Unit 7 Notes – Cell Cycle and Genetics
DNA
I.
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DNA IS THE GENETIC MATERIAL
There are several famous experiments that proved that DNA is responsible for inheritance.
A. Bacterial Transformation Experiment (Griffith’s Experiment)
 Griffith used two strains of the Streptococcus pneumoniae bacterium that causes pneumonia in
mammals. One strain was diseases-causing (pathogenic) while the other was a non-pathogenic
strain.
 Griffith could change the harmless strain of the bacterium into a disease causing strain just by
mixing dead harmful bacteria with live harmless bacteria.
 Transformation – 1. A change in genotype and phenotype due to the assimilation of external
DNA by a cell.
 Question remains: What is the factor that is responsible for transformation?
B. Avery, McCarty and MacLeod’s Experiments:
 They purified various molecules (proteins, carbohydrates, lipids and nucleic acids) from heatkilled bacteria and tried to use the purified molecules to transfer pathogenic characteristics into
non-pathogenic bacteria.
 They used bioassays to determine the pathogenicity of various molecules. A bioassay is
determining the activity of various molecules by testing their effects on living organisms and
comparing the activity to various known molecules’ activity.
 Result: DNA is responsible for inheritance
C. Bacteriophage Experiment (Hershey and Chase Experiment)
 Bacteriophages – viruses that kill bacteria (viruses are mostly composed of DNA or RNA and
proteins)
 In this experiment, T2 phages were used that infect E. coli bacteria
 Results: Phage proteins remained outside of the bacterial cells while phage DNA entered the
cells – radioactive DNA was detected inside of infected bacteria.
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Conclusion: DNA, not proteins are responsible for inheritance
D. Chargaff’s Experiment:
 He analyzed the base composition of DNA from various organisms.
 Results:
a. DNA composition varies from one species to another – evidence of molecular diversity
among species
b. In each species, the number of adenine bases approximately equaled the number of
thymine bases; the number of cytosine bases equaled the number of guanine bases.
(Chargaff’s rule)
E. X-ray Crystallography (Franklin):
 Her X-ray crystallography photograph of DNA leads to the discovery of the structure of DNA.
F. Watson and Crick
 Built the first model of the DNA molecule and described the structure of the molecule.
 They also predicted the process of DNA replication but did not have experimental evidence to
support it.
G. Messelson-Stahl Experiment
 Designed an experiment to determine DNA replication by tracing the origin of the replicated
DNA.
 To tell the difference between the parental (template) DNA and the newly synthesized
complementary DNA they developed a tagging system by using two different kinds of nitrogen
isotopes. One isotope (14N) is the normal, light nitrogen, while the other (15N) is a heavy isotope.
They could use centrifugation to separate heavy, medium weight and light DNA molecules from
each other.
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II.
Once they used heavy DNA as templates and allowed light DNA nucleotides to assemble with
them, they got medium weight DNA molecules that showed that one half of the newly
synthesized DNA was old (heavy) and the other half was new (light).
DNA STRUCTURE
Review this section from biochemistry or from Module 45 from your book.
III.
DNA REPLICATION:
A. The Basic Ideas on DNA Replication
 Base-pairing rules apply when the DNA bases pair up
 The two strands are complementary, so each strand serves as a template for ordering
nucleotides into a new complementary strand
 The process starts with one double helix and ends up with two DNA molecules, both double
stranded and identical to the parent DNA
 Enzymes link the nucleotides together at their sugar-phosphate groups.
 The replication is semiconservative because every new DNA molecule contains one new strand
and one old strand.
http://www.sumanasinc.com/webcontent/animations/content/meselson.html
B. A Closer Look at DNA Replication
 DNA replication is extremely accurate and efficient
 Although we know more about DNA replication in prokaryotes than in eukaryotes, we also know
that the two processes are very similar.
