Chapter 2: Chromosomes and Cellular Reproduction PDF

2 Chromosomes and Cellular Reproduction THE BLIND MEN’S RIDDLE I...

2 Chromosomes and Cellular Reproduction THE BLIND MEN’S RIDDLE I n a well-known riddle, two blind men by chance enter a department store at the same time, go to the same counter, and both order five pairs of socks, each pair a different color. The sales clerk is so befuddled by this strange coincidence that he places all ten pairs (two black pairs, two blue pairs, two gray pairs, two brown pairs, and two green pairs) into a single shopping bag and gives the bag with all ten pairs to one blind man and an empty bag to the other. The two blind men happen to meet on the street outside, where they discover that one of their bags contains all ten pairs of socks. How do the blind men, without seeing and without any out- side help, sort out the socks so that each man goes home with exactly five pairs of different colored socks? Can you come up with a solution to the riddle? By an interesting coincidence, cells have the same dilem- ma as that of the blind men in the riddle. Most organisms possess two sets of genetic information, one set inherited from each parent. Before cell division, the DNA in each chromo- some replicates; after replication, there are two copies—called sister chromatids—of each chromosome. At the end of cell division, it is critical that each new cell receives a complete copy of the genetic material, just as each blind man needed to go home with a complete set of socks. Chromosomes in mitosis, the process through which each new cell The solution to the riddle is simple. Socks are sold as receives a complete copy of the genetic material. [Photograph by pairs; the two socks of a pair are typically connected by a thread. Conly L. Reider/Biological Photo Service.] As a pair is removed from the bag, the men each grasp a different sock of the pair and pull in opposite directions. When the socks are pulled tight, it is easy for one of the men to take a pocket knife and cut the thread connecting the pair. Each man then deposits his single sock in his own bag. At the end of the process, each man’s bag will contain exactly two black socks, two blue socks, two gray socks, two brown socks, and two green socks.* Remarkably, cells employ a similar solution for separating their chromosomes into new daughter cells. As we will learn in this chapter, the replicated chromosomes line up at the center of a cell undergoing division and, like the socks in the riddle, the sister chroma- tids of each chromosome are pulled in opposite directions. Like the thread connecting two socks of a pair, a molecule called cohesin holds the sister chromatids together until severed *This analogy is adapted from K. Nasmyth. Disseminating the genome: joining, resolving, and separating sister chromatids, during mitosis and meiosis. Annual Review of Genetics 35:673–745, 2001. 15 16 Chapter 2 by a molecular knife called separase. The two resulting chromosomes separate and the cell divides, ensuring that a complete set of chromosomes is deposited in each cell. In this analogy, the blind men and cells differ in one critical regard: if the blind men make a mistake, one man ends up with an extra sock and the other is a sock short, but no great harm results. The same cannot be said for human cells. Errors in chromosome separa- tion, producing cells with too many or too few chromosomes, are frequently catastrophic, leading to cancer, miscarriage, or—in some cases—a child with severe handicaps. T his chapter explores the process of cell reproduction and how a complete set of genetic information is trans- mitted to new cells. In prokaryotic cells, reproduction is Grasping mitosis and meiosis requires more than sim- ply memorizing the sequences of events that take place in each stage, although these events are important. The key is to relatively simple, because prokaryotic cells possess a single understand how genetic information is apportioned in the chromosome. In eukaryotic cells, multiple chromosomes course of cell reproduction through a dynamic interplay of must be copied and distributed to each of the new cells, DNA synthesis, chromosome movement, and cell division. and so cell reproduction is more complex. Cell division in These processes bring about the transmission of genetic eukaryotes takes place through mitosis or meiosis, processes information and are the basis of similarities and differences that serve as the foundation for much of genetics. between parents and progeny. Prokaryote Eukaryote Animal cell Plant cell Cell wall Nucleus Plasma Nuclear envelope membrane Endoplasmic Ribosomes reticulum Ribosomes DNA Mitochondrion Vacuole Chloroplast Golgi apparatus Eubacterium Plasma membrane Cell wall Archaebacterium Prokaryotic cells Eukaryotic cells Nucleus Absent Present Cell diameter Relatively small, from 1 to 10 μm Relatively large, from 10 to 100 μm Genome Usually one circular DNA molecule Multiple linear DNA molecules DNA Not complexed with histones in Complexed with histones eubacteria; some histones in archaea Amount of DNA Relatively small Relatively large Membrane-bounded organelles Absent Present Cytoskeleton Absent Present 2.1 Prokaryotic and eukaryotic cells differ in structure. [Photographs (left to right) by T. J. Beveridge/ Visuals Unlimited/Getty Images (prokaryotes); W. Baumeister/Science Photo Library/Photo Researchers; G. Murti/Phototake; Biophoto Associates/Photo Researchers.]  Chromosomes and Cellular Reproduction 17 2.1 Prokaryotic and Eukaryotic (a) Histone proteins Cells Differ in a Number DNA of Genetic Characteristics Biologists traditionally classify all living organisms into two major groups, the prokaryotes and the eukaryotes (Figure 2.1). Chromatin A prokaryote is a unicellular organism with a relatively sim- ple cell structure. A eukaryote has a compartmentalized cell structure with components bounded by intracellular mem- branes; eukaryotes are either unicellular or multicellular. Research indicates that a division of life into two major (b) groups, the prokaryotes and eukaryotes, is not so simple. Although similar in cell structure, prokaryotes include at least two fundamentally distinct types of bacteria: the eubacteria (true bacteria) and the archaea (ancient bacte- ria). An examination of equivalent DNA sequences reveals that eubacteria and archaea are as distantly related to one another as they are to the eukaryotes. Although eubacteria and archaea are similar in cell structure, some genetic pro- cesses in archaea (such as transcription) are more similar to those in eukaryotes, and the archaea are actually closer evolutionarily to eukaryotes than to eubacteria. Thus, from an evolutionary perspective, there are three major groups of organisms: eubacteria, archaea, and eukaryotes. In this book, the prokaryotic–eukaryotic distinction will be made 2.2 Eukaryotic chromosomes consist of DNA and histone proteins. (a) DNA wraps around the histone proteins to form frequently, but important eubacterial–archaeal differences chromatin, the material that makes up chromosomes. (b) A eukaryotic also will be noted. chromosome. [Part b: Biophoto Associates/Photo Researchers.] From the perspective of genetics, a major difference between prokaryotic and eukaryotic cells is that a eukaryote usually linear DNA molecules (multiple chromosomes). has a nuclear envelope, which surrounds the genetic material Eukaryotic cells therefore require