Lecture 4 Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. Interphase G1 checkpoint Cell cycle main checkpoint. If DNA is damaged, apoptosis will occur. Otherwise, the cell is committed to divide when growth signals are present and nutrients are available. S (growth and DNA replication) G 1 G1 (growth) Insert figure 9.1 here G M 0 G2 (growth and final preparations for division) G 2 G2 checkpoint Mitosis checkpoint. Mitosis will occur if DNA has replicated properly. . Apoptosis will occur if the DNA is damaged and cannot be repaired. M MCAT Prep Exam Reproduction M checkpoint Spindle assembly checkpoint. Mitosis will not continue if chromosomes are not properly aligned. © SPL/Photo Researchers, Inc.; PowerPoint® Lecture Slides are prepared by Dr. Isaac Barjis, Biology Instructor 1 The Cell Cycle An orderly set of stages from the first division to the time the daughter cells divide Just prior to next division: The cell grows larger The number of organelles doubles The DNA is replicated The two major stages of the cell cycle: Interphase Mitosis 2 The Cell Cycle Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. Interphase G1 checkpoint Cell cycle main checkpoint. If DNA is damaged, apoptosis will occur. Otherwise, the cell is committed to divide when growth signals are present and nutrients are available. S (growth and DNA replication) G1 G0 G1 (growth) M G2 (growth and final preparations for G2 division) G2 checkpoint Mitosis checkpoint. Mitosis will occur if DNA has replicated properly. Apoptosis will occur if the DNA is damaged and cannot be repaired. M M checkpoint Spindle assembly checkpoint. Mitosis will not continue if chromosomes are not properly aligned. 3 Interphase Most of the cell cycle is spent in interphase (as much as 90% of their time) Cell performs its usual functions Time spent in interphase varies by cell type Nerve and muscle cells do not complete the cell cycle (remain in the G0 stage) 4 Interphase Interphase consists of: G1, S and G2 phases G1 Phase: Recovery from previous division Cell doubles its organelles Cell grows in size Accumulates raw materials for DNA synthesis (DNA replication) Passage into S phase is governed by restriction points or check points 5 Interphase Interphase consists of: G1, S and G2 phases S Phase: DNA replication Proteins associated with DNA are synthesized Chromosomes enter with 1 chromatid each Chromosomes leave with 2 identical chromatids each (called sister chromatids) G2 Phase: Between DNA replication and onset of mitosis Cell synthesizes proteins necessary for division 6 Mitotic (M) Stage Includes: Mitosis (karyokinesis) Nuclear division Daughter chromosomes distributed to two daughter nuclei Cytokinesis Cytoplasm division Results in two genetically identical daughter cells 7 Cell Cycle Control Cell cycle controlled by internal and external signals A signal is a molecule that either stimulates or inhibits a metabolic event. External signals Growth factors Internal signals Family of proteins called cyclins Increase and decrease as cell cycle continues Without them cycle stops at G1, M or G2 (checkpoints) Allows time for any damage to be repaired 8 Chromosome Number The diploid (2n) number includes two sets of chromosomes of each type Humans have 23 different types of chromosomes Each type is represented twice in each body cell (Diploid) One set of 23 from individual’s father (paternal) Other set of 23 from individual’s mother (maternal) Only sperm and eggs have one of each type (haploid) 9 Chromosome Structure At end of S phase: Each chromosome internally duplicated Consists of two identical DNA chains Sister chromatids (two strands of genetically identical chromosomes) Attached together at a single point (called centromere) During mitosis: Centromeres holding sister chromatids together simultaneously break Sister chromatids separate Each becomes a daughter chromosome Sisters of each type distributed to opposite daughter nuclei 10 Mitosis in Animal Cells: Prophase Prophase Chromatin has condensed Chromosomes distinguishable with microscope Visible double (two sister chromatids attached at centromere) Nucleolus disappears Nuclear envelope disintegrates Spindle begins to take shape Two centrosomes (region where centrioles are located) move away from each other Form microtubules in star-like arrays – asters 11 Mitosis in Animal Cells: Prometaphase Prometaphase Centromere of each chromosome develops two kinetochores Specialized protein complex One over each sister chromatid Physically hook sister chromatids up with