamber
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Gill arches
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Gill petals
A Fish
Air sac
Cross-beams
B Amphibians
Spongy lungs
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Trachea
C Reptiles
Bronchi
Alveoli
D Birds
Fig. 13.20. Evolution of respiratory system of vertebrates
E Mammals
Bronchi
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The respiratory apparatus of reptiles are the lungs. The lungs have cross-beams, so respiratory surface increases (Fig.13.20C). The respiratory tract is divided into the pharynx,
cartilaginous trachea and two bronchi. Intercostal muscles participate in expiration and
inspiration mechanisms.
The lungs of birds are compact and spongy. The bronchioles pierce the lungs opening
into the air sacks that provide accumulation of the air (Fig.13.20D). During the fly saturation
with oxygen in lungs takes place in both inspiration and expiration (double respiration).
Increasing of respiratory surface is one of the factors providing homeothermy.
The lungs of mammals are of alveolar structure (Fig.13.20E). The bronchi form
a branched bronchial tree. A functional unit of the lung is an acinus. It consists of terminal
bronchiole, alveolar vesicles (alveoli) and a net of capillaries. Aeration goes through capillary and alveolar walls. Alveoli increase the surface area used for gas exchange. In humans
this area is up to 100 m2, which is 50 times larger than the skin area (1,5–2 m2). Oxygen
passes to blood, carbon dioxide passes to alveolar space by diffusion. Intercostal muscles
and diaphragm participate in expiration and inspiration mechanisms.
Main directions of respiratory system evolution are follows:
`` reduction of respiration units with simultaneous increase of respiratory surface in
aquatic animals;
`` development of lungs in terrestrial animals and increasing of respiratory surface of
lungs;
`` differentiation of respiratory tract in terrestrial vertebrates;
`` improvement of the pulmonary ventilation mechanism.
Main congenital defects of ontophylogenic origin are tracheoesophageal fistulas
(see Fig. 13.19), pulmonary agenesis (failure of lung formation), hypoplasia of lungs – a reduced number of the lung segments.
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Evolution of Circulatory System
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The circulatory system originates from mesoderm. The blood delivers nutritious substances to organs and tissues, provides aeration, excretion and performs protective and
regulatory tasks.
The lancelet has a single circulatory system. The ventral aorta serves as the heart and
gives off paired lateral branches (the afferent branchial arteries that pass deoxygenated
blood into the gills). The afferent branchial arteries in which oxygenation of blood takes
place run upwards without breaking into capillaries. Then oxygenated blood passes in the
efferent branchial arteries, which open into the lateral dorsal aorta and then goes in arteries to tissues. Carotid arteries carry the oxygenated blood to cranial side. Deoxygenated
blood from tissues is collected in the anterior and posterior cardinal veins that pass blood
to ventral aorta.
The blood vascular system of vertebrates is of closed type (vessels do not open into the
body cavity). The heart is muscular and situated ventrally to the digestive tract. It may be
made up of two, three or four chambers.
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Fish have a two-chambered heart that consists of an atrium and a ventricle. There are
two additional chambers: sinus venosus that opens into atrium and bulbus arteriosus that
arises from ventricle (Fig. 13.21A). Aorta goes out from the latter and gives off afferent branchial arteries. The heart contains deoxygenated blood. Blood is oxygenated in the branchial arteries of gill petals which contain a capillaries network. There is a single circulatory
system similar to that of the lancelet. The hepatic and renal portal systems are present.
Amphibians spend some of their lifetime on dry land, so their circulation system is
adapted for that. Gills are replaced by lungs; gas exchange in water is performed by skin.
Amphibians have double circulatory system: pulmocutaneous and systemic. The heart
consists of three chambers – two atria and one ventricle (Fig. 13.21B). The ventricle receives
deoxygenated blood from right atrium and oxygenated blood from left atrium. There is
some mixing of the blood in the ventricle, which reduces the efficiency of oxygenation.
One vessel (truncus or conus arteriosus) with spiral valve arises from the ventricle. Truncus
arteriosus is divided into 3 pairs of arteries: pulmocutaneous arches; arches of aorta (systemic arches); and carotid arches. With the help of spiral valve different portions of blood
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3a
2
C Reptiles
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3a
2a
E Mammals
3b
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3a
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Fig. 13.21. Evolution of circulatory system of vertebrates: 1 – bulbus arteriosus; 2 – ventricle (2a – right ventricle, 2b – left ventricle); 3 – atrium (3b – left atrium, 3a – right atrium); 4 – sinus venosus
13.2. Phylogenesis of organ systems in chordates
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are directed into different vessels: deoxygenated blood to the pulmocutaneous arches;
mixed blood to the arches of aorta and oxygenated blood to the carotid arches. Deoxygenated blood from the systemic circulatory system is collected into the anterior and posterior
venae cava, which get into a right atrium. Oxygenated blood enters the left atrium through
the two pulmonary veins.
The reptiles have also double circulatory system (pulmonary and systemic).The heart
of reptiles is three-chambered similar to the amphibian heart (Fig. 13.21C). The ventricle
contains an incomplete muscular septum which results in less mixing of oxygenated and
deoxygenated blood. Three blood vessels leave the ventricle. The right arch of the aorta
goes from the left part of ventricle and carries oxygenated blood, the left arch of the aorta
exits the middle part of the ventricle and carries mixed blood, the pulmonary artery comes
from the right part of ventricle and carries deoxygenated blood to the lungs. The dorsal
aorta of reptiles is formed by fusion of right and left aorta arches. It contains higher blood
oxygen than in amphibians because one arch carries mixed blood and the other one oxygenated blood. Carotid arteries originate from the right arch of the aorta, thus the head is
provided with oxygenated blood. Some reptiles (crocodiles) have a complete septum and
four-chambered heart.
In birds and mammals circulatory system is double, the heart is four-chambered with
two atria and two ventricles. The oxygenated and deoxygenated blood is not mixed, which
improves oxygenation of tissues, intensify metabolism and makes mammals and birds
warm-blooded. One of the aortal arches is reduced. The right arch of the aorta is characteristic for birds (Fig. 13.21D), the left arch is present in mammals (Fig. 13.21E).
Evolution of arterial arches. Early embryo of vertebrates (including humans) has ventral aorta with six aortal arches (homologous of gills arteries of the lancelet) and dorsal
aorta (Fig. 13.22A). Aortal arches are located in the pharyngeal region. First and second
of them are reduced in all vertebrates. Remaining four pairs function as gill arteries in fish
(Fig. 13.22B).
In terrestrial vertebrates the third pair of arches and part of dorsal aorta turns into carotid arteries. The fourth pair turns into arches of the aorta (Fig. 13.22C, D). In birds and
mammals just one arch of the aorta develops, the second one reduces (Fig. 13.22E, F).
The fifth pair of arches is reduced. The sixth pair forms pulmonary arteries.
Caudata amphibians and some reptiles have a vessel connecting the pulmonary artery with the dorsal (descending) aorta – ductus arteriosus (Botallo duct). The rest of adult
species of higher vertebrates have this vessel reduced. In humans it functions in prenatal
period; after birth it closes and in several months becomes ligamentum arteriosum.
The main directions of the cardiovascular system evolution are:
`` formation and progressive development of the heart from the two-chambered to
four-chambered one;
`` formation of the double circulatory system with pulmonary circulation;
`` complete separation of oxygenated and deoxygenated blood;
`` decreasing of arterial arches number. Reduction of the one arch in birds (left, see
Fig. 13.21E) and mammals (right, see Fig. 13.21F) had promoted their homeothermy.
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Fig. 13.22. Evolution of arterial arches: A – Embryo: 1–6 – pairs of arterial arches; 7 – ventral aorta; 8 – dorsal
aorta; B – Fish: 1,2 – reduced; 3–6 – branchial arteries; 7 – ventral aorta; 8 – dorsal aorta; C – Amphibians; D –
Reptiles; E – Birds; F – Mammals: 1, 2 – reduced; 3 – carotid arteries, 4 – arches of aorta; 5 – reduced; 6 – pulmonary arteries; 7 – ventral aorta; 8 – dorsal aorta; 9 – Botallo duct; 10 – right arch of aorta; 11 – left arch of aorta
Human pathology basing on ontophylogenic failure are acardia – absence of heart; two
or three chambered heart, incomplete septum of the ventricle (ventrical septal defect), persistence of two aortal arches and formation of aortal ring compressing trachea and esophagus
(Fig. 13.23A, B); truncus arteriosus (Fig. 13.24A) – common outflow tract; persistence of ductus arteriosus (Botallo duct) that causes mixing of oxygenated and deoxygenated blood (Fig. 13.24B).
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Evolution of Nervous System
The nervous system of a lancelet consists of a single tubular nerve cord that lies above the
notochord (see Fig. 13.11). Anteriorly the cord is modified into a cerebral vesicle having an olfactory pit and eye spot. The nerve cord gives out a pair of segmental nerves in each segment.
Vertebrates have a nervous tube that differentiates into the brain and spinal cord at
the embryonic period. The brain is well protected inside the cranium. The brain sends out
10–12 pairs of cranial nerves. They are sensory and motor in function.
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B
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Fig. 13.23. Congenital defects of heart – aortal ring (A – persisting of the distal part of the right arch of aorta
in embryo; B – formation of aortal ring compressing trachea and esophagus): 1 – the persisted segment of
the right dorsal aorta; 2 – ascending aorta; 3 – right aortal arch; 4 – common carotid arteries; 5 – trachea;
6 – esophagus; 7 – left subclavian artery; 8 – left aortal arch; 9 – descending aorta
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A
4
B
Fig. 13.24. Congenital defects of heart (A – truncus arteriosus; B – persistence of ductus arteriosus (Botallo
duct)): 1 – aorta; 2 – truncus arteriosus; 3 – ventricular septal defect; 4 – pulmonary artery; 5 – ductus arteriosus
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The brain of vertebrates is developed by the accumulation of nerve cells at the cephalic
end of the nerve tube. The embryonic brain passes through the stages of three and five
brain vesicles (Fig. 13.25). The primary brain vesicles are forebrain (prosencephalon), midbrain (mesencephalon), hindbrain (rhombencephalon). Later the forebrain subdivides into
two secondary brain vesicles: telencephalon and diencephalon. The hindbrain subdivides
into metencephalon that differentiates into pons and cerebellum and myelencephalon
(medulla oblongata). Thus, the brain of all vertebrates consists of 5 parts: telencephalon, diencephalon, mesencephalon, metencephalon and myelencephalon (medulla oblongata).
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Fig. 13.25. Development of the brain (scheme): (A – stage of three brain vesicles (with eye vesicles); B – stage
of five brain vesicles (with eye cups)): 1 – forebrain; 2 – midbrain; 3 – hindbrain; 4 – telencephalon; 5 – diencephalon; 6 – mesencephalon; 7 – metencephalon; 8 – myelencephalon, 9 – eye vesicle, 10 – eye cup
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Early in the evolution of vertebrates, a special sensory system became associated with each
part of the brain: the olfactory organs with the forebrain, the eye with the midbrain, and
the ear with the hindbrain .
The brain of fish (Fig. 13.26A) has a primitive structure (small in volume with a poorly
developed frontal part). Telencephalon is not divided into hemispheres, its roof is thin and
consists of epithelial tissue. The floor is thickened, consists of nervous tissue and contains
corpora striata. Olfactory bulbs are nearly as large as the corpora striata and are closely
to the anterior end of the cerebrum. The mesencephalon is located behind the forebrain,
serves as an optic center (optic bulbs). It is the leading integrative system receiving information from all sensory organs. Such a type of the brain is termed as ichtyopsidic one.
The cerebellum (the movements coordinate center) is well-developed in fish. It covers the
myelencephalon, which has the centers of respiration and blood circulation. Ten pairs of
cranial nerves originate from cerebrum.
The telencephalon of amphibians (Fig. 13.26B) has a greater volume and is divided into
two hemispheres which end by olfactory bulbs. The roof and dorso-lateral walls of the ventricles are relatively thin, consist of nervous tissue, and known as a pallium (archipallium).
The mesencephalon of amphibians is small comparatively with fish, but is still the main integrative center. So, the brain is of ichtyopsidic type. The cerebellum is developed poorly that
corresponds to simple movements of amphibians. Ten pairs of the cranial nerves are present.
Reptiles (Fig. 13.26C) are the first true terrestrial vertebrates, their brain is moderately
developed. The telencephalon is large, olfactory lobes are separated from it. The enlargement of the telencephalon occurs because of progressive development of corpora striatum, i.e. floor. The roof is thin, but reptiles are the first to have cortex of cerebral hemi-
13.2. Phylogenesis of organ systems in chordates
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Fig. 13.26. Evolution of brain of vertebrates (A – bony fish; B – amphibians; C – reptiles; D – birds; E – mammals): 1 – olfactory lobe; 2 – telencephalon; 3 – diencephalon; 4 – mesencephalon; 5 – cerebellum; 6 – medulla oblongata
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spheres. It appears as two small regions (medial and lateral islands). This cortex is primitive
and thus called archicortex. The floor (corpora striata) is highly developed and is an integrative center of nervous activities. Such a type of the cerebrum is termed as sauropsydic
(striatic) one. The size of the mesencephalon decreases, cerebellum is developed better
than in amphibians. The cerebrum possesses 12 pairs of cranial nerves.
In birds (Fig. 13.26D) the brain is large, the mesencephalon and cerebellum are well
developed. Progressive development of telencephalon is provided by enlargement of corpora striatum; the cortex does not progress. The corpora striata are an integrating center so
the brain is of sauropsydic type (like in reptiles). There are 12 pairs of cranial nerves.
The cerebrum of mammals (Fig. 13.26E) is characterized by considerable development
of the cerebral hemispheres. The cortex covers the surface of hemispheres completely and
is called neocortex. Higher mammals have the convolutions of the cortex (gyri and sulci),
thus its surface is increased. The number of the nervous cells in mammal cortex exceeds
billions. They are responsible for high degree of coordination in activities and learning and
retention of memory. All higher sensory and motor centers are located in the cortex. It is
also the seat of intelligence, will and emotions. Brain with neocortex that is integrating
center is called mammalian brain type. The cerebellum in mammals is large. There are 12
pairs of cranial nerves.
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The cerebral hemispheres are maximally
developed in humans. Speech, abstract thinking, intelligence are characteristic of humans.
Thus the cerebral hemispheres are the material substrate of psychic activity.
The main directions of nervous system
evolution are:
`` Development of cerebrum at anterior
part of the neural tube.
`` Progressive development of telencephalon, formation of cortex and enlargement of it surface.
Fig. 13.27. Congenital defect of brain: a child
`` Replacing of the integrating centers of
with anencephaly. Usually such children die in
nervous activities from mesencephalon a few hours after birth
(ichtyopsidic type) to the corpora striatum of telencephalon (sauropsydic type) and to the cortex of cerebral hemispheres
(mammalian type).
`` Increasing in number of cranial nerves.
The ontophylogenic congenital defects of the brain are anencephalia (absence of brain)
(Fig. 13.27), microcephalia, atelencephalia (absence of fore-brain), agyria (smooth cortex),
cerebral hernia (encephalocele) and cerebrospinal hernia (myelocele).
Evolution of excretory and reproductive systems
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In the lancelet the excretion is carried out by about 100 pairs of nephridia which resemble protonephridia of invertebrates. The sexes are separate, and both males and females
have multiple paired gonads. Eggs are fertilized externally, development is indirect.
In the existing vertebrates the kidney develops in two or three successive phases: pronephros (cranial kidney), mesonephros (trunk kidney), and where applicable, metanephros
(pelvic kidney). The structural and functional unit of the kidney is nephron.
Pronephros functions during the embryonic period of all vertebrates and in some adult
Cyclostomata. Pronephros is located in the cranial part of the body, the number of nephrons doesn’t exceed ten. Nephrons consist of pronephric tubules and funnels, which open
into coelomic cavity (Fig. 13.28A). There is no direct interaction between nephrons and
circulatory system. Glomerulus of capillaries are under the coelomic epithelium. Products
of metabolism are excreted into the coelom and through pronephric funnels and tubules
to the pronephric duct. The latter runs backwards outside the somatic mesoderm to open
into the cloaca.
The mesonephros functions in the embryos and adults of Anamniota (some Cyclostomata, fish, amphibians) and at the embryonic period of higher vertebrates (reptiles, birds,
mammals). The mesonephros appears in trunk behind the pronephros. Nephrons are directly connected with circulatory system forming double walled cups (Bowmen’s capsules)
13.2. Phylogenesis of organ systems in chordates
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Fig. 13.28. Evolution of nephron. Principle scheme of nephron in A – pronephros; B – mesonephros; C – metanephros. Nephron of mammalian kidney (D): 1 – glomerulus; 2 – tubule of nephron; 3 – funnel; 4 – renal
corpuscle; 5 – convoluted tubules; 6 – Henle loop; 7 – collecting duct
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with a network of capillaries inside (glomerulus). This structure is called renal corpuscule.
Some nehrons retain funnels and connection with coelom (Fig. 13.28B). Tubules of nephron become long and coiled, partial reabsorption of water and glucose takes place. The
number of nephrons is up to several hundred.
The metanephros arises behind the mesonephros in the pelvic region. The number of
nephrons reaches one million (in humans). The funnels are absent, conection with coelom
is lost. Tubules are longer than in mesonephric nephrons (Fig. 13.28C). In mammals nephron
consists of renal corpuscule (glomerulus and Bowmen’s capsule), proximal convoluted tubule,
Henle loop, and distal convoluted tubule (Fig. 13.28D). Such structure of nephron provides
effective filtration and reabsorption of water and other substances that is important for terrestrial animals. The metanephros functions in adults of Amniota (reptiles, birds, mammals).
Reproductive system develops simultaneously with the excretory one. Early stages
are same in both sexes. Non-differentiated primary gonads are formed from intermediate mesoderm (nephrogonotom between somits and ventral mesoderm) near the mesonephros. Differentiation of gonads is described in Chapter 7.5. Paired pronephric ducts
connect the tubules of each of the pronephros with the cloaca in early embryo of all vertebrates (Fig. 13.29). With the development of mesonephros pronephric ducts split into
mesonephric (Wolffian) ducts and paramesonephric (Mullerian) ducts. These ducts present
in embryos in both sexes of vertebrates and participate in formation of male and female
reproductive systems.
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In females of Anamniota the Mullerian duct fuse with funnels of pronehpric nephrons
and functions as an oviduct; the Wolffian duct becomes urinary duct. In males of Anamniota the Wolffian duct serves as common urinary and efferent duct of the testis, and the Mullerian duct is reduced. In both sexes excretory and reproductive systems open into cloaca.
In Amniota the ureter (metanephric duct) is formed separately along with metanephros
development. In females of Amniota the Wolffian duct reduces. The Mullerian duct fuse
with funnels of pronehpric nephrons. In reptiles and birds it functions as an oviduct and
opens into cloaca. In mammals the lower part of Mullerian ducts widens to form uterus and
upper part of vagina, urethra and vagina open separately. In males of Amniota the Wolffian
duct serves as efferent duct of the testis, and the Mullerian duct is reduced (see Fig. 13.29).
The main directions of evolution of the excretory and reproductive systems are:
`` Evolutionary development of kidney as an excretory organ.
