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The Cell Cycle and How Cells Divide 1 Phases of the Cell Cycle • The cell cycle consists of – Interphase – normal cell activity – The mitotic phase – cell divsion INTERPHASE Growth G1 (DNA synthesis) Growth G2 2 Functions of Cell Division 100 µm (a) Reproduction. An amoeba, a single-celled eukaryote, is dividing into two cells. Each new cell will be an individual organism (LM). 200 µm 20 µm (b) Growth and development. (c) Tissue renewal. These dividing This micrograph shows a bone marrow cells (arrow) will sand dollar embryo shortly after give rise to new blood cells (LM). the fertilized egg divided, forming two cells (LM). 3 Cell Division • • • An integral part of the cell cycle Results in genetically identical daughter cells Cells duplicate their genetic material – Before they divide, ensuring that each daughter cell receives an exact copy of the genetic material, DNA 4 DNA • • Genetic information - genome Packaged into chromosomes Figure 12.3 50 µm 5 DNA And Chromosomes • • An average eukaryotic cell has about 1,000 times more DNA then an average prokaryotic cell. The DNA in a eukaryotic cell is organized into several linear chromosomes, whose organization is much more complex than the single, circular DNA molecule in a prokaryotic cell 6 Chromosomes • All eukaryotic cells store genetic information in chromosomes. – Most eukaryotes have between 10 and 50 chromosomes in their body cells. – Human cells have 46 chromosomes. – 23 nearly-identical pairs 7 Structure of Chromosomes • • • Chromosomes are composed of a complex of DNA and protein called chromatin that condenses during cell division DNA exists as a single, long, doublestranded fiber extending chromosome’s entire length. Each unduplicated chromosome contains one DNA molecule, which may be several inches long 8 Structure of Chromosomes Every 200 nucleotide pairs, the DNA wraps twice around a group of 8 histone proteins to form a nucleosome. Higher order coiling and supercoiling also help condense and package the chromatin inside the nucleus: 9 Structure of Chromosomes The degree of coiling can vary in different regions of the chromatin: Heterochromatin refers to highly coiled regions where genes aren’t expressed. Euchromatin refers to loosely coiled regions where genes can be expressed. 10 Structure of Chromosomes • • • Prior to cell division each chromosome duplicates itself. During this time, only the heterochromatin is visible, as dense granules inside the nucleus. There is also a dense area of RNA production called the nucleolus: 11 Karyotype • • • An ordered, visual representation of the chromosomes in a cell Chromosomes are photographed when they are highly condensed, then photos of the individual chromosomes are arranged in order of decreasing size: In humans each somatic cell has 46 chromosomes, made up of two sets, one set of chromosomes comes from each parent Pair of homologous chromosomes 5 µm Centromere Sister chromatids 12 Chromosomes • • • Non-homologous chromosomes – Look different – Control different traits Sex chromosomes – Are distinct from each other in their characteristics – Are represented as X and Y – Determine the sex of the individual, XX being female, XY being male In a diploid cell, the chromosomes occur in pairs. The 2 members of each pair are called homologous chromosomes or homologues. 13 Chromosomes • • • A diploid cell has two sets of each of its chromosomes 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 Maternal set of chromosomes (n = 3) 2n = 6 Paternal set of chromosomes (n = 3) Two sister chromatids of one replicated chromosome Centromere Two nonsister chromatids in a homologous pair Pair of homologous chromosomes (one from each set) 14 Homologues • Homologous chromosomes: • Look the same • Control the same traits • May code for different forms of each trait • Independent origin - each one was inherited from a different parent 15 Chromosome Duplication • • In preparation for cell division, DNA is replicated and the chromosomes condense Each duplicated chromosome has two sister chromatids, which separate during cell division 0.5 µm 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. Chromosome duplication (including DNA synthesis) Centromere Separation of sister chromatids Sister chromatids 16 Centrometers Sister chromatids Chromosome Duplication • • 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: Non-sister chromatids Centromere Duplication Sister chromatids Two unduplicated chromosomes Sister chromatids Two duplicated chromosomes Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. 