Cellular Reproduction, Part 2: Meiosis Lecture 10 Fall 2008 1 Mitosis & Meiosis Mitosis • Form of cell division that leads to identical daughter cells with the full complement of DNA • Occurs in somatic cells Karyotype – Cells of body that are not reproductive cells – In humans, have 46 chromosomes • 2 sets of 23 chromosomes Fig. 13.3 2 Mitosis & Meiosis • Homologous chromosomes – Matched pair of chromosomes that carry potentially different versions of the same genes – Alleles: alternate forms of a gene – Locus (Loci): a genes specific location on a chromosome • Diploid (2n) – Contains homologous pairs of chromosomes Karyotype Fig. 13.4 Fig. 13.3 3 Mitosis & Meiosis • Sex chromosomes (X, Y in mammals) – Determines the sex of an organism – In females, all 23 chromosomes are homologous • XX = females – In males, 22 are homologous, one pair does not match • XY = male • Autosomes – Chromosomes that are not sex chromosomes Karyotype Fig. 13.3 Mitosis & Meiosis Meiosis • Form of cell division that leads to non-identical daughter cells with one-half the complement of DNA • Forms gametes – Reproductive cells (sperm cells & egg cells) • Haploid (n) – Contains only one member of each homologous chromosome pair – 23 chromosomes (human) – 22 autosomes & 1 sex chromosome 4 5 Meiosis Meiosis • Part of sexual reproduction – Egg & sperm haploid (1n) – Egg & sperm fuse into one cell (fertilization) – Fertilized egg (zygote) now diploid (2n) – Zygote grows by a series of mitotic cell division • Life cycle – Generation to generation sequence of stages in the reproductive history of an organism Fig. 13.5 Meiosis Differs from mitosis • Halves the number of chromosomes – Two rounds of cell division in meiosis – Mitosis ends with 2 cells, meiosis with 4 cells • Allows for exchange of genetic material – Crossing over of homologous chromosomes 6 Meiosis 2 rounds of cell division Meiosis 1 • One cell divides into two cells • Homologous chromosomes separate – – – – Prophase 1 Metaphase 1 Anaphase 1 Telophase 1 & Cytokinesis Meiosis 2 • Each of the above cells divides into two cells • End with total of 4 cells • Sister chromatids separate – – – – Prophase 2 Metaphase 2 Anaphase 2 Telophase 2 & Cytokinesis 7 • Activity 8 Meiosis Fig. 13.7 9 Meiosis G2 of Interphase Same as mitosis • Chromosomes duplicated – Each chromosome is two identical sister chromatids • Chromosomes still uncondensed • Centrosome – Centrosome replicates into 2 In this example: Red = chromosome from mother Blue = chromosome from father Meiosis 1: Homologous Chromosomes Separate Prophase 1 • Chromosomes condense • Breakdown of nuclear envelope • Homologous chromosomes attached in pairs – Each chromosome is made up of 2 sister chromatids – 4 chromatids = tetrad • Crossing over occurs – Exchange of genetic material between nonsister chromatids • Formation of mitotic spindle • Microtubules attach to tetrads & move them towards the center of the cell Fig. 13.8 10 11 Meiosis 1: Homologous Chromosomes Separate Metaphase 1 • Mitotic spindle fully formed • Tetrads lined up at equator of cell (metaphase plate) • Both chromatids of one homolog are attached to microtubules from one pole Fig. 13.8 12 Meiosis 1: Homologous Chromosomes Separate Anaphase 1 • Pairs of homologous chromosomes are split up – Homologous chromosomes drawn to opposite poles of cell • Cohesins broken down along chromatid arms – Still doubled - remain as sister chromatids • Cohesins remains at centromere • Cell elongates • Read Fig. 13.10 Inquiry Fig. 13.8 13 Meiosis 1: Homologous Chromosomes Separate Telophase 1 • Chromosomes at poles of cell • Two daughter nuclei begin to form in the cell • Chromosomes become less condensed (depending on species) • Mitotic spindle goes away Cytokinesis • Two haploid cells produced – Have only one member of each homologous chromosome pair – That chromosome is still duplicated (sister chromatids) Fig.13.8 Meiosis II: Sister Chromatids Separate 14 Meiosis II is basically the same process as Mitosis, EXCEPT • Starts with the two haploid cells produced at the end of Meiosis 1, and • Ends with four cells, each haploid, each genetically different Fig. 13.8 15 A Comparison of Mitosis & Meiosis Fig. 13.9 A Comparison of Mitosis & Meiosis Fig. 13.9 16 Genetic Variation in Sexual Life Cycles Meiosis • Form of cell division that leads to non-identical daughter cells with one-half the complement of DNA Three forms of variation • Independent assortment of chromosomes • Random Fertilization • Crossing Over 17 Genetic Variation in Sexual Life Cycles 18 Independent assortment of chromosomes • 2n possibilities • 223 = ~ 8.4 million possibilities Fig. 13.11 19 Genetic Variation in Sexual Life Cycles Random fertilization • Sperm cell ~ 8.4 million combinations • Egg cell ~ 8.4 million combinations • ~70 trillion (223 X 223) possibilities!!! Genetic Variation in Sexual Life Cycles Crossing