Cell Division and Reproduction Help (page 2)
All somatic cells in a multicellular organism are descendants of one original cell, the fertilized egg, or zygote, through a divisional process called mitosis. During mitosis an exact copy of each chromosome is created and then distributed, through division of the original (mother) cell, into each of the two daughter cells. Interphase is the period between successive mitoses and it consists of three phases: G1, S, and G2 (Fig. 1-3).
During S (synthesis) phase, the DNA molecules (see Fig. 3-1) of each chromosome are replicated (see Fig. 3-10) producing an identical pair of DNA molecules called chromatids (sometimes called "sister" chromatids). Each replicated chromosome thus enters mitosis with two identical DNA molecules. Thin chromatin strands commonly appear as amorphous granular material in the nucleus of stained cells during interphase.
Before and after S phase, there are two periods of intense metabolic activity, growth and differentiation, called G1 (gap 1) and G2 (gap 2). During G1, cells prepare for DNA synthesis (S phase) and during G2, cell growth and expansion occurs. Cells can leave the cell cycle and enter a resting, or G0, stage from G1. G0 cells are nonproliferative, but viable and metabolically active. Cells may reenter the cell cycle by returning to G1. Once a cell enters G1 and the cell cycle, it is committed to completing the cycle. The M phase, or mitosis, consists of four major phases detailed below: prophase, metaphase, anaphase, and telophase (see Fig. 1-4). Mitosis is usually the shortest phase of the cell cycle, taking 1 h of an 18–24 h total cell cycle time in an idealized animal cell. The amount of time spent in the other phases can vary, but a typical G1 phase lasts 6–12 h, S phase 6–8 h, and G2 phase 3–4 h. The times spent in each phase of mitosis are quite different. Prophase usually requires far longer than the other phases; metaphase is the shortest.
The progression of a cell through cell division is controlled by three checkpoints that ensure proper progress is beingmade before proceeding to the next stage: at the G1/S transition, at the G2/M transition, and during the M phase. For example, if DNA replication has not occurred during S phase (checked at the G2/M transition), it is pointless for the cell to proceed through mitosis. Cancers arise primarily due to unregulated cell division and, in fact, many human cancers are, in part, caused by mutations in genes that control cell cycle checkpoints. When checkpoints are not properly monitored, abnormal cells may continue to divide and result in a tumor (refer to Cancer and Genetics Help).
Different Phases of the Cell Cycle
At the biochemical level, enzymes called cyclin-dependent kinases (CDKs) control key events of the cell cycle by adding phosphate groups to other proteins, which in turn have functions in specific cell cycle activities. The addition of phosphate groups, referred to as phosphorylation, results in changes in the activity level of the modified protein (e.g., they are active or inactive in their cellular function). CDK enzymes are dependent upon an association with other proteins, called cyclins. There are different types of cyclin proteins that are present in other different phases of the cell cycle. When a specific cyclin protein associates with a CDK molecule, the phosphorylation targets of the CDK enzyme are altered. The modification of proteins by changes in phosphorylation activity causes progression through the cell cycle.
- Prophase. In prophase, the chromosomes condense (see Cytogenetics) and then becoming progressively shorter and thicker as they coil around histone proteins and then supercoil upon themselves.
EXAMPLE 1.2 A toy airplane can be used as a model to explain the condensation of the chromosomes. A rubber band, fixed at one end, is attached to the propeller at its other end. As the prop is turned, the rubber band coils and supercoils on itself, becoming shorter and thicker in the process. Something akin to this process occurs during the condensation of the chromosomes. However, as a chromosome condenses, the DNA wraps itself around histone proteins to form little balls of nucleoprotein called nucleosomes, like beads on a string. At the next higher level of condensation, the beaded string spirals into a kind of cylinder. The cylindrical structure then folds back and forth on itself. Thus, the interphase chromosome becomes condensed several hundred times its length by the end of prophase (see Fig. 7-1).