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Six major steps of replication:
a. Origins of replication: The site where DNA replication begins. In prokaryotic cells there
is only one origin of replication, in eukaryotic cells there are hundreds or thousands to
speed up replication. An enzyme (helicase) is used to untwist the DNA molecule.
b. Initiation proteins recognize the origins of replication and open up the DNA double helix
forming a replication bubble. Than replication proceeds in both directions until the
entire DNA molecule is copied. Each opened DNA molecule where the replication takes
place forms a replication fork. RNA nucleotides (primer) are used to mark the start of
replication on each DNA polynucleotide chain.
c. Elongating a new strand: Elongation is catalyzed by enzymes called DNA polymerases.
d. Individual nucleotides align with complementary nucleotides along a template strand of
DNA. DNA polymerase adds them one by one to the growing end of the new DNA
molecule. DNA polymerize identifies the starting point by attaching to the prime of the
RNA nucleotides In prokaryotes, there are two different DNA polymerases while in
eukaryotes there are at least 11. The added nucleotides are actually nucleoside
triphosphates (ATP, GTP, TTP, CTP but with deoxyribose sugar not ribose). When the Pi
groups are broken down of the nucleotides, energy is released. This energy release
fuels DNA replication.
e. Antiparallel elongation: Because the two strands of the DNA molecule are antiparallel,
so they are oriented in the opposite direction. The new DNA molecules also have to
orient in the same direction. However, DNA polymerase can attach nucleotides only to
the 3’ end and grows the chain toward the 5’end of the original chain. The original 3’5’ strand is called the leading strand because the DNA polymerase simply attaches new
nucleotides by using the template of the old DNA chain and forms a new polynucleotide
chain. To elongate the other new strand in the 5’- 3’ direction, the DNA polymerase
works away from the replication fork, backwards. It forms small segments of the new
polynucleotide chain that is going to be attached together later. These small segments
are called Okazaki fragments. Another enzyme, (DNA ligase), attaches the Okazaki
fragments together later.
f.
Only one primer is required to start the 3’ end but each Okazaki fragment requires a
primer on the lagging strand. DNA polymerase I replaces the RNA primers with DNA
molecular segments. An enzyme joins the sugar-phosphate backbones of the Okazaki
fragments to form a continuous DNA polynucleotide chain.
http://www.wiley.com/college/pratt/0471393878/student/animations/dna_replication/index.html -more detailed animation of DNA replication
http://highered.mcgraw-hill.com/sites/0072437316/student_view0/chapter14/animations.html -- many
things on DNA replication and the experiments
http://207.207.4.198/pub/flash/24/menu.swf -- DNA replication, also very good
http://www.fed.cuhk.edu.hk/~johnson/teaching/genetics/animations/dna_replication.htm -- basic DNA
replication
C. Proofreading and Repairing DNA
 In general there is only 1 error out of 10 billion nucleotides when the DNA molecule is being
assembled. But the initial error rate is higher. DNA polymerases proofread the DNA molecule
as it is being made and they replace the incorrectly placed nucleotide.
 Cells also have special repair enzymes to fix incorrectly paired nucleotides later.
 Most common factors that can result in the damage of DNA are: chemicals from metabolic
reactions of the cell or from the environment, radioactive emissions, X-rays, UV light,
spontaneous chemical changes of the DNA molecule.
IV.
Replicating the Ends of DNA Molecules:
 Because the end of the DNA molecule on the lagging end runs out of 3’ ends, it cannot be
copied. As a result, each repeated round of replication produce shorter and shorter DNA
molecules. The part of chromosomes that get lost at each DNA replication is called the
telomere. Telomeres do not contain genes, they only have multiple repetitions of one short
nucleotide segments (TTAGGG in humans).
 An enzyme called telomerase catalyzes the lengthening of telomeres in eukaryotic germ cells
with the help of a short RNA segment.
THE CELL CYCLE
I. Overview
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Cells divide to replace old, dead or damaged cells, to grow the organism, the heal wounds, to
reproduce the organism and maintain the species.
Cells can divide by different methods:
o Binary fission – the division type of bacteria and archaea
o Mitosis – the type of cell division that produces identical copies of the same type of cell.