mechanisms that ensure to form a nucleus and separates the DNA from the other cel- that a copy of each chromosome is faithfully transmitted to lular contents. In prokaryotic cells, the genetic material is in each new cell. This generalization—a single, circular chro- close contact with other components of the cell—a property mosome in prokaryotes and multiple, linear chromosomes that has important consequences for the way in which genes in eukaryotes—is not always true. A few bacteria have more are controlled. than one chromosome, and important bacterial genes are Another fundamental difference between prokaryotes frequently found on other DNA molecules called plasmids and eukaryotes lies in the packaging of their DNA. In eukary- (see Chapter 8). Furthermore, in some eukaryotes, a few otes, DNA is closely associated with a special class of proteins, genes are located on circular DNA molecules found in cer- the histones, to form tightly packed chromosomes. This tain organelles (see Chapter 21). complex of DNA and histone proteins is termed chromatin, which is the stuff of eukaryotic chromosomes (Figure 2.2). Histone proteins limit the accessibility of enzymes and other proteins that copy and read the DNA, but they enable the DNA to fit into the nucleus. Eukaryotic DNA must separate from the histones before the genetic information in the DNA can be accessed. Archaea also have some histone proteins that complex with DNA, but the structure of their chromatin is different from that found in eukaryotes. Eubacteria do not possess histones; so their DNA does not exist in the highly ordered, tightly packed arrangement found in eukaryotic cells (Figure 2.3). The copying and reading of DNA are therefore simpler processes in eubacteria. Genes of prokaryotic cells are generally on a single, 2.3 Prokaryotic DNA (shown in red) is neither surrounded by circular molecule of DNA—the chromosome of a prokary- a nuclear membrane nor complexed with histone proteins. otic cell. In eukaryotic cells, genes are located on multiple, [A. B. Dowsett/Science Photo Library/Photo Researchers.] 18 Chapter 2 closely related to their hosts: the genes of a plant virus are CONCEPTS more similar to those in a plant cell than to those in ani- Organisms are classified as prokaryotes or eukaryotes, and pro- mal viruses, which suggests that viruses evolved from their karyotes consist of archaea and eubacteria. A prokaryote is a hosts, rather than from other viruses. The close relationship unicellular organism that lacks a nucleus, its DNA is not com- plexed to histone proteins, and its genome is usually a single between the genes of virus and host makes viruses useful for chromosome. Eukaryotes are either unicellular or multicellular, studying the genetics of host organisms. their cells possess a nucleus, their DNA is complexed to histone proteins, and their genomes consist of multiple chromosomes. 2.2 Cell Reproduction Requires the ✔ CONCEPT CHECK 1 Copying of the Genetic Material, List several characteristics that eubacteria and archaea have in com- Separation of the Copies, and mon and that distinguish them from eukaryotes. Cell Division For any cell to reproduce successfully, three fundamental Viruses are neither prokaryotic nor eukaryotic, because events must take place: (1) its genetic information must they do not possess a cellular structure. Viruses are actually be copied, (2) the copies of genetic information must be simple structures composed of an outer protein coat sur- separated from each other, and (3) the cell must divide. All rounding nucleic acid (either DNA or RNA; Figure 2.4). cellular reproduction includes these three events, but the Neither are viruses primitive forms of life: they can repro- processes that lead to these events differ in prokaryotic and duce only within host cells, which means that they must have eukaryotic cells because of their structural differences. evolved after, rather than before, cells evolved. In addition, viruses are not an evolutionarily distinct group but are most Prokaryotic Cell Reproduction When prokaryotic cells reproduce, the circular chromosome 1 A virus consists of of the bacterium replicates and the cell divides in a process a protein coat… Viral protein called binary fission (Figure 2.5). Replication usually begins coat at a specific place on the bacterial chromosome, called the origin of replication. In a process that is not fully under- DNA stood, the origins of the two newly replicated chromosomes move away from each other and toward opposite ends of the cell. In at least some bacteria, proteins bind near the replication origins and anchor the new chromosomes to the plasma membrane at opposite ends of the cell. Finally, a new cell wall forms between the two chromosomes, producing two cells, each with an identical copy of the chromosome. Under optimal conditions, some bacterial cells divide every 20 minutes. At this rate, a single bacterial cell could produce a billion descendants in a mere 10 hours. Eukaryotic Cell Reproduction 2 …surrounding a piece of nucleic acid—in this case, DNA. Like prokaryotic cell reproduction, eukaryotic cell repro- duction requires the processes of DNA replication, copy separation, and division of the cytoplasm. However, the presence of multiple DNA molecules requires a more-com- plex mechanism to ensure that exactly one copy of each molecule ends up in each of the new cells. Eukaryotic chromosomes are separated from the cyto- plasm by the nuclear envelope. The nucleus was once thought to be a fluid-filled bag in which the chromosomes floated, but we now know that the nucleus has a highly orga- nized internal scaffolding called the nuclear matrix. This matrix consists of a network of protein fibers that maintains 2.4 A virus is a simple replicative structure consisting of protein precise spatial relations among the nuclear components and nucleic acid. Adenoviruses are shown in the micrograph. and takes part in DNA replication, the expression of genes, [Micrograph by Hans Gelderblom/Visuals Unlimited.] and the modification of gene products before they leave the  Chromosomes and Cellular Reproduction 19 (a) A prokaryotic cell contains a complexity of an organism and its number of chromosomes single circular chromosome. per cell. In most eukaryotic cells, there are two sets of chromo- Bacterium somes. The presence of two sets is a consequence of sexual reproduction: one set is inherited from the male parent and the other from the female parent. Each chromosome DNA in one set has a corresponding chromosome in the other As the chromosome replicates, the set, together constituting a homologous pair (Figure 2.6). Origin of origins segregate to opposite sides. Human cells, for example, have 46 chromosomes, constitut- replication ing 23 homologous pairs. The two chromosomes of a homologous pair are usu- Origin of ally alike in structure and size, and each carries genetic infor- replication mation for the same set of hereditary characteristics. (The sex chromosomes are an exception and will be discussed in Chapter 4.) For example, if a gene on a particular chromo- some encodes a characteristic such as hair color, another The origins are anchored copy of the gene (each copy is called an allele) at the same to opposite sides of the cell. position on that chromosome’s homolog also encodes hair color. However, these two alleles need not be identical: one might encode brown hair and the other might encode blond