specialized microtubules (kinetochore fibers) These connect sisters to opposite poles of mother cell 12 Mitosis in Animal Cells: Metaphase & Anaphase Metaphase Chromosomes are pulled around by kinetochore fibers Forced to align across equatorial plane of cell Appear to be spread out on a piece of glass Metaphase plate Represents plane through which mother cell will be divided Anaphase Sister chromatids separate Now called daughter chromosomes Pulled to opposite poles along kinetochore fibers Centromere dissolves, releasing sister chromatids 13 Mitosis in Animal Cells: Telophase Telophase Spindle disappears Now two clusters of daughter chromosomes Nuclear envelopes form around the two incipient daughter nuclei Chromosomes uncoil and become diffuse chromatin again Nucleolus reappears in each daughter nucleus 14 Cytokinesis: Animal Cells Division of cytoplasm Allocates mother cell’s cytoplasm equally to daughter nucleus Encloses each in it’s own plasma membrane Often begins in anaphase Animal cytokinesis: A cleavage furrow appears between daughter nuclei Formed by a contractile ring of actin filaments Like pulling on a draw string Eventually pinches mother cell in two 15 Function of Mitosis Permits growth and repair. In plants it retains the ability to divide throughout the life of the plant In mammals, mitosis is necessary: Fertilized egg becomes an embryo Embryo becomes a fetus Allows a cut to heal or a broken bone to mend 16 Prokaryotic Cell Division Prokaryotic chromosome a ring of DNA Folded up in an area called the nucleoid Replicated into two rings prior to division Replicate rings attach to plasma membrane 17 Asexual Reproduction Binary fission Splitting in two between the two replicate chromosomes Produces two daughter cells identical to original cell – Asexual Reproduction Budding Regeneration Oarthenogenesis 18 Meiosis: Halves the Chromosome Number Special type of cell division Used only for sexual reproduction Halves the chromosome number prior to fertilization Parents diploid Meiosis produces haploid gametes Gametes fuse in fertilization to form diploid zygote Becomes the next diploid generation 19 Homologous Pairs of Chromosomes In diploid body cells chromosomes occur in pairs Humans have 23 different types of chromosomes Diploid cells have two of each type Chromosomes of the same type are said to be homologous They have the same length Their centromeres are positioned in the same place One came from the father (the paternal homolog) the other from the mother (the maternal homolog) When stained, they show similar banding patterns A location on one homologue contains gene for the same trait that occurs at this locus on the other homologue Although the genes may code for different variations of that trait Alternate forms of a gene are called alleles 20 Homologous Pairs of Chromosomes Homologous chromosomes have genes controlling the same trait at the same position Each gene occurs in duplicate A maternal copy from the mother A paternal copy from the father Many genes exist in several variant forms in a large population Homologous copies of a gene may encode identical or differing genetic information The variants that exist for a gene are called alleles An individual may have: Identical alleles for a specific gene on both homologs (homozygous for the trait), or A maternal allele that differs from the corresponding paternal allele (heterozygous for the trait) 21 Phases of Meiosis I: Prophase I & Metaphase I Meiosis I (reductional division): Prophase I Each chromosome internally duplicated (consists of two identical sister chromatids) Homologous chromosomes pair up – synapsis Physically align themselves against each other end to end End view would show four chromatids – Tetrad Metaphase I Homologous pairs arranged onto the metaphase plate 22 Phases of Meiosis I: Anaphase I & Telophase I Anaphase I Synapsis breaks up Homologous chromosomes separate from one another Homologues move towards opposite poles Each is still an internally duplicate chromosome with two chromatids Telophase I Daughter cells have one internally duplicate chromosome from each homologous pair One (internally duplicate) chromosome of each type (1n, haploid) 23 Phases of Meiosis I: Cytokinesis I & Interkinesis Cytokinesis I Two daughter cells Both with one internally duplicate chromosome of each type Haploid Meiosis I is reductional (halves chromosome number) Interkinesis Similar to mitotic interphase Usually shorter No replication of DNA 24 Genetic Variation: Crossing Over Meiosis brings about genetic