`` Evolution of kidney: disappearing of funnels and direct interconnection of circulatory and excretory systems, enlargement of filtration surface by increasing the number of nephrones, elongation of the excretory tubules and improving of reabsorption
mechanisms.
`` Separation of terminal parts of the excretory and reproductive systems in females.
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Ontophilogenic defects of these systems are polycystic kidneys (persistence of funnels),
segmented kidney with several ureters, pelvic kidney or primary descendent kidney (if kidney fails to ascend), renal agenesis (absence of kidney); recto-urethral fistulae (openings
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Fig. 13.29. Development of excretory and reproductive systems in Anamniota and Amniota. A – embryo of
Anamniota vertebrate; B – female Anamniota; C – male Anamniota; D – embryo of Amniota vertebrate
(mammals); E – female Anamniota; F – male Amniota: 1 – pronephros; 2 – mesonephros; 3 – metanephros;
4 – pronephric duct; 5 – Mullerian duct; 6 – Wolffian duct, 7 – uterus; 8 – ureter; 9 – urinary bladder; 10 –
cloaca; 11 – urogenital sinus; 12 – penis or clitoris; 13 – ovary or testis; 14 – rectum
13.2. Phylogenesis of organ systems in chordates
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between rectum and urethra), urogenital sinus (persistence of cloaca). Examples of uterus
defects in humans are double uterus (uterus didelphys), normally characteristic for rodents
and bicornuate uterus (lower part is unitary and upper part bifurcated) characteristic for
pigs, cetaceans and some other mammals. The defects develop when embryogenetic fusion of Mullerian ducts fails to occur (Fig. 13.30). Example of congenital defects in males is
cryptorchidism – one or both testis undescend into scrotum.
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Fig. 13.30. Congenital defects of uterus: A – double; B – bicornuate
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TASKS & QUESTIONS
`` MULTIPLE CHOICE QUESTIONS (Choose one correct answer):
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1. Progressive changes in organisms that persist over time is:
A. Evolution
D. Isolation
B. Natural selection
E. Heredity
C. Hardy-Weinberg principle
2. Analogous organs indicate
A. Common descendent
D. Natural selection
B. Parallel evolution
E. None of the above
C. Convergent evolution
3. Which of the following factors is most likely to contribute to gene flow between populations?
A. Random mating
C. Mutation
E. Genetic drift
B. Migration
D. Inbreeding
4. Congenital defects of the skin are:
A. Polydactyly
C. Brachydactyly
E. Cleft palate
B. Cleft lip
D. Hypertrichosis
5. Heterodontous teeth are typical for:
A. Reptiles
C. Bony fish
E. Mammals
B. Birds
D. Amphibians
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6. Which pair of arterial arches gives the origin to carotid arteries?
A. First
D. Fourth
B. Second
E. Fifth
C. Third
7. How many arterial arches are in a human embryo?
D. 5
A. 2
B. 3
E. 6
C. 4
8. Incomplete septum in the ventricle is typical for:
A. Fish
D. Birds
B. Amphibians
E. Mammals
C. Reptiles
9. All types of kidneys are present in vertebrates embryogenesis except:
C. Metanephros
A. Pronephros
B. Mesonephros
D. Protonephridia
10. The hindbrain develops into:
A. Forebrain
C. Mesencephalon
B. Mesencephalon and diencephalon
D. Cerebellum
E. Myelencephalon and metencephalon
11. The ichtyopsidic type of cerebrum refers to:
A. Human
D. Birds
B. Fish
E. Mammals
C. Reptiles
12. For the first time archicortex appears in:
A. Fish
D. Birds
B. Amphibians
E. Mammals
C. Reptiles
13. Mesonephros ... in male Anamniota.
A. Reduces
B. Transforms into ureter
C. Transforms into sperm duct
D. Partially transforms into testis appendix
E. Functions
14. Ancestral congenital defects of the circulatory system are:
A. Acardia
B. Ventricle septal defect
C. Persistence of two arches of aorta – “aortal ring”
D. Persistence of Botallo duct
E. All of the above
15. There are South and North strains in Plasmodium vivax that differ in the duration of
the incubation period. In the South strain it is short, and in the North one is long. This
reflects the selection:
A. Disruptive
C. Artificial
E. Driving
B. Stabilizing
D. Sexual
13.2. Phylogenesis of organ systems in chordates
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`` TRUE OR FALSE:
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1. Catagenesis is reached by __________________ .
2. Example of the convergence is similar body shape in ichthyosaurs, ___________ and
________________.
3. “Ontogeny recapitulates phylogeny” is a law formulated by _______________ .
4. Interrupted ecological equilibrium in ecosystem would most likely initially result in
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1. Divergence is a discrepancy of features, separations onto groups as an aftermath of
adjustment to various conditions.
True
False
2. A bird’s wing is homologous to a butterfly wing.
True
False
3. Biological progress is characterized by decrease of quantity, area, number of systematic groups which may lead to extinction.
True
False
4. A species is a group of similar organisms that can breed and produce fertile offspring.
True
False
5. Comparative anatomy can show similarities in structure that supports the idea of
evolutionary relationship and common ancestry.
True
False
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Ecology. Biosphere as human environment.
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The term ecology (from Greek eikos – house or dwelling and logos – science) was originally coined by the German zoologist Ernst Haeckel in 1866. He defined ecology as the
comprehensive science of the relationship of the organisms to their environment (total of
inorganic and organic environment). Now we define ecology as the branch of biology that
studies relations and interactions between organisms, populations and communities
and their environment including other organisms. Ecology is divided into two branches:
autecology and synecology. Autecology deals with the biological relationship between an
individual organism or an individual species and its environment. Synecology studies the
relations between groups of organisms of coexisting biological communities.
14.1. Ecological factors. Ecosystems
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The environment is a set of factors that can directly or indirectly influence the living
organisms. A habitat is an environmental area that is inhabited by a particular species of
organisms. The term refers to a part of nature that surrounds the organisms and where
they can find food, shelter, protection and mates for reproduction. Habitat includes specific
biotic and abiotic conditions in which the given organisms (population) live. Habitat can be
aquatic (marine and fresh-water), terrestrial, soil. Habitat of parasites is the host’s organism.
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Each type of habitat is characterized by specific set of factors that can directly or indirectly influence the living organisms. Any factor that influences living organism is termed
as ecological factor.
The influence of the ecological factor on the organism’s adaptation depends on its nature and intensity (Fig. 14.1). Every organism has an ecological minimum and maximum for
every factor (critical minimum zone and critical maximum zone respectively). The critical
minimum zone is the minimum limit of intensity, below which the grows and development
of the organism is impossible. The critical maximum zone is the highest maximum limit
above which the growth and development of the organism ceases. The range between
these two limits is known as limits of tolerance or zone of tolerance. The intensity of ecological factor which is optimal for growth, existence and reproduction of an organism is
termed as optimal zone. Organisms are characterized by maximal fitness and successful
reproduction in optimal range of tolerance. If intensity of ecological factor is more or less
14.1. Ecological factors. Ecosystems
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Zone of tolerance
Zone of
Intolerance
zone of
physiological
stress
Minimum limit
Optimal zone
Optimum
zone of
physiological
stress
Death
Maximum limit
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Zone of
Intolerance
Environmental factor
Fig. 14.1. The influence of the ecological factor on the organism’s adaptation
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than optimal range but within a zone of tolerance, physiological activities of an organism
are suppressed (zones of physiological stress).The zone below critical minimum and above
the critical maximum is zone of intolerance.
The range of tolerance is specific for every species. Any ecological factor less than minimum limit or more than maximum limit is called limiting factor as it restricts distribution
of particular species in certain area. Limiting factors in terrestrial habitat might be temperature, water, soil nutrients. In aquatic ecosystems these are salinity, sunlight, temperature,
dissolved oxygen. To explain the effect of limiting factors several laws were proposed.
The Liebig’s law of minimum (proposed by German chemist Justus Liebig) states that if
the factor is depleted below the critical minimum level the organism will fail to grow or will
grow abnormally. By other words, success of an organism is determined by crucial ingredient that is in short supply.
Blackman’s law of limiting factor (proposed by British plant physiologist Frederick Blackman) states that any organism is under the action of number of ecological factors and
deficiency of any of them will affect an organism.
Shelford’s law of tolerance (proposed by American zoologist Victor Shelford) states that
not only less but also the excess amount of the same factor can be limiting.
The summary effect of ecological factors can potentiate or compensate action of any
factor.
There is a variation of tolerance between species with respect to a particular factor. An
organism may have narrow range of tolerance for one factor but wide range of tolerance for
other factors. Species that can thrive only in a narrow range of environmental conditions are
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called specialist species. Organisms having wide range of tolerance to all factors are called
generalist species. They have better chances for survival and are widely distributed.
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Ecological factors can be classified into:
`` abiotic;
`` biotic;
`` anthropogenic.
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Classification of ecological factors
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1. Abiotic factors are the factors of inanimate nature. These are climatic factors (light,
temperature, humidity, precipitation, wind), type of soil, topography, chemical factors
(concentration of gases, minerals, pH). Some most important for humans abiotic factors
are described below.
Temperature is the most variable abiotic factor in terrestrial habitat with annual and
daily fluctuations. Most organisms survive at temperature range of 0 to 40 °C. Some organisms are adapted to survive at 60–90 °C (hot springs bacteria) and –30 to –50 °C (Arctic
and Antarctic organisms). Temperature influences reproduction, migration, rate of growth
and nearly all other vital activities. The geographical distribution and migrartion of living
organisms are also influenced by temperature. According to organism’s reaction to temperature all animals are divided into poikilothermic (cool-blooded) and homeothermic
(warm-blooded). Poikilothermic are animals whose body temperature varies considerably
depending on external temperature. They are more influenced by temperature than homeothermic ones. Both types of animals have developed some adaptations for surviving in
cold or extremely hot seasons. They can fall into hibernation in winter or aestivation (summer sleep) in summer in hot and dry regions, migrate in more favorable regions and other.
The Bergman’s and Allen’s rules describe the effect of temperature on morphological
features of homeothermic organisms. Bergman’s rule states that warm-blooded animals
tend to have larger size and greater body mass with the increasing latitude (towards the
poles) and decreasing average temperatures. Poikilothermic animals demonstrate opposite
tendency. Allen’s rule adds that warm-blooded animals tend to have protruding body parts
(limbs, ears, tails) longer in hot climate and more compact body shape in cold climate. It is
explained by the importance of the ratio of surface area to body volume: when organism is
more linear, it tends to lose more heat; when organism is more compact, it tends to conserve
heat. The same regularity is observed in people in different geographical areas: populations
toward the pole tend to be shorter and have shorter limbs than people on the equator.
People have been adapted to a great diversity of climates with different temperature
regimes. This is achieved by both physiological and behavioral mechanisms and due to
social adaptations – use of clothing, housing, heating.
Light is an essential factor for life. The energy for almost all living organism in the biosphere comes directly or indirectly from sunlight. In plants light is required for photosynthesis and plays an important role in growth, metabolism regulating and distribution. In
14.1. Ecological factors. Ecosystems
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animals light of visible spectrum permits vision, infrared waves provide heating, ultraviolet waves (UV) are both useful (stimulate synthesis of melanin and vitamin D in skin) and
harmful (have mutagenic and cancerogenic effect). Adaptive feature to the intensive UV
irradiation is dark skin color due to melanin synthesis. Skin is march darker in people of
equatorial latitude and lightens towards the poles. In the regions with temperate climate
skin darkens in summer (san tan). Short-wave ultraviolet rays with a wavelength of less
than 290 nm are detrimental to living organisms, but the Earth is protected from them by
the ozone screen.
Periodic changes of day and night cause diurnal biological rhythms. Physiological reactions of the organism to season changes of the length of day or night are termed as
photoperiodism (see Chapter 6.6). It plays an important role in life cycle of many organisms: flowering and growth in plants, breeding cycles in animals, bird migration, coat color
changes and other.
Water is the most important substance necessary for life. It forms 60 % to 90 % of cell
contents. All the biochemical processes of the cell take place in water medium. It is needed
for photosynthesis in plants. In all species of organisms water is important for thermoregulation (see Chapter 1.3.). Water medium is a habitat for many organisms.
Depending on the requirement of water plants can be classified into: hydrophytes (live
in water and require large quantities of water), xerophytes (terrestrial plants which can
pass through long periods without water) and mesophytes (terrestrial plants which require
moderate quantity of water). Animals are divided into hydrocoles, xerocoles and mesocoles respectively. Insufficient amount of water in the body can be compensated in several
ways: behavioral compensation (water search, some organisms fall into hibernation during
the dry period), morphological (accumulation of water in certain organs), and biochemical
compensation (the production of metabolic water during the breakdown of fats).
Gloger’s rule states that within homeothermic species more heavily pigmented forms
tend to be found in more humid environment.
Gases that are vital for organisms are oxygen and carbon dioxide. According to oxygen
requirements all organisms are divided into aerobic and anaerobic. Aerobic organisms produce energy (in form of ATP molecules) through a process of aerobic cellular respiration.
Oxygen serves as the final electron acceptor at the end of electron transport chain in mitochondria cristae (or cell membrane in prokaryotes). Aerobes do not survive without oxygen. Partial oxygen pressure is very important factor for human being in mountains. Low
amount of oxygen in high altitude causes altitude disease (“mountain disease”). Symptoms
include headache, dizziness, fatigue, sleep disturbance.
Anaerobic organisms use fermentation or anaerobic cellular respiration (other, than oxygen molecules act as final electron acceptors) to produce ATP. Many bacteria, organisms
living deep in the soil, and intestinal parasites are anaerobes.
Carbon dioxide is essential for photosynthesis in plants. In animals concentration of CO2
in blood is important factor for regulation of breathing. Excessively high level of carbon
dioxide in blood (hypercapnia) causes abnormally rapid breathing, headache, flashed skin,
raised blood pressure.
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2. Biotic factors are activities of living organisms that affect other living organisms
within their environment. These may be of the following types: competition, neutralism,
antibiosis and symbiosis.
Competition is the kind of interaction when organisms with similar needs compete
with each other for the same limited recourses. Intraspecific competition occurs between
the individuals of the same population and interspecific competition occurs between the
individuals of different species inhabiting common area. For example plants of same or different species compete for water, nutrients and light. Herbivorous animals compete with
other herbivorous, and carnivorous animals with other predators for food supplies. Russian
biologist G. F. Gause formulated the principle of competitive exclusion: if two species are
competing with one another for the same limited recourse, than one of the species will be
able to use this recourse more efficiently than the other and will reproduce at higher rate
as a result. The fate of less effective species is local extinction. For example, gray squirrels
that were introduced to Britain from the end of XIX century, have gradually replaced by
red squirrels. In Europe gray rats drove out the black rats from usual habitats. Species with
similar needs can coexist if occupy different ecological niches.
Both types of competition are the mechanisms of Darwin’s struggle for existence and
serve as important evolutionary factors.
Neutralism is the most common type of interspecific interactions when neither population directly affects the other ones. For example, robin birds and squirrels living in a forest is
an example of neutralism as neither serve as food for each other nor compete for recourses
although they can inhabit the same tree.
Antibiosis is antagonistic interaction between members of different species in which
one of them is exterminated. Examples of antibiosis are predation and allelopathy. Predation is the interaction between individuals of two species, one of which captures, kills
and eats up the other. The species that captures is called the predator, and the one that is
caught is the prey. It is considered that predators are carnivorous animals, but interaction
of herbivorous animals and grass is similar with predation as such animals remove from
the population the organisms on which they feed. The predator cannot survive without
the pray. Predation keeps the predator and pray population more or less balanced. Allelopathy is a biological phenomenon by which one organism produces biochemicals that
influence growth and reproduction of other organisms. This phenomenon is common in
plants, fungi and bacteria. For example moulds and some bacteria produce antibiotics,
some plants (especially conifers) produce phytoncides. Both antibiotics and phytoncides
inhibit the growth of many bacteria.
Symbiosis is interaction between organisms of different spices meaning “living together”. Main forms of symbiosis (i.e., mutualism, commensalism and parasitism) are described
in Chapter 10.1.
3. Anthropogenic factors are caused by human activities. One of the earliest anthropogenic activities that still matter is domestication of animals, selection of animals and
plants, introduction of new species. According to the nature anthropogenic factors can be
14.1. Ecological factors. Ecosystems
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divided into chemical, physical and combined (climatic, relief-forming). Changes caused
by human activities became significant with Industrial Revolution. The factors responding
for that are numerous, but the apparent ones are the explosive population growth, rapid
industrialization, and urbanization leading to destruction of natural ecosystems. Examples
of some unfavorable anthropogenic influences are given below.
Pollution is the unfavorable alteration of our environment as a result of human activity.
It is one of the most horrible ecologic factors we are facing today. Pollutants are any substances that are present in the wrong quantities or concentration or in the wrong place.
Certain common pollutants are soot, tar, sulphur dioxide, carbon monoxide, ammonia,
chlorinate, pesticides, radioactive substances and other. Toxic dumps and oil spills are the
main two forms of pollutants that damage the biosphere.
All pollutants can be classified into non-degradable and biodegradable. Non-degradable toxins do not degrade or degrade too slowly in natural environment. They accumulate
in nature and can be taken from soil by plants and ingested, absorbed through the skin or
inhaled by animals. Fat-soluble non-degradable pollutants demonstrate bioaccumulation,
i.e. toxins are transferred by food chains and reach maximal concentration at the organisms
of top predators, including man. Toxins accumulate in fat tissue, release in blood and affect
all organ systems. They are also released from breast tissue with milk and affect offspring.
Examples of such pollutants are DDT (chlorinated hydrocarbon pesticide) and some other
pesticides, polycyclic aromatic hydrocarbons, heavy metals (mercury, lead, cobalt, chromium, etc).
Biodegradable pollutants include domestic sewage, heat etc. The domestic sewage can
be decomposed by natural processes or engineered systems that enhance nature capacity
to decompose and recycle. Problems with biodegradable pollutants arise if their input exceeds the decomposition capacity of ecosystem. Bioremediation is a waste management
technique that involves the use of organisms to neutralize pollutants from a contaminated
site. Some types of pollution can be reduced, and habitats restored with the help of living
organisms.
Air pollution with sulphur dioxide and nitrogen oxides leads to acid rains. Emitted into
the atmosphere the pollutants react with the water molecules and produce acids. The acid
droplets then fall to earth as rain, snow or mist. This can increase the acidity of the soil, and
affect the chemical balance of lakes and streams.
Synthetic gases chloroflurocarbons (CFCs) that were used in aerosol cans and as refrigerants cause ozone depletion. It is a slow, steady decline of about 3 percent per decade in
the total amount of ozone in Earth’s stratosphere during the past twenty years. CFCs also
play a certain role in greenhouse effect.
The greenhouse effect or global warming is caused mainly by the increase in atmospheric carbon dioxide. Carbon dioxide retards the radiation of heat from the earth back
into outer space that warms a planet. However, is slightly increasing temperature of the
earth a result of human activity or of a natural long-term climate changes is an unanswered
question.