over • The exchange of corresponding segments between two nonsister chromatids – Homologous chromosomes carry different alleles • Occurs during Prophase 1 of Meiosis • Synapsis – Connection of homologous chromosomes • Synaptonemal complex (proteins) • Chiasma – site of crossing over – Connection remains after synapsis ends Fig. 13.12 20 Genetic Variation in Sexual Life Cycles Crossing over • Recombinant chromosomes – Chromosomes that carry genes derived from two different parents • Affects multiple genes • Can be multiple crossovers Fig. 13.12 21 22 Sexual vs. Asexual Reproduction Asexual reproduction • Reproduction involving only one parent that produces genetically identical (clone) offspring • Process of mitosis Sexual reproduction • Fertilization of an egg by a sperm creating offspring that are genetically different from the parent • Sperm & egg created by meiosis Sexual vs. Asexual Reproduction • • • • Benefits of sexual reproduction? Costs of sexual reproduction? Benefits of asexual reproduction? Costs of asexual reproduction? 23 24 Regulation of Cell Cycle • Regulation of timing and rate of cell cycle critical for normal growth, development and maintenance • Cell cycle control system – Cyclically operating set of molecules in cell that triggers and coordinates key events • Highly conserved evolutionarily in eukaryotes – Same molecules found in many species • Read Inquiry Fig. 12.13 12.14 Regulation of Cell Cycle • Checkpoints – Regulatory point – Stop or go-ahead signals • May have built in “stop” that must be overridden by “go-ahead” signal • Cellular surveillance mechanisms – Check that processes have been completed correctly – Signal a go-ahead • Some signals come from outside of cell • Major checkpoints – G1, G2, M 25 Regulation of Cell Cycle • G1 checkpoint – restriction point • If go-ahead, then moves on to S phase • If go-ahead not received, then switch to G0 phase – Non-dividing state • Most cells in G0 phase – Nerve, muscle never divides 12.15 26 Regulation of Cell Cycle • Control of cell cycle based on abundance of regulatory molecules • Concentration of molecules fluctuate cyclically • Regulatory molecules – Protein kinases • Proteins that activate/inactivate other molecules through phosphorylation • Typically present in constant concentration in cells – Inactive – Cyclins • Protein whose concentration fluctuates cyclically • Attaches to kinases to activate them – Cyclin-dependent kinases (Cdks) 27 28 Internal Signals • Control at the G2 checkpoint • MPF (maturation-promoting factor) – Initiates mitosis by phosphorylating many proteins • Phosphorylates proteins in nuclear lamina – promotes fragmentation of nuclear envelope • Role in chromosome condensation • Role in mitotic spindle formation • Concentration of MPF tied to cyclin concentration – Cyclin-CDK complex • Read Fig. 12.6 Inquiry and Interview on pgs. 92-93 Fig. 12.17 Internal Signals 29 • Cyclin synthesis begins in S phase – Concentration levels rise • Cyclin and Cdk molecules combine to form MPF • MPF promotes mitosis • Cyclin starts to degrade – Anaphase • Cdk remains in cell Fig. 12.17 30 Internal Signals • Control within Mitosis – All chromosomes must have the mitotic spindle properly attached to the kinetochore before Anaphase will begin – Go-ahead signal is non-cdk regulatory proteins activated • Cleavage of cohesins • Sister chromatids can separate Control by external factors • Growth factors – Protein released by some cells that stimulate other cells to divide – 50+ identified – Growth factors act as go-ahead signals • Density-dependent inhibition • Crowded cells stop dividing • Cells release inhibitors • Anchorage dependence – Cells must be attached to a substrate to divide – Signal evolves communication between extra-cellular matrix and cytoskeleton 31 32 Cancer: Loss of Cell Cycle Controls • Cancer – Uncontrolled cell division • Do not respond to density dependent inhibition or anchorage dependence • Do not respond to absence of growth factors • Continue to divide indefinitely if supplied with nutrients – Normal cells die after 20-50 divisions • If dividing stopped, it is at random location in cycle, not at checkpoint Cancer: Loss of Cell Cycle Controls • Transformation – Process that converts normal cell to cancer cell – Alteration of genes influencing cell cycle regulation • Benign tumor – Abnormal cells remain at original site • Malignant tumor – Cells invade other tissue • Metastasis – Spread of cancer cells to locations distant from original tumor • Lymph or blood vessels 33 Cancer: Loss of Cell Cycle Controls • Chemotherapy – Targets specific steps in cell cycle – Damages any actively dividing cells – E.g., Taxol • Prevents microtubule depolymerization • Microtubules cannot shorten, so cell stuck in metaphase • Radiation – Damages cancer cells more than normal cells – Reduced ability to repair from radiation damage 34