17 Structure of Chromosomes • • The centromere is a constricted region of the chromosome containing a specific DNA sequence, to which is bound 2 discs of protein called kinetochores. Kinetochores serve as points of attachment for microtubules that move the chromosomes during cell division: Metaphase chromosome Centromere region of chromosome Kinetochore Kinetochore microtubules Sister Chromatids 18 Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. Structure of Chromosomes – – Diploid - A cell possessing two copies of each chromosome (human body cells). Homologous chromosomes are made up of sister chromatids joined at the centromere. Haploid - A cell possessing a single copy of each chromosome (human sex cells). 19 Phases of the Cell Cycle • • • Interphase – G1 - primary growth – S - genome replicated – G2 - secondary growth M - mitosis C - cytokinesis 20 Interphase • • G1 - Cells undergo majority of growth S - Each chromosome replicates (Synthesizes) to produce sister chromatids – Attached at centromere – Contains attachment site (kinetochore) • G2 - Chromosomes condense - Assemble machinery for division such as centrioles 21 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 22 Mitotic Division of an Animal Cell G2 OF INTERPHASE Centrosomes (with centriole pairs) Nucleolus Chromatin (duplicated) Nuclear Plasma envelope membrane PROPHASE Early mitotic spindle Aster Centromere Chromosome, consisting of two sister chromatids PROMETAPHASE Fragments of nuclear envelope Kinetochore Nonkinetochore microtubules Kinetochore microtubule 23 Mitotic Division of an Animal Cell METAPHASE ANAPHASE Metaphase plate Spindle Centrosome at Daughter one spindle pole chromosomes TELOPHASE AND CYTOKINESIS Cleavage furrow Nucleolus forming Nuclear envelope forming 24 G2 of Interphase • A nuclear envelope bounds the nucleus. • The nucleus contains one or more nucleoli (singular, nucleolus). • Two centrosomes have formed by replication of a single centrosome. • In animal cells, each centrosome features two centrioles. • Chromosomes, duplicated during S phase, cannot be seen individually because they have not yet condensed. G2 OF INTERPHASE Centrosomes (with centriole pairs) Chromatin (duplicated) The light micrographs show dividing lung cells from a newt, which has 22 chromosomes in its somatic cells (chromosomes appear blue, microtubules green, intermediate filaments red). For simplicity, the drawings show only four chromosomes. Nucleolus Nuclear Plasma envelope membrane 25 Prophase • The chromatin fibers become more tightly coiled, condensing into discrete chromosomes observable with a light microscope. • The nucleoli disappear. • Each duplicated chromosome appears as two identical sister chromatids joined together. • The mitotic spindle begins to form. It is composed of the centrosomes and the microtubules that extend from them. The radial arrays of shorter microtubules that extend from the centrosomes are called asters (“stars”). • The centrosomes move away from each other, apparently propelled by the lengthening microtubules between them. PROPHASE Early mitotic spindle Aster Centromere Chromosome, consisting of two sister chromatids 26 Metaphase • Metaphase is the longest stage of mitosis, lasting about 20 minutes. • The centrosomes are now at opposite ends of the cell. •The chromosomes convene on the metaphase plate, an imaginary plane that is equidistant between the spindle’s two poles. The chromosomes’ centromeres lie on the metaphase plate. • For each chromosome, the kinetochores of the sister chromatids are attached to kinetochore microtubules coming from opposite poles. • The entire apparatus of microtubules is called the spindle because of its shape. METAPHASE Metaphase plate Spindle Centrosome at one spindle pole 27 The Mitotic Spindle • • • • • The spindle includes the centrosomes, the spindle microtubules, and the asters The apparatus of microtubules controls chromosome movement during mitosis The centrosome replicates, forming two centrosomes that migrate to opposite ends of the cell Assembly of spindle microtubules begins in the centrosome, the microtubule organizing center An aster (a radial array of short microtubules) extends from each centrosome 28 The Mitotic Spindle • • Some spindle microtubules attach to the kinetochores of chromosomes and move the chromosomes to the metaphase plate In anaphase, sister chromatids separate and move along the kinetochore microtubules toward opposite ends of the cell Aster Microtubules Sister chromatids Chromosomes Centrosome Metaphase plate Kinetochores Centrosome 1 µm Overlapping nonkinetochore microtubules Kinetochore microtubules 0.5 µm 29 Anaphase • Anaphase is the shortest stage of mitosis, lasting only a few minutes. • Anaphase begins when the two sister chromatids of each pair suddenly part. Each chromatid thus becomes a fullfledged chromosome. • The two liberated chromosomes begin moving toward opposite ends of the cell, as their kinetochore microtubules shorten. Because these microtubules are attached at the centromere region, the chromosomes move centromere first (at about 1 µm/min). • The cell elongates as the nonkinetochore microtubules lengthen. • By the end of anaphase, the two ends of the cell have equivalent—and complete—collections of chromosomes. ANAPHASE Daughter chromosomes 30 Telophase • Two daughter nuclei begin to form in the cell. • Nuclear envelopes arise from the fragments of the parent cell’s nuclear envelope and other portions of the endomembrane system. • The chromosomes become less condensed. • Mitosis, the division of one nucleus into two genetically identical nuclei, is now complete. TELOPHASE AND CYTOKINESIS Cleavage furrow Nucleolus forming Nuclear envelope forming 31 Mitosis in a plant cell Chromatine Nucleus Nucleolus condensing 1 Prophase. The chromatin is condensing. The nucleolus is beginning to disappear. Although not yet visible in the micrograph, the mitotic spindle is staring to from. Chromosome Metaphase. The 2 Prometaphase. 3 4 spindle is complete, We now see discrete and the chromosomes, chromosomes; each attached to microtubules consists of two at their kinetochores, identical sister are all at the metaphase chromatids. Later plate. in prometaphase, the nuclear envelop will fragment. 5 Anaphase. The chromatids of each chromosome have separated, and the daughter chromosomes are moving to the ends of cell as their kinetochore microtubles shorten. Telophase. Daughter nuclei are forming. Meanwhile, cytokinesis has started: The cell plate, which will divided the cytoplasm in two, is growing toward the perimeter of the parent cell. 32 Cytokinesis • Cleavage of cell into two halves – Animal cells Constriction belt of actin filaments – Plant cells Cell plate – Fungi and protists Mitosis occurs within the nucleus 33 Cytokinesis In Animal And Plant Cells 100 µm Cleavage furrow Contractile ring of microfilaments Vesicles forming cell plate Wall of patent cell 1 µm Cell plate New cell wall Daughter cells Daughter cells (a) Cleavage of an animal cell (SEM) (b) Cell plate formation in a plant cell (SEM) 34 35 Meiosis and Sexual Life Cycles • • • Living organisms are distinguished by their ability to reproduce their own kind Heredity – Is the transmission of traits from one generation to the next Variation – Shows that offspring differ somewhat in appearance from parents and siblings 36 Inheritance of Genes • • • Genes are segments of DNA, units of heredity Offspring acquire genes from parents by inheriting chromosomes Genetics is the scientific study of heredity and hereditary variation 37 Inheritance of Genes • • • Each gene in an organism’s DNA has a specific locus on a certain chromosome We inherit one set of chromosomes from our mother and one set from our father Two parents give rise to offspring that have unique combinations of genes inherited from the two parents - sexual reproduction 38 Asexual Reproduction • In asexual reproduction, one parent produces genetically identical offspring by mitosis Parent Bud Figure 13.2 0.5 mm 39 Sexual Reproduction • • Fertilization and meiosis alternate in sexual life cycles A life cycle is the generation-to-generation sequence of stages in the reproductive history of an organism Key Haploid Diploid n n Gametes n MEIOSIS FERTILIZATION Zygote 2n Diploid multicellular organism 2n Mitosis (a) Animals 40 Sex Cells - Gametes • • Unlike somatic cells, sperm and egg cells are haploid cells, containing only one set of chromosomes At sexual maturity the ovaries and testes produce haploid gametes by meiosis 41 Sexual Reproduction - The Human Life Cycle Haploid gametes (n = 23) • • During fertilization, sperm and ovum fuse forming a diploid zygote The zygote develops into an adult organism Haploid (n) Diploid (2n) Ovum (n) Sperm Cell (n) FERTILIZATION MEIOSIS Ovary Testis Diploid zygote (2n = 46) Mitosis and development Multicellular diploid adults (2n = 46) 42 Meiosis • • • Reduces the chromosome number such that each daughter