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14.2. Ecological systems. Biosphere
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Ecological systems can be arranged in progressively increasing levels of organizational complexity. A natural association of the interdependent populations of different
species inhabiting a common environment is called biocenosis (biotic community). It
includes zoocenosis (fauna community), phytocenosis (flora community), and microbiocenosis (microbial community). A geographic area of uniform environmental conditions
providing a living place to certain biotic community is called biotope. Biotope with inhabiting it biocenosis form ecosystem or biogeocenosis. Ecosystem exists as a stable
open self-regulating system with certain spatial boundaries, energy flow and matter
recycling. Based on the biotope peculiarities ecosystems are fresh-water, marine or terrestrial.
Any ecosystem is characterized by certain set of species linked through the food chains.
Number of species that occur in ecosystem is species diversity. It influences stability of
population: the more is species diversity the more stable is population. The species with
the greatest impact on both the biotic and abiotic components of the ecosystem is referred
to as the dominant species. Natural ecosystems are often named for their dominant species (pinery, redwood forest). Each species occupies certain ecological niche. It is defined
by the full set of conditions, resources, and interactions species needs.
The structure of feeding relationship in ecosystem is called trophic structure. Plants
are the foundation of most ecosystem trophic structure as they are able to produce organic matter (biomass) through photosynthesis. Because of that plants are considered
to be producers. The biomass produced by plants is used by herbivorous animals – primary consumers, which convert plant biomass into animal biomass. Carnivorous that
feed on herbivorous are called secondary consumers. Carnivorous, that eat secondary
consumers are tertiary consumers and so on. A large amount of biomass in a form of
dead organisms and fecal matter is broken down by decomposers (saprotrophic microorganisms and fungi) with releasing of energy. The decomposition process returns some
biomass to the soil as organic matter. A pass of food consumption is called a food chain.
Most animals consume a varied diet and in turn, provide food for many organisms forming a food webs (Fig. 14.2).
Each level of consumption is considered to be different trophic level (Table 15.1), so
food chain reflects the trophic relationships among species in ecosystem.
Table 15.1. Trophic levels in ecosystem
Type of organism
Trophic role
Trophic level
Type of nutrition
Plants
Producers
First
Autotrophic
Herbivores
Primary consumers
Second
Heterotrophic
Carnivores and
parasites
Secondary consumers
(and higher)
Third (and higher)
Heterotrophic
14.2. Ecological systems. Biosphere
Food Web
(all possible energy paths)
Quaternary
consumers
5th trophic level
Tertiary
consumers
4th trophic level
Secondary
consumers
3rd trophic level
Primary
consumers
2nd trophic level
Primary
producers
1st trophic level
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Food Chain
(just 1 path of energy)
Carnivore
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Herbivore
Plant
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Fig. 14.2. Food chain and food web in terrestrial ecosystem
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Functioning of natural ecosystem is characterized by flow of energy and cycling of nutrients. The earth receives energy from the sun as light and heat. Green plants (the producers) capture light energy and change it into chemical energy of organic molecules trough
photosynthesis. Plants use only about 1 % of solar energy reaching the earth. The amount
of organic matter synthesized by producers per unit area in unit time is called gross primary productivity. Plants use for respiration 40 % to 70 % of gross primary production. The
amount of organic matter stored by producers (exclude the energy utilized for respiration)
and available for next trophic level is called net primary productivity. The rate of increase
in the biomass of heterotrophs per unit time and area is called secondary productivity.
Chemical energy passes through the food chain from one trophic level to the next one.
Only about 10 % of biomass and chemical energy at one trophic level is converted into
biomass and energy at the next trophic level. It is explained by loss of energy for maintaining the organisms at each level; large portion of biomass also is used by detritivores
and decomposers. The decrease of the total available energy and biomass at each higher
trophic level is called pyramid of energy and pyramid of biomass. Pyramid of energy is
always upward with the large energy at the bottom (first trophic level). Pyramid of biomass
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B
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Fig. 14.3. Scheme of biomass pyramids (A – upward terrestrial; B – inverted aquatic): 1 – the first trophic level
(producers); 2 – the second trophic level (primary consumers); 3 – the third trophic level (secondary consumers); 4 – the fourth trophic level (tertiay consumers)
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is almost always upward. Exclusion is some aquatic systems in which periodic reproduction of phytoplankton causes inverted pyramid of biomass (Fig. 14.3). Pyramid of numbers
represents the total number of individuals of different species at each trophic level. It can
be upright, inverted or spindle-shaped depending on size of the organisms.
The flow of energy in the ecosystem is unidirectional: from the son to producers, to consumers to the environment (Fig. 14.4). The nutrients move in cycles as biomass eventually
returns in the soil as organic matter and can be used by producers again. The biomass transferred between trophic levels contains both energy in chemical bonds and matter serving
as nutrients, thus the cycling of nutrients in ecosystem is linked to the flow of energy.
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Producers
Net primary
productivity
Heat
Respiration
Respiration
Herbivores
Decomposition,
and waste
Decomposition
and wasted
food
Decomposer
biomass and heat
Fig. 14.4. Ecosystem energy flow (after Stephen R. Gliessman)
Heat
Carnivores
Decomposer
biomass and heat
Heat
Top carnivores
Decomposer
biomass and heat
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The totality of ecosystems of same climate zone is called biome. Each biome has unique
weather and temperature patterns, plant and animal communities. The main terrestrial biomes are tundra, forest (tropical rain forest, temperate deciduous forest, taiga), grassland
and desert. Aquatic biomes include fresh-water, ocean and coral reef biomes. Sum of biomes make up a biosphere. Biosphere is the part of our planet in which life exists and it is
the largest scale of ecological organisation.
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The biosphere (from Greek bios – life and sphaira – sphere) is the layer of the planet
Earth where life exists. It is a sum of all ecosystems. In other words the biosphere is the
global ecological system integrating all living beings and their interaction with the elements of the lithosphere (the solid portion of the earth), hydrosphere (the water on the
surface of the globe), and atmosphere (the mixture of gases around the earth). The term
“biosphere” was proposed by the Austrian geologist and paleontologist Eduard Suess in
1875. The biosphere theory was created in 20th years of XX century by the Soviet geochemist Vladimir Vernadsky, who identified the boundaries if the biosphere, its structural organization, energetics and dynamics.
Biosphere occupies the entire hydrosphere, the upper part of the lithosphere (to
a depth of 3.5 km or even more) and the lower part of the atmosphere (up to 15–20 kilometers above sea level). The upper bound in the atmosphere is determined by the ozone
screen, and the lower bound in the lithosphere is limited by the high temperature. At the
limiting boundaries of the atmosphere and the lithosphere only spores of some bacteria
were found.
In fact the life supporting zone of the Earth for most organisms is less than given above.
The spread of most living organisms in the lithosphere actually is limited to several meters
by absence of light and low concentration of oxygen. The upper atmosphere has little oxygen, very low temperatures and high cosmic radiation. At great depth in the oceans light
is a limiting factor for water vegetation. Life is more abundant at the interfaces between
the air, sea and land. It is not distributed in the biosphere uniformly. Maximum life occurs
in the tropical rain forests and coral reefs and minimal in extremely dry regions, high in the
mountains, in the tundra and poles.
The lithosphere, hydrosphere, and atmosphere are non-living components of the environment (abiotic or inert matter). The biotic component (living matter) includes plants,
animals, fungi, and microorganisms. A constant interaction between the abiotic and biotic components of the biosphere results in the cycling of matter and energy flow, which
makes it dynamic but stable system.
Biosphere is an opened system as it receives solar energy. After passing through the
transformations that keep all living things alive, energy returns to outer space as heat (energy flow). The number of atoms can be used to form living organisms is limited. However,
life exists in our planet more than 3 billion years as these atoms are used repeatedly. The
cyclic movement of chemical elements of biosphere between biotic and abiotic compo-
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nents is known as biogeochemical cycle. The examples are the Carbon, Oxygen, Nitrogen,
Sulfur, Phosphorus cycles and other, including the water cycle. Thus, living matter is the
active component of the biosphere in geochemical processes and influences the face of
our planet. For example, Oxygen in atmosphere is a result of photosynthesis; coal, oil and
some other minerals are of biogenic origin; sedimentary rocks and soil were formed as a
result of interaction of biotic and abiotic biosphere components. According to V.Vernadsky
biosphere is a global ecosystem in which connections among the gaseous, liquid and solid
envelops are regulated by living matter and the biosphere’s basic properties result from
the activity of these envelopes.
English chemist James Lovelock and American microbiologist Lynn Margulis in 1970s
proposed the Gaia hypothesis (from Greek goddess of the Earth Gaia). According to this
hypothesis the Earth functions as an interactive system in which living things help to maintain and perpetuate the conditions for life on the planet (global temperature, ocean salinity, oxygen in atmosphere and other).
Development of biosphere historically was driven by two main factors: natural geologic
and climatic changes in the planet and changes in number and species of living organisms
during the biological evolution. Now they are joined by the third factor–human society.
Modern state of biosphere is termed as noospher (From Greek noos – mind and sphaira –
sphere). Concept of nooshere was introduced by V. Vernadsky. He considered the growth
of science and technology would make human intervention in nature more purposeful
and deliberate that will create new state of biosphere – noosphere. Thus, noosphere is the
sphere of interaction between society and nature, within the limits of which reasonable
human activity becomes the determining factor of development.
14.3. Human ecology
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Human ecology is the study of the mutual relationships, interactions or interconnections between people and their environments (thus their natural, social and built environment) at multiple scales and multiple time frames. At this basic level, human ecology can
be thought of as the study of the environmental conditions in which human beings developed, and the relationship of humans to the ecosystems that support them and which
they affect.
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Human habitat
Environment in which human beings exist and interact include:
`` Natural habitat – natural ecosystems, inhabited by certain human populations. This
environment directly or indirectly affects the human species and, in turn, is affected
by human activities.
`` Agroecosystems – natural ecosystems that have been modified by humans for the
production of food. These are orchards, arable land, cattle-grazed grasslands and
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other. Agroecosystem retains some characteristics of natural ecosystem, but the purpose of establishing an agricultural production makes it different from natural ecosystem in many important aspects (Table 15.2). Such ecosystem is human-dependent and without control its temporal permanence is very short.
Table 15.2. Important differences between natural ecosystem and agroecosystem
Characteristic
Natural ecosystem
Agroecosystem
Energy that leaves the system is mostly in
the form of heat, generated by the respiration and by the decomposition of biomass
Considerable energy is directed
out of the system at the time of
each harvest
Nutrient cycles
Closed
Opened, nutrient lost with the
harvest; requires human inputs
Species diversity
High
Trophic interactions
Complex
Stability
High
Net productivity
Medium
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Low, typically it includes one to
four major crop species and six
to ten major pest species
Simple and linear because of low
species diversity
Low, self-regulation is absent
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`` Built environment (built world) is the man made surrounding that provides people
with living, working and recreational space. The urban ecosystem is an example of
built environment. Urban ecosystem (urbanocenosis) is an ecological system located
within a city, town or other densely settled area. It differs from natural one in several
important aspects. Urban ecosystems completely or partially lack producers, so are
strongly dependent from energy and matter input (heterotrophic ecosystem). It is
characterized by more active energy flow with usage of electricity and fuel energy
and produced excess heat. Rainwater infiltration into the local soil is less. Air and
soil is polluted with heavy metals, dust, different toxins, and waste materials. Urban
ecosystem is human-dominated and governed mainly by demographic, social and
economic factors. Diversity of animal and plant species is restricted to those become
adapted to urban conditions. High density of human population promotes circulation of infectious and parasitic disorders. High rate of life, constant noise, low physical activity, calorie rich food, constant stresses are the factors causing dysfunction of
nervous, circulatory, digestive systems, allergy and metabolic disorders.
Human adaptations
Important question of human ecology is adaptation to the habitat. Adaptation is the
process by which an animal (including human being) or plant species becomes fitted to its
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environment. It is the result of natural selection that supports traits (genotypes) useful in a
particular environment. Such beneficial traits include morphological features, ability to utilize a new food source, physiological peculiarities, resistance to certain disorders and other.
Most animal and plant species have limited adaptability and are restricted to relatively few or
even one environment. Humans demonstrate high adaptation capacity to occupy a diversity
of habitats (from tropical rain forests to the Arctic), that is explained by several mechanisms.
The evolutionary first human habitat was natural habitat. Genetic analysis suggests
a sub-Saharan African origin for modern humans approximately 140,000 years ago. One
of the major expansion of humans out-of Africa into other geographical region occurred
around 130,000 years ago. Adaptation of ancient people to different climate conditions led
to the formation of human races. Race is large human population that has common origin,
stable set of morpho-physiological traits and reflects adaptation to certain environment.
Races can be defined as distinct evolutionary lineage within a same species, so are characterized by same evolutionary level. Most anthropologists recognize three main races:
Caucasian (or Europid), Mongoloid and Australo-Negroid (Fig. 14.5).
Caucasian race includes populations of Europe, the Caucasus, North Africa, North India,
Asia Minor. Caucasoids have light or swarthy skin (adaptive in low UV radiation in order to
make sufficient vitamin D), straight or wavy light hair, large eyes of gray or blue color, narrow long nose (heating of air), thin lips. Blood cholesterol level is higher than in individuals
of other races.
Mongoloid race populations inhabit Asia, North and South America, Arctic, and the Pacific Islands. Individuals within these populations have light or dark skin, straight dark hair,
narrow eyes with epicanthal folds (skin fold in the inner eye corner, protects eyes from
wind carrying dust and sand), broad nose, thin lips.
Fig. 14.5. Three main races recognized by most anthropologists: A – Caucasian; B – Australo-Negroid;
C – Mongoloid
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Australo-Negroid populations inhabit Africa, Australia, South Asia. The typical features
are dark skin color (adaptive in high UV radiation in order to protect from mutations), dark
curly hair, large dark eyes, broad nose, thick lips, and increased perspiration.
Each major race is subdivided into distinct anthropologic types called minor races (totally 22), the latter, in turn, include ethnic groups.
However, none of the racial classification reflects actual genetic similarity and genealogy of human population. Genetic differences within one race might be more expressed
that between representatives of different races, thus racial classification requires revision
based on modern molecular-genetic data.
Adaptation mechanisms to same specific environment (hot or cold temperature, high
or low humidity, high altitude) are similar in humans even of different races. For example,
the same traits of adaptation to the conditions of the tropical zone are typical for the indigenous people of Africa (Negroid), for the Caucasoids of India, and the Australians. A population of organisms that share one or more adaptations (morphological, physiological,
biochemical) to certain habitat is called adaptive type or ecotype. The main adaptive ecotypes in humans are:
`` arctic ecotype;
`` mounting ecotype;
`` tropical ecotype;
`` arid ecotype;
`` ecotype of temperate climate.
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Arctic adaptive type is characteristic for Arctic indigenous people: Saami (in circumpolar areas of Finland), Nenets, Khanty, Evenk and Chukchi (in Siberia), Aleut, Yupik and Inuit
or Eskimo (in Alaska). The Arctic climate is characterized by cold winters (in average – 40 °C)
and cool summers, long polar day and polar night. Arctic ecotype demonstrates adaptation to cold moist climate. People are short with comparatively large trunk and short limbs
(illustration of the Bergman’s and Allen’s rules). Musculoskeletal system is well developed,
bone mineralization is high, level of hemoglobin, proteins and cholesterol in blood is elevated. Important morphological adaptation is fat insulation of vital organs.
Period of vegetation in tundra is short, so vegetative food in a diet is irregular, and proportion of carbohydrates is low. Meat and seafood diet with high amount of proteins and
fats, microelements is prevalent. High fat content in food and blood serum combined with
increased ability for its utilization is one of the important factors of high metabolic rate and
increased heat production. People of Arctic ecotype in average have basic metabolic rate
13–16 % more intensive than strangers.
Air and soil contains small number of microorganisms, eggs of helminths and cysts of
protists do not survive in low temperature, so people of Arctic type have relatively low immunity.
Mounting adaptive type was formed in the highlanders (Andeans, Tibetans, the Ethiopian Highlands inhabitants and other highland populations) who are adapted to high
altitudes with low partial oxygen pressure and hypoxia. Highlanders have enlarged lung
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volumes and breath more rapidly. Better oxygenation is reached by high hemoglobin concentration (in Andeans) and high oxygen saturation, increased net of capillaries. Level of
myoglobin is elevated also. Intensive oxygen delivery, including cerebral flow, is provided
by high level of nitric oxide in blood (nitric oxide dilates blood vessels).
Tropical adaptive type is observed in populations of tropical and sub-tropical regions.
The main ecological factors here are high temperature with high humidity that makes losing the excess body heat hard. Vegetative food with low protein is prevalent. Air, soil and
water contain a lot of bacteria, environmental conditions favor circulation of parasitic disorders.
People of tropical adaptive type usually are tall and thin with comparatively short
trunk and long extremities (illustration of the Bergman’s and Allen’s rules), narrow chest,
decreased muscle mass and little body fat. Number of sweat gland per 1 cm2 of skin is increased, perspiration is more active (however, inhabitants of tropical rain forests sweat less
as sweat cannot evaporate). Basic metabolic rate and blood cholesterol is low; regulation
of water-salt balance is specific.
Arid adaptive type was formed among the inhabitants of deserts. They are adapted to
the hot dry air and large diurnal temperature fluctuations. In these conditions same morphological features as in tropics are more common, the muscular and fatty components
develop poorly. However, the total body size of the inhabitants of the deserts is greater
(reaction to lower environmental temperatures). The level of basal metabolism, blood cholesterol, mineralization of the skeleton is low. In people of arid adaptive type vascular regulation of heat loss is more effective.
Ecotype of temperate climate is characterised by temperature and humidity that
doesn’t reach critical values, climatic changes are seasonal, external conditions vary from
arid regions (desert, semidesert, steppe) to deciduous forests and taiga. People inhabiting
moderate climate area demonstrate intermediate morphological features and metabolic
rate between Arctic and tropic adaptive types.
The biological processes that influence tolerance to climatic extremes are likely to
play important roles in pathogenesis of common metabolic disorders such as obesity,
hypertension, and dyslipidemia. For example, obesity risk might be related to variation
in basic metabolic rate, energy balance, body mass index and variation in food intake.
The climate related selection acted on the genes influencing water retention and sodium
homeostasis might explain inter-ethnic differences in the prevalence of salt-sensitive hypertension.
Adaptive ecotypes are similar in individuals of different races. Mountain adaptive
ecotype was formed in Negroid population of Ethiopian plateau, Mongoloid populations
of Tibet, Tien Shan, Ands and Caucasian populations of Alps, Caucasus and Pamir. Tropical
adaptive type is met in inhabitants of Africa and tropical forests of Central and South America. Ecotype of moderate climate was formed in Caucasians and Mongoloids in Europe, Asia
and North America.
Though morphological and physiological adaptations facilitate human settlement in
different geographic zones, our behavioral adaptations are no less important. The tech-
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nical development in clothing, housing, transportation and food supply buffers us from
climatic stress.
Currently, a new ecological type of people is forming as the result of adaptation to urban environment (urban ecotype). It is characterized by the lability of mental reactions,
which allow experiencing a state of constant stress and high rate of life. Accumulation
of environmental pollution, overcrowding, increase in cigarette smoking, alcohol and fat
consumption, sedentary lifestyle in urban populations result in increased incidence and
prevalence of “diseases of civilization”. This term is used for chronic disorders that become
a dominant health problem in industrialized countries. Cancer, disorders of cardiovascular
system, bronchial asthma and other disorders with allergic component, metabolic disorders (obesity, diabetes) can be referred to “diseases of civilization”.
