Lecture 7 Mitosis & Meiosis Cell Division Essential for body growth and tissue repair Interphase G 1 phase Primary cell growth phase S phase DNA replication G 2 phase Microtubule synthesis Mitosis Nuclear division Cytokinesis Cytoplasmic division Chromosomes: Carriers of Inherited Traits Chromosomes were first observed by the German embryologist Walther Fleming in 1882 Chromosomes exist in somatic cells as pairs Homologous chromosomes or homologues The number of chromosomes varies enormously from species to species The Australian ant Myrmecia spp. has only 1 pair Some ferns have more than 500 pairs 1
Human Chromosomes Humans have 46 chromosomes The 23 pairs of homologous chromosomes can be organized by size This display is termed a karyotype Basic Terminology Diploid cells have two copies of each chromosome Replicated chromosomes consist of two sister chromatids These are held together at the centromere Chromosomes Chromosomes are composed of chromatin Complex of DNA (~ 40%) and proteins (~ 60%) A typical human chromosome contains about 140 million nucleotides in its DNA This is equivalent to About 5 cm in stretched length 2,000 printed books of 1,000 pages each! In the cell, however, the DNA is coiled 2
Chromosomes: Packaged DNA The DNA helix is wrapped around positively-charged proteins, called histones 200 nucleotides of DNA coil around a core of eight histones, forming a nucleosome The nucleosomes coil into solenoids Solenoids are then organized into looped domains The looped domains appear to form rosettes on scaffolds Mitosis The phases of mitosis are: Prophase Metaphase Anaphase Telophase X m X Xf m Xf If I m m If If Condense Line Up Separate Divide Cytokinesis Cleavage furrow formed in late anaphase by contractile ring Cytoplasm is pinched into two parts after mitosis ends Early Prophase Asters are seen as chromatin condenses into chromosomes Early mitotic spindle Pair of centrioles Centromere Aster Prophase Chromosome, consisting of two sister chromatids Early prophase Figure 3.32.2 3
Late Prophase Nucleoli disappear Centriole pairs separate and the mitotic spindle is formed Fragments of nuclear envelope Polar microtubules Kinetochore Kinetochore microtubule Spindle pole Prometaphase Late prophase Figure 3.32.2 Metaphase Chromosomes cluster at the middle of the cell with their centromeres aligned at the exact center, or equator, of the cell This arrangement of chromosomes along a plane midway between the poles is called the metaphase plate Metaphase plate Metaphase Spindle Metaphase Figure 3.32.4 Anaphase Centromeres of the chromosomes split Motor proteins in kinetochores pull chromosomes toward poles Anaphase Daughter chromosomes Anaphase Figure 3.32.5 4
Telophase and Cytokinesis New sets of chromosomes extend into chromatin New nuclear membrane is formed from the rough ER Nucleoli reappear Generally cytokinesis completes cell division Contractile ring at cleavage furrow Nucleolus forming Telophase Nuclear envelope forming Telophase and cytokinesis Controlling the Cell Cycle G 0 is an extended rest period The eukaryotic cell cycle is controlled by feedback at three checkpoints 1. Cell growth is assessed at the G 1 checkpoint 2. DNA replication is assessed at the G 2 checkpoint 3. Mitosis is assessed at the M checkpoint Cell Death Fingers and toes form from these paddle-like hands and feet During fetal development, many cells are programmed to die Human cells appear to be programmed to undergo only so many cell divisions About 50 in cell cultures Only cancer cells can divide endlessly Programmed cell death 5
What is Cancer? Cancer is unrestrained cell growth and division The result is a cluster of cells termed a tumor Benign tumors Encapsulated and noninvasive Malignant tumors Not encapsulated and invasive Can undergo metastasis Leave the tumor and spread throughout the body What is Cancer? Most cancers result from mutations in growth-regulating genes There are two general classes of these genes 1. Proto-oncogenes Encode proteins that stimulate cell division If mutated, they become oncogenes 2. Tumor-suppressor genes Encode proteins that inhibit cell division Cancer can be caused by chemicals, radiation or even some viruses Cancer and Control of the Cell Cycle The p53 gene plays a key role in the G 1 checkpoint of cell division The p53 protein (the gene s product), monitors the integrity of DNA If DNA is damaged, the protein halts cell division and stimulates repair enzymes If the p53 gene is mutated Cancerous cells repeatedly divide No stopping at the G 1 checkpoint 6