variation in two key ways: Crossing-over between homologous chromosomes, and Independent assortment of homologous chromosomes Crossing Over: Exchange of genetic material between nonsister chromatids during meiosis I At synapsis, a nucleoprotein lattice (called the synaptonemal complex) appears between homologues Holds homologues together Aligns DNA of nonsister chromatids Allows crossing-over to occur Then homologues separate and are distributed to different daughter cells 25 Genetic Variation: Significance Asexual reproduction produces genetically identical clones Sexual reproduction cause novel genetic recombinations Asexual reproduction is advantageous when environment is stable However, if environment changes, genetic variability introduced by sexual reproduction may be advantageous Offspring adapt to that environment 26 Phases of Meiosis II: Similar to Mitosis Metaphase II Prophase II – Chromosomes condense Metaphase II – Chromosomes align at metaphase plate Anaphase II Unremarkable Virtually indistinguishable from mitosis of two haploid cells Centromere dissolves Sister chromatids separate and become daughter chromosomes Telophase II and cytokinesis II Four haploid cells All genetically unique 27 Meiosis vs. Mitosis Meiosis Requires two nuclear divisions Chromosomes synapse and cross over Centromeres survive Anaphase I Halves chromosome number Produces four daughter nuclei Produces daughter cells genetically different from parent and each other Used only for sexual reproduction Mitosis Requires one nuclear division Chromosomes do not synapse nor cross over Centromeres dissolve in mitotic anaphase Preserves chromosome number Produces two daughter nuclei Produces daughter cells genetically identical to parent and to each other Used for asexual reproduction and growth 28 Meiosis I Compared to Mitosis 29 Meiosis II Compared to Mitosis 30 The Human Life Cycle Sperm and egg are produced by meiosis A sperm and egg fuse at fertilization Results in a zygote The one-celled stage of an individual of the next generation Undergoes mitosis Results in multicellular embryo that gradually takes on features determined when zygote was formed All growth occurs as mitotic division As a result of mitosis, each somatic cell in body Has same number of chromosomes as zygote Has genetic makeup determined when zygote was formed 31 The Human Life Cycle Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. MITOSIS 2n 2n 2n MITOSIS 2n zygote 2n = 46 diploid (2n) MEIOSIS FERTILIZATION haploid (n) n = 23 n n egg sperm 32 Gametogenesis in Mammals Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. SPERMATOGENESIS Primary spermatocyte 2n Meiosis I Secondary spermatocytes n Meiosis II spermatids n Metamorphosis and maturation sperm n OOGENESIS Primary oocyte 2n Meiosis I First polar body n Secondary oocyte n Meiosis II Second polar body n Fertilization cont'd sperm nucleus n fusion of sperm nucleus and egg nucleus Meiosis II is completed after entry of sperm egg n zygote 2n 33 Changes in Chromosome Number Euploid is the correct number of chromosomes in a species. Aneuploid is change in the chromosome number Results from nondisjunction Monosomy - only one of a particular type of chromosome, Trisomy - three of a particular type of chromosome 34 Changes in Chromosome Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. pair of homologous chromosomes pair of homologous chromosomes Meiosis I nondisjunction normal nondisjunction Meiosis II normal Fertilization Zygote 2n a. 2n 2n + 1 2n - 1 2n + 1 2n + 1 2n - 1 2n - 1 b. 35 Trisomy Trisome 21 Occurs when an individual has three of a particular type of chromosome The most common autosomal trisomy seen among humans Also called Down syndrome Recognized by these characteristics: short stature eyelid fold flat face stubby finger wide gap between first and second toes 36 Changes in Sex Chromosome Result from inheriting too many or too few X or Y chromosomes Nondisjunction during oogenesis or spermatogenesis Turner syndrome (XO) Female with single X chromosome Short, with broad chest and widely spaced nipples Can be of normal intelligence and function with hormone therapy Klinefelter syndrome (XXY) – a male Male with underdeveloped testes and prostate; some breast overdevelopment Long arms and legs; large hands Near normal intelligence unless XXXY, XXXXY, etc. No matter how many X chromosomes, presence of Y renders individual male 37 Changes in Chromosome Structure Changes in chromosome structure include: Deletions Duplications One or both ends of a chromosome