Formation of adaptive ecological types is a result of long lasting evolutionary process,
which supported reproduction of individuals with most favorable characteristics. Thus, adaptation is genetically determined and takes place over many generations. Non-hereditary
short-term changes in which an individual organism adjusts to it environment (a change
in altitude, temperature, humidity) within the lifetime is called acclimatization. Examples
are tanning in summer or polycythemia (high volume percentage of red blood cells), which
occurs naturally at high altitudes. If acclimatization occurs during organism’s growth and
development it can cause irreversible changes, known as developmental adjustment or
developmental acclimatization. For example, people who moved at high altitudes in childhood develop larger chest volume and lung capacity than those who moved their being
adults. By the fact, both short-term and developmental acclimatization are modifications
(see Chapter 8.1).
Successfulness and rate of acclimatization is influenced by genetic polymorphism.
There are several types of human constitution according to reaction towards new
extreme conditions: ”sprinter”, “stayer” and “mixt”. “Sprinters” are able to develop
powerful physiological responses to the violent short-term effects of extreme environment. They are easier to adapt to extreme environmental factors during the first
months after falling into new conditions. It is explained by large reserve of regulating
and life support systems and a high capacity for their rapid mobilization. However,
the restoration processes proceed slowly, so long-term action of unfavourable factors, even of relatively low intensity, is poorly tolerated by “sprinters”. The “stayers”
are poorly adapted to the powerful short-term environmental stress, as their backup
capacity and ability of rapid mobilization are low. However, after a short-term adjustment, they are able to tolerate long, monotonous influence of environmental stressors. Working loads in “stayers” are accompanied by optimal restoration processes.
“Mixt” type is characterized by intermediate abilities to adaptation. Types of functional reactions are important in different situations including adaptation to stresses
of modern urbanized society, working conditions and other. Concept of general adaptation syndrome (stress) was proposed by Hans Selye in 1936. It is a set of adaptive reactions of humans and animals towards significant in strength and duration
external factors-stressors (see Chapter 6.6).
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14.4. Poisonous organisms
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Poison is defined as any chemical substance which, when taken into the organism, acts
injuriously, tending to cause death or serious detriment to health. The poisonous organisms are met in all continents of the world and represented by all kingdoms, including
animals, plants and fungi.
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Poisonous animals can be primary or secondary poisonous.
Primary poisonous animals produce toxins by themselves. They can be passively or
actively poisonous. Passively poisonous are animals that accumulate toxic products of metabolism in certain organs or tissues. Eating of such organs causes intoxication. Example
is fresh water cyprinid fish marinka (Schizothorax intermedius) in Central Asia and Ukraine
(Fig. 14.6). Ovary, testis and gills of this fish are highly toxic (especially in spring), but the
fish freed from the entrails are harmless and tasteful. Another famous example of passively
poisonous animal is fugu fish, described below.
Actively poisonous animals possess special organs for poison production and accumulation. They are considered as armed if have special organs for toxin inoculation (spines,
sting, fangs and other). Spiders, insects, some fish, snakes are the examples. Unarmed actively poisonous organisms don’t have special organs of poison injection and toxin acts if
get on the skin or mucose membranes of a victim (frogs).
The fields of medicine and zoology often distinguish a poison from venom, though
these terms are interchangeable. Poison is absorbed through the skin or ingested, while
venom is injected into another organism by a bite or sting. Thus, fungi and plants are poisonous and animals can be poisonous (some fish, frogs, salamander and other) or venomous (spiders, scorpions, insects, some fish, snakes).
Secondary poisonous organisms do not produce toxins by themselves. They accumulate toxins taken up from the food or produced by symbionts. If the level of toxicity is
Fig. 14.6. Fresh water cyprinid fish marinka (Schizothorax intermedius)
14.4. Poisonous organisms
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high, consuming of such organisms result in secondary poisoning. For instance, during the
blooms of toxic marine dinoflagellates algae, feeding bivalve mollusks of Saxidomus genus
concentrate the toxin. Consuming of the mollusks contaminated with toxic level of algae
saxitoxin leads to neurological symptoms, hypertension and tachycardia (paralytic shellfish
poisoning). While most patients recover without treatment, weakness may progress to respiratory paralysis and death.
Representatives of several animal phylums are dangerous to human beings.
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Portuguese man o’war or physalia (Physalia physalis) belongs to phylum Cnidaria (formerly referred to phylum Coelenterata), class Hydrozoa (Fig. 14.7).
It is the most dangerous jellyfish found in European waters, most commonly found in
the open ocean in tropical and subtropical regions. By the fact it is a colony of tiny animals
known as zooids. Colony is translucent, bilaterally symmetrical, with the tentacles at one
end. It gets its name from a gas filled blue, purple, pink, or mauve bladder (pneumatophore) which sits above the water and resembles a type of 18th century Portuguese war
ship. Tentacles grow in average to 10 meters and can reach some times 30 meter in length.
They carry the stinging specialized capsules with venomous threads – nematocysts.
The venom-filled nematocysts in the tentacles of the Portuguese man o’ war can paralyze small fish and other prey. Venom of physalia affects cell membranes, contains ATPase,
DNAase, RNAase, fibrinolysin and other enzymes. Stings usually cause severe pain, leaving whip-like, red welts on the skin that normally last two or three days after the initial
sting, though the pain should subside after about 1 to 3 hours. However, the venom may
cause fever, swelling of the larynx, airway
Pneumatophore
blockage, cardiac distress, and an inability to
(Sail)
breathe. In extreme cases can cause death.
The First Aid begins with the application
of salt water to rinse away any remaining microscopic nematocysts – rubbing or touchClusters
of Polyps
ing the wound causes it the discharge of any
nematocysts still attached to the skin.
Box Jellyfish or sea wasp (Chironex
Fleckeri) belongs to phylum Cnidaria, class
Cubozoa (Fig. 14.8).
This jellyfish or the cubozoan bell (named
Venomous
as it is square in horizontal cross section) is
Tentacles
widely regarded as the most poisonous animal in the world. Although the notoriously
dangerous species of box jellyfish are largely
restricted to the tropical Indo-Pacific region,
various species of box jellyfish can be found
widely, including the Atlantic Ocean and the Fig. 14.7. Portuguese man o’war (Physalia physalis)
Chapter 14. Ecology. Biosphere as human environment. Poisonous organisms
Fig. 14.8. Box Jellyfish or sea wasp (Chironex Fleckeri)
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east Pacific Ocean, the Mediterranean Sea, coastal waters of Japan and South Africa.
The bell of the box jellyfish is so transparent that it is nearly invisible; tentacles produce
nematocysts with venom. Venom action is necrotic and hemolytic. The immediate sensation is sharp burning pain, after that dermatitis and skin necrosis develop. Once the toxin
reaches the blood, blood pressure increases. This can lead to a heart attack, and ultimately
death.
The First Aid. Flushing with vinegar is used to deactivate undercharged nematocysts to
prevent the release of additional venom.
Arthropods include spiders and scorpions (class Arachnida), centipedes and milli-
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pedes (subphylum Myriapoda) and insects (class Insecta) with both venomous and poisonous (certain beetles release toxins when are crashed) representatives. Some venomous
spiders and scorpions are discussed in Chapter 13.2.
Millipedes and centipedes have an elongated body composed of various numbers of
segments. They are worldwide in distribution. Millipedes release toxin when pressed or
crushed (for instance, while putting a shoe with a millipede inside). Their body fluids contain toxins (cyanides and other) that cause local inflammation and hyperpigmentation of
skin. As a first aid applying alcohol that is toxin solvent soon after contact is useful. Centipedes, that are carnivorous arthropods, inject their venom into a prey by modified first
pair of legs. The bite of centipede cause intense pain, local edema and redness. In some
cases headache, malaise and anxiety are observed. The representatives of Scolopendra genus (Fig. 14.9) reach up to 25–30 cm long and can cause serious injuries. First aid includes
washing site of bite with soap and water and application of cold compress.
Representatives of several orders of class Insecta are venomous. Bees, wasps and hornets are venomous insects of order Hymenoptera. They inject venom using a stinger in the
abdomen. A honey bee (Apis mellifera, family Apoidea) was one of the first domesticated
insect that is kept to this day for production (honey, beeswax, royal jelly, propolis, pol-
14.4. Poisonous organisms
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len) and pollination activities (Fig. 14.10).
Venom apparatus includes two glands
(venom or acidic gland and the alkaline
gland) that are associated with the base
of the stinger (modified ovipositor). There
are backward pointing barbs on a stinger
that make its removing difficult. When the
bee pulls the stinger away it remains in
the skin along with part of the hindgut of
the bee, so after the stinging the bee dies.
Bee venom contains at least 50 toxic pro- Fig. 14.9. Tiger Centipede (Scolopendra polymorpha)
teins and peptides (melittin, hyaluronidase, phospholipase A, acid phosphatase,
histamine and other). These components
affect cell membranes by influencing activity of membrane-anchored enzymes
and blockage of Ca-dependent potassium channels. Sting of a single bee causes
pain, local irritation and swelling. Multiple stings cause renal failure, heart failure
and sometimes death. If one has allergy
to bee venom even a single sting can
cause anaphylactic shock and death. The
Fig. 14.10. Honey bee (Apis mellifera)
aggressive hybrids of African and European bees originated in Brazil have caused
envenomations and deaths across the
B
Americas. The first aid is careful removing
of remaining stinger.
A
The wasps and hornets belong to the
family Vespidae. Example is common wasp
(Vespula vulgaris) that originally was native to Europe, but now is met in North
America, Africa and Australia and Asian giant hornet (Vespa mandarinia), the world’s
largest hornet, native to temperate and
Fig. 14.11. Poisonous insects:
tropical Eastern Asia (Fig. 14.11). The strucA – common wasp (Vespula vulgaris);
ture of venomous apparatus is similar to B – giant hornet (Vespa mandarinia)
that of honey bee, but stinger is easily
removed by the insect. Venom contains mixture of different proteins and peptides with
neurotoxic and enzymatic activities, some components can cause hypotension, increasing in vessels permeability and contraction of smooth muscles. Stings are painful. A large
number of stings or allergy can lead to death.
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Fig. 14.12. Poisonous stingrays: А – common stingray (Dasiatis pastinaca); B – ocellate river stingray (Potamotrygon motoro)
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Venomous and poisonous Fish belongs to phylum Chordata, class Chondrichthyes
(cartilage fish) and Osteichthyes (bony fish).
Example of venomous cartilage fish is common stingray (Dasiatis pastinaca) (Fig. 14.12A).
It is found in the northeastern Atlantic Ocean, and the Mediterranean and Black seas. The
common stingray has venomous tail span by which it can inflict excruciating wound. Venom
causes hypotension, breathing failure and sometimes leads to convulsions and collapse. Another example of venomous stingray species is ocellate river stingray (Potamotrygon motoro) (Fig. 14.12B) inhabiting river basins in tropical and subtropical South America. Stingrays
are dangerous for people who wade in shallow water and tread on them.
The most venomous known bony fish is reef stonefish (Synanceia verrucosa)(Fig. 14.13).
It inhabits tropical waters of the Pacific and Indian oceans. Reef stone fish is an ambush
predator, waiting its prey on the bottom. Its dorsal area is lined with sharp and stiff spines,
each of which has venom sacs. Venom has hemolytic and cardyotoxic action. If one steps
on the fish spine, it pierces the sole and venom is injected. It results in severe pain, tissue
necrosis, paralysis and can be fatal if not treated.
The lionfish (twelve species of Pterois genus) (Fig. 14.14) is a venomous coral reef fish.
They were thought to be the most venomous fish until recent years when stonefish stole
the title. These fish have venomous dorsal, anal,
and pelvic spines covered by a loose sheath that
moves down and compresses venom glands
when the spine punctures tissue. A sting from
these fish can cause extreme pain, swelling, and
in very severe cases, cardiovascular collapse.
First aid includes removing of affected individual away from the water, removing the stinger
(if visible) and immersion of the affected limb in a
hot water to denature the proteins in the venom. Fig. 14.13. Reef stonefish (Synanceia verrucosa)
14.4. Poisonous organisms
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6 anal-fin rays
Two venemous spines in pelvic fins
3 venemous anal spines
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Fig. 14.14. Lionfish (Pterois genus)
Fig. 14.15. Grass puffer fish (Takifugu niphobles)
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Example of passively poisonous fish is grass puffer fish (Takifugu niphobles) (Fig. 14.15).
The species of the pufferfish family are met in the northwest Pacific Ocean. Their intestine,
liver and ovary contain the extremely potent poison tetrodotoxin. The poison has neurotoxic action blocking sodium channels of neurons. Consuming of inadequate cooked
puffer fish is potentially lethal to human.
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Poisonous Amphibians belong to phylum Chordata, class Amphibia.
In most of cases intoxication of humans is caused by the contact with skin glands of
poisonous amphibians. Example is fire salamander (Salamandra salamandra) (Fig. 14.16)
of Caudata order which is met in Europe including Ukraine. The distinct feature of fire salamander is black color with yellow spots or strips to a varying degree. The colored portions
of the animal skin coincide with location of poisonous glands (usually are concentrated
around the head). Toxin causes hypertension and muscle convulsions.
Extremely toxic are poison dart frogs (order Anura) of family Dendrobatidae (Fig. 14.17).
It includes about 130 species, inhabiting Central and South America. Examples are Phyl-
Chapter 14. Ecology. Biosphere as human environment. Poisonous organisms
lobates terribilis or yellow poison frog, Phyllobates
aurotaenia or Kokoe poison frog, Dendrobatus auratus or green-and-black poison dart frog. These
are small frogs (up to 47 mm) with brightly colored
bodies; intensity of coloration correlates with the
toxicity of the species. Steroid alkaloid batrachotoxin and other components of frog’s poison keep
sodium channels of nerve cells open depolarizing
nerve and muscle cells irreversibly. Simply touching of frog can induce life-threatened loss of muscle
control, convulsions, paralysis, high fever, arrhythmia and eventually cardiac failure. The amphibians
got name “dart frogs” as indigenous American Indians used toxic secretion of these frogs to poison the
tips of blow darts.
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Fig. 14.16. Fire salamander
(Salamandra salamandra)
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Venemous reptiles belong to phylum Chordata, class Reptilia, order Squamata, suborder Serpentes. The venom apparatus of poisonous snakes
consists of a modified teeth (the fangs) by which
venom is delivered into prey, and the venom glands
where toxin is produced and stored.
The most dangerous of Europe’s snakes are
representative of Viperidae family (vipers). Different
species (about 60) are found throughout Europe,
Asia and Africa. Examples are asp viper or Vipera
aspis (southwestern Europe), common European
viper or Vipera berus (southeastern Europe, including
Ukraine) and meadow viper or Vipera ursine
(Fig. 14.18) (steppes of Europe and Asia, including
Ukraine), blunt-nosed viper or Vipera lebetina (North
Africa, Middle East, India)
The length varies in different species from 60–
65 cm (European vipers) to 160 cm (blunt-nosed
viper). Head is broad, triangular and distinct from
neck. Most have some kind of zigzag dorsal pattern
down the entire length of their bodies and tails. The
head usually has distinctive dark V or X-shaped pattern on the back. Venom is produced in main venom
glands behind each eye. The fangs are movable and
turned to lie to the roof of mouth. This folding allows
vipers to have the longest fangs of all venomous
Fig. 14.17. Poisonous amphibians:
A – yellow poison frog (Phyllobates terribilis); B – Kokoe poison frog (Phyllobates
aurotaenia); C – green-and-black poison
dart frog (Dendrobatus auratus)
14.4. Poisonous organisms
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snakes. The hollow poison canal runs through
the fangs opening at the tip.
Poison has hemolytic action. Severity of affection depends on species. In case of European
vipers bite local symptoms include intense pain
and local swelling. Further symptoms may include hemorrhagic necrosis (the breakdown of
blood vessels) at the place of bite and in inner organs, sometimes cardiovascular failure and faints
are observed. In severe cases bite causes death
(1 % in case of common European viper bite and
10% in case of blunt-nosed viper bite).
Famous subfamily of Viperids is pit vipers or
crotaline snakes found in Eurasia and in North
and South America. They are distinguished by Fig. 14.18. Meadow viper (Vipera ursine)
the presence of a heat-sensing pit organ located
between the eye and the nostril on either side of
the head. Representatives of pit vipers are rattlesnakes, lanceheads (endemic to Central and
South America) and Asian pit vipers. Rattlesnakes
(genus Crotalus) range in size from 50–60 cm to
over 150 cm. Most species are easily recognized
by their characteristic rattle on the end of their
tail (Fig. 14.19). Venom is hemotoxic and neurotoxic. Common symptoms include swelling,
severe pain, tingling, weakness, anxiety, nausea
and vomiting, hemorrhaging, perspiration, and
eventually heart failure and death.
First Aid for bites by Viperid snakes is to keep
person calm and at rest, remaining to keep
venom from spreading. The place of bite should
be kept below the level of the patient’s heart.
Wound should be covered with loose bandage.
Most traditional first aid measures are useless
and potentially dangerous (cauterization, incision, and suction by mouth). Patient must be Fig. 14.19. Rattlesnake (Crotalus durissus)
transported to the hospital as soon as possible
for antitoxic serum injection.
One of the most dangerous families of snakes is Elapidae family found in tropical and
sub-tropical regions around the world. Examples are King cobra (Ophiophagus hannah),
Egyptian cobra (Naja haje), Indian cobra (Naja naja) (Fig. 14.20), spitting cobra (Naja sputatrix), Dendroaspis sp. (mamba).
Chapter 14. Ecology. Biosphere as human environment. Poisonous organisms
Fig. 14.20. Indian cobra (Naja naja)
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Cobra snakes are recognizable by their wide hoods, and are able to spit their toxins. Size
of these snakes varies from 2 to 5,5 meters depending on species.
Cobras have several methods for delivering their venom to their prey. Some cobras
can spit their venom into a victim’s eyes, causing extreme pain and blindness. However,
the most common method of venom delivery is injection into a victim’s body through
their bite. The fangs are small and non-retractable with anterior groove for venom delivering. Venom is mostly neurotoxic. Ohanin, a protein component of the king cobra venom,
causes inhibition of locomotor activity and hyperalgesia (increased sensitivity to pain)
in mammals. Other components have cardiotoxic and cytotoxic effects. The ammount of
neurotoxin king cobra can deliver in a single bite is enough to kill an elephant or twenty
human beings. The toxin is immensely painful, and once it enters the blood stream, it can
cause human death within thirty minutes.
Black mamba (Dendroaspis polylepis) (Fig. 14.21) is a very dangerous African snake.
Black mambas are fast, nervous, and when threatened, highly aggressive. They have been
blamed for numerous human deaths. The adult snake is up to three meters long with olive,
brownish, gray, or sometimes khaki back skin color. Mamba got its name because of inky
black mouth. Poison is neurotoxic and cardiotoxic, causes initial headache, profuse perspiration and salivation, than collapse and death.
First Aid is same as in Viperid bite. Proper and immediate treatment with antitoxic serum
is critical to avoid death.