By late prophase, a chromosome may be sufficiently condensed to be seen under the microscope as consisting of two chromatids connected at their centromeres. The centrosome consists of a pair of centrioles and is the site where microtubules, composed of tubulin proteins, organize to form the mitotic spindle. Centrioles are made of microtubules and during prophase, each pair of centrioles is replicated and migrates toward opposite polar regions of the cell. There they establish a microtubule organizing center (MTOC) from which a spindle-shaped network of microtubules (called the spindle) develops. Microtubules extend from a MTOC to the kinetochore, a multiprotein structure attached to centromeric DNA on each chromosome. Most plants, fungi, and some algae lack centrioles but are able to form spindle fibers; thus, centrioles are not required for spindle formation in all organisms. By late prophase, the nuclear membrane has disappeared and the spindle has fully formed. Mitosis can be arrested at this stage by exposing cells to the alkaloid chemical colchicine that interferes with assembly of the spindle fibers. Such treated cells cannot proceed to metaphase until the colchicine is removed. Experimental treatment of cells with colchicine results in inhibition of chromosome separation during mitosis (or meiosis), which causes increases in the chromosome number (or ploidy) of the resulting cells.
- Metaphase. During metaphase, kinetochore fibers from opposite MTOCs push and pull on the joined centromeres of sister chromatids causing each chromosome to move to a plane usually near the center of the cell, a position designated the metaphase plate. The chromosomes are kept in this position by the tension from fibers of opposite MTOCs.
- Anaphase. During anaphase, sister chromatids separate at the centromere and are pulled to opposite poles. As each chromatid moves through the viscous cytosol, its arms drag along behind its centromere (attached to spindle fibers via the kinetochore), giving it a characteristic shape depending upon the location of the centromere.
- Telophase. In telophase, each set of separated chromatids is assembled at the two poles of the cell. The chromatids (now, referred to again as chromosomes) begin to uncoil and return to an interphase condition. The spindle degenerates, the nuclearmembrane reforms, and the cytoplasm divides in a process called cytokinesis. In animals, cytokinesis is accomplished by the formation of a cleavage furrow that deepens and eventually "pinches" the cell in two as shown in Fig. 1-4. Cytokinesis in most plants involves the construction of a cell plate of pectin originating in the center of the cell and spreading laterally to the cell wall. Later, cellulose and other strengthening materials are added, converting it into a new cell wall.
The two products of mitosis are called daughter cells, or progeny cells, and may or may not be of equal size depending upon where the plane of cytokinesis sections the cell. Thus, while there is no assurance of equal distribution of cytoplasmic components to daughter cells, they do contain exactly the same type and number of chromosomes and hence possess exactly the same genetic information.
Sexual reproduction involves the production of gametes (gametogenesis) and the union of a male and a female gamete (fertilization) to produce a zygote. In animals, male gametes are sperms and female gametes are eggs, or ova (ovum, singular). Gametogenesis occurs only in the specialized cells (germ line) of the reproductive organs (gonads). In animals, the testes are male gonads and the ovaries are female gonads. Gamete cells are produced through the process of meiosis. Meiosis (Fig. 1-5) consists of two specialized, consecutive cell divisions in which the chromosome number of the resulting cells is reduced by half from a diploid (2n) to a haploid (n) number. This reduction maintains the chromosome number characteristic of the species after fertilization.
Specifically, meiosis involves one DNA replication and two divisions of the chromosomes and cytoplasm. The first meiotic division (meiosis I) is a reductional division that produces two haploid cells from a single diploid cell. The second meiotic division (meiosis II) is an equational division wherein sister chromatids of the haploid cells are separated. Each of the twomeiotic divisions (meiosis I and II) consists of fourmajor phases (detailed below).Note that the DNA replicates during the interphase precedingmeiosis I; it does not replicate between telophase I and prophase II.
- Meiosis I. In the beginning of meiosis I, replicated chromosomes thicken and condense. Prophase I of meiosis differs from the prophase of mitosis in that homologous chromosomes come to lie side by side in a pairing process called synapsis. Each pair of synapsed chromosomes is called a bivalent (two chromosomes) or a tetrad (four chromatids). Each chromosome consists of two identical (replicated) sister chromatids at this stage; the cell contains one set of maternally derived and one set of paternally derived chromosomes. During synapsis, chromatids may cross over and exchange genetic material in a process called crossing over and recombination. The events of prophase I are complex and can be subdivided into five stages.