hair. Thus, most cells carry two sets of genetic information; these cells are diploid. But not all eukaryotic cells are dip- loid: reproductive cells (such as eggs, sperm, and spores) and The cell divides. Each new even nonreproductive cells of some organisms may contain cell has an identical copy a single set of chromosomes. Cells with a single set of chro- of the original chromosome. mosomes are haploid. A haploid cell has only one copy of each gene. CONCEPTS Cells reproduce by copying and separating their genetic infor- mation and then dividing. Because eukaryotes possess multi- (b) ple chromosomes, mechanisms exist to ensure that each new cell receives one copy of each chromosome. Most eukaryotic cells are diploid, and their two chromosome sets can be arranged in homologous pairs. Haploid cells contain a single set of chromosomes. ✔ CONCEPT CHECK 2 Diploid cells have a. two chromosomes b. two sets of chromosomes c. one set of chromosomes 2.5 Prokaryotic cells reproduce by binary fission. (a) Process of d. two pairs of homologous chromosomes binary fission. (b) Micrograph showing a bacterial cell undergoing binary fission. [Part b: Lee D. Simon/Photo Researchers.] nucleus. We will now take a closer look at the structure of Chromosome structure The chromosomes of eukary- eukaryotic chromosomes. otic cells are larger and more complex than those found in prokaryotes, but each unreplicated chromosome neverthe- Eukaryotic chromosomes Each eukaryotic species has less consists of a single molecule of DNA. Although linear, a characteristic number of chromosomes per cell: potatoes the DNA molecules in eukaryotic chromosomes are highly have 48 chromosomes, fruit flies have 8, and humans have folded and condensed; if stretched out, some human chro- 46. There appears to be no special relation between the mosomes would be several centimeters long—thousands of 20 Chapter 2 A diploid organism has two Humans have 23 pairs of sets of chromosomes organized chromosomes. as homologous pairs. (a) (b) 2.6 Diploid eukaryotic cells have two sets of chromosomes. (a) A set of chromosomes from a female human cell. Each pair of chromosomes is hybridized to a uniquely colored probe, giving it a Allele A Allele a distinct color. (b) The chromosomes are present in homologous pairs, which consist of chromosomes that are alike in size and structure and carry information for These two versions of a gene the same characteristics. [Part a: Courtesy of Dr. Thomas encode a trait such as hair color. Ried and Dr. Evelin Schrock.] times as long as the span of a typical nucleus. To package mere; later, spindle microtubules attach to the kinetochore. such a tremendous length of DNA into this small volume, Chromosomes lacking a centromere cannot be drawn into each DNA molecule is coiled again and again and tightly the newly formed nuclei; these chromosomes are lost, often packed around histone proteins, forming a rod-shaped with catastrophic consequences for the cell. On the basis of chromosome. Most of the time, the chromosomes are thin the location of the centromere, chromosomes are classified and difficult to observe but, before cell division, they con- into four types: metacentric, submetacentric, acrocentric, dense further into thick, readily observed structures; it is at and telocentric (Figure 2.8). One of the two arms of a chro- this stage that chromosomes are usually studied. mosome (the short arm of a submetacentric or acrocentric A functional chromosome has three essential elements: chromosome) is designated by the letter p and the other arm a centromere, a pair of telomeres, and origins of replication. is designated by q. The centromere is the attachment point for spindle microtu- Telomeres are the natural ends, the tips, of a whole lin- bules—the filaments responsible for moving chromosomes ear chromosome (see Figure 2.7). Just as plastic tips protect in cell division (Figure 2.7). The centromere appears as the ends of a shoelace, telomeres protect and stabilize the a constricted region. Before cell division, a multiprotein chromosome ends. If a chromosome breaks, producing new complex called the kinetochore assembles on the centro- ends, the chromosome is degraded at the newly broken ends. At times, a chromosome …at other times, consists of a it consists of two single chromatid;… (sister) chromatids. The telomeres are the stable Metacentric ends of chromosomes. Telomere Centromere Kinetochore Submetacentric Two (sister) chromatids Spindle microtubules Telomere The centromere is a Acrocentric constricted region of the One One chromosome where the chromosome chromosome kinetochores form and the spindle microtubules attach. 2.8 Eukaryotic chromosomes exist in four major 2.7 Each eukaryotic chromosome has a centromere and types based on the position of the centromere. Telocentric telomeres. [Micrograph by L. Lisco, D. W. Fawcett/Visuals Unlimited.]  Chromosomes and Cellular Reproduction 21 Telomeres provide chromosome stability. Research shows cell cycle, the genetic instructions for all characteristics are that telomeres also participate in limiting cell division and passed from parent to daughter cells. A new cycle begins after may play important roles in aging and cancer (discussed in a cell has divided and produced two new cells. Each new cell Chapter 12). metabolizes, grows, and develops. At the end of its cycle, the Origins of replication are the sites where DNA synthe- cell divides to produce two cells, which can then undergo sis begins; they are not easily observed by microscopy. Their additional cell cycles. Progression through the cell cycle is structure and function will be discussed in more detail in regulated at key transition points called checkpoints. Chapter 12. In preparation for cell division, each chromo- The cell cycle consists of two major phases. The first is some replicates, making a copy of itself, as already mentioned. interphase, the period between cell divisions, in which the These two initially identical copies, called sister chromatids, cell grows, develops, and functions. In interphase, critical are held together at the centromere (see Figure 2.7). Each events necessary for cell division also take place. The second sister chromatid consists of a single molecule of DNA. major phase is the M phase (mitotic phase), the period of active cell division. The M phase includes mitosis, the CONCEPTS process of nuclear division, and cytokinesis, or cytoplasmic Sister chromatids are copies of a chromosome held together at division. Let’s take a closer look at the details of interphase the centromere. Functional chromosomes contain centromeres, and the M phase. telomeres, and origins of replication. The kinetochore is the point of attachment for the spindle microtubules; telomeres are the Interphase Interphase is the extended period of growth stabilizing ends of a chromosome; origins of replication are sites and development between cell divisions. Although little where DNA synthesis begins. activity can be observed with a light microscope, the cell is quite busy: DNA is being synthesized, RNA and proteins ✔ CONCEPT CHECK 3 are being produced, and hundreds of biochemical reactions What would be the result if a chromosome did not have a kinetochore? necessary for cellular functions are taking place. In addition to growth and development, interphase includes several checkpoints, which regulate the cell cycle by allowing or The Cell Cycle and Mitosis prohibiting the cell’s division. These checkpoints, like the The cell cycle is the life story of a cell, the stages through checkpoints in the M phase, ensure that all cellular com- which it passes from one division to the next (Figure 2.9). ponents are present and in good working order before the This process is critical to genetics because, through the cell proceeds to the next stage. Checkpoints are necessary to 1 During G1, the cell grows. Spindle- assembly 2 Cells may enter 7 Mitosis and cytokinesis Cytokinesis checkpoint G0, a non- (cell division) take dividing phase. place in M phase. is G1 G0 os G2/M checkpoint it M M phase: 6 After the G2/M nuclear and G1/S checkpoint checkpoint, the cell division cell can divide. 