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Poisonous plants are the plants that produce toxins as a defense from consuming by
herbivores animals. Plant toxins (phytotoxins) include vast array of different chemicals like
alkaloids, glycosides, terpenoids, anthocyanins, phenols and other that either kill or retard
the development of the herbivores. According to the action phytotoxins are divided into
neurotoxic, hepatotoxic and nephrotoxic. Some irritates digestive tract, affect skin and
have teratogenic action. Same chemical can affect several organs simultaneously.
Examples of poisonous plants are given below.
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Fig. 14.21. Black Mamba (Dendroaspis polylepis)
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Aconite or wolfsbane (Aconitum napellus) belongs to the flowering plants (Angiosperms
or Magnoliophyta), family Ranunculaceae. The name wolfsbane comes from its use by ancient Greek shepherds who would tip there arrows in aconite to kill wolves. Aconite growths
throughout northern Europe and Asia and is possibly the most poisonous plant in Europe.
It is a perennial plant up to 1 meter tall with hairless stem and rounded leaves divided into
5 to 7 deeply lobed segments. The flowers are dark purple to bluish purple (Fig. 14.22).
All parts of the plant contain alkaloid aconitine. It is a potent neurotoxin that can causes
vomiting and diarrhea, irregular heartbeat and death from respiratory failure. Just touching
the plant can cause severe symptoms whilst ingesting often proves fatal. First aid: make a
proper assessment of airway, breathing, circulation and neurological status of the patient.
Symptomatic patients should be hospitalized for 24 hours.
Lily of the Valley (Convallaria majalis)
(Fig. 14.23) belongs to the flowering plants
(Angiosperms or Magnoliophyta), family Asparagaceae.
It’s a perennial flower that grows in
the valley (thus its name). It is native of
Europe but can be found throughout the
cool temeperature Northen hemispere.
The stems grow to 15–30 cm tall, with one
or two leaves. The flowering plants have a
raceme of 5–15 bell-shaped white flowers on the stem apex. All parts of the plant
are toxic, containing more than 30 different glycosids with heart-arresting action
and saponins. Some clinical symptoms of
ingesting this plant include nausea, vomiting, diarrhea, irregular heartbeat and pulse,
mental confusion. In extreme cases, it can
lead to coma and death. In medicine lily of
the valley is effectively used for the treatment of some cardiovascular diseases.
Fig. 14.22. Aconite sp. (Aconitum soongaricum)
424
Chapter 14. Ecology. Biosphere as human environment. Poisonous organisms
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Oleander (Nerium oleander) belongs to the flowering plants (Angiosperms or Magnoliophyta), family
Apocynaceae (Fig. 14.24). It is widely cultivated as a garden tree all over the world. Oleander is an evergreen
small tree 2 to 6 m tall, with erect stems. The leaves are
narrow, dark-green and are situated usually in groups
of three. The flowers are tubular with five lobes, usually red or pink and grow in clusters at the end of each
branch. The fruit is a long narrow capsule 5–23 cm long,
which splits along one side to release numerous seeds.
All parts of the oleander plant are toxic and contain
cardiac glycosides (oleandrin, neriine) and saponins. Ingestion of this plant can cause nausea and vomiting,
excess salivation, abdominal pain, diarrhea, irregular
heart rate, tremors or shaking of the muscles, seizures,
collapse, and even coma that can lead to death. Oleandrin is used for treating of cardiac diseases.
Water hemlock (Cicuta maculata) (Fig. 14.25) beFig. 14.23. Lily of the Valley
longs to the flowering plants (Angiosperms or Mag(Convallaria majalis)
noliophyta), family Apiaceae. It is native to temperate
regions of Europe and North America. It is perennial
plant with hollow stem 1,0–1,5 m long. The leaves are
large and double or triple-compound with alternative arrangement. The leaflets are lanceolate in shape
and serrate. Inflorescence resembles that of other
representatives of carrot family (umbrella shape). The
rootstocks contain a yellowish oily liquid which turns
reddish brown on exposure to air and emits a characteristic smell of raw parsnip, so water hemlock is sometimes confused with edible parsnips or celery. All parts
of the plant are neurotoxic as contain cicutoxin (unsaturated aliphatic alcohol). It mostly concentrated in
the rootstocks and stems. Occasional ingestion of the
plant causes nausea, vomiting, convulsions and death.
Poison hemlock (Conium maculatum) (Fig. 14.26)
belongs to the same family of plants as water hemlock.
It is biennial plant 90 cm to 2 m in length. It is similar
Fig. 14.24. Oleander (Nerium oleander)
with appearance to water hemlock. It got name “maculatum’ or spotted as is usually spotted or streaked with red or purple on the lower half of
the stem. All plant parts are poisonous containing alkaloid coniine. Occasional ingestion of
the plant causes headache, nausea, vomiting, paralyses (toxin blocks neuromuscular transmission), respiratory dysfunction and death. It also has toxic effect on the kidneys.
14.4. Poisonous organisms
425
Fig. 14.25. Northern Water Hemlock
(Cicuta virosa)
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Poisons produced by fungi are called mycotoxins. Examples of disease causing mycotoxins
produced by microfungi are ergot alkaloids and
aflatoxin. Ergotamine is produced in the sclerotia of ergot fungus (genus Claviceps) (Fig. 14.27),
which are common parasites of various cereals (wheat, maize and other herbs). Consuming
of bread baked from contaminated flour causes
ergotism (St. Anthony’s fire). It manifests in two
forms: gangrenous and convulsive. Gangrenous
form is caused by abnormal blood supply to the
extremities due to vasoconstriction. Fingers and
toes are mostly affected. Convulsive form is a result of ergotamine neurotoxic effect and manifests
as headache, painful seizers and psychosis. Ergot
alkaloids are used in medicine as pharmaceuticals.
Aflatoxins are produced by mold fungi of Aspergillus species. These are saprotrophic species
that colonize peanuts, maize, and pistachios during gather, transit and storage of harvest. Aflatoxin
B1 produced by Aspergillus flavus is the most potent natural carcinogen that causes liver cancer if
consumed with food.
Mushrooms regularly cause people poisoning.
It is a seasonal phenomenon, associated with the
mass gathering of mushrooms, usually in summer
and autumn. It can be caused by toxins produced
by fungi or accumulation of environmental toxic
substances if mushrooms were gathered near the
highway, the industrial enterprises and agricultural lands on which chemicals are used. The most famous example of poisonous mushrooms is death
cap (Amanita phalloides) of phylum Basidiomycota
(Fig. 14.28).
A. phalloides forms ectomycorrhizas with various broadleaved trees. It is common for Europe,
northern Africa and west Asia. In some cases the
death cap has been introduced to new regions
with the cultivation of non-native species of oak,
chestnut, and pine. The large fruiting bodies
D
Poisonous Fungi
Fig. 14.26. Poison hemlock (Conium maculatum)
Spike of Triticum sp.
Fig. 14.27. Sclerotia of
Claviceps purpurea
TE
Sclerotium
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Chapter 14. Ecology. Biosphere as human environment. Poisonous organisms
Fig. 14.28. Death cap
(Amanita phalloides)
IC
426
Fig. 14.29. Fly agaric or fly
amanita (Amanita muscaris)
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(mushrooms) appear in summer and autumn; the caps are generally greenish in colour,
with a white stipe and gills.
It contains two groups of peptide toxins – the amatoxins and phallotoxins. The main
amatoxin – α-amanitin inhibits RNA-polymerase II that arrest synthesis of mRNA (transcription) thus synthesis of essential proteins that kills cells. Mostly liver and kidneys are affected. Phallotoxins have toxic effect on liver cells.
If a person consumes a death cap by accident, symptoms do not manifest immediately.
Symptoms are delayed but severe affection of internal organs at this period takes place.
The first symptoms resolve two to three days after the ingestion. They include abdominal
pain, diarrhea and vomiting, later hypotension, tachycardia and jaundice develop. Coma
due to fulminant liver failure and accumulation of normally liver-removed substances ends
with death in six to sixteen days after the poisoning.
Another well-known poisonous mushroom is fly agaric or fly amanita (Amanita muscaris (Fig. 14.29) of phylum Basidiomycota. It is common throughout the temperate and
boreal regions of the Northern Hemisphere. Fly agaric has red cap with yellow to yellowish-white warts. Amanita muscaris contains several toxins one of which, muscimol, is psychoactive. In case of the mushroom consumtion toxic effect appears in 20 to 90 minutes.
Manifestations vary and include nausea, low blood pressure, salivation, sweating, loss of
equilibrium and mood changes. In severe cases delirium develops.
Medical aid. In most of cases consuming of poisonous plants and mushrooms require
immediate specialized medical aid and is fatal without treatment.
14.4. Poisonous organisms
427
TASKS & QUESTIONS
D
`` MULTIPLE CHOICE QUESTIONS (Choose one correct answer):
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EC
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IC
TE
1. A male has straight black hair and overhanging skin fold of superior eyelid–epicanthus. What race does he most probably represent?
A. Mongoloid
C. Europid
E. Ethiopian
B. Negroid
D. Australoid
2. For human it is hard to stay at the altitude of over 7,000 meters above sea level without oxygen tanks. What is the limiting factor for surviving in this case?
A. Level of ultraviolet irradiation
D. Temperature
B. Partial pressure of oxygen in the air
E. Gravity
C. Humidity level
3. What physiological changes will be observed in habitants of the high land?
A. Increasing of the hemoglobin level
B. Increasing of the leukocytes number
C. Decreasing of the leukocytes number
D. Decrease heart rate
E. Increased diameter of the blood vessels
4. The human population with such characteristics as elongated body, reduced muscle
volume, long limbs, slim chest, increased sweating, decreased level of metabolism
and fat production. To which adaptive types this population belongs to?
C. Desert
E. Intermediate
A. Tropical
B. Arctic
D. Mountain
5. After arriving in Pamir researchers from Australia have complained of nervous disorders, loss of appetite, weakness for several months. What process has been disrupted
in extreme conditions?
C. Tachyphylaxis
E. Reparation
A. Adaptation
B. Tolerance
D. Stress
6. Ability of organisms to produce antibiotics and phytoncides is an example of:
A. Neutralism
C. Symbiosis
E. Allelopathy
B. Predation
D. Competition
7. Adaptation to high rate of life, liability of mental reactions, tolerance to stress is characteristic to adaptive ecological type of humans:
A. Arid
C. Arctic
E. Urban
B. Tropical
D. Temperate climate
8. Formation of different adaptive ecological human types reflects the selection:
A. Artificial
C. Stabilizing
E. Sexual
B. Disruptive
D. Driving
428
Chapter 14. Ecology. Biosphere as human environment. Poisonous organisms
Death cap
Water hemlock
Meadow viper
D
9. The most potent natural carcinogen aflatoxin B is produced by:
A. Fungi of Aspergillus
B. Ergot fungus
D.
species
C. Fly agaric
E.
10. Passively poisonous is:
A. Honey bee
C. Lion fish
E.
B. Tiger centipede
D. Salamandra
11. Rattle snakes are identified by the:
A. Rattle sound
C. Big eyes
E.
B. Black body
D. Long body
12. King cobra is found in:
A. India
C. Europe
E.
B. Japan
D. Africa
13. Black mamba’s back skin color is:
A. Red
C. Black
E.
B. Brownish
D. White
TE
Shock sound
Arabia
IC
Yellow
`` FILL IN THE BLANKS:
TR
1. Any ecological factor less than minimum or more than maximum is called
___________.
2. ________________ are animals whose body temperature varies considerably depending on ___________________.
3. A natural association of populations of different species inhabiting a common environment is called ________________.
4. Modern state of biosphere is termed as _______________.
5. Main types of human constitution according to reactions towards new extreme conditions are ___________, __________, ___________.
EC
`` TRUE OR FALSE:
R
1. Abiotic factors are the factors of animate nature.
True
False
2. The zone below the critical minimum and above the critical maximum of environmental
factor is zone of intolerance.
True
False
3. Neutralism is type of intraspecific interaction when neither population directly affects
other ones.
True
False
4. In ecosystem carnivores and parasites occupy the first trophic level.
True
False
5. Biomass and energy in ecosystem increases at each higher trophic level.
True
False
6. Fungi and plants are poisonous and animals can be poisonous or venomous.
True
False
429
References
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EC
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IC
TE
D
1. Медична біологія : підручник / за ред. В. П. Пішака, Ю. І. Бажори. – Вид. 3-тє. – Вінниця
: Нова Книга, 2017. – 608 с. : іл.
2. Медична біологія : навч. посібник до практичних занять / Ю. І. Бажора, Н. М. Гламаздіна, М. М. Чеснокова, В. В. Ніколаєвський. – Одеса: Одес. держ. мед ун-т, 2006. – 352 с. –
Мова англ.
3. Мушкамбаров Н. Н. Молекулярная биология : учебное пособие / Н. Н. Мушкамбаров,
С. Л. Кузнецов. – М. : «Медицинское информационное агентство», 2003. – 544 с. : ил.
4. Биология : ученик : в 2 т. / под. ред. В. Н. Ярыгина. – М. : ГЭОТАР-Медиа, 2015. – Т. 1. –
736 с. : ил.
5. Биология : ученик : в 2 т. / под. ред. В. Н. Ярыгина. – М. : ГЭОТАР-Медиа, 2015. – Т. 2. –
728 с. : ил.
6. Молекулярна біологія : підручник / А. В. Сиволоб. – К. : Видавничополіграфічний
центр “Київський університет”, 2008. – 384 с.
7. Основи медичної паразитології: Навч. посібник до практ. занять для студентів І курсу
/ Ю. І. Бажора, Л. Г. Кириченко, А. В. Шевеленкова та ін. – Одеса: Одес. держ. мед. ун-т,
2001. – 175 с.
8. Наследственные болезни : национальное руководство / под. ред. Н. П. Бочкова,
Е. К. Гинтера, В. П. Пузырева. – М. : ГОЭТАР-Медиа, 2013. – 936 с.
9. Медицинская паразитология. Атлас / Под ред. Ю. И. Бажоры. – Одесса: ОГМУ, 2001. –
110 с.
10. Emery’s Elements of medical genetics. 15th ed. / Peter Turnpenny, Sian Ellard. – Elsevier,
2017. – 400 pp.
11. Young Ian. D. Medical genetics. – 2nd ed. – Oxford university press, 2010. – 304 pp.
12. Vogel and Motulsky’s human genetics. Problems and approaches / M. R. Speicher, S. E. Antonarakis, F. G. Motulsky. 4th addition. – Springer, 2010. – 981 pp.
13. OMIM (Online Mendelian Inheritance in Man) – An Online Catalog of Human Genes and
Genetic Disorders http://omim.org/
14. Паразитарные болезни человека: руководство для врачей / под ред. В. П. Сергеева. –
СПб : «Издательство Фолиант», 2006. – 592 с. : ил.
15. Human parasitology / Bruton J. Bogitsh, Clint E. Carter. – 4th ed. – Elsevier, 2013. – 430 pp.
16. Markell and Voge’s Medical parasitology / David. T. John, William A. Petri. – 9th ed. – Elsevier,
2017. – 463 pp.
17. Chiodini P. L. Atlas of Medical Helmintology and Protozoology 4th ed. – Churchill Livingstone, 2003. – 87 pp.
18. Langman’s medical embryology / T. W. Salder. – 13th ed. – Wolter Kluwer Health, 2015. –
423 pp.
19. Before we are born : Essentials of embryology and birth defects / Keith L. Moore, T. V. N.
Persaud, Mark G. Torchia. – 8th ed. – Elsevier, 2013. – 348 pp.
20. Medical genetics/ Lynn B.Jorde, John C.Carey, Michael J. Bamshad. – 4th ed. – Elsevier,
2010. – 368 pp.
21. Campbell biology / Lisa Urry, Michael Cain, Steven Wasserman, Peter Minorsky, Jane
Reece. – 11th ed. – Hoboken : Pearson Higher Education, 2016.
430
KEY ANSWERS
MCQ: 1–A; 2–E; 3–A; 4–C; 5–D; 6–B; 7–C; 8–D; 9–C; 10–D; 11–B.
Fill in the blanks: 1 – 2, 1; 2 – O, C, H, N; 3 – skeleton.
TE
True or false: False, False, True, True.
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Chapter 1
Chapter 2
MCQ: 1–C; 2–E; 3–C; 4–A; 5–E; 6–B; 7–C; 8–D; 9–A; 10–D; 11–C; 12–C.
6 – nucleus;
7 – plasmids;
8 – Archaebacteria and Eubacteria;
9 – nucleoid.
IC
Fill in the blanks:
1 – virion;
2 – prions;
3 – viroids;
4 – 30;
5 – R. Virchov;
TR
True or false: True, True, False, True, False, True.
Chapter 3
MCQ: 1–B; 2–E; 3–D; 4–C; 5–E; 6–E; 7–D; 8–E; 9–A; 10–A; 11–E; 12–A.
EC
Fill in the blanks:
1 – nucleus and membranous organelles;
6 – mitochondria, oxidation;
2 – fluid-mosaic model;
7 – histone and DNA;
3 – phospholipids, cholesterol and proteins; 8 – sister chromatids, centromere or primary
4 – facilitated;
constriction;
5 – primary, digestive, phagolysosome or
9 – acrocentric, rRNA, nucleolar organizer.
secondary lysosome;
True or false: False, False, True, True, False, True.
Chapter 4
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MCQ: 1–D; 2–C; 3–D; 4–B; 5–A; 6–B; 7–E; 8–C; 9–D; 10–E; 11–A; 12–B; 13–D; 14–A; 15–C;
16–B; 17–B.
Fill in the blanks:
1 – hydrogen, complementarity principle;
2 – leading, lagging, Okazaki;
3 – sn RNA;
4 – ribosomes, initiation, elongation, termination;
5 – 13, 18, 21.
14.4. Poisonous organisms
431
True or false: False, True, True, True, False.
Chapter 5
D
MCQ: 1–B; 2–A;3–E; 4–E; 5–C; 6–A; 7–B; 8–C; 9–E; 10–C; 11–A; 12–B; 13–B; 14–A; 15–A;
16–C.
Chapter 6
IC
TE
Fill in the blanks:
1 – neurons, cardiomyocytes, cells of strifactor;
ated muscles;
6 – phosphorilation;
2 – HeLa, cervical;
7 – slow down cell division;
3 – endomitosis;
8 – haploid, secondary oocyte, polar body;
4 – caspases;
9 – diploid, 46, zygote;
5 – insulin-like-growth factors, platelet-de- 10 – identical, reproductive, therapeutic.
rived growth factor, epidermal growth
True or false: False, False, True, True, False, True.
MCQ: 1–C; 2–A; 3–D; 4–B; 5–C; 6–C; 7–A; 8–C; 9–A; 10–A; 11–A; 12–B; 13–C; 14–D; 15–D;
16–C; 17–B; 18–C;
EC
TR
Fill in the blanks:
1 – 266, 38;
6 – ectomorphic (asthenic), long, low, active;
2 – human chorionic gonadotrophin (hCG); 7 – wear-and-tear theory;
3 – neurulation, neurula;
8 – regeneration;
4 – fetus;
9 – chronological or passport.
5 – placenta;
True or false: True, False, False, False, True, False, True, False.