Cell has a haploid set of chromosomes Ensures that the next generation will have: – Diploid number of chromosome – Exchange of genetic information (combination of traits – that differs from that of either parent) 43 Meiosis • • • • Only diploid cells can divide by meiosis. Prior to meiosis I, DNA replication occurs. During meiosis, there will be two nuclear divisions, and the result will be four haploid nuclei. No replication of DNA occurs between meiosis I and meiosis II. 44 Meiosis Interphase • • Meiosis reduces the number of chromosome sets from diploid to haploid Meiosis takes place in two sets of divisions – – Meiosis I reduces the number of chromosomes from diploid to haploid Meiosis II produces four haploid daughter cells Figure 13.7 Homologous pair of chromosomes in diploid parent cell Chromosomes replicate Homologous pair of replicated chromosomes Sister chromatids Diploid cell with replicated chromosomes Meiosis I 1 Homologous chromosomes separate Haploid cells with replicated chromosomes Meiosis II 2 Sister chromatids separate Haploid cells with unreplicated chromosomes 45 Meiosis Phases • • • • Meiosis involves the same four phases seen in mitosis prophase metaphase anaphase telophase They are repeated during both meiosis I and meiosis II. The period of time between meiosis I and meiosis II is called interkinesis. No replication of DNA occurs during interkinesis because the DNA is already duplicated. 46 Prophase I • • • • • Prophase I occupies more than 90% of the time required for meiosis Chromosomes begin to condense In synapsis, the 2 members of each homologous pair of chromosomes line up side-by-side, aligned gene by gene, to form a tetrad consisting of 4 chromatids During synapsis, sometimes there is an exchange of homologous parts between non-sister chromatids. This exchange is called crossing over Each tetrad usually has one or more chiasmata, X-shaped regions where crossing over occurred Nonsister chromatids Prophase I of meiosis Tetrad Chiasma, site of crossing over 47 Metaphase I • • • At metaphase I, tetrads line up at the metaphase plate, with one chromosome facing each pole Microtubules from one pole are attached to the kinetochore of one chromosome of each tetrad Microtubules from the other pole are attached to the kinetochore of the other chromosome PROPHASE I Sister chromatids Tetrad METAPHASE I ANAPHASE I Sister chromatids remain attached Centromere (with kinetochore) Chiasmata Metaphase plate Spindle Microtubule attached to kinetochore Homologous chromosomes (red and blue) pair and exchange segments; 2n = 6 Homologous chromosomes separate Tetrads line up Pairs of homologous chromosomes split up 48 Anaphase I • • • In anaphase I, pairs of homologous chromosomes separate One chromosome moves toward each pole, guided by the spindle apparatus Sister chromatids remain attached at the centromere and move as one unit toward the pole PROPHASE I Sister chromatids Tetrad METAPHASE I ANAPHASE I Sister chromatids remain attached Centromere (with kinetochore) Chiasmata Metaphase plate Spindle Microtubule attached to kinetochore Homologous chromosomes (red and blue) pair and exchange segments; 2n = 6 Homologous chromosomes separate Tetrads line up Pairs of homologous chromosomes split up 49 Telophase I and Cytokinesis • • • • In the beginning of telophase I, each half of the cell has a haploid set of chromosomes; each chromosome still consists of two sister chromatids Cytokinesis usually occurs simultaneously, forming two haploid daughter cells In animal cells, a cleavage furrow forms; in plant cells, a cell plate forms No chromosome replication occurs between the end of meiosis I and the beginning of meiosis II because the chromosomes are already replicated 50 Prophase II • • • Meiosis II is very similar to mitosis In prophase II, a spindle apparatus forms In late prophase II, chromosomes (each still composed of two chromatids) move toward the metaphase plate TELOPHASE I AND CYTOKINESIS PROPHASE II Cleavage furrow METAPHASE II ANAPHASE II Sister chromatids separate TELOPHASE II AND CYTOKINESIS Haploid daughter cells forming 51 Metaphase II • • • At metaphase II, the sister chromatids are at the metaphase plate Because of crossing over in meiosis I, the two sister chromatids of each chromosome are no longer genetically identical The kinetochores of sister chromatids attach to microtubules extending from opposite poles TELOPHASE I AND CYTOKINESIS PROPHASE II Cleavage furrow METAPHASE II ANAPHASE II Sister chromatids separate TELOPHASE II AND