3 After the G1/S checkpoint, the cell is committed to dividing. G2 Interphase: 5 In G2, the cell prepares for mitosis. cell growth 4 In S, DNA S duplicates. 2.9 The cell cycle consists of interphase and M phase. 22 Chapter 2 prevent cells with damaged or missing chromosomes from Prophase. As a cell enters prophase, the chromo- proliferating. Defects in checkpoints can lead to unregulated somes become visible under a light microscope. Because cell growth, as is seen in some cancers. The molecular basis the chromosome was duplicated in the preceding S phase, of these checkpoints will be discussed in Chapter 23. each chromosome possesses two chromatids attached at By convention, interphase is divided into three sub- the centromere. The mitotic spindle, an organized array of phases: G1, S, and G2 (see Figure 2.9). Interphase begins with microtubules that move the chromosomes in mitosis, forms. G1 (for gap 1). In G1, the cell grows, and proteins necessary In animal cells, the spindle grows out from a pair of cen- for cell division are synthesized; this phase typically lasts trosomes that migrate to opposite sides of the cell. Within several hours. Near the end of G1, a critical point termed the each centrosome is a special organelle, the centriole, which G1/S checkpoint holds the cell in G1 until the cell has all of also is composed of microtubules. Some plant cells do not the enzymes necessary for the replication of DNA. After this have centrosomes or centrioles, but they do have mitotic checkpoint has been passed, the cell is committed to divide. spindles. Before reaching the G1/S checkpoint, cells may exit from the active cell cycle in response to regulatory signals and pass Prometaphase. Disintegration of the nuclear mem- into a nondividing phase called G0, which is a stable state brane marks the start of prometaphase. Spindle microtu- during which cells usually maintain a constant size. They bules, which until now have been outside the nucleus, enter can remain in G0 for an extended length of time, even indefi- the nuclear region. The ends of certain microtubules make nitely, or they can reenter G1 and the active cell cycle. Many contact with the chromosomes. For each chromosome, cells never enter G0; rather, they cycle continuously. a microtubule from one of the centrosomes anchors to After G1, the cell enters the S phase (for DNA synthesis), the kinetochore of one of the sister chromatids; a micro- in which each chromosome duplicates. Although the cell tubule from the opposite centrosome then attaches to is committed to divide after the G1/S checkpoint has been the other sister chromatid, and so the chromosome is passed, DNA synthesis must take place before the cell can anchored to both of the centrosomes. The microtubules proceed to mitosis. If DNA synthesis is blocked (by drugs or lengthen and shorten, pushing and pulling the chromo- by a mutation), the cell will not be able to undergo mitosis. somes about. Some microtubules extend from each cen- Before the S phase, each chromosome is unreplicated; after trosome toward the center of the spindle but do not attach the S phase, each chromosome is composed of two chroma- to a chromosome. tids (see Figure 2.7). Metaphase. During metaphase, the chromosomes After the S phase, the cell enters G2 (gap 2). In this become arranged in a single plane, the metaphase plate, phase, several additional biochemical events necessary for between the two centrosomes. The centrosomes, now at cell division take place. The important G2/M checkpoint is opposite ends of the cell with microtubules radiating out- reached near the end of G2. This checkpoint is passed only if ward and meeting in the middle of the cell, center at the the cell’s DNA is undamaged. Damaged DNA can inhibit the spindle poles. A spindle-assembly checkpoint ensures that activation of some proteins that are necessary for mitosis to each chromosome is aligned on the metaphase plate and take place. After the G2/M checkpoint has been passed, the attached to spindle fibers from opposite poles. cell is ready to divide and enters the M phase. Although the The passage of a cell through the spindle-assembly length of interphase varies from cell type to cell type, a typi- checkpoint depends on tension generated at the kinetochore cal dividing mammalian cell spends about 10 hours in G1, 9 as the two conjoined chromatids are pulled in opposite hours in S, and 4 hours in G2 (see Figure 2.9). directions by the spindle fibers. This tension is required for Throughout interphase, the chromosomes are in a the cell to pass through the spindle-assembly checkpoint. If a relaxed, but by no means uncoiled, state, and individual microtubule attaches to one chromatid but not to the other, chromosomes cannot be seen with a microscope. This no tension is generated and the cell is unable to progress to condition changes dramatically when interphase draws to a the next stage of the cell cycle. The spindle-assembly check- close and the cell enters the M phase. point is able to detect even a single pair of chromosomes that are not properly attached to microtubules. The importance M phase The M phase is the part of the cell cycle in which of this checkpoint is illustrated by cells that are defective in the copies of the cell’s chromosomes (sister chromatids) their spindle-assembly checkpoint; these cells often end up separate and the cell undergoes division. The separation of with abnormal numbers of chromosomes. sister chromatids in the M phase is a critical process that results in a complete set of genetic information for each Anaphase. After the spindle-assembly checkpoint has of the resulting cells. Biologists usually divide the M phase been passed, the connection between sister chromatids into six stages: the five stages of mitosis (prophase, prometa- breaks down and the sister chromatids separate. This chro- phase, metaphase, anaphase, and telophase), illustrated in matid separation marks the beginning of anaphase, during Figure 2.10, and cytokinesis. It’s important to keep in mind which the chromosomes move toward opposite spindle that the M phase is a continuous process, and its separation poles. The microtubules that connect the chromosomes to into these six stages is somewhat arbitrary. the spindle poles are composed of subunits of a protein  Interphase Prophase Prometaphase Disintegrating Nucleus Centrosomes Developing nuclear spindle envelope Centrosome Nuclear Chromatids of Mitotic envelope a chromosome spindle The nuclear membrane is present Chromosomes condense. Each The nuclear membrane disintegrates. and chromosomes are relaxed. chromosome possesses two chromatids. Spindle microtubules attach to The mitotic spindle forms. chromatids. Telophase Anaphase Metaphase Daughter Metaphase plate chromosomes Spindle pole Chromosomes arrive at spindle poles. Sister chromatids separate and Chromsomes line up on The nuclear membrane re-forms and move toward opposite poles. the metaphase plate. the chromosomes relax. 