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1 Cell Cycle, Mitosis & Meiosis. Chromosomes All eukaryotic cells store genetic information in chromosomes. All eukaryotic cells store genetic information.

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Presentation on theme: "1 Cell Cycle, Mitosis & Meiosis. Chromosomes All eukaryotic cells store genetic information in chromosomes. All eukaryotic cells store genetic information."— Presentation transcript:

1 1 Cell Cycle, Mitosis & Meiosis

2 Chromosomes All eukaryotic cells store genetic information in chromosomes. All eukaryotic cells store genetic information in chromosomes. Most eukaryotes have between 10 and 50 chromosomes in their body cells.Most eukaryotes have between 10 and 50 chromosomes in their body cells. Human cells have 46 chromosomes.Human cells have 46 chromosomes. 23 nearly-identical pairs23 nearly-identical pairs

3 Chromosomes A diploid cell has two sets of each of its chromosomes A diploid cell has two sets of each of its chromosomes A human has 46 chromosomes (2n = 46) A human has 46 chromosomes (2n = 46) In a cell in which DNA synthesis has occurred all the chromosomes are duplicated and thus each consists of two identical sister chromatids In a cell in which DNA synthesis has occurred all the chromosomes are duplicated and thus each consists of two identical sister chromatids Maternal set of chromosomes (n = 3) Paternal set of chromosomes (n = 3) 2n = 6 Two sister chromatids of one replicated chromosome Two nonsister chromatids in a homologous pair Pair of homologous chromosomes (one from each set) Centromere

4 Chromosome Duplication 0.5 µm Chromosome duplication (including DNA synthesis) Centromere Separation of sister chromatids Sister chromatids Centrometers Sister chromatids A eukaryotic cell has multiple chromosomes, one of which is represented here. Before duplication, each chromosome has a single DNA molecule. Once duplicated, a chromosome consists of two sister chromatids connected at the centromere. Each chromatid contains a copy of the DNA molecule. Mechanical processes separate the sister chromatids into two chromosomes and distribute them to two daughter cells. In preparation for cell division, DNA is replicated and the chromosomes condense In preparation for cell division, DNA is replicated and the chromosomes condense Each duplicated chromosome has two sister chromatids, which separate during cell division Each duplicated chromosome has two sister chromatids, which separate during cell division

5 Because of duplication, each condensed chromosome consists of 2 identical chromatids joined by a centromere. Because of duplication, each condensed chromosome consists of 2 identical chromatids joined by a centromere. Each duplicated chromosome contains 2 identical DNA molecules (unless a mutation occurred), one in each chromatid: Each duplicated chromosome contains 2 identical DNA molecules (unless a mutation occurred), one in each chromatid: Chromosome Duplication Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. Two unduplicated chromosomes Centromere Sister chromatids Sister chromatids Duplication Non-sister chromatids Two duplicated chromosomes

6 6 Chromosomes, ploidy and n

7 7 2 Types of Cell Division Mitosis – ordinary somatic cell division Mitosis – ordinary somatic cell division 2 daughter cells with identical chromosomes and genes to parents2 daughter cells with identical chromosomes and genes to parents Diploid cells – 2n chromosome complementDiploid cells – 2n chromosome complement Meiosis – germline cell division Meiosis – germline cell division Results in formation of gametes – cells with only 23 chromosomesResults in formation of gametes – cells with only 23 chromosomes Haploid cells – n chromosome complementHaploid cells – n chromosome complement

8 Phases of the Cell Cycle Interphase Interphase G 1 - primary growthG 1 - primary growth S - genome replicatedS - genome replicated G 2 - secondary growthG 2 - secondary growth M - mitosis M - mitosis C - cytokinesis C - cytokinesis

9 Interphase G 1 - Cells undergo majority of growth G 1 - Cells undergo majority of growth S - Each chromosome replicates (Synthesizes) to produce sister chromatids S - Each chromosome replicates (Synthesizes) to produce sister chromatids Attached at centromereAttached at centromere Contains attachment site (kinetochore)Contains attachment site (kinetochore) G 2 - Chromosomes condense - Assemble machinery for division such as centrioles G 2 - Chromosomes condense - Assemble machinery for division such as centrioles