Cell division and p53 protein New molecular therapies for cancer Receiving the signal to divide Stopping tumor growth Passing the signal via a relay switch Amplifying the signal Stepping on the gas Checking that everything is ready Releasing the brake Potential cancer therapies are being developed to target seven different stages in the cancer process Stages 1-6 Prevent the start of cancer within cells Focus on the decision-making process to divide Stage 7 Act outside cancer cells Prevents tumors from growing and spreading Importance of Generating Diversity Diversity is what allows gene populations to survive changes in their environment The greater the diversity, the more likely some individuals will have the traits to survive a major change Genetic diversity is the raw material that fuels evolution No genetic process generates diversity more quickly than sexual reproduction 7
Two Types of Reproduction Asexual reproduction Creates a faithful copy Does not involve fertilization Contain one set of chromosomes Sexual reproduction Maximizes diversity Involves the alternation of meiosis and fertilization Meiosis halves the number of chromosomes from each parent cell Fertilization restores the number of chromosomes Contains two sets of chromosomes The Sexual Life Cycle The life cycles of all sexually-reproducing organisms follows the same basic pattern Haploid cells or organisms alternate with diploid cells or organisms There are three basic types of sexual life cycles Spend most of life in haploid form Spend most of life in diploid form Spend half of life in haploid form and half in diploid form The Sexual Life Cycle in Humans 8
m m Discovery of Meiosis Meiosis was first observed by the Belgian cytologist Pierre- Joseph van Beneden in 1887 Gametes (eggs and sperm) contain half the complement of chromosomes found in other cells The fusion of gametes is called fertilization or syngamy It creates the zygote, which contains two copies of each chromosome Meiosis Prophase Metaphase Anaphase Telophase Mitosis X m X Xf m Xf If f I m m If If Condense Line Up Separate Divide Meiosis I fx fx fx fx Xf Meiosis II Xf Xf I f IIm m Differences Between Mitosis & Meiosis Mitosis Meiosis Purpose Create a faithful copy Create diversity Where it occurs Body cells Special reproductive organs Number of divisions after one chromatin replication event How chromosomes Line up at metaphase Number of daughter cells Homologous chromosomes in daughter cells Makeup of daughter cells vs. parent cell One Individually Two Two (diploid) Same as parent cell Two Homologous pairs in Meiosis I, Individually in Meiosis II Four One (haploid) Different from parent cell 9
Meiotic Cell Division: Meiosis I Figure 27.7 Tetrads line up at the spindle equator during metaphase I In anaphase I, homologous chromosomes still composed of joined sister chromatids are distributed to opposite ends of the cell At the end of meiosis I each daughter cell has: Two copies of either a maternal or paternal chromosome A 2n amount of DNA and haploid number of chromosomes In telophase I: The nuclear membranes re-form around the chromosomal masses The spindle breaks down The chromatin reappears, forming two daughter cells Metaphase I, Anaphase I, Telophase I Meiotic Cell Division: Meiosis II Mirrors mitosis except that chromosomes are not replicated before it begins Meiosis accomplishes two tasks: It reduces the chromosome number by half (2n to n) It introduces genetic variability Meiosis II Evolutionary Consequences of Sex Sexual reproduction increases genetic diversity through three key mechanisms 1. Independent assortment 2. Crossing over 3. Random fertilization 10
Independent assortment Three chromosome pairs 2 3 combinations In humans, a gamete receives one homologue of each of the 23 chromosomes Humans have 23 pairs of chromosomes 2 23 combinations in an egg or sperm 8,388,608 possible kinds of gametes Crossing over DNA exchanges between maternal and paternal chromatid pairs This adds even more recombination to independent assortment that occurs later Random fertilization The zygote is formed by the union of two independentlyproduced gametes Therefore, the possible combinations in an offspring 8,388,608 X 8,388,608 = 70,368,744,177,664 More than 70 trillion! And this number does not count crossing-over 11