breaks off Two simultaneous breaks lead to loss of an internal segment Presence of a chromosomal segment more than once in the same chromosome Translocations A segment from one chromosome moves to a nonhomologous chromosome Follows breakage of two nonhomologous chromosomes and improper re-assembly 38 Changes in Chromosome Structure Duplication A segment of a chromosome is repeated in the same chromosome Inversion Occurs as a result of two breaks in a chromosome The internal segment is reversed before re-insertion Genes occur in reverse order in inverted segment 39 Types of Chromosomal Mutation Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. a s a s b t b t c c u a. d v e u translocation d v w e w f x f x g y y g h z z h b. b: American Journal of Human Genetics by N. B. Spinner. Copyright 1994 by Elsevier Science & Technology Journals. Reproduced with permission of Elsevier Science & Technology Journals in the format Textbook via Copyright Clearance Center 40 Reproductive System The only system not essential for life, but ensures continued human existence Functions of Reproductive system include: Production of gametes Storage gametes Nourishment gametes Transport gametes In female additional functions such as provide nutrient and support to the developing embryo, fetus and infant Fertilization Fusion of male and female gametes to form a zygote Reproductive system includes: Organs of reproductive system include: 1) Gonads (testes, ovaries) – produce sperm/egg 2) Ducts – a passageway that opens to the exterior and transport gamete Testes produce gametes (spermatozoa/ sperm) 1.5 billion each day and secrete sex hormones (testosterone) Ovaries release one immature gamete (oocyte) per month Sperm is mixed with secretion of accessory glands along ducts and converted to semen Oocyte travels along uterine tube to uterus 3) Accessory glands and organs – these organs secrete fluid e.g. seminal vesicle secrete seminal fluid 4) External genitalia Male Reproductive System: Sperm Passageway 1. Spermatozoa is produced in testes in the seminiferous tubules Seminiferous tubules are tightly coiled tubes found in lobules of testes From seminiferous tubules sperms are passed to afferent ductules 3. Afferent ductules pass the sperm to rete stestes 4. From rete testes spearm leave the testes by efferent tuctules 5. Efferent tuctules deliver the sperm to the epididymis 2. The Structure of the Testes Male Reproductive System: Sperm Passageway Epididymis pass the sperms to the duct deference 7. From ductus deferens, sperms are passed to the ejaculatory duct 8. Ejaculatory duct is connected to the urethra Accessory organs of male reproductive system 1. Seminal vesicles 2. Prostate gland 3. Bulbourethral glands 4. Scrotal sac encloses testes 5. Penis 6. The Male Reproductive System Sperm production: Spermatogenesis • Sperm production takes place in seminiferous tubules • Seminiferous tubules contain sustencular cells and stem cells called spermatogonia • Stem cells involved in spermatogenesis • Sustencular cells sustain and promote development of sperm • Interstitial cells between seminiferous tubules secrete sex hormones (testosterone) Sperm production: Spermatogenesis Spermatogenesis involves three processes 1) Mitosis 2) Meiosis In this process spermatocytes are produced from spermatogonium In this process spermatocytes go through meiosis I and meiosis II and produce 4 spermatids 3) Spermiogenesis In this process spermatids differentiate into spermatozoa Anatomy of spermatozoon Each spermatozoon is divided into 3 part: 1) Head that contains: 2) Middle piece that contains Nucleus and densely packed chromosomes Mitochondria that produce the ATP needed to move the tail 3) Tail The only cell with flagellum in the human body It enables the spermatozoa to swim Male reproductive tract: Epididymus Epididymus is elongated tubule with head, body and tail regions Functions of epididymus are to: 1) Monitor and adjust fluid in seminiferous tubules 2) Store and protect spermatozoa 3) act as a recycling center for damaged spermatozoa 4) Facilitates functional maturation of spermatozoa Ductus deferens AKA vas deferens Begins at epididymus Passes through inguinal canal Enlarges to form ampulla Peristaltic contractions propel spermatozoa and fluid along the duct Functions of Duct Deferens: Transport spermatozoa, Store spermatozoa (for several months) The junction of the ampulla with the duct of the seminal vesicle marks the start of the ejaculatory duct Ejaculatory duct is a short passageway that penetrates