CYTOKINESIS Haploid daughter cells forming 52 Anaphase II • • At anaphase II, the sister chromatids separate The sister chromatids of each chromosome now move as two newly individual chromosomes toward opposite poles TELOPHASE I AND CYTOKINESIS PROPHASE II Cleavage furrow METAPHASE II ANAPHASE II Sister chromatids separate TELOPHASE II AND CYTOKINESIS Haploid daughter cells forming 53 Telophase II and Cytokinesis • • • • • In telophase II, the chromosomes arrive at opposite poles Nuclei form, and the chromosomes begin decondensing Cytokinesis separates the cytoplasm At the end of meiosis, there are four daughter cells, each with a haploid set of unreplicated chromosomes Each daughter cell is genetically distinct from the others and from the parent cell TELOPHASE I AND CYTOKINESIS PROPHASE II Cleavage furrow METAPHASE II ANAPHASE II Sister chromatids separate TELOPHASE II AND CYTOKINESIS Haploid daughter cells forming 54 A Comparison of Mitosis and Meiosis • • • Mitosis conserves the number of chromosome sets, producing cells that are genetically identical to the parent cell Meiosis reduces the number of chromosomes sets from two (diploid) to one (haploid), producing cells that differ genetically from each other and from the parent cell The mechanism for separating sister chromatids is virtually identical in meiosis II and mitosis 55 A Comparison of Mitosis and Meiosis • Three events are unique to meiosis, and all three occur in meiosis l: – – – Synapsis and crossing over in prophase I: Homologous chromosomes physically connect and exchange genetic information At the metaphase plate, there are paired homologous chromosomes (tetrads), instead of individual replicated chromosomes At anaphase I of meiosis, homologous pairs move toward opposite poles of the cell. In anaphase II of meiosis, the sister chromatids separate 56 A Comparison Of Mitosis And Meiosis MITOSIS MEIOSIS Chiasma (site of crossing over) Parent cell (before chromosome replication) MEIOSIS I Prophase I Prophase Chromosome replication Duplicated chromosome (two sister chromatids) Chromosome replication Tetrad formed by synapsis of homologous chromosomes 2n = 6 Chromosomes positioned at the metaphase plate Metaphase Sister chromatids separate during anaphase Anaphase Telophase 2n Tetrads positioned at the metaphase plate Homologues separate during anaphase I; sister chromatids remain together Metaphase I Anaphase I Telophase I Haploid n=3 Daughter cells of meiosis I 2n MEIOSIS II Daughter cells of mitosis n n n n Daughter cells of meiosis II Sister chromatids separate during anaphase II 57 Comparison • • • • • • Meiosis DNA duplication followed by 2 cell divisions Sysnapsis Crossing-over One diploid cell produces 4 haploid cells Each new cell has a unique combination of genes • • • • • Mitosis Homologous chromosomes do not pair up No genetic exchange between homologous chromosomes One diploid cell produces 2 diploid cells or one haploid cell produces 2 haploid cells New cells are genetically identical to original cell (except for mutation) 58 Sexual Reproduction - The Human Life Cycle Haploid gametes (n = 23) • • During fertilization, sperm and ovum fuse forming a diploid zygote The zygote develops into an adult organism Haploid (n) Diploid (2n) Ovum (n) Sperm Cell (n) FERTILIZATION MEIOSIS Ovary Testis Diploid zygote (2n = 46) Mitosis and development Multicellular diploid adults (2n = 46) 59 Spermatocytes to Spermatids • • • • • Primary spermatocytes undergo meiosis I, forming two haploid cells called secondary spermatocytes Secondary spermatocytes undergo meiosis II and their daughter cells are called spermatids Spermatids are small round cells seen close to the lumen of the tubule Late in spermatogenesis, spermatids are nonmotile Spermiogenesis – spermatids lose excess cytoplasm and form a tail, becoming motile sperm 60 Spermatogenesis Figure 27.8b, c 61 Oogenesis • • • • • • • Production of female sex cells by meiosis In the fetal period, oogonia (2n ovarian stem cells) multiply by mitosis and store nutrients Primordial follicles appear as oogonia are transformed into primary oocytes Primary oocytes begin meiosis but stall in prophase I From puberty, each month one activated primary oocyte completes meiosis one to produce two haploid cells – The first polar body – The secondary oocyte The secondary oocyte arrests in metaphase II and is ovulated If penetrated by sperm the second oocyte completes meiosis II, yielding: – One large ovum (the functional gamete) – A tiny second polar body 62 Oogenesis 63