Mitosis & 1 Cellular Reproduction, Part 2: Lecture 10 Fall 2008 Mitosis Form of cell division that leads to identical daughter cells with the full complement of DNA Occurs in somatic cells Cells of body that are not reproductive cells In humans, have 46 chromosomes 2 sets of 23 chromosomes Karyotype Fig. 13.3 Mitosis & 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 Fig. 13.4 Karyotype 2 Mitosis & 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 3 Fig. 13.3 Fig. 13.3 Karyotype
Mitosis & 4 5 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 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 6 7 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 2 rounds of cell division 1 One cell divides into two cells Homologous chromosomes separate Prophase 1 Metaphase 1 Anaphase 1 Telophase 1 & Cytokinesis 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
8 Activity Fig. 13.7 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 9 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
1: Homologous Chromosomes Separate 11 1: Homologous Chromosomes Separate 12 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 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 Fig. 13.8 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) 13 II: Sister Chromatids Separate II is basically the same process as Mitosis, EXCEPT Starts with the two haploid cells produced at the end of 1, and Ends with four cells, each haploid, each genetically different 14 Fig.13.8 Fig. 13.8
A Comparison of Mitosis & 15 A Comparison of Mitosis & 16 Fig. 13.9 Fig. 13.9 Genetic Variation in Sexual Life Cycles 17 Genetic Variation in Sexual Life Cycles 18 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 Independent assortment of chromosomes 2 n possibilities 2 23 = ~ 8.4 million possibilities Fig. 13.11
Genetic Variation in Sexual Life Cycles Random fertilization Sperm cell ~ 8.4 million combinations Egg cell ~ 8.4 million combinations ~70 trillion (2 23 X 2 23) possibilities!!! 19 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 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 21 Sexual vs. Asexual Reproduction 22 Crossing over Recombinant chromosomes Chromosomes that carry genes derived from two different parents Affects multiple genes Can be multiple crossovers 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 Fig. 13.12
Sexual vs. Asexual Reproduction 23 Regulation of Cell Cycle 24 Benefits of sexual reproduction? Costs of sexual reproduction? Benefits of asexual reproduction? Costs of asexual reproduction? 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 25 Regulation of Cell Cycle 26 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 G 1 checkpoint restriction point If go-ahead, then moves on to S phase If go-ahead not received, then switch to G 0 phase Non-dividing state Most cells in G 0 phase Nerve, muscle never divides 12.15
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 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 28 Internal Signals 29 Internal Signals 30 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 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 31 Cancer: Loss of Cell Cycle Controls 32 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 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 33 Cancer: Loss of Cell Cycle Controls 34 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 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