10 Mitosis  Some haploid & diploid cells divide by mitosis.  Each new cell receives one copy of every chromosome that was present in the original cell.  Produces 2 new cells that are both genetically identical to the original cell. DNA duplication during interphase Mitosis Diploid Cell

11 Embryonic cell cycles The duration of the phases varies considerably in different kinds of cells. The duration of the phases varies considerably in different kinds of cells. Early embryos may have cell cycles of 30 minutes, but Early embryos may have cell cycles of 30 minutes, but there is no growth (G 1 or G 2 ) phase. In contrast, some cells in adult animals cease division altogether (e.g., nerve cells). In contrast, some cells in adult animals cease division altogether (e.g., nerve cells). Others may divide only occasionally, to replace cells that have been lost. Others may divide only occasionally, to replace cells that have been lost.

12 12 The Cell Cycle G 1 No DNA synthesisNo DNA synthesis Lasts hours, days or yearsLasts hours, days or years Occurs after mitosis and before S phaseOccurs after mitosis and before S phase The availability of growth factors controls the animal cell cycle at a point in late G1 called the restriction point. If growth factors are not available during G1, the cells enter a quiescent stage of the cycle called G0.

13 13 The Cell Cycle S phase Stage of DNA synthesisStage of DNA synthesis The major variants of histones are predominantly synthesized during S phaseThe major variants of histones are predominantly synthesized during S phase Each chromosome replicates  bipartite chromosome made up of sister chromatidsEach chromosome replicates  bipartite chromosome made up of sister chromatids End of each chromatid marked by telomeres – specialized DNA sequences that ensure integrity of chromosomes during divisionEnd of each chromatid marked by telomeres – specialized DNA sequences that ensure integrity of chromosomes during division Sister chromatids held together at centromere – region of DNA associated with kinetochoreSister chromatids held together at centromere – region of DNA associated with kinetochore DNA replication happens at thousands of origins of DNA replicationDNA replication happens at thousands of origins of DNA replication

14 14 The Cell Cycle G 2 phase The cell is preparing for mitosisThe cell is preparing for mitosis Cell’s DNA doubled in S phaseCell’s DNA doubled in S phase Brief stageBrief stage G 0 phase G 0 phase Resting stage/quiescent stageResting stage/quiescent stage Neurons, RBCs arrested in G 1 = G 0 phase – permanent G 1 phaseNeurons, RBCs arrested in G 1 = G 0 phase – permanent G 1 phase Liver cells enter G 0 but on damage  G 1 and cell cycle continuesLiver cells enter G 0 but on damage  G 1 and cell cycle continues

15 Figure Molecular Biology of the Cell (© Garland Science 2008) Centriole Replication At a certain point in G1, the two centrioles of the pair separate. At a certain point in G1, the two centrioles of the pair separate. During S phase, a daughter centriole begins to grow near the base of each mother centriole and at a right angle to it. During S phase, a daughter centriole begins to grow near the base of each mother centriole and at a right angle to it. The elongation of the daughter centriole is usually completed by G2 The elongation of the daughter centriole is usually completed by G2

16 16 Mitosis Mitosis: shortest of 4 stages Mitosis: shortest of 4 stages Important component: chromosomal segregation – process of distributing copy of each chromosome to each daughter cell Important component: chromosomal segregation – process of distributing copy of each chromosome to each daughter cell Errors  genetic imbalances, tumors Errors  genetic imbalances, tumors 5 stages: 5 stages: 1. Prophase 2. Prometaphase 3. Metaphase 4. Anaphase 5. Telophase