2.10 The cell cycle is divided into stages. [Photographs by Conly L. Rieder/Biological Photo Service.] Animation 2.1 illustrates events of the cell cycle dynamically.  www.whfreeman.com/pierce4e See what happens if different processes in the cycle fail. 23 24 Tubulin Spindle microtubules are subunits composed of tubulin subunits. Genetic Consequences of the Cell Cycle + – What are the genetically important results of the cell cycle? From a single cell, the cell cycle produces two cells that con- tain the same genetic instructions. The resulting daughter cells are genetically identical with each other and with their parent cell because DNA synthesis in the S phase creates an exact copy of each DNA molecule, giving rise to two geneti- Centrosome cally identical sister chromatids. Mitosis then ensures that + one of the two sister chromatids from each replicated chro- – mosome passes into each new cell. Another genetically important result of the cell cycle is that Microtubules lengthen each of the cells produced contains a full complement of chro- and shorten at both mosomes: there is no net reduction or increase in chromosome the + + and the – ends. number. Each cell also contains approximately half the cyto- Chromosome plasm and organelle content of the original parental cell, but no precise mechanism analogous to mitosis ensures that organelles 2.11 Microtubules are composed of tubulin subunits. Each microtubule has its plus (⫹) end at the kinetochore and its negative (⫺) are evenly divided. Consequently, not all cells resulting from the end at the centrosome. cell cycle are identical in their cytoplasmic content. called tubulin (Figure 2.11). Chromosome movement is CONCEPTS due to the disassembly of tubulin molecules at both the The active cell cycle phases are interphase and the M phase. kinetochore end (called the ⫹ end) and the spindle end Interphase consists of G1, S, and G2. In G1, the cell grows and pre- (called the ⫺ end) of the spindle fiber. Special proteins pares for cell division; in the S phase, DNA synthesis takes place; in G2, other biochemical events necessary for cell division take called molecular motors disassemble tubulin molecules place. Some cells enter a quiescent phase called G0. The M phase from the spindle and generate forces that pull the chromo- includes mitosis and cytokinesis and is divided into prophase, some toward the spindle pole. prometaphase, metaphase, anaphase, and telophase. The cell Telophase. After the chromatids have separated, cycle produces two genetically identical cells each of which pos- each is considered a separate chromosome. Telophase is sesses a full complement of chromosomes. marked by the arrival of the chromosomes at the spindle poles. The nuclear membrane re-forms around each set ✔ CONCEPT CHECK 4 of chromosomes, producing two separate nuclei within Which is the correct order of stages in the cell cycle? the cell. The chromosomes relax and lengthen, once again a. G1, S, prophase, metaphase, anaphase disappearing from view. In many cells, division of the b. S, G1, prophase, metaphase, anaphase cytoplasm (cytokinesis) is simultaneous with telophase. c. Prophase, S, G1, metaphase, anaphase The major features of the cell cycle are summarized in d. S, G1, anaphase, prophase, metaphase Table 2.1. TRY PROBLEM 22 Table 2.1 Features of the cell cycle Stage Major Features G0 phase Stable, nondividing period of variable length. Interphase G1 phase Growth and development of the cell; G1/S checkpoint. S phase Synthesis of DNA. G2 phase Preparation for division; G2/M checkpoint. M phase Prophase Chromosomes condense and mitotic spindle forms. Prometaphase Nuclear envelope disintegrates, and spindle microtubules anchor to kinetochores. Metaphase Chromosomes align on the metaphase plate; spindle-assembly checkpoint. Anaphase Sister chromatids separate, becoming individual chromosomes that migrate toward spindle poles. Telophase Chromosomes arrive at spindle poles, the nuclear envelope re-forms, and the condensed chromosomes relax. Cytokinesis Cytoplasm divides; cell wall forms in plant cells.  Chromosomes and Cellular Reproduction 25 Prophase and Telophase and G1 S G2 Metaphase Anaphase prometaphase cytokinesis Number of chromosomes 4 4 4 4 4 8 4 per cell Number of DNA 4 4 8 8 8 8 8 4 molecules per cell 2.12 The number of chromosomes and the number of DNA molecules change in the course of the cell cycle. The number of chromosomes per cell equals the number of functional centromeres. The number of DNA molecules per cell equals the number of chromosomes when the chromosomes are unreplicated (no sister chromatids present) and twice the number of chromosomes when sister chromosomes are present. functional centromere, and so each is considered a separate chro- CONNECTING CONCEPTS mosome. Until cytokinesis, the cell contains eight unreplicated Counting Chromosomes and DNA Molecules chromosomes; thus, there are still eight DNA molecules present. The relations among chromosomes, chromatids, and DNA molecules After cytokinesis, the eight chromosomes (eight DNA molecules) frequently cause confusion. At certain times, chromosomes are are distributed equally between two cells; so each new cell contains unreplicated; at other times, each possesses two chromatids (see four chromosomes and four DNA molecules, the number present at Figure 2.7). Chromosomes sometimes consist of a single DNA mol- the beginning of the cell cycle. ecule; at other times, they consist of two DNA molecules. How can In summary, the number of chromosomes increases only in we keep track of the number of these structures in the cell cycle? anaphase, when the two chromatids of a chromosome separate There are two simple rules for counting chromosomes and and become distinct chromosomes. The number of chromosomes DNA molecules: (1) to determine the number of chromosomes, decreases only through cytokinesis. The number of DNA mole- count the number of functional centromeres; (2) to determine the cules increases only in the S phase and decreases only through number of DNA molecules, first determine if sister chromatids are cytokinesis. TRY PROBLEM 23 present. If sister chromatids are present, the chromosome has repli- cated and the number of DNA molecules is twice the number of chromosomes. If sister chromatids are not present, the chromosome has not replicated and the number of DNA molecules is the same as the number of chromosomes. 