This division is used in all cases when any somatic cell (body cell) forms.
o Meiosis – produces haploid daughter cells that are genetically unique. These cells
become the gametes (reproductive cells) of the organism.
II. Binary Fission
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A simple process in which bacteria increase in size, replicate its simple circular DNA, grows some
more and splits into two new identical cells.
Scientists use fluorescent molecules to view this process under microscope.
During harsh environments, bacteria switch to a division that produces endospores – resistant,
dormant cell forms. Some of these forms can survive for thousands of years.
Some bacteria produce spores normally as part of their life cycle. Others can perform budding,
growing a new cell on the tip of the parent cell.
III. Eukaryotic Cell Division
This is your spring break assignment
IV. Cell Cycle Control
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Different types of cells divide at different schedules. Skin cells divide continuously, liver cells
divide only if some other cells died around them, muscle cells don’t divide, they can only repair
themselves.
Cell cycle control mechanisms determine if the cell will remain in the G1 or G0 phase of the cell
cycle or continue to other phases.
There are several different control mechanisms.
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Major cell cycle controls include:
o Checkpoints – Protein signaling pathways are used to interact with molecules that are
part of the cell cycle. These protein signaling pathways allow the cell cycle to continue
only if the molecules that they interact with are complete and healthy. There is a
checkpoint in the G1 phase, that check the size of the cell and the condition of the DNA.
If this checkpoint is not passed, the cell remains in G0 phase and will not divide. There is
another checkpoint in G2 to check if the DNA replicated properly in S phase and if the
cell is large enough to divide. There is a last checkpoint during mitosis in metaphase to
check if all the chromosomes attached to the spindle fibers.
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Cyclin and kinase complexes – The cell cycle is also regulated by proteins called cyclins that
increase in concentration at the end of each phase of the cell cycle. Cyclins bind with cyclindependent kinase (Cdks) molecules that are molecules with a constant concentration in the
cell. The cyclin-cdk complexes are activated together to help the cell to switch to another
phase of the cell cycle. After a new phase begins, the cyclins break down and the cdks
become inactive again until the next increase in cyclin concentration. There are different
types of cyclins produced in different phases of the cell cycle. These cyclin-cdk complexes
trigger various cell signaling pathways.
Cell cycle controls respond to various internal and external cues to determine when the cell
needs to divide.
External cues to regulate the cell cycle include:
o Availability of nutrients
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Growth factors – paracrine signals that are released by all kinds of cells to stimulate the
division of certain area cells
o Density-dependent inhibition – cells don’t divide if they touch other cells on all sides.
There are surface proteins that bind cells to other cells. When all surface proteins are
connected to other cells, the cell division will be inhibited until space opens up around
the cell. Cancer cells don’t stop dividing and don’t recognize density-dependent
inhibition. As a result, they form tumors.
o Anchorage dependence – most animal cells don’t divide if they are not anchored to
surface tissues. Cancer cells may not follow anchorage dependence, so they can divide
during metastasis.
Internal factors include the age of the cell. Normal cells divide only about 20-50 times before
they die. Cancer cells can divide indefinitely so they are considered immortal.
V.
What Happens When the Regulatory Mechanisms Fail?
 Cancer is uncontrolled cell division of abnormal cells in the body.
 Cancer cells are different from normal cells because they don’t stop dividing when they fill up
the available space or when they are not anchored to surfaces. They are also immortal in the
sense that they don’t stop dividing.
 Cancer is caused by a set of mutations. These mutations make the cell recognizable for the
immune system and in most cases cytotoxic T cells and natural killer cells destroy cancer cells.
But in some cases, the immune system fails to detect these cells. Than after further mutations
the following stages of cancer occur:
o Stage 1 – benign tumors – increased cell division forms small tumors
o Stage 2 – benign tumors – small tumors increase in size and grow blood vessels to get
nutrient and oxygen supply
o Stage 3 – malignant tumors – tumor cells get into the blood stream and move to other
parts of the body (metastasis)
o Stage 4 – malignant tumors – secondary tumors grow all over the body.