Chapter 7
MCQ: 1–A; 2–D; 3–A; 4–B; 5–D; 6–B; 7–C; 8–C; 9–A; 10–C; 11–A; 12–D; 13–A; 14–D; 15–D;
16–A; 17–B; 18–C; 19–A; 20–A; 21–E; 22–A; 23–A; 24–A; 25–B; 26–B; 27–A.
R
Fill in the blanks:
1 – alternative traits, alleles;
6 – purity of gametes, do not, only one;
2 – lethal;
7 – innate, adaptive;
3 – the first filial generation, filia;
8 – criss-cross inheritance;
4 – independent assortment, 9:3:3:1;
9 – complete;
5 – penetrance;
10 – holandric.
True or false: True, True, False, True, True, True, False.
Chapter 8
432
KEY ANSWERS Ecology. Biosphere as human environment. Poisonous organisms...
MCQ: 1–C; 2–A; 3–A; 4–A; 5–A; 6–A; 7–B; 8–A; 9–C; 10–C; 11–A; 12–B; 13–B; 14–E; 15–D;
16–C; 17–D; 18–C; 19–A; 20–B.
TE
D
Fill in the blanks:
1 – modifications;
4 – non-disjunction, all, two sperms;
2 – mass, modifications;
5 – Philadelphia, reciprocal, 22;
3 – they are inheritable, during
6 – carcinogens;
gametogenesis;
7 – β-carotene, vitamin C, dosage.
True or false: False, True, True, False, False, True.
Chapter 9
TR
IC
MCQ
1–E; 2–C; 3–B; 4–D; 5–C; 6–A; 7–D; 8–A; 9–A; 10–B; 11–C; 12–B; 13–E; 14–E; 15–D; 16–E; 17–E;
18–A; 19–D; 20–E; 21–D; 22–E; 23–D.
Fill in the blanks:
5 – X-inactivation center, long arm, X- chro1 – XAY, XAXA, XAXa;
2 – mitochondrial;
mosome;
3 – 40 to 60 %, 4 to 18 %;
6 – denaturation, annealing, extension;
4 – microdeletions, FISH;
7 – isolate, over 90 %.
True or false: False, True, False, False, True, False, True.
Chapter 10
MCQ: 1–A; 2–C; 3–C; 4–C; 5–A; 6–A; 7–E; 8–D; 9–A; 10–C; 11–C; 12–C; 13–B; 14–A; 15–C;
16–A; 17–B; 18–A; 19–C; 20–A; 21–B; 22–A; 23–C; 24–B; 25–E; 26–A; 27–A; 28–C; 29–E;
30–C; 31–C; 32–E; 33–D.
EC
Fill in the blanks:
1 – mutualism;
2 – facultative;
3 – monoxenous;
4 – amebiasis, giardiasis, balantidiasis;
R
5 – Ameboids (Sarcodina), Flagellates, Sporozoans, Ciliates;
6 – epithelium of small intestine;
7 – Tryponosoma and Leishmania;
8 – hypnozoites, vivax, ovale.
True or false: False, False, True, False, True, False, False.
Chapter 11
MCQ: 1–D; 2–B; 3–D; 4–C; 5–B; 6–D; 7–B; 8–C; 9–A; 10–E; 11–E; 12–D; 13–D; 14–C; 15–D
16–E; 17–A; 18–D; 19–E; 20–C; 21–E; 22–E; 23–E; 24–C; 25–B; 26–A; 27–B; 28–A; 29–A;
30–C; 31–B; 32–D; 33–C.
Fill in the blanks:
14.4. Poisonous organisms
433
5 – opistorchiasis, diphyllobothriasis, chlonorchiasis;
6 – armed tapeworm, cysticercus;
7 – broadtapeworm, fish;
8 – hematophage, small intestine;
9 – small intestine, muscles;
10 – ancylostomides, larvoscopy.
True or false: False, True, False, True, True, False, True, True, True.
TE
D
1 – biohelminths;
2 – sporocyst, redia, cercaria;
3 – ants, metacercaria;
4 – water, cercaria;
Chapter 12
MCQ: 1–A; 2–E; 3–A; 4–A; 5–B; 6–A; 7–B; 8–E; 9–D; 10–B; 11–D; 12–B; 13–E; 14–A; 15–D;
16–C; 17–B; 18–B; 19–E; 20–B; 21–D; 22–A; 23–C; 24–A; 25–B.
TR
IC
Fill in the blanks:
7 – parallel, Japanese encephalitis, tu1 – mixocoel, hemolymph;
2 – venomous, inflammation;
laremia, filariasis;
3 – fused, idiosoma;
8 – Myiasis, tissues;
4 – preabdomen, postabdomen;
9 – humanus humanus, ectoparasite, folds
5 – intraskin, the contact with the patient,
of underwear;
clothes and bed linen;
10 – pediculosis capitis, epidemic typhus,
6 – supraesophageal, “brain” (“encephalon”);
lice-borne relapsing fever.
True or false: True, False, True, True, False, False, False, True, False, False.
Chapter 13
MCQ: 1–A; 2–C; 3–B; 4–D; 5–E; 6–C; 7–E; 8–C; 9–D; 10–E; 11–B; 12–C; 13–E; 14–E; 15–A.
EC
Fill in the blanks:
1 – general degeneration;
2 – sharks, dolphins;
3 – Ernst Haeckel in 1866;
True or false: True, False, False, True, True.
4 – extinction of some species and active
evolution of other ones.
R
Chapter 14
MCQ: 1–A; 2–B; 3–A; 4–A; 5–A; 6–E; 7–E; 8–B; 9–A; 10–D; 11–A; 12–A; 13–B.
Fill in the blanks:
1 – limiting;
4 – noosphere;
2 – poikilothermic, external temperature;
5 – sprinter, stayer, mixt.
3 – biocenosis;
True or false: False, True, False, False, False, True.
434
Index
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EC
D
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IC
Acanthamoeba (Hartmanella) Culbertsoni . . . . . . . . .
Acceleration . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
Acclimatization . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
Acetylation of histone proteins . . . . . . . . . . . . . . . . . . .
Aconite or wolfsbane (Aconitum napellus) . . . . . . . .
Acrosomal reaction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
Acrosome . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
Activation of amino acids . . . . . . . . . . . . . . . . . . . . . . . .
Active transport . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
Adaptation . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
Adaptive immunity (see Immunity) . . . . . . . . . . . . . . .
Adaptive radiation . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
Adenin . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
Adaptive type (see ecotypes) . . . . . . . . . . . . . . . . . . . . .
Adolescaria . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
Aerobic organisms . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
Aflatoxins . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
Age
- chronological (passport) . . . . . . . . . . . . . . . . . . . . . .
- biological . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
Aging . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
Aging theory . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
Allantois . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
Allele
- dominant . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
- lethal . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
- multiple . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
- recessive . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
Allelopathy . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
Allogenesis . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
Allomorphosis . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
Alternative traits . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
Alveococcosis . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
Alveococcus multilocularis
(Echinococcus multilocularis)
- geographical distribution . . . . . . . . . . . . . . . . . . . .
- location . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
- morphology . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
- life cycle . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
- pathogenecity . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
- diagnosis . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
- prophylaxis . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
American hookworm (see Necator americanus) . . . .
Amino acids . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
Amitosis . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
Amniocentesis . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
Amnion . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
Amniota . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
Amoeba dysenteric (see Entamoeba histolytica) . . .
Amoebiasis
- extraintestinal . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
- intestinal . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
Amoebic abscesses (see extraintestinal
amoebiasis) . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
Amoeboid protozoa (Sarcodina) . . . . . . . . . . . . . . . . . .
Amphibians . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
Anabolism (see Assimilation) . . . . . . . . . . . . . . . . . . . . .
Anaerobic organisms . . . . . . . . . . . . . . . . . . . . . . . . . . . .
Analogous organs . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
Anamniota . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
Anaphase of mitosis . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
Ancylostoma duodenale (Hookworm)
- geographical distribution . . . . . . . . . . . . . . . . . . . . .
- morphology . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
- location . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
- life cycle . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
- pathogenecity . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
- diagnosis . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
- prophylaxis . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
Androgens . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
Androgen receptors . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
Anemia sickle-cell . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
Aneuploidy . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
Anisogamy . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
Anopheles mosquitoe . . . . . . . . . . . . . . . . . . . . . . . . . . . .
Antibiosis . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
Antimutagens . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
Anthroponosis . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
Anthropozoonosis . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
Antibodies . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
Anticodon . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
Antigens . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
Apicomplexa (Sporozoa) . . . . . . . . . . . . . . . . . . . . . . . . . .
Apoptosis (see Cell Death Apoptosis) . . . . . . . . . . . . .
Arachnoentomology . . . . . . . . . . . . . . . . . . . . . . . . . . . .
Area . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
Arm of chromosome (see Chromosome arm) . . . . .
Arogenesis . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
Aromorphosis . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
Ascaris lumbricoides
- geographical distribution . . . . . . . . . . . . . . . . . . . .
- morphology . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
- location . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
- life cycle . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
TE
A
14.4. Poisonous organisms
B
D
TE
C
Capacitation . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
Capping . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
Caspases . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
Carbohydrates . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
Catabolism (see Dissimilation) . . . . . . . . . . . . . . . . . . . .
Catagenesis . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
Cell
- cycle (mitotic) . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
- cycle checkpoints . . . . . . . . . . . . . . . . . . . . . . . . . . . .
- death . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
- apoptosis . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
- necrosis . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
- eukaryotic . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
- germ . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
- inclusions . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
- line . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
- metabolism . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
- nucleus . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
- organelles . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
- reproduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
- somatic . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
- structure . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
- theory . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
- prokaryotic . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
Cell membrane
- chemical components . . . . . . . . . . . . . . . . . . . . . . . .
- structure . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
Cell-mediated immunity (see Immunity) . . . . . . . . .
Centipedes . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
EC
TR
B-lymphocyte . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
Bacteria . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
Balantidium coli
- geographical distribution . . . . . . . . . . . . . . . . . . . .
- morphology . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
- location . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
- life cycle . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
- pathogenecity . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
- diagnosis . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
- prophylaxis . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
Barr bodies detection (see sex chromatin
detection) . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
Beef tapeworm or Unarmed tapeworm
(see Taeniarhynchus saginatus) . . . . . . . . . . . . . . . . . . .
Biocenosis . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
Biogenetic low . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
Biogeocenosis (see Ecosystem) . . . . . . . . . . . . . . . . . . .
Biohelminths . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
Biological progress . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
Biological regress . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
Biology
- medical . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
- molecular . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
Biomass . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
Biological rhythms
- circadian rhythms . . . . . . . . . . . . . . . . . . . . . . . . . . . .
- ultradian rhythms . . . . . . . . . . . . . . . . . . . . . . . . . . . .
- infradian rhythms . . . . . . . . . . . . . . . . . . . . . . . . . . . .
- adaptive . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
- circannual . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
R
Biosphere . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
Biotope . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
Blastocoel . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
Blastomeres . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
Blastopore . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
Blastula . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
Blastulation . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
Blood groups . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
Body louse (see Pediculus humanus humanus) . . . .
Bombay phenomenon . . . . . . . . . . . . . . . . . . . . . . . . . . .
Bottleneck effect . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
Box Jellyfish or sea wasp (Chironex Fleckeri) . . . . . . .
Broad or Fish tapeworm
(see Diphyllobothrium latum) . . . . . . . . . . . . . . . . . . . . .
Brugia malayi . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
Budding . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
Bug (Heteroptera)
- bed (Cimex lectularius) . . . . . . . . . . . . . . . . . . . . . . . .
- kissing (see Triatomine bug) . . . . . . . . . . . . . . . . . .
IC
- pathogenecity . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
- diagnosis . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
- prophylaxis . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
Ascariasis . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
Aspergillus species . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
Assimilation (Anabolism) . . . . . . . . . . . . . . . . . . . . . . . . .
Atavism . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
Atmosphere . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
Autoinvasion . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
Autoreinfection . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
Autosomal-recessive inheritance
(see inheritance autosomal-recessive) . . . . . . . . . . . .
Autosomal-dominant inheritance
(see inheritance autosomal-dominant) . . . . . . . . . . .
Autosomes . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
Autotrophs . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
Aves . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
Axostyle . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
435
Index Ecology. Biosphere as human environment. Poisonous organisms...
D
TR
EC
R
Commensalism . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
Compensatory hypertrophy . . . . . . . . . . . . . . . . . . . . .
Competition . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
Complementary gene interaction . . . . . . . . . . . . . . . .
Complementary principle . . . . . . . . . . . . . . . . . . . . . . . .
Complex Golgi (see Apparatus Golgi) . . . . . . . . . . . . .
Concordance (coefficient) . . . . . . . . . . . . . . . . . . . . . . . .
Concordant twins . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
Congenital defects
- hereditary . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
- multifactorial . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
- ontophylogenic . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
- teratogenic . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
Conjugation . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
Constitution type
- Ectomorphic (Asthenic) . . . . . . . . . . . . . . . . . . . . . . .
- Endomorphic (Hypersthenic) . . . . . . . . . . . . . . . . .
- Mesomorphic (Normosthenic) . . . . . . . . . . . . . . . .
Consumers primary
- secondary . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
- tertiary . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
Convergence . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
Copulation (see Syngamy) . . . . . . . . . . . . . . . . . . . . . . . .
Coracidium . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
Cortical reaction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
Cristae . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
Critical periods of embryogenesis
- of postnatal period . . . . . . . . . . . . . . . . . . . . . . . . . . .
Crossing-over . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
Crustaceans . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
Culex mosquitoe . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
Culicidae (Mosquitoes) genera . . . . . . . . . . . . . . . . . . . .
- Anopheles . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
- Culex . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
- Aedes . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
Cuticle . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
Cyclin . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
Cyclin-dependent kinase . . . . . . . . . . . . . . . . . . . . . . . .
Cyclostomata . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
Cysticercoid . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
Cysticercus . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
Cytokinesis . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
Cytosine . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
Cytogenetic methods . . . . . . . . . . . . . . . . . . . . . . . . . . . .
Cytoplasm . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
Cytoskeleton . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
IC
Centromere (primary constriction) . . . . . . . . . . . . . . .
Centrosome (Centrioles) . . . . . . . . . . . . . . . . . . . . . . . . .
Cercariae . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
Cestodes (Tapeworms) . . . . . . . . . . . . . . . . . . . . . . . . . . .
Chagas’ disease (Trypanosomiasis American) . . . . . .
Chargaff’s rule . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
Checkpoints of cell cycle (see Cell cycle
checkpoints) . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
Chelicerates (arachnids) . . . . . . . . . . . . . . . . . . . . . . . . . .
Chemical compounds
- inorganic . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
- organic . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
Chemical elements
- macroelements . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
- minor elements . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
- organic elements . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
Chorion . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
Chromatid . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
Chromatin . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
Chromosomal aberrations . . . . . . . . . . . . . . . . . . . . . . . .
Chromosome mapping (see Map chromosome) . . .
Chromosome theory of heredity . . . . . . . . . . . . . . . . .
Chromosome
- arm . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
- centromere . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
- chemical composition . . . . . . . . . . . . . . . . . . . . . . . .
- giant . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
- map . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
- satellite . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
- secondary constriction . . . . . . . . . . . . . . . . . . . . . . .
- shape . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
Chronobiology . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
Ciliata . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
Cimex lectularius (bug bed) . . . . . . . . . . . . . . . . . . . . . . .
Cleavage . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
Clone . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
Cloning . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
Clonorchis sinensis (Chinese liver fluke) . . . . . . . . . . . .
Co-mutagens . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
Cobra
- King (Ophiophagus Hannah) . . . . . . . . . . . . . . . . . .
- Egyptian (Naja Haje) . . . . . . . . . . . . . . . . . . . . . . . . . .
- Indian (Naja naja) . . . . . . . . . . . . . . . . . . . . . . . . . . . .
- spitting (Naja sputatrix) . . . . . . . . . . . . . . . . . . . . . . .
Codominance . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
Codon (triplet)
- synonyms . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
- stop (nonsense) . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
- start (initiating) . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
Coefficient of heredity
- of environment influence . . . . . . . . . . . . . . . . . . . . .
TE
436
D
Darwinism . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
Death
14.4. Poisonous organisms
D
TE
TR
EC
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DNA (see Deoxyribonucleic acid)
- diagnosis (analysis) . . . . . . . . . . . . . . . . . . . . . . . . . . .
- denature . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
- ligase . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
- microarrays . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
- of human sequences (see Sequences
of human DNA) . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
- polymerase . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
- repair . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
- replication . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
- sequencing . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
DNA strand
- template . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
- coding (sense) . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
- lagging . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
- leading . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
DNA testing (see DNA diagnosis)
Dog tick (see Ixodes ricinus) . . . . . . . . . . . . . . . . . . . . . .
Dominance
- incomplete . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
- complete . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
Dominant trait . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
Dracunculus medinensis (Guinea worm)
- geographical distribution . . . . . . . . . . . . . . . . . . . .
- location . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
- morphology . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
- life cycle . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
- pathogenecity . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
- diagnosis . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
- prophylaxis . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
Duplication . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
Dysentery (see amebiasis) . . . . . . . . . . . . . . . . . . . . . . . .
Dwarf tapeworm (see Hymenolepis nana) . . . . . . . . .
IC
- biological . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
- apparent (clinical) . . . . . . . . . . . . . . . . . . . . . . . . . . . .
Death cap (Amanita phalloides) . . . . . . . . . . . . . . . . . . .
Decomposers . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
Deletion . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
Demodex folliculorum (see follicle mite) . . . . . . . . . . .
Denaturation (melting) . . . . . . . . . . . . . . . . . . . . . . . . . .
Deoxyribonucleic acid (DNA)
- double helix . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
- mitochondrial (see Mitochondrial DNA) . . . . . . .
Deoxyribonucleotide . . . . . . . . . . . . . . . . . . . . . . . . . . . .
Derma . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
Dermacentor pictus (see meadow tick) . . . . . . . . . . . .
Dermatoglyphics . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
Desynchronosis (circadian rhythm disorders) . . . . .
Determination . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
Development
- direct . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
- Indirect . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
- Individual (see Ontogenesis) . . . . . . . . . . . . . . . . . .
- embryonic (see Ontogenesis) . . . . . . . . . . . . . . . . .
- postembryonic (see Ontogenesis) . . . . . . . . . . . . .
Diakinesis . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
Dicrocoelium lanceatum (lancet fluke) . . . . . . . . . . . . .
Dictyotene phase . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
Diencephalon . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
Differential chromosome staining . . . . . . . . . . . . . . . .
Differentiation . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
Diffusion
- osmosis . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
- simple diffusion . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
- facilitated diffusion . . . . . . . . . . . . . . . . . . . . . . . . . . .
Dihybrid cross . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
Diphyllobothrium latum (fish or broad
tapeworm) . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
- geographical distribution . . . . . . . . . . . . . . . . . . . . .
- location . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
- morphology . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
- life cycle . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
- pathogenecity . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
- diagnosis . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
- prophylaxis . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
Diploid set (see diploid set of chromosomes) . . . . .
Diploid set of chromosomes . . . . . . . . . . . . . . . . . . . . .
Diptera . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
Diplotene (Diplonema) . . . . . . . . . . . . . . . . . . . . . . . . . .
Dirofilaria . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
Disaccharides . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
Discordant twins . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
Dissimilation (Catabolism) . . . . . . . . . . . . . . . . . . . . . . . .