2.3 Sexual Reproduction Produces Let’s examine a hypothetical cell as it passes through the cell Genetic Variation Through the cycle (Figure 2.12). At the beginning of G1, this diploid cell has two Process of Meiosis complete sets of chromosomes, inherited from its parent cell. Each chromosome is unreplicated and consists of a single molecule of If all reproduction were accomplished through mitosis, life DNA, and so there are four DNA molecules in the cell during G1. In would be quite dull, because mitosis produces only geneti- the S phase, each DNA molecule is copied. The two resulting DNA cally identical progeny. With only mitosis, you, your chil- molecules combine with histones and other proteins to form sister dren, your parents, your brothers and sisters, your cousins, chromatids. Although the amount of DNA doubles in the S phase, and many people you don’t even know would be clones— the number of chromosomes remains the same because the sister copies of one another. Only the occasional mutation would chromatids are tethered together and share a single functional cen- introduce any genetic variability. All organisms reproduced tromere. At the end of the S phase, this cell still contains four chro- mosomes, each with two sister chromatids; so 4 ⫻ 2 ⫽ 8 DNA in this way for the first 2 billion years of Earth’s existence molecules are present. (and it is the way in which some organisms still reproduce Through prophase, prometaphase, and metaphase, the cell today). Then, some 1.5 billion to 2 billion years ago, some- has four chromosomes and eight DNA molecules. At anaphase, thing remarkable evolved: cells that produce genetically however, the sister chromatids separate. Each now has its own variable offspring through sexual reproduction. 26 Chapter 2 MEIOSIS I MEIOSIS II Meiosis The words mitosis and meiosis are sometimes confused. They sound a bit alike, and both refer to chromosome divi- sion and cytokinesis. But don’t be deceived. The outcomes of mitosis and meiosis are radically different, and several unique events that have important genetic consequences take place only in meiosis. n How does meiosis differ from mitosis? Mitosis consists Reduction Equational of a single nuclear division and is usually accompanied by a division division single cell division. Meiosis, on the other hand, consists of two divisions. After mitosis, chromosome number in newly formed cells is the same as that in the original cell, whereas 2n meiosis causes chromosome number in the newly formed cells to be reduced by half. Finally, mitosis produces geneti- cally identical cells, whereas meiosis produces genetically variable cells. Let’s see how these differences arise. n Like mitosis, meiosis is preceded by an interphase stage that includes G1, S, and G2 phases. Meiosis consists of two n distinct processes: meiosis I and meiosis II, each of which includes a cell division. The first division, which comes 2.13 Meiosis includes two cell divisions. In this illustration, the at the end of meiosis I, is termed the reduction division original cell is 2n ⫽ 4. After two meiotic divisions, each resulting because the number of chromosomes per cell is reduced by cell is 1n ⫽ 2. half (Figure 2.13). The second division, which comes at the end of meiosis II, is sometimes termed the equational divi- The evolution of sexual reproduction is one of the most sion. The events of meiosis II are similar to those of mitosis. significant events in the history of life. As will be discussed However, meiosis II differs from mitosis in that chromo- in Chapters 24 and 25, the pace of evolution depends on the some number has already been halved in meiosis I, and the amount of genetic variation present. By shuffling the genetic cell does not begin with the same number of chromosomes information from two parents, sexual reproduction greatly as it does in mitosis (see Figure 2.13). increases the amount of genetic variation and allows for accelerated evolution. Most of the tremendous diversity of Meiosis I During interphase, the chromosomes are life on Earth is a direct result of sexual reproduction. relaxed and visible as diffuse chromatin. Prophase I is a Sexual reproduction consists of two processes. The first lengthy stage, divided into five substages (Figure 2.14). is meiosis, which leads to gametes in which chromosome In leptotene, the chromosomes contract and become vis- number is reduced by half. The second process is fertiliza- ible. In zygotene, the chromosomes continue to condense; tion, in which two haploid gametes fuse and restore chro- homologous chromosomes pair up and begin synapsis, a mosome number to its original diploid value. very close pairing association. Each homologous pair of Crossing over Chromosomes pair Synaptonemal Chiasmata complex Leptotene Zygotene Pachytene Diplotene Diakinesis Synaptonemal Bivalent complex or tetrad Chiasmata 2.14 Crossing over takes place in prophase I.  Chromosomes and Cellular Reproduction 27 synapsed chromosomes consists of four chromatids called a Anaphase I is marked by the separation of homologous bivalent or tetrad. In pachytene, the chromosomes become chromosomes. The two chromosomes of a homologous pair shorter and thicker, and a three-part synaptonemal com- are pulled toward opposite poles. Although the homolo- plex develops between homologous chromosomes. The gous chromosomes separate, the sister chromatids remain function of the synaptonemal complex is unclear, but the attached and travel together. In telophase I, the chromo- chromosomes of many cells deficient in this complex do somes arrive at the spindle poles and the cytoplasm divides. not separate properly. Crossing over takes place in prophase I, in which Meiosis II The period between meiosis I and meiosis II homologous chromosomes exchange genetic information. is interkinesis, in which the nuclear membrane re-forms Crossing over generates genetic variation (see Sources of around the chromosomes clustered at each pole, the spindle Genetic Variation in Meiosis later in this chapter) and breaks down, and the chromosomes relax. These cells then is essential for the proper alignment and separation of pass through prophase II, in which the events of interkine- homologous chromosomes. The centromeres of the paired sis are reversed: the chromosomes recondense, the spindle chromosomes move apart in diplotene; the two homologs re-forms, and the nuclear envelope once again breaks down. remain attached at each chiasma (plural, chiasmata), which In interkinesis in some types of cells, the chromosomes is the result of crossing over. In diakinesis, chromosome remain condensed, and the spindle does not break down. condensation continues, and the chiasmata move toward These cells move directly from cytokinesis into metaphase the ends of the chromosomes as the strands slip apart; so II, which is similar to metaphase of mitosis: the individual the homologs remain paired only at the tips. Near the end chromosomes line up on the metaphase plate, with the sister of prophase I, the nuclear membrane breaks down and the chromatids facing opposite poles. spindle forms, setting the stage for metaphase I. The stages In anaphase II, the kinetochores of the sister chromatids of meiosis are outlined in Figure 2.15. separate and the chromatids are pulled to opposite poles. Each Metaphase I is initiated when homologous pairs of chromatid is now a distinct chromosome. In telophase II, the chromosomes align along the metaphase plate (see Figure chromosomes arrive at the spindle poles, a nuclear envelope 2.15). A microtubule from one pole attaches to one chro- re-forms around the chromosomes, and the cytoplasm divides. mosome of a homologous pair, and a microtubule from The chromosomes relax and are no longer visible. The major the other pole attaches to the other member of the pair. events of meiosis are summarized in Table 2.2. Table 2.2 Major events in each stage of meiosis Stage Major Events Meiosis I Prophase I Chromosomes condense, homologous chromosomes synapse, crossing over takes place, the nuclear envelope breaks down, and the mitotic spindle forms. Metaphase I Homologous pairs of chromosomes line up on the metaphase plate. Anaphase I The two chromosomes (each with two