17 17 Mitosis is subdivided into prophase, prometaphase, metaphase, anaphase, and telophase Prophase: Condensed chromosome start to become visible, Centrosomes start moving apart, Nucleolus starts disappearing Prophase: Condensed chromosome start to become visible, Centrosomes start moving apart, Nucleolus starts disappearing Prometaphase: Nuclear membrane breaks down Prometaphase: Nuclear membrane breaks down Metaphase: Chromosomes maximally condensed and align at the metaphase plate Metaphase: Chromosomes maximally condensed and align at the metaphase plate Anaphase: The two sister chromatids separate and move toward opposite poles Anaphase: The two sister chromatids separate and move toward opposite poles Telophase: nucleus reassembly occurs, cytokinesis occurs Telophase: nucleus reassembly occurs, cytokinesis occurs

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19 Stages of mitosis in an animal cell

20 Fluorescence micrographs of chromatin, keratin, and microtubules during mitosis

21 21Prophase Condensation of chromosomes Condensation of chromosomes Disintegration and disappearance of nucleolus Disintegration and disappearance of nucleolus Formation of mitotic spindle – microtubule network Formation of mitotic spindle – microtubule network Prometaphase Nuclear membrane breaks up Nuclear membrane breaks up Congression occurs – chromosomes move to point midway between spindle poles Congression occurs – chromosomes move to point midway between spindle poles Condensation of chromosomes continue Condensation of chromosomes continue

22 22Metaphase Maximum condensation of chromosomes reached Maximum condensation of chromosomes reached Arranged at equatorial plane of cell Arranged at equatorial plane of cell Balanced forces of microtubules from opposite poles at kinetochores Balanced forces of microtubules from opposite poles at kinetochores

23 23 The mitotic spindle is responsible for chromosome movements during mitosis Spindle assembly and chromosome attachment Spindle assembly and chromosome attachment Minus ends anchored in centrosomeMinus ends anchored in centrosome Kinetochore: a platelike, three layer structure made of proteins attached to CEN sequences located in the centromeres’ DNAKinetochore: a platelike, three layer structure made of proteins attached to CEN sequences located in the centromeres’ DNA Two kinetochores are located on opposite sides of a chromosome and anchor kinetochore microtubulesTwo kinetochores are located on opposite sides of a chromosome and anchor kinetochore microtubules

24 24Anaphase Begins when sister chromatids separate Begins when sister chromatids separate Sister chromatids separate into daughter chromosomes Sister chromatids separate into daughter chromosomes Daughter chromosomes move to opposite poles Daughter chromosomes move to opposite poles

25 25 Telophase and Cytokinesis Telophase Telophase Chromosomes decondenseChromosomes decondense Nuclear membrane reformsNuclear membrane reforms Cytokinesis divides the cytoplasm Cytokinesis divides the cytoplasm Cleavage begins as a slight indentation in cell surface deepens into a cleavage furrow.Cleavage begins as a slight indentation in cell surface deepens into a cleavage furrow. Actin contractile ring and myosin motors drive the processActin contractile ring and myosin motors drive the process Cytoplasm cleaves separating daughter cellsCytoplasm cleaves separating daughter cells

26 26Meiosis One round of DNA synthesis  2 rounds of chromosomal segregation One round of DNA synthesis  2 rounds of chromosomal segregation Meiosis I – reduction division – chromosome no. goes from diploid  haploidMeiosis I – reduction division – chromosome no. goes from diploid  haploid Meiotic crossing over or recombination also occurs here: homologous segments of DNA exchanged between nonsister chromatids of pair of homologous chromosomes Meiotic crossing over or recombination also occurs here: homologous segments of DNA exchanged between nonsister chromatids of pair of homologous chromosomes Recombination important also for chromosome segregation Recombination important also for chromosome segregation Meiosis II – like mitosis without a preceding DNA replication stageMeiosis II – like mitosis without a preceding DNA replication stage Sister chromatids separate Sister chromatids separate