the muscular wall of the prostate gland and empties into the urethra Urethra This passageway is used by both urinary and reproductive systems This passageway begins at the urinary bladder and ends at the tip of the penis Urethra divides into three regions Prostatic Membranous Penile Accessory glands Important glands include the seminal vesicles, the prostate gland, and the bulbourethral glands Seminal vesicles Contributes about 60% of the total volume of semen Secretions of seminal vesicle contain fructose, prostaglandins, fibrinogen Fructose is metabolized by spermatozoa and used as a source of energy Prostaglandins stimulates smooth muscle contractions along the reproductive tracts (e.g. vagina), thus it helps spermatozoa to move Fibrinogen forms a temporary clot within the vagina to prevent damage to the spermatozoa by the acidic environment of vagina. Spermatozoa become mobile after mixing with seminal vesicles secretion Accessory glands Prostate gland Secretes an alkaline prostatic fluid that accounts for about 20-30 % of semen volume Contains seminalplasmin (an antibiotic that prevents urinary tract infection) The alkaline secretion helps to neutralizes acid along the urethra and in the vagina Bulbourethral glands Secrete alkaline mucus with lubricating properties Contents of Semen Typical ejaculate = 2-5 ml fluid that contain: 1) Contains between 20 – 100 million spermatozoa per ml 2) Seminal Fluid about 60% 3) Prostatic Fluid about 20-30 % 4) Enzymes such as: Protease – helps dissolve mucous secretion in the vagina Seminalplasmin – antibiotic enzyme that kills bacteria Enzymes that convert fibrinogen to fibrin that will clot the semen Fibrinolysis – liquefies the clotted semen after the virginal environment is neutralized Hormones of male and female reproductive system At puberty Hypothalamus produces GnRH (Gonadotropin releasing hormone) GnRH stimulates production of FHS and LH by the pituitary gland FSH (Follicle stimulating hormone) In male FSH targets sustentacular cells of testes and stimulates spermatogenesis (production of sperm) In female FSH stimulates development of follicle (egg) Developing follicle produces estrogen LH (leutinizing hormone) In male LH causes secretion of testosterone and other androgens by the interstitial cells In female LH stimulates secretion of progesterone by corpus luteum In female LH surge leads to ovulation Hormones of male and female reproductive system Testosterone 1) stimulating spermatogenesis 2) affect sexual drive(libido) 3) stimulate metabolism 4) stimulate the male secondary sexual characteristics 5) maintaining accessory glands and organs of male reproductive tract Progesterone Stimulate endometrial growth and secretion Estrogen 1) stimulating bone and muscle growth 2) stimulate female secondary sexual characteristics 3) initiating the repair and growth of the endometrium The Reproductive System of the Female Principle organs of the female reproductive system Ovaries Uterine tubes Uterus Vagina Oogenesis • Oogenesis is the process of ovum production • It occurs monthly in ovarian follicles • Part of ovarian cycle • Follicular phase (preovulatory) • Luteal phase (postovulatory) The ovarian cycle Steps in the ovarian cycle 1) Formation of primary, secondary, and tertiary follicles 2) Ovulation 3) Formation and degeneration of the corpus luteum Corpus luteum begins to degenerate roughly 12 days after ovulation if fertilization does not occur 4) Degradation of the corpus luteum The uterus The uterus is a muscular organ Its functions are: 1) Mechanical protection 2) Nutritional support 3) Waste removal for the developing embryo and fetus The Uterine Wall • Uterine wall consists of 3 layer: • Myometrium – outer muscular layer • Endometrium – a thin, inner, glandular mucosa • Perimetrium – an incomplete serosa continuous with the peritoneum Uterine cycle Repeating series of changes in the endometrium Uterine cycle continues from menarche (the first minstruation) to menopause (the last minstruation) Uterine cycle is divided into 3 phases: 1) Menses Degeneration of the endometrium Menstruation 2) Proliferative phase Restoration of the endometrium 3) Secretory phase Endometrial glands enlarge and accelerate their rates of secretion Hormones of the female reproductive cycle Control the reproductive cycle Coordinate the ovarian and uterine cycles The Hormonal Regulation of the Female Reproductive Cycle The Hormonal Regulation of the Female Reproductive Cycle Animation: Regulation of the Female Reproductive Cycle (see tutorial)