chromatids) of each homologous pair separate and move toward opposite poles. Telophase I Chromosomes arrive at the spindle poles. Cytokinesis The cytoplasm divides to produce two cells, each having half the original number of chromosomes. Interkinesis In some types of cells, the spindle breaks down, chromosomes relax, and a nuclear envelope re-forms, but no DNA synthesis takes place. Meiosis II Prophase II* Chromosomes condense, the spindle forms, and the nuclear envelope disintegrates. Metaphase II Individual chromosomes line up on the metaphase plate. Anaphase II Sister chromatids separate and move as individual chromosomes toward the spindle poles. Telophase II Chromosomes arrive at the spindle poles; the spindle breaks down and a nuclear envelope re-forms. Cytokinesis The cytoplasm divides. *Only in cells in which the spindle has broken down, chromosomes have relaxed, and the nuclear envelope has re-formed in telophase I. Other types of cells proceed directly to metaphase II after cytokinesis. Meiosis I Middle Prophase I Late Prophase I Late Prophase I Centrosomes Pairs of homologs Chiasmata Chromosomes begin to condense, Homologous chromosomes pair. Crossing over takes place, and the and the spindle forms. nuclear membrane breaks down. Meiosis II Prophase II Metaphase II Anaphase II Equatorial plate The chromosomes recondense. Individual chromosomes line Sister chromatids separate and up on the equatorial plate. move toward opposite poles. CONCEPTS ✔ CONCEPT CHECK 5 Meiosis consists of two distinct processes: meiosis I and meiosis Which of the following events takes place in metaphase I? II. Meiosis I includes the reduction division, in which homolo- a. Crossing over gous chromosomes separate and chromosome number is reduced by half. In meiosis II (the equational division) chroma- b. Chromosomes contract. tids separate. c. Homologous pairs of chromosomes line up on the metaphase plate. d. Individual chromosomes line up on the metaphase plate. 28  Chromosomes and Cellular Reproduction 29 Metaphase I Anaphase I Telophase I Metaphase plate Homologous pairs of chromosomes Homologous chromosomes separate Chromosomes arrive at the spindle line up along the metaphase plate. and move toward opposite poles. poles and the cytoplasm divides. Telophase II Products 2.15 Meiosis is divided into stages. [Photographs by C. A. Hasenkampf/Biological Photo Service.]  www.whfreeman.com/pierce4e Examine meiosis and the consequences of its failure by viewing Animation 2.2. Chromosomes arrive at the spindle poles and the cytoplasm divides. Sources of Genetic Variation in Meiosis Crossing over Crossing over, which takes place in pro- What are the overall consequences of meiosis? First, meio- phase I, refers to the exchange of genes between nonsister sis comprises two divisions; so each original cell produces chromatids (chromatids from different homologous chro- four cells (there are exceptions to this generalization, as, for mosomes). Evidence from yeast suggests that crossing over example, in many female animals; see Figure 2.20b). Second, is initiated in zygotene, before the synaptonemal complex chromosome number is reduced by half; so cells produced develops, and is not completed until near the end of pro- by meiosis are haploid. Third, cells produced by meiosis are phase I (see Figure 2.14). In other organisms, recombination genetically different from one another and from the parental is initiated after the formation of the synaptonemal complex cell. Genetic differences among cells result from two pro- and, in yet others, there is no synaptonemal complex. cesses that are unique to meiosis: crossing over and random After crossing over has taken place, the sister chromatids separation of homologous chromosomes. may no longer be identical. Crossing over is the basis for 30 Chapter 2 (d) 1 One chromosome 2 …and the homologous 3 DNA replication 4 During crossing over in 5 After meiosis I and II, A possesses the chromosome possesses in the S phase prophase I, segments of each of the resulting A and B alleles… the a and b alleles. produces identical nonsister chromatids cells carries a unique sister chromatids. are exchanged. combination of alleles. B (a) (b) (c) a A a A Aa a A aA a B DNA Crossing Meiosis synthesis over I and II A B b B Bb b B Bb b b a 2.16 Crossing over produces genetic variation. Explore how crossing over affects genetic variation by  www.whfreeman.com/pierce4e viewing Animation 2.3. b intrachromosomal recombination, creating new combina- How each pair of homologs aligns and separates is ran- tions of alleles on a chromatid. To see how crossing over pro- dom and independent of how other pairs of chromosomes duces genetic variation, consider two pairs of alleles, which align and separate (Figure 2.17b). By chance, all the maternal we will abbreviate Aa and Bb. Assume that one chromosome chromosomes might migrate to one side, with all the paternal possesses the A and B alleles and its homolog possesses the a chromosomes migrating to the other. After division, one cell and b alleles (Figure 2.16a). When DNA is replicated in the would contain chromosomes Im, IIm, and IIIm, and the other, S phase, each chromosome duplicates, and so the resulting Ip, IIp, and IIIp. Alternatively, the Im, IIm, and IIIp chromo- sister chromatids are identical (Figure 2.16b). somes might move to one side, and the Ip, IIp, and IIIm chro- In the process of crossing over, there are breaks in the mosomes to the other. The different migrations would pro- DNA strands and the breaks are repaired in such a way that duce different combinations of chromosomes in the resulting segments of nonsister chromatids are exchanged (Figure cells (Figure 2.17c). There are four ways in which a diploid 2.16c). The molecular basis of this process will be described cell with three pairs of chromosomes can divide, producing a in more detail in Chapter 12. The important thing here is that, total of eight different combinations of chromosomes in the after crossing over has taken place, the two sister chromatids gametes. In general, the number of possible combinations is are no longer identical: one chromatid has alleles A and B, 2n, where n equals the number of homologous pairs. As the whereas its sister chromatid (the chromatid that underwent number of chromosome pairs increases, the number of com- crossing over) has alleles a and B. Likewise, one chromatid binations quickly becomes very large. In humans, who have of the other chromosome has alleles a and b, and the other 23 pairs of chromosomes, there are 223, or 8,388,608, different chromatid has alleles A and b. Each of the four chromatids combinations of chromosomes possible from the random now carries a unique combination of alleles: A B , a B , separation of homologous chromosomes. The genetic conse- A b , and a b. Eventually, the two homologous chro- quences of this process, termed independent assortment, will mosomes separate, each going into a different cell. In meiosis be explored in more detail in Chapter 3. II, the two chromatids of each chromosome separate, and In summary, crossing over shuffles alleles on the same thus each of the four cells resulting from meiosis carries a chromosome into new combinations, whereas the random different combination of alleles (Figure 2.16d). distribution of maternal and paternal chromosomes shuffles alleles on different chromosomes into new combinations. Random Separation of Homologous Chromosomes Together, these two processes are capable of producing The second process of meiosis that contributes to genetic tremendous amounts of genetic variation among the cells variation is the random distribution of chromosomes in resulting from meiosis. TRY PROBLEMS 30 AND 31 anaphase I after their random alignment in metaphase I. To illustrate this process, consider a cell with three pairs of chro- mosomes, I, II, and III (Figure 2.17a). One chromosome of CONCEPTS each pair is maternal in origin (Im, IIm, and IIIm); the other The two mechanisms that produce genetic variation in meiosis are is paternal in origin (Ip, IIp, and IIIp). The chromosome pairs crossing over and the random distribution of maternal and pater- line up in the center of the cell in metaphase I and, in ana- nal chromosomes. phase I, the chromosomes of each homologous pair separate.  