27 27Meiosis Meiosis can convert one diploid cell into four haploid cells Meiosis can convert one diploid cell into four haploid cells Meiosis I: the first meiotic divisionMeiosis I: the first meiotic division Homologous pairs join together to form a bivalentHomologous pairs join together to form a bivalent Meiosis I produces two haploid cells that have chromosomes composed of sister chromatids Meiosis I produces two haploid cells that have chromosomes composed of sister chromatids Unlike mitosis, in meiosis I, sister chromatids stay together.Unlike mitosis, in meiosis I, sister chromatids stay together. Thus, the cells at the end of meiosis I are considered haploid because it contains only one of the two chromosomes of each bivalentThus, the cells at the end of meiosis I are considered haploid because it contains only one of the two chromosomes of each bivalent Genetic recombinationGenetic recombination

28 28 Meiosis I Prophase I: Homologous chromosomes become paired and exchange DNA Prophase I: Homologous chromosomes become paired and exchange DNA Divided into 5 stagesDivided into 5 stages Formation of synaptonemal complex and crossing-over occursFormation of synaptonemal complex and crossing-over occurs Metaphase I: Bivalents align at the spindle equator Metaphase I: Bivalents align at the spindle equator The kinetochores of sister chromatids lie side by side and face the same pole of the cellThe kinetochores of sister chromatids lie side by side and face the same pole of the cell Random orientation of maternal or paternal chromosomesRandom orientation of maternal or paternal chromosomes Chromosomes held together by chiasmataChromosomes held together by chiasmata Anaphase I: Homologous chromosomes move to opposite spindle poles Anaphase I: Homologous chromosomes move to opposite spindle poles Telophase I and cytokinesis: Two haploid cells are produced Telophase I and cytokinesis: Two haploid cells are produced

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30 30 Prophase I Leptotene Leptotene chromatin begins to condense, 2 sister chromatids so close, cannot be distinguishedchromatin begins to condense, 2 sister chromatids so close, cannot be distinguished Zygotene Zygotene Homologs pair along entire length – synapsisHomologs pair along entire length – synapsis Chromosomes held together by synaptonemal complexChromosomes held together by synaptonemal complex Pachytene Pachytene Synapsis complete, chromosome more tightly coiledSynapsis complete, chromosome more tightly coiled Chromosome appear bivalent – tetrad formationChromosome appear bivalent – tetrad formation Recombination takes placeRecombination takes place Diplotene Diplotene Synaptonemal complex disappearsSynaptonemal complex disappears Bivalents begin to separate but held together at centromeres and ~ 50 points of crossing over – chiasmataBivalents begin to separate but held together at centromeres and ~ 50 points of crossing over – chiasmata Diakinesis – stage of max condensation Diakinesis – stage of max condensation

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32 32 Bivalent Formation and Crossing-over

33 33 Anaphase I Disjunction occurs – members of each bivalent move apart Disjunction occurs – members of each bivalent move apart HOMOLOGS (and usually alleles) SEPARATE!!!HOMOLOGS (and usually alleles) SEPARATE!!! Maternal and paternal chromosomes sort independently  2 23 combinations Maternal and paternal chromosomes sort independently  2 23 combinations Add to this the variation due to crossing over e.g. chr 1 typically contains 3-5 segmentsAdd to this the variation due to crossing over e.g. chr 1 typically contains 3-5 segments Error-prone step: particularly nondisjunction Error-prone step: particularly nondisjunction Metaphase I Nuclear membrane disappears Nuclear membrane disappears Spindle forms Spindle forms Bivalents align at equator Bivalents align at equator

34 Chromosome segregation in meiosis I

35 35 Telophase I & Cytokinesis Telophase I – 2 chromosome sets group at opposite poles Telophase I – 2 chromosome sets group at opposite poles Cytokinesis – cell divides into daughter cells  enter meiotic interphase (no DNA synthesis) Cytokinesis – cell divides into daughter cells  enter meiotic interphase (no DNA synthesis) Spermatogenesis: equalSpermatogenesis: equal Oogenesis: secondary oocyte receives most cytoplasm, other cell  1 st polar bodyOogenesis: secondary oocyte receives most cytoplasm, other cell  1 st polar body

36 36 Meiosis II Meiosis II resembles a mitotic division Meiosis II resembles a mitotic division Prophase II is very brief Prophase II is very brief Metaphase II Metaphase II Kinetochores of sister chromatids now face in opposite directionsKinetochores of sister chromatids now face in opposite directions Anaphase II Anaphase II Sister chromatids separateSister chromatids separate