Divergence . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
437
E
Echinococcus granulosus (hydatid worm)
- geographical distribution . . . . . . . . . . . . . . . . . . . .
- location . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
- morphology . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
- life cycle . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
- pathogenecity . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
- diagnosis . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
- prophylaxis . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
Echinococcus multilocularis (see Alveococcus
multilocularis) . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
Ecological factors
- abiotic . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
- biotic . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
- anthropogenic . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
- critical minimum zone . . . . . . . . . . . . . . . . . . . . . . . .
Index Ecology. Biosphere as human environment. Poisonous organisms...
D
TR
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R
- diagnosis . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
- prophylaxis . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
- gingivalis . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
- coli . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
Enterobius vermicularis (pinworm)
- geographical distribution . . . . . . . . . . . . . . . . . . . .
- morphology . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
- location . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
- life cycle . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
- pathogenecity . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
- diagnosis . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
- prophylaxis . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
Environment . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
Epidemic typhus . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
Epigenetic regulation . . . . . . . . . . . . . . . . . . . . . . . . . . . .
Epimorphosis . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
Epistasis . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
Euchromatin . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
Eukaryotes . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
Erythrocyte . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
Evolution
- Darwin . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
- Lamarck . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
- Synthetic theory . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
- of the Skin . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
- of the Skeleton . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
- of the Digestive System . . . . . . . . . . . . . . . . . . . . . . .
- of Respiratory system . . . . . . . . . . . . . . . . . . . . . . . . .
- of Circulatory System . . . . . . . . . . . . . . . . . . . . . . . . .
- of Nervous System . . . . . . . . . . . . . . . . . . . . . . . . . . . .
- of excretory and reproductive systems . . . . . . . .
Exocytosis . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
Exons . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
Expression of genes (see Gene expression) . . . . . . . .
Expressivity . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
IC
- critical maximum zone . . . . . . . . . . . . . . . . . . . . . . . .
- zone of tolerance . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
- optimal zone . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
- limiting factor . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
- ecological niche . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
Ecology . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
Ecosystem (biogeocenosis)
- natural . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
- agroecosystem . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
- urban . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
Ecotype (Adaptive type)
- arctic ecotype . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
- mounting ecotyp . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
- tropical ecotype . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
- arid ecotype . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
- of moderate climate . . . . . . . . . . . . . . . . . . . . . . . . . .
- urban . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
Ectoderm . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
Ectoparasite . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
Ectoplasm . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
Embryo . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
Embryoblast . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
Embryonic period (Embryogenesis) (see
Ontogenesis embryonic period) . . . . . . . . . . . . . . . . . .
Embryology . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
Embryonic induction . . . . . . . . . . . . . . . . . . . . . . . . . . . .
Encephalitis . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
Encystation . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
Endocytosis . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
Endoderm . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
Endodyogony (see Budding) . . . . . . . . . . . . . . . . . . . . .
Endomitosis . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
Endomorphosis . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
Endoparasite . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
Endoplasm . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
Endoplasmic reticulum
- smooth . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
- rough . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
Energy flow in a cell . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
Engineering
- gene (see gene engineering) . . . . . . . . . . . . . . . . . .
- cellular . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
Entamoeba histolytica
- cystic form . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
- magna form . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
- minuta form . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
- geographical distribution . . . . . . . . . . . . . . . . . . . .
- morphology . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
- location . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
- life cycle . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
- pathogenecity . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
TE
438
F
Fasciola Hepatica (see liver fluke) . . . . . . . . . . . . . . . . .
Fertilization . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
- in vitro (IVF) . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
Filariidae (Filariae) . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
FISH method (see Fluorescent In Situ
Hybridization) . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
Fish or broad tapeworm (see Diphyllobothrium
latum) . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
Fission . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
Flagellum . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
Flagellates . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
Flea
- human (Pulex irritans) . . . . . . . . . . . . . . . . . . . . . . . .
14.4. Poisonous organisms
D
TE
G
Gall bladder . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
Gametes . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
Gametocytes . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
Gametogenesis . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
Gametogony . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
Giardia Lamblia (see Lamblia intestinalis)
- geographical distribution . . . . . . . . . . . . . . . . . . . .
- location . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
- morphology . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
- life cycle . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
- pathogenecity . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
- diagnosis . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
- prophylaxis . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
Gastrula . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
Gastrulation . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
Gene (s)
- allelic . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
- drift . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
- linkage . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
- expression . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
- mosaicism . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
- regulatory . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
- structural . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
Gene engineering . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
Gene interactions
- allelic . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
- non-allelic . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
Genealogic method (Pedigree analysis) . . . . . . . . . . .
Genetics
- ecological . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
- human . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
- medical . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
- molecular . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
- population . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
Genetic
- analysis . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
- code . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
- counseling . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
TR
EC
R
- prophylaxis . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
Fluorescent In Situ Hybridization . . . . . . . . . . . . . . . . .
Fly agaric or fly amanita (Amanita muscaris) . . . . . . .
Follicle mite (see Demodex folliculorum) . . . . . . . . . . .
Folling’s test . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
Founder effect . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
Fragmentation . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
Frog poison yellow (Phyllobates terribilis) . . . . . . . . . .
- Kokoe (Phyllobates aurotaenia) . . . . . . . . . . . . . . . .
- dart green-and-black (Dendrobatus auratus) . . .
IC
- rat (Xenopsylla cheopis) . . . . . . . . . . . . . . . . . . . . . . .
Flies (Muscidae) . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
Fluid mosaic model . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
Flukes (Trematodes) . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
blood
- geographical distribution . . . . . . . . . . . . . . . . . . . .
- location . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
- morphology . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
- life cycle . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
- pathogenecity . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
- diagnosis . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
- prophylaxis . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
cat
- geographical distribution . . . . . . . . . . . . . . . . . . . .
- location . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
- morphology . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
- life cycle . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
- pathogenecity . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
- diagnosis . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
- prophylaxis . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
chinese liver
- geographical distribution . . . . . . . . . . . . . . . . . . . .
- location . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
- morphology . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
- life cycle . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
- pathogenecity . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
- diagnosis . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
- prophylaxis . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
lancet
- geographical distribution . . . . . . . . . . . . . . . . . . . .
- location . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
- morphology . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
- life cycle . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
- pathogenecity . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
- diagnosis . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
- prophylaxis . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
liver
- geographical distribution . . . . . . . . . . . . . . . . . . . .
- location . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
- morphology . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
- life cycle . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
- pathogenecity . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
- diagnosis . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
- prophylaxis . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
lung
- geographical distribution . . . . . . . . . . . . . . . . . . . .
- location . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
- morphology . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
- life cycle . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
- pathogenecity . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
- diagnosis . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
439
Index Ecology. Biosphere as human environment. Poisonous organisms...
D
Healthy carrier . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
Helminthology . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
Helminthoscopy . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
Hemlock Poison (Conium maculatum)
- Water (Cicuta maculata) . . . . . . . . . . . . . . . . . . . . . . .
Hemoglobin . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
Hematophages . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
Hemizygotic . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
Hemolymph . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
Hereditary disorders
- Chromosomal disorders . . . . . . . . . . . . . . . . . . . . . .
- Single gene disorders . . . . . . . . . . . . . . . . . . . . . . . .
- Multifactorial disorders . . . . . . . . . . . . . . . . . . . . . . .
Heterochromatin . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
Heterotrophs . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
Heredity . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
Hexapods (insects) . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
Histogenesis . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
Histones . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
HLA antigens (see human leukocyte
antigens) . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
Holandric . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
Homeostasis . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
Homeothermic animals . . . . . . . . . . . . . . . . . . . . . . . . . .
Homologous organs . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
Honey bee (Apis mellifera) . . . . . . . . . . . . . . . . . . . . . . . .
Hook worm (see Ancylostoma) . . . . . . . . . . . . . . . . . . . .
Hormones . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
Hornet giant (Vespa mandarinia) . . . . . . . . . . . . . . . . . .
Host
- definitive . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
- intermediate . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
- reservoir . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
- natural . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
- accidental . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
House fly (Musca domestica) . . . . . . . . . . . . . . . . . . . . . .
Human genetics peculiarities . . . . . . . . . . . . . . . . . . . . .
Human leukocyte antigens . . . . . . . . . . . . . . . . . . . . . . .
Humoral immunity (see Immunity humoral) . . . . . .
Hybrids . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
Hybridization . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
Hydatid worm (see Echinococcus granulosus) . . . . . .
hydatid cyst . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
Hydrosphere . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
Hymenolepis nana (Dwarf tapeworm)
- geographical distribution . . . . . . . . . . . . . . . . . . . .
- location . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
- morphology . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
- life cycle . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
- pathogenecity . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
- diagnosis . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
R
EC
TR
IC
- drift . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
- imprinting . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
- monitoring . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
- information . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
- map (see Map genetic) . . . . . . . . . . . . . . . . . . . . . . .
Genome
- Human Genome . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
- Human Genome Project . . . . . . . . . . . . . . . . . . . . . .
Genomic variability . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
Genotype
- heterozygous . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
- homozygous . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
Geriatrics . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
Gerontology . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
Geohelminths . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
Germ layers . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
Glycocalyx . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
Golgi apparatus (complex) . . . . . . . . . . . . . . . . . . . . . . .
Gonades . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
Grafting (Transplantation)
- Autografting (Autotransplantation) . . . . . . . . . . .
- Isografting (Isotransplantation) . . . . . . . . . . . . . . .
- Allografting (Allo- or
Homotransplantation) . . . . . . . . . . . . . . . . . . . . . . . .
- Xenografting (Xenotransplantation
or heterotransplantation) . . . . . . . . . . . . . . . . . . . . .
Grass puffer fish (Takifugu niphobles) . . . . . . . . . . . . . .
Growth
- isometric . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
- allometric . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
- limited or definite . . . . . . . . . . . . . . . . . . . . . . . . . . . .
- unlimited or indefinite . . . . . . . . . . . . . . . . . . . . . . . .
- periodic or discontinuous . . . . . . . . . . . . . . . . . . . . .
- accretionary . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
- appositional . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
- auxetic . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
- multiplicative . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
- curve . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
- regulation . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
Growth factors . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
Guanine . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
Guinea worm (see Dracunculus medinensis) . . . . . . .
TE
440
H
Habitat . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
Haploidy . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
Haploid
- set . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
- number . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
Head louse (Pediculus humanus capitis) . . . . . . . . . . .
14.4. Poisonous organisms
Lactose . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
Lagging strand (see DNA strand) . . . . . . . . . . . . . . . . .
Lamarck theory . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
Lamblia intestinalis (see Giardia Lamblia) . . . . . . . . . .
Lancelet . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
Larvae . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
Larva migrans . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
Larvocyst (see phynn) . . . . . . . . . . . . . . . . . . . . . . . . . . .
Larvoscopy methods . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
Latrodectus tredecimguttatus (see Karakurt or
steppe spider) . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
Law of dominance (First Mendel’s law)
- of homologous series of variation . . . . . . . . . . . . .
- independent assortment
(Third Mendel’s law) . . . . . . . . . . . . . . . . . . . . . . . . . .
- purity of gametes . . . . . . . . . . . . . . . . . . . . . . . . . . . .
- segregation (Second Mendel’s law) . . . . . . . . . . .
- biogenetic (Haeckel – Muller) . . . . . . . . . . . . . . . . .
- Hardy – Weinberg . . . . . . . . . . . . . . . . . . . . . . . . . . . .
- Mendel . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
Leading strand (see DNA strand) . . . . . . . . . . . . . . . . . .
Leishmania species . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
Agents of visceral leishmaniasis
- geographical distribution . . . . . . . . . . . . . . . . . . . .
- location . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
- morphology . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
- life cycle . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
- pathogenecity . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
- diagnosis . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
- prophylaxis . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
Agents of cutaneous leishmaniasis
- geographical distribution . . . . . . . . . . . . . . . . . . . .
- location . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
- morphology . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
- life cycle . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
- pathogenecity . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
TR
EC
R
L
IC
Idioadaptation (see Allomorphosis) . . . . . . . . . . . . . . .
Immune incompatibility . . . . . . . . . . . . . . . . . . . . . . . . .
Immune response . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
Immunity . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
- innate . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
- adaptive . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
- humoral . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
- cell-mediated . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
Immunodeficiency disorders Inherited . . . . . . . . . . .
Immunogenetics . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
Immunologic methods (Serodiagnosis or
serologic tests) . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
Implantation . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
Inborn errors of metabolism . . . . . . . . . . . . . . . . . . . . .
Inclusions . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
In Vitro Fertilization
(IVF (see Fertilization In Vitro)) . . . . . . . . . . . . . . . . . . . .
Inheritance autosomal-dominant
- autosomal-recessive . . . . . . . . . . . . . . . . . . . . . . . . . .
- mitochondrial . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
- X-linked dominant . . . . . . . . . . . . . . . . . . . . . . . . . . .
- X-linked recessive . . . . . . . . . . . . . . . . . . . . . . . . . . . .
- Y-linked . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
Innate immunity (see Immunity innate) . . . . . . . . . .
Insecta (Insects) . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
Interphase
- presynthetic (post-mitotic) period (G1) . . . . . . . .
- synthetic period (S) . . . . . . . . . . . . . . . . . . . . . . . . . .
- premitotic (post-synthetic) period (G2) . . . . . . . .
- resting phase(G0) . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
Intra-skin allergic test . . . . . . . . . . . . . . . . . . . . . . . . . . . .
Introns . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
Invertebrates . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
Isogamy . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
Isolation
- genetic . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
- geographical . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
- reproductive . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
- ecological . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
Itch mite (see Sarcoptes scabiei) . . . . . . . . . . . . . . . . . . .
Ixodes ricinus (see dog tick) . . . . . . . . . . . . . . . . . . . . . . .
Ixodes persulcatus (see taiga tick) . . . . . . . . . . . . . . . . .
Karakurt or steppe spider (Latrodectus
tredecimguttatus) . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
Karyogamy . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
Karyokinesis . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
Karyotype . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
Karyotyping . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
Kinase cyclin-dependent (see Cyclin-depend
ent kinase) . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
Kinetoplast . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
Kinetochore . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
D
I
K
TE
- prophylaxis . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
Hypnozoites . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
Hypoderm . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
Hypothalamus . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
441
Index Ecology. Biosphere as human environment. Poisonous organisms...
D
- failure . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
Mendel’s Law (see Law of Mendel) . . . . . . . . . . . . . . . .
Mendelian traits . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
Mesencephalon . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
Mesoderm . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
Mesonephros (trunk kidney) . . . . . . . . . . . . . . . . . . . . .
Metanephros (pelvic kidney) . . . . . . . . . . . . . . . . . . . . .
Metabolism . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
Metacercariae . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
Metagonimus yokogawai . . . . . . . . . . . . . . . . . . . . . . . . .
Metamorphoses . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
Metaphase of mitosis . . . . . . . . . . . . . . . . . . . . . . . . . . . .
Metencephalon . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
Methylation of DNA (cytosine) . . . . . . . . . . . . . . . . . . . .
Microevolution . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
Microfilaments . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
Microfilaria . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
Microorganisms . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
Microtubules . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
Millipedes . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
Miracidium . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
Mitosis (Mitotic phase) . . . . . . . . . . . . . . . . . . . . . . . . . . .
Mitosis failure . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
Mitotic activity . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
- cycle . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
- index . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
Mitochondria . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
Mitochondrial inheritance . . . . . . . . . . . . . . . . . . . . . . .
- DNA . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
Modifications . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
Molecular-cytogenetic methods . . . . . . . . . . . . . . . . . .
Monohybrid cross . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
Monomer . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
Monosaccharides . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
Monospermy . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
Morphallaxis . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
Morphogenesis . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
Mosaicism . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
Mosquitoes
- Aedes . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
- Anopheles . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
- Culex . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
Mullerian (paramesonephric) duct . . . . . . . . . . . . . . .
Multiple fission (see Schizogony) . . . . . . . . . . . . . . . . .
Multipotent . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
Musca domestica (see house fly) . . . . . . . . . . . . . . . . . .
Muscidae (see Flies) . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
Mushrooms . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
Mutagenesis . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
Mutagenic factors
- biological . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
TR
IC
- diagnosis . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
- prophylaxis . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
Leishmaniasis mucocutaneous . . . . . . . . . . . . . . . . . . .
Leptotene (Leptonema) . . . . . . . . . . . . . . . . . . . . . . . . . .
Levels of organization of life . . . . . . . . . . . . . . . . . . . . . .
Leukocyte . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
Lice-borne relapsing fever . . . . . . . . . . . . . . . . . . . . . . .
Life
- latent form . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
- oscillating form . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
- permanent (free) form . . . . . . . . . . . . . . . . . . . . . . . .
Lily of the Valley (Convallaria majalis) . . . . . . . . . . . . .
Linkage group . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
Lionfish (Pterois genus) . . . . . . . . . . . . . . . . . . . . . . . . . . .
Lipids . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
Lithosphere . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
Loa-loa (eye worm) . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
Louse (Lice)
- body (see Pediculus humanus corporis) . . . . . . .
- head (see Pediculus humanus capitis) . . . . . . . . .
- pubic (see Phtirus pubis) . . . . . . . . . . . . . . . . . . . . . .
Lycosa singoriensis (see tarantula or wolf . . . . . . . . . .
spider) . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
Lymphocytes . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
Lyon’s hypothesis . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
Lysosomes . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
TE
442
M
R
EC
Macroevolution . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
Macromolecule . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
Macrophages . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
Major histocompatibility complex (MHC) . . . . . . . . .
Malaria parasites (Plasmodium sp.)
- geographical distribution . . . . . . . . . . . . . . . . . . . .
- location . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
- morphology . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
- life cycle . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
- pathogenecity . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
- diagnosis . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
- prophylaxis . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
Mamba (Dendroaspis sp.) . . . . . . . . . . . . . . . . . . . . . . . . .
Mammalia . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
Map genetic
- chromosome . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
- physical . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
Meadow tick (Dermacentor pictus) . . . . . . . . . . . . . . . .
Medulla oblongata (see Myelencephalon) . . . . . . . .
Meiosis
- First Meiotic Division (reduction) . . . . . . . . . . . . . .
- Second Meiotic Division (equation) . . . . . . . . . . .
14.4. Poisonous organisms
N
D
TR
EC
R
Oleander (Nerium oleander) . . . . . . . . . . . . . . . . . . . . . .
Onchocerca volvulus . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
Oncogenes . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
Oncosphere . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
Ontophilogenic defects . . . . . . . . . . . . . . . . . . . . . . . . . .
Ontogenesis
- embryonic (prenatal period) . . . . . . . . . . . . . . . . . .
- postembryonic (postnatal period) . . . . . . . . . . . . .
Oocyte . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
Oocyst . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
Oogenesis . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
Oogonia . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
Ookinete . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
Ooplasmic segregation . . . . . . . . . . . . . . . . . . . . . . . . . .
Operator gene . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
Operon . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
Opisthorchis felineus (see cat fluke) . . . . . . . . . . . . . . . .
Organelles
- double-membranous . . . . . . . . . . . . . . . . . . . . . . . . .
- single-membranous . . . . . . . . . . . . . . . . . . . . . . . . . .