Chromosomes and Cellular Reproduction 31 (a) (b) (c) Gametes 1 This cell has three 2 One of each pair is homologous pairs maternal in origin of chromosomes. (Im, IIm, IIIm)… Im Ip 2* I m II m III m II m II p II m Im III p III m III p 2* I p II p III p Im III m DNA II m replication III m Ip II p III p II p Ip Im Ip 2* I m II m III p II m II p 3 …and the other is paternal (Ip, IIp, IIIp). III p III m 2* I p II p III m 4 There are four possible ways for the three pairs to align in metaphase I. Im Ip 2* I m II p III p II p II m III p III m 2* I p II m III m Im Ip 2* I m II p III m II p II m 2.17 Genetic variation is produced through the random distribution of chromosomes in meiosis. In this example, the cell III m III p 2* I p II m III p possesses three homologous pairs of chromosomes. Explore the  www.whfreeman.com/pierce4e random distribution Conclusion: Eight different combinations of chromosomes of chromosomes by viewing Animation 2.3. in the gametes are possible, depending on how the chromosomes align and separate in meiosis I and II. Mitosis and meiosis also differ in the behavior of chromosomes CONNECTING CONCEPTS in metaphase and anaphase. In metaphase I of meiosis, homologous Mitosis and Meiosis Compared pairs of chromosomes line up on the metaphase plate, whereas individual chromosomes line up on the metaphase plate in meta- Now that we have examined the details of mitosis and meiosis, let’s phase of mitosis (and in metaphase II of meiosis). In anaphase I of compare the two processes (Figure 2.18 and Table 2.3). In both meiosis, paired chromosomes separate and migrate toward opposite mitosis and meiosis, the chromosomes contract and become visible; spindle poles, each chromosome possessing two chromatids both processes include the movement of chromosomes toward the attached at the centromere. In contrast, in anaphase of mitosis (and spindle poles, and both are accompanied by cell division. Beyond in anaphase II of meiosis), sister chromatids separate, and each these similarities, the processes are quite different. chromosome that moves toward a spindle pole is unreplicated. Mitosis results in a single cell division and usually produces TRY PROBLEMS 25 AND 26 two daughter cells. Meiosis, in contrast, comprises two cell divisions and usually produces four cells. In diploid cells, homologous chro- mosomes are present before both meiosis and mitosis, but the pairing of homologs takes place only in meiosis. Another difference is that, in meiosis, chromosome number is The Separation of Sister Chromatids reduced by half as a consequence of the separation of homologous and Homologous Chromosomes pairs of chromosomes in anaphase I, but no chromosome reduction takes place in mitosis. Furthermore, meiosis is characterized by two In recent years, some of the molecules required for the join- processes that produce genetic variation: crossing over (in prophase I) ing and separation of chromatids and homologous chromo- and the random distribution of maternal and paternal chromosomes (in somes have been identified. Cohesin, a protein that holds the anaphase I). There are normally no equivalent processes in mitosis. chromatids together, is key to the behavior of chromosomes 32 Chapter 2 Mitosis Parent cell (2n) Prophase Metaphase Anaphase Two daughter cells, each 2n 2n 2n Individual chromosomes align Chromatids on the metaphase plate. separate. Meiosis Parent cell (2n) Prophase I Metaphase I Anaphase I Crossing over Homologous pairs of chromosomes Pairs of chromosomes takes place. align on the metaphase plate. separate. Interkinesis Metaphase II Anaphase II Four daughter cells, each n n n n n Individual chromosomes align. Chromatids separate. 2.18 Mitosis and meiosis compared. in mitosis and meiosis (Figure 2.19a). The sister chromatids Table 2.3 Comparison of Mitosis, Meiosis I, and are held together by cohesin, which is established in the S Meiosis II phase and persists through G2 and early mitosis. In anaphase of mitosis, cohesin along the entire length of the chromo- Event Mitosis Meiosis I Meiosis II some is broken down by an enzyme called separase, allowing the sister chromatids to separate. Cell division Yes Yes Yes As we have seen, mitosis and meiosis differ funda- Chromosome No Yes No mentally in the behavior of chromosomes in anaphase (see reduction Figure 2.18). Why do homologs separate in anaphase I of Genetic No Yes No meiosis, whereas chromatids separate in anaphase of mitosis variation and anaphase II of meiosis? It is important to note that the produced forms of cohesin used in mitosis and meiosis differ. At the Crossing over No Yes No beginning of meiosis, the meiosis-specific cohesin is found Random No Yes No along the entire length of a chromosome’s arms (Figure distribution 2.19b). The cohesin also acts on the chromosome arms of of maternal homologs at the chiasmata, tethering two homologs together and paternal at their ends. chromosomes In anaphase I, cohesin along the chromosome arms is Metaphase Individual Homologous Individual broken, allowing the two homologs to separate. However, chromosomes pairs chromosomes cohesin at the centromere is protected by a protein called line up line up line up shugoshin, which means “guardian spirit” in Japanese. Anaphase Chromatids Homologous Chromatids Because of this protective action by shugoshin, the centro- separate chromosomes separate meric cohesin remains intact and prevents the separation separate of the two sister chromatids during anaphase I of meiosis. Shugoshin is subsequently degraded. At the end of meta-  Chromosomes and Cellular Reproduction 33 (a) Mitosis 1 Sister kinetochores orient 2 …and cohesin keeps sister 3 The breakdown of cohesin allows toward different poles,… chromatids together. sister chromatids to separate. Spindle fibers Cohesin Breakdown of cohesin Chromatid Metaphase Anaphase (b) Meiosis 4 Cohesin along chromosome 5 Cohesin along chromosome 6 …but cohesin at the 7 Shugoshin is degraded. arms holds homologs arms breaks down, allowing centromere is protected Cohesin at the centromeres together at chiasmata. homologs to separate,… by shugoshin. breaks down, allowing chromatids to separate. Chiasma Breakdown Breakdown of cohesin of centromeric along arms cohesin Shugoshin Metaphase I Anaphase I Anaphase II 2.19 Cohesin controls the separation of chromatids and chromosomes in mitosis and meiosis. phase II, the centromeric cohesin—no longer protected by Meiosis in the Life Cycles of Animals shugoshin—breaks down, allowing the sister chromatids to and Plants separate in anaphase II, just as they do in mitosis (Figure 2.19b). TRY PROBLEM 27