37 37 Genetic Consequences of Meiosis At the end of meiosis II there are four daughter cells, each containing a haploid set of chromosomes At the end of meiosis II there are four daughter cells, each containing a haploid set of chromosomes Reduction of chromosome numberReduction of chromosome number Segregation of alleles Segregation of alleles Random assortment of the homologues (law of independent assortment) Random assortment of the homologues (law of independent assortment) Meiosis generates genetic diversityMeiosis generates genetic diversity Over 8 million different combinations of chromosomesOver 8 million different combinations of chromosomes Additional shuffling by crossing over Additional shuffling by crossing over Nondisjunction refers to the failure of the two members of a homologous chromosome pair to separate during anaphase Nondisjunction refers to the failure of the two members of a homologous chromosome pair to separate during anaphase Leads to aneuploidy diseases (trisomy 21-Down syndrome)Leads to aneuploidy diseases (trisomy 21-Down syndrome)

38 Solve This Question A couple in their late 30's has a baby girl with a trisomy 21 karyotype. Genetic analysis of a polymorphic VNTR locus on chromosome 21 reveals that the baby has allelic variants A, C, D; the mother has alleles A, D; the father has alleles B, C. When did meiotic nondisjunction most likely occur and in which parent? A couple in their late 30's has a baby girl with a trisomy 21 karyotype. Genetic analysis of a polymorphic VNTR locus on chromosome 21 reveals that the baby has allelic variants A, C, D; the mother has alleles A, D; the father has alleles B, C. When did meiotic nondisjunction most likely occur and in which parent? Answer: Nondisjunction occurred during meiosis I in the mother. Answer: Nondisjunction occurred during meiosis I in the mother. 38

39 Comparison of meiosis and mitosis

40 40 Human Gametogenesis

41 41Spermatogenesis Sperm formed in seminiferous tubules after sexual maturity Sperm formed in seminiferous tubules after sexual maturity Tubules lined with spermatogonia in different stages of differentiation Tubules lined with spermatogonia in different stages of differentiation Last cell type is primary spermatocyte  meiosis I  2 haploid secondary spermatocytes  meiosis II  4 spermatids  sperm Last cell type is primary spermatocyte  meiosis I  2 haploid secondary spermatocytes  meiosis II  4 spermatids  sperm Process takes 64 daysProcess takes 64 days 200 million sperm produced per ejaculate and in a lifetime200 million sperm produced per ejaculate and in a lifetime

42 42 Oogenesis Occurs only during prenatal development Occurs only during prenatal development Oogonia in ovarian cortex originate from primordial germ cells by about 30 mitoses Oogonia in ovarian cortex originate from primordial germ cells by about 30 mitoses By 3 rd month, oogonia  primary oocytes which enter prophase I By 3 rd month, oogonia  primary oocytes which enter prophase I No primary oocytes develop after month 5 of fetal life At birth, ~ 2.5 million primary oogonia, only ~ 400 eventually mature At birth, ~ 2.5 million primary oogonia, only ~ 400 eventually mature At sexual maturity, individual follicles mature, oocyte completes meiosis I  one secondary oocyte (ovum) At sexual maturity, individual follicles mature, oocyte completes meiosis I  one secondary oocyte (ovum) Meiosis II begins but is arrested in metaphase until fertilization Meiosis II begins but is arrested in metaphase until fertilization

43 Oogenesis - Continued If fertilization takes place, this secondary oocyte will complete 2 nd meiotic division. If fertilization takes place, this secondary oocyte will complete 2 nd meiotic division. Most of the cytoplasm is retained by the fertilized secondary oocyte and the 2 nd polar body receives very little cytoplasm. Most of the cytoplasm is retained by the fertilized secondary oocyte and the 2 nd polar body receives very little cytoplasm. The 2 nd polar body is extruded and maturation of oocyte is completed The 2 nd polar body is extruded and maturation of oocyte is completed 43

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