 Cancer cells may look different under the microscope from normal cells and various changes
occur in them.
 Genes that cause cancer are called oncogenes – the normal forms of these genes are called
proto-oncogenes. These genes are normally responsible for controlling the cell cycle by for
example producing cyclin proteins.
 Other genes called tumor-suppressor genes normally inhibit cell division. These genes stop cell
division or stimulate apoptosis if the cell has mutations in their oncogenes. The most frequently
altered tumor-suppressor gene is p53, which is mutated in more than half of all tumors in
humans.
Biointeractive – p53 activity
Use your honors biology notes for the description of the cell cycle, mitosis and meiosis.
THE SEXUAL LIFE CYCLE
I. The Organization of Chromosomes
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Life Cycle – the sequence of stages an organism passes through from one generation to the
next.
The DNA of a cell is contained within structures called chromosomes which pass from one
generation to the next.
Diploid cells – have 2 copies of each type of chromosomes. If an organism has n types of
chromosomes, diploid cells always have 2n by number. The two copies of chromosomes that
carry the same type of genes but may carry different alleles of them are called homologous
chromosomes. Somatic cells (cells that build up the body) are generally diploid in plants and
animals. Haploid cells on the other hand have only one copy of each type of chromosome.
Haploid cells are egg and sperm cells or gametes.
Most animals and plants reproduce sexually by the fusion of two cells, the egg and sperm cells.
Most single celled organism however reproduces asexually, with the splitting of one cell. These
organisms have other ways to increase genetic variety. For example, bacteria can reach genetic
diversity by transformation, conjugation and transduction.
To form haploid cells, meiosis is performed. During this process diploid germ cells divide to
form haploid gametes. Mitosis is the cell division of somatic cells.
Karyotypes (a picture that has the chromosomes arranged in decreasing order by size and the
sex chromosomes last) are used to determine gender or various chromosomal disorders.
Cells contain two kinds of chromosomes, autosomes and sex chromosomes. Sex chromosomes
determine the gender of an organism and secondary sex characteristics. In most organisms, XX
stands for females, while XY stands for males.
The number of chromosomes is a fixed number in each species but different species have
different chromosome numbers.
Later on we will use karyotypes and learn how to analyze them.
II. Factors That Increase Genetic Variation
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Mutations -- sudden changes in the genetic makeup of an organism can result in new genetic
combination.
Random fertilization – during fertilization, any single sperm cell can fertilize any egg. As a
result, the variety that is produced by the mating of the same two organisms can be
tremendous.
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Crossing over – the process of the homologous chromosomes forming tetrads, overlapping with
each other and exchanging some of their DNA during prophase I of meiosis, can result in a wide
variety of genetic combinations.
Independent assortment – During metaphase I of meiosis, homologous chromosomes (one
from the dad one from the mom) line up in a random arrangement and separate from each
other during the formation of gametes.
GENETICS
MENDEL’S PRINCIPLES
I. Overview
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Gregor Mendel used pea plants to study inheritance. He came up with the basic principles of
genetics in the mid-1800s.
Pea plants were ideal experimental subjects because
o They are inexpensive
o Easily grown
o Grows rapidly
o Produces many seeds in a short time
o Clearly observable traits
o Easy to artificially fertilize
The following key terms are necessary to understand Mendelian genetics:
o P generation
o F1 generation
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F2 generation
True breeding
Homozygous
Hybrid
Heterozygous
Test cross
Monohybrid cross
Dihybrid cross
Genotype
Phenotype
II. Mendel’s Principles:
A. The Principle of Dominance
 Mendel said: Phenotypes depend on the particular inheritance of factors (alleles) coding for
dominant and recessive traits. Only one copy of a factor (allele) coding for a dominant trait
has to be inherited for that trait to be expressed in the phenotype.
 Today: The factors are alleles of the same gene
 Correction: Many traits do not follow dominant and recessive inheritance. These are called
non-Mendelian traits.
B. The Principle of Segregation
 Mendel said: Each organism has two factors (alleles) for each gene, one from each parent.
Factors for the SAME trait are separated from each other during the formation gametes and
get rearranged after fertilization.
 Today: Alleles for the same gene get separated during meiosis (haploid cells form) and get
paired up again during fertilization.
 Correction: None
C. The Principle of Independent Assortment
 Mendel said: Factors for DIFFERENT traits separate from each other during the formation of
gametes and get rearranged again during fertilization.
 Today: Alleles for different traits separate from each other during meiosis and get
rearranged again during fertilization.
 Correction: It is chromosomes not genes that separate, so if two genes are located on the
same chromosomes, they do not assort independently, they are said to be linked genes and
inherited together.
III. Laws of Probability
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Probability examines how likely it is that an event will occur. Probability ranges from 0 to 1.
Multiplication rule – Predicts the probability of independent events. Each individual probability
is multiplied to obtain an overall probability.
Addition rule – predicts the probability of mutually exclusive events. Mutually exclusive means
that if one event occurs, the other event cannot occur simultaneously. So the probability of
event A is added to the probability of event B. (If you flip a coin and you get a head, than you
have no chance of getting a tail during the same toss.)
IV. Monohybrid and Dihybrid Crosses
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We use Punnett squares to determine the potential outcome of each cross during a genetic
problem. On one side of the Punnett square we list the father’s gametes, than on the other side
it lists the mother’s gametes. The cells of the square represent the possible outcome of the
cross for the next generation.
Monohybrid crosses are used to determine the possible outcome of the next generation by
following one trait at a time of two heterozygous parents.
Dihybrid crosses are used to determine the possible outcome of the next generation by
following two traits at a time of two heterozygous parents.
See your Spring Break Assignment II for practice problems.
VI.
Chi-Square in Genetics
 We can test if a genetic cross follows the predicted type of inheritance and independent
assortment by using Chi-square tests.
 If the observed data differ substantially from what would have been expected from our Punnett
square and probability calculations, we can assume that the original prediction of inheritance
type and independent assortment are not true.
 The null hypothesis (H0) in this case should be the predicted type of inheritance or the fact that
the observed traits follow independent assortment.
We will practice this on a handout and during a lab activity.
VII. Non-Mendelian Patterns of Inheritance
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Genes that don’t follow simple dominant-recessive inheritance are categorized into following
non-Mendelian inheritance.
Incomplete dominance – In this type of inheritance the dominant allele is not strong enough to
overpower the recessive allele. As a result, the heterozygous genotypes will have an
intermediate phenotype of the dominant and recessive phenotype. (Like the colors of
snapdragons, white and red, becomes pink when heterozygous)
Codominance – alleles that are equally dominant combine to form a phenotype. (Like IA and IB
combine to form AB blood group.)
Polygenic inheritance – some traits are determined by multiple genes and the phenotypes can
occur on a range instead of having two distinct types. The range of the phenotypes can be
represented with a bell curve. (Ex. Human skin color, height, hair color etc.)
The environment may also affect the phenotype – multifactorial characteristics – for example
human skin color is affected by the exposure to the sun. The environmental factor can be
related to diet, climate, illness and stress. (Other examples: plants grow shorter on higher
elevations, humans grow shorter if nutrition is not sufficient, hydrangea plants have different
flower colors depending on the pH of the soil – blue in acidic and pink in basic soil)
VIII. Inheritance Patterns in Humans
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There are very few human traits (consistency of earwax, Huntington’s disease, albinism) that
follow simple dominant and recessive inheritance. Most traits are more complex and may
have multiple inheritance types depending on what level of organization we are examining.
Sickle cell anemia: a blood disease that is characterized by crescent shaped red blood cells
due to misfolded hemoglobin molecules. These red blood cells get stuck in small capillaries
and cause pain and decreased blood supply. Sickle cell anemia is caused by a recessive gene
(point mutation). Heterozygous form causes sickle cell trait, a milder form of the disorder.
Review the evolutionary significance of sickle cell anemia.
THE CHROMOSOME THEORY OF INHERITANCE