- non-membranous . . . . . . . . . . . . . . . . . . . . . . . . . . . .
Organisms
- autotrophic . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
- aerobic . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
- anaerobic . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
- multicellular . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
- heterozygous . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
- heterotrophic . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
- homozygous . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
- unicellular . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
Organogenesis . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
Ornithodoros papillipes . . . . . . . . . . . . . . . . . . . . . . . . . .
Oviparous . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
Ovoviviparous . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
Ovoscopy
- quantitative . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
- qualitative . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
- concentration techniques . . . . . . . . . . . . . . . . . . . . .
Ovulation . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
Ovum
- isolecithal . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
- centrolecithal . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
- telolecithal . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
IC
Naegleria Fowleri . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
Nanophyetus (Troglotrema) salmincola . . . . . . . . . . . .
Natural focus . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
Natural selection (see Selection) . . . . . . . . . . . . . . . . . .
Necator americanus (American hookworm)
- geographical distribution . . . . . . . . . . . . . . . . . . . .
- location . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
- morphology . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
- life cycle . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
- pathogenecity . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
- diagnosis . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
- prophylaxis . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
Necrosis (see Cell Death Necrosis) . . . . . . . . . . . . . . . .
Nematodes (Roundworms) . . . . . . . . . . . . . . . . . . . . . . .
Neutralism . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
Non-cellular organisms . . . . . . . . . . . . . . . . . . . . . . . . . . .
Noosphere . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
Norm of reaction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
Nuclear envelope
- matrix . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
- pores . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
Nucleic acid . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
see DNA . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
see RNA . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
Nucleic acid hybridization techniques . . . . . . . . . . . .
Nucleoid . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
Nucleolar organizer region (secondary
constriction) . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
Nucleolus . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
Nucleosome . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
Nucleotide . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
Nucleus . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
Nymph . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
O
TE
- physical . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
- chemical . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
Mutations
- germ-line (germinal) . . . . . . . . . . . . . . . . . . . . . . . . .
- gene . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
- genome . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
- induced . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
- somatic . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
- spontaneous . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
- chromosomal . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
Mutualism . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
Myelencephalon (medulla oblongata) . . . . . . . . . . . .
Myiasis tissue
- intestinal . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
- urinary . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
443
P
Pachytene (Pachynema) . . . . . . . . . . . . . . . . . . . . . . . . . .
Panmixis . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
Index Ecology. Biosphere as human environment. Poisonous organisms...
D
TR
EC
R
Plasma membrane . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
Plasmids . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
Plasmodium species (see Malaria parasites) . . . . . . . .
Pleiotropy
- primary . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
- secondary . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
Plerocercoid . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
Pluripotent . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
Poikilothermic animals . . . . . . . . . . . . . . . . . . . . . . . . . . .
Poison . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
Poisonous animals
- primary . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
- secondary . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
Polar body (polocyte) . . . . . . . . . . . . . . . . . . . . . . . . . . . .
Polyadenylation . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
Polygenic inheritance (polymeria) . . . . . . . . . . . . . . . .
Polyhybrid . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
Polymeria (see Polygenic inheritance) . . . . . . . . . . . .
Polysaccharides . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
Polysome (polyribosome) . . . . . . . . . . . . . . . . . . . . . . . .
Polymerase chain reaction (PCR) . . . . . . . . . . . . . . . . . .
Polyploidy . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
Polyteny . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
Population
- ideal . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
- natural . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
- small . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
- isolate . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
- deme . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
Portuguese man o’war (Physalia physalis) . . . . . . . . .
Postembryonic (postnatal) period (see
Ontogenesis postembryonic period) . . . . . . . . . . . . . .
Post-translational modification . . . . . . . . . . . . . . . . . .
Precursor mRNA (pre-mRNA) . . . . . . . . . . . . . . . . . . . . .
Predation . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
Prenatal diagnosis . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
Presynthetic period (see Interphase) . . . . . . . . . . . . . .
Prion disease
- Kuru . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
- Creutzfeldt-Jacob . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
Prions . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
Proband . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
Procercoid . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
Processing . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
Producers . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
Productivity . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
- primary . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
- secondary . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
Proglottids . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
- immature . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
- mature (hermaphrodite) . . . . . . . . . . . . . . . . . . . . . .
IC
Paragonimus westermani or ringeri
(see lung fluke) . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
Parallelism . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
Parasitism . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
Parasite
- obligate . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
- facultative . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
- accidental . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
- aberrant . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
- permanent . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
- temporary . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
- ectoparasite . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
- endoparasite . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
- monoxenous . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
- panxenous . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
Parasitology . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
Parthenogenesis . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
Passive transport . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
Pathogenic effect . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
Pediculosis (see Louse) . . . . . . . . . . . . . . . . . . . . . . . . . . .
Pedigree analysis (genealogic method) . . . . . . . . . . .
Pellicle . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
Penetrance . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
Periods of development (see Ontogenesis) . . . . . . .
Peroxisomes . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
Phagocytosis . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
Phenocopy . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
Phenotype . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
Phenylketonuria . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
Phlebotomus (see Sand fly) . . . . . . . . . . . . . . . . . . . . . . .
Phospholipid molecule
- bilayer . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
Photoperiodism . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
Phtirus pubis
Phylogenesis . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
Phynn (larvocyst) . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
Pili . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
Pinocytosis . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
Pinworm (see Enterobius vermicularis)
- geographical distribution . . . . . . . . . . . . . . . . . . . .
- location . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
- morphology . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
- life cycle . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
- pathogenecity . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
- diagnosis . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
- prophylaxis . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
Pisces (Fishes) . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
Pituitary gland . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
Placenta . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
Plague . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
Plasma cells . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
TE
444
14.4. Poisonous organisms
TE
D
- asexual . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
- sexual . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
Reptilia . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
Resuscitation (reanimation) . . . . . . . . . . . . . . . . . . . . . .
Rhesus factor
- conflict . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
Ribonucleic acid (RNA)
- mRNA . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
- rRNA . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
- tRNA . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
- snRNA . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
- miRNA . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
Ribose . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
Ribosomes . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
RNA (see Ribonucleic acid) . . . . . . . . . . . . . . . . . . . . . . .
RNA polymerase . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
Rudiments (see Vestigial organs) . . . . . . . . . . . . . . . . .
Rhythms (see Biological rhythms) . . . . . . . . . . . . . . . . .
IC
- gravid . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
Progress Biological (see Biological Progress) . . . . . .
Prokaryotes
- archaebacterial (Archeae) . . . . . . . . . . . . . . . . . . . . .
- Bacterias (Eubacteria) . . . . . . . . . . . . . . . . . . . . . . . . .
Prometaphase of mitosis . . . . . . . . . . . . . . . . . . . . . . . .
Promoter . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
Pronephros (cranial kidney) . . . . . . . . . . . . . . . . . . . . . .
Pronucleus . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
Prophase of mitosis . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
Proteins
- biosynthesis . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
- acid non-histone . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
- basic histone (see Histones) . . . . . . . . . . . . . . . . . . .
- molecule . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
- structure . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
Protozoans (protists) . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
Protozoology . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
“Pseudocyst” (“colony”) . . . . . . . . . . . . . . . . . . . . . . . . . . .
Pseudogenes . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
Punnett square . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
Purines . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
Pyramid . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
of biomass . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
of energy . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
of numbers . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
Pyrimidines . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
EC
Recapitulation . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
Race
- Caucasian (or Europid) . . . . . . . . . . . . . . . . . . . . . . . .
- Mongoloid . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
- Australo-Negroid . . . . . . . . . . . . . . . . . . . . . . . . . . . .
Receptors . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
Recessive trait . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
Recombination . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
Reduviid or kissing (see Triatomine) bug . . . . . . . . . .
Rediae . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
Regeneration
- physiological . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
- reparative . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
Regress Biological (see Biological regress) . . . . . . . . .
Regulator gene . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
Renaturation (annealing) . . . . . . . . . . . . . . . . . . . . . . . . .
Repair of DNA (see DNA repair) . . . . . . . . . . . . . . . . . . .
Replicon . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
Replication . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
Repressor . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
Reproduction
R
S
Salamander fire (Salamadra salamandra) . . . . . . . . .
Sand fly (Phlebotomus) . . . . . . . . . . . . . . . . . . . . . . . . . . .
Sarcodina (see Amoeboid protozoa) . . . . . . . . . . . . . .
Sarcoptes scabiei (see itch mite) . . . . . . . . . . . . . . . . . . .
Satellite DNA . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
Schizogony (Multiple fission) . . . . . . . . . . . . . . . . . . . . .
Schistosoma (Bilharzia) species
(blood flukes) . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
- haematobium . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
- Mansoni . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
- japonicum . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
Scolex . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
Scolopendra . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
Scorpions . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
Screening of Newborn
- selective . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
Selection
- natural . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
- directed . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
- disruptive . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
- stabilizing . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
Semi-conservative . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
Serodiagnosis or serologic tests
(see immunologic methods) . . . . . . . . . . . . . . . . . . . . . .
Sequences of human DNA
- Protein-coding genes and gene-related
sequences . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
- Gene-related sequences . . . . . . . . . . . . . . . . . . . . . .
- Genes of non-protein-coding RNA . . . . . . . . . . . .
- Repetitive DNA sequences . . . . . . . . . . . . . . . . . . . .
TR
R
445
Index Ecology. Biosphere as human environment. Poisonous organisms...
D
H
Heredity, methods of study
- biochemical . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
- twin . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
- genealogy . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
- dermatological . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
- molecular genetic . . . . . . . . . . . . . . . . . . . . . . . . . . . .
- population-statistical . . . . . . . . . . . . . . . . . . . . . . . .
- sex chromatin . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
- cytogenetic . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
T
Taeniarhynchus saginatus
(Unarmed tapeworm or Beef tapeworm)
- geographical distribution . . . . . . . . . . . . . . . . . . . .
- location . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
- morphology . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
- life cycle . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
- pathogenecity . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
- diagnosis . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
- prophylaxis . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
Taiga tick (see Ixodes persulcatus) . . . . . . . . . . . . . . . .
Tarantula or wolf spider (Lycosa singoriensis) . . . . .
Telencephalon . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
Telomere . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
Telophase of mitosis . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
Teratogenic factors . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
Teratology . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
Terminator . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
Test cross . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
Thanatology . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
Threadworm (see Strongyloides stercoralis) . . . . . . . .
Thymine . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
Thyroid gland . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
Tick-borne or endemic relapsing fever . . . . . . . . . . .
Ticks
- Acariformes . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
- Argasidae . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
- Gamasoidea . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
- Ixodidae . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
- Parasitiformes . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
- Sarcoptiformes . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
Totipotent . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
Toxoplasma gondii
- geographical distribution . . . . . . . . . . . . . . . . . . . .
TR
EC
R
Symbiosis . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
Syngamy (copulation) . . . . . . . . . . . . . . . . . . . . . . . . . . . .
Synthetic theory of evolution . . . . . . . . . . . . . . . . . . . . .
IC
Sex chromatin detection (Barr bodies detection) . .
Sex determination
- chromosomes . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
- linked inheritance . . . . . . . . . . . . . . . . . . . . . . . . . . . .
- linked incompletely (or partially) . . . . . . . . . . . . . .
Sex-determining Region of Y chromosome
(see SRY) . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
Sex-influenced traits . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
Sex-limited traits . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
Sexual dimorphism . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
Sickle-cell anemia (see Anemia sickle-cell ) . . . . . . . .
Sleeping sickness (see Trypanosomiasis . . . . . . . . . .
African) . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
Snakes venomous . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
Sodium-Potassium Pump . . . . . . . . . . . . . . . . . . . . . . . .
Solifugae (phalanges) . . . . . . . . . . . . . . . . . . . . . . . . . . . .
Somatic cell nuclear transfer (SCNT) . . . . . . . . . . . . . .
Somites of mesoderm . . . . . . . . . . . . . . . . . . . . . . . . . . . .
Species . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
Sperm cell (spermatozoon) . . . . . . . . . . . . . . . . . . . . . . .
Spermatids . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
Spermatogenesis . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
Spermatogonia . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
Spermatocytes . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
Spermiogenesis . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
Splicing . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
Sporogony . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
Sporozoites . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
Sporocyst . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
”sprinter” . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
SRY (Sex-determining Region of Y chromosome) . .
Stable Fly (Stomoxys calcitrans) . . . . . . . . . . . . . . . . . . .
“stayer” . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
Stomoxys calcitrans (see stable fly) . . . . . . . . . . . . . . . .
Stonefish reef (Synanceia verrucosa) . . . . . . . . . . . . . .
Stress . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
Stem cell therapy . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
Stem cells
- embryonic . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
- adult (somatic) . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
Stingray common (Dasiatis pastinaca) . . . . . . . . . . . .
Stingray ocellate river (Potamotrygon motoro) . . . . .
Strobila . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
Strongyloides stercoralis (Threadworm)
- geographical distribution . . . . . . . . . . . . . . . . . . . .
- location . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
- morphology . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
- life cycle . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
- pathogenecity . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
- diagnosis . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
- prophylaxis . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
TE
446
14.4. Poisonous organisms
D
TE
U
Unarmed tapeworm or Beef tapeworm
(see Taeniarhynchus saginatus) . . . . . . . . . . . . . . . . . . .
Unicellular . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
Uracil . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
Uterus . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
TR
EC
R
- diagnosis . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
- prophylaxis . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
Trypanosomiasis American (Chagas’ disease)
- geographical distribution . . . . . . . . . . . . . . . . . . . .
- location . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
- morphology . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
- life cycle . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
- pathogenecity . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
- diagnosis . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
- prophylaxis . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
Tsetse flies (Glossina) . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
Twins
- monozygotic (identical) . . . . . . . . . . . . . . . . . . . . . .
- dizygotic (fraternal) . . . . . . . . . . . . . . . . . . . . . . . . . . .
Twins method . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
Tumor growth
- benign . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
- malignant . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
Tumor suppressor genes . . . . . . . . . . . . . . . . . . . . . . . . .
IC
- location . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
- morphology . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
- life cycle . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
- pathogenecity . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
- diagnosis . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
- prophylaxis . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
Transcription . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
Transduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
Transformation . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
Translation . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
Transplantation (see grafting) . . . . . . . . . . . . . . . . . . . .
Trematodes (see Flukes) . . . . . . . . . . . . . . . . . . . . . . . . . .
Triatoma infestans (bug “kissing” or triatomine or
Reduviid) . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
Trichinella spiralis (Trichina Worm)
- geographical distribution . . . . . . . . . . . . . . . . . . . .
- location . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
- morphology . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
- life cycle . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
- pathogenecity . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
- diagnosis . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
- prophylaxis . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
Thrichocephalus trichiurus or Trichiurus
trichiura (Whipworm)
- geographical distribution . . . . . . . . . . . . . . . . . . . .
- location . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
- morphology . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
- life cycle . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
- pathogenecity . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
- diagnosis . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
- prophylaxis . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
Trichomonas vaginalis
- geographical distribution . . . . . . . . . . . . . . . . . . . .
- location . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
- morphology . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
- life cycle . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
- pathogenecity . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
- diagnosis . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
- prophylaxis . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
- hominis . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
- tenax . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
Triplet (see Codon) . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
Trophoblast . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
Trophozoite (vegetative stage) . . . . . . . . . . . . . . . . . . .
Trypanosoma species . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
Trypanosomiasis African (sleeping sickness)
- geographical distribution . . . . . . . . . . . . . . . . . . . .
- location . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
- morphology . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
- life cycle . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
- pathogenecity . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
447
V
Vacuole . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
Variation
- genotypic . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
- mutation . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
- recombinant . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
- phenotypic (see Modification) . . . . . . . . . . . . . . . .
Vector mechanical . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
- specific . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
Vector-born diseases . . . . . . . . . . . . . . . . . . . . . . . . . . . .
Vegetative stage (see Trophozoite) . . . . . . . . . . . . . . .
Venemous or Poisonous Coelenterata
- Arthropods . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
- Fish . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
- Amphibians . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
- Reptiles . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
- Plants . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
- Fungi . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
Vertebrates . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
Vestigial organs (rudiments) . . . . . . . . . . . . . . . . . . . . . .
Viper asp (Vipera aspis) . . . . . . . . . . . . . . . . . . . . . . . . . . .
448
Index Ecology. Biosphere as human environment. Poisonous organisms...
X
IC
Wasp (Vespula vulgaris) . . . . . . . . . . . . . . . . . . . . . . . . . . .
Ways of transmission of parasitic disease . . . . . . . . .
Whipworm (see Thrichocephalus trichiurus) . . . . . . .
Wohlfahrtia fly (Wohlfahrtia magnifica) . . . . . . . . . . .
Wohlfahrtia magnifica (see wohlfahrtia fly
or spotted flesh fly) . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
Wolffian (mesonephric) duct . . . . . . . . . . . . . . . . . . . . .
Wuchereria bancrofti . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
TE
W
D
Viper European common (Vipera berus) . . . . . . . . . . .
Viper meadow (Vipera ursine) . . . . . . . . . . . . . . . . . . . . .
Viper blunt-nosed (Vipera lebetina) . . . . . . . . . . . . . . .
Virion . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
Viroids . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
Viruses . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
Vitamins . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
Viviparous . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
TR
X-linked recessive inheritance
(see inheritance X-linked recessive) . . . . . . . . . . . . . . .
X-linked dominant inheritance
(see inheritance X-linked dominant) . . . . . . . . . . . . . .
Xenodiagnosis . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
Y
EC
Y-linked inheritance (see inheritance Y-linked) . . . .
Yolk . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
Yolk sac . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
Z
R
Zoonosis . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
Zygote . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
Zygotene (Zygonema) . . . . . . . . . . . . . . . . . . . . . . . . . . .
TE
IC
TR
EC
R
449
D
14.4. Poisonous organisms
TE
Навчальне видання
Бажора Юрій Iванович
Булик Роман Євгенович
Чеснокова Mарина Mихайлівна та ін.
IC
Медична біологія
Навчальний посібник
TR
Редактор О. В. Марчук
Технічний редактор Ж. С. Швець
Коректор Ю. В. Анвар
Комп’ютерна верстка: О. С. Парфенюк
Підписано до друку ??.??.??. Формат 70×100. Папір офсетний.
Гарнітура Таймс. Друк офсетний. Ум. друк. арк. ??,??. Зам. № ???.
ПП “Нова Книга”
21029, м. Вінниця, вул. М. Ващука, 20
Свідоцтво про внесення суб’єкта видавничої справи
до Державного реєстру видавців, виготівників
і розповсюджувачів видавничої продукції
ДК № 2646 від 11.10.2006 р.
Тел. (0432) 56-01-87. Факс 56-01-88
E-mail: info@novaknyha.com.ua
www.novaknyha.com.ua
EC
R
D
У цьому посібнику висвітлені основні питання загальної та медичної біології. Представлені загальні
закономірності життя, вивчення клітини, включаючи основи цитогенетики людини, вивчення спадковості та
непостійності, включаючи генетику людини, закони філогенетичного розвитку організмів, основи загальної
паразитології, біологія найбільш значущих паразитів людини, спосіб передачи, діагностики та профілактики
паразитарних захворювань.
Навчальний матеріал розподілений за темами відповідно до плану з курсів медичної біології. Призначений для
англомовних студентів першого курсу.