- Leptotene (thin-thread stage): The long, thin chromosomes start to condense and begin to appear in the formerly amorphous nuclear chromatin material.
- Zygotene (joined-thread stage): During this stage, homologous chromosome partners are joined together by a ribbonlike protein structure called the synaptonemal complex. This is the beginning of synapsis. Synapsis occurs intermittently along the paired chromosomes at sites where the homologues share similar genetic information. When synaptonemal complexes are not properly formed, synapsis is not as complete and crossing over is markedly reduced or eliminated.
- Pachytene (thick-thread stage): Synapsis is complete. recombination nodules begin to appear along the chromosomes. At these sites, nonsister chromatids (one from each of the paired chromosomes) of a tetrad cross over, trade DNA strands and reunite, resulting in an exchange of genetic material (see Fig. 6-1). The point of exchange appears under a microscope as a cross-shaped figure called a chiasma (chiasmata, plural). At a given chiasma, only two of the four chromatids cross over randomly. Generally, the number of crossovers per bivalent increases with the length of the chromosome. By the breakage and reunion of nonsister chromatids within a chiasma, linked genes become recombined into crossover-type chromatids; the two chromatids within that same chiasma that did not exchange segments maintain the original linkage arrangement of genes as noncrossover or parental-type chromatids. Crossing over is usually a genetic phenomenon that can be inferred only from the results of breeding experiments.
- Diplotene (double-thread stage): This stage begins when the synaptonemal complex begins to disappear so that individual chromatids and chiasmata can be more readily seen. Chiasmata are also still visible.
- Diakinesis (double movement stage): Chromosomes reach their maximal condensation. Nucleoli and nuclear membrane disappear and the spindle apparatus begins to form.
- Interkinesis. The period between the first and second meiotic divisions is called interkinesis. Depending on the species, interkinesis may be brief or continue for an extended period of time. It is important to note one important difference between mitotic interphase and meiotic interkinesis; i.e., no DNA synthesis occurs during interkinesis!
- Meiosis II. In prophase II, the spindle apparatus reforms and the chromosomes recondense. By metaphase II, the individual chromosomes have lined up on the equatorial plane. During anaphase II, the centromeres of each chromosome separate, allowing the sister chromatids to be pulled apart in an equational division (mitotis-like) by the attached spindle fibers. During telophase II, the chromosomes gather at opposite poles and the nuclear membrane reappears. Each cell then divides by cytokinesis into two progeny cells. Thus, a diploid mother cell becomes four haploid progeny cells as a consequence of a meiotic cycle (meiosis I and meiosis II). The characteristics that distinguish mitosis from meiosis are summarized in Table 1.2.
During metaphase I, the synapsed chromosomes orient at randomon the equatorial plane. At anaphase I, the centromeres do not separate, but continue to hold sister chromatids together. The chiasmata begin to dissolve, allowing the homologous pairs of chromosomes to separate and move to opposite poles; i.e., whole chromosomes (each consisting of two sister chromatids) move apart. This movement reduces the chromosome number from diploid (2n) to haploid (n). Telophase I occurs when the nuclear membrane reforms and the chromosomes have reached their polar destinations. Cytokinesis follows and results in a division of the diploid mother cell into two haploid daughter cells. Each haploid cell receives a random assortment of maternal and paternal chromosomes; i.e., the chromosomes in one daughter cell will not be uniformly of eithermaternal or paternal origin. Also, because of crossovers, sister chromatids (still attached at the centromere) may no longer be genetically identical. This ends the first meiotic division.
Genetic aberrations can occur if mistakes are made during the separation of chromosomes during meiosis. If homologues or sisters fail to come apart (or disjoin) and both migrate to the same pole (called nondisjunction), the resulting gametes will contain two of those chromosomes, instead of just one. When such a gamete fuses with another during fertilization, the resulting zygote will have three of that particular chromosome. This condition is called a trisomy (see Cytogenetics). Most trisomies are lethal; however, trisomy 21 (also called Down syndrome), results in an individual who has three copies of chromosome number 21. This trisomy is not lethal, but produces individuals who are mentally and physically disabled. Trisomies of the sex chromosomes also occur without lethality, but also result in genetic abnormalities.
Practice problems for these concepts can be found at: