A diploid organism has two copies of each chromosome. If it has four chromosomes, there are two pairs, A and A’ and B and B’, not four different chromosomes A, B, C and D. One copy of each chromosome came from its father (e.g. A and B) and one copy of each came from its mother (e.g. A’ and B’). Meiosis is the process of reductive division whereby a diploid organism generates haploid germ cells (in this case, with two chromosomes), and each germ cell has a single copy of each chromosome. In this example, meiosis does not generate germ cells with A and A’ or B and B’, rather it produces cells with A and B, or A and B’, or A’ and B, or A’ and B’. The homologous chromosomes, each consisting of two sister chromatids, are paired during the first phase of meiosis, e.g., A with A’ and B with B’ (Figure 8.3; see also Figs. 1.3 and 1.4). Then the homologous chromosomes are moved to separate cells at the end of the first phase, insuring that the two homologs do not stay together during reductive division in the second phase of meiosis. Thus each germ cell receives the haploid complement of the genetic material, i.e. one copy of each chromosome. The combination of two haploid sets of chromosomes during fertilization restores the diploid state, and the cycle can resume. Failure to distribute one copy of each chromosome to each germ cell has severe consequences. Absence of one copy of a chromosome in an otherwise diploid zygote is likely fatal. Having an extra copy of a chromosome (trisomy) also causes problems. In humans, trisomy for chromosomes 15 or 18 results in perinatal death and trisomy 21 leads to developmental defects known as Down’s syndrome.
If this diploid organism with chromosomes A, A’, B and B’ underwent meiosis without homologous pairing and separation of the homologs to different cells, what fraction of the resulting haploid cells would have an A-type chromosome (A or A’) and a B-type chromosome (B or B’)?
The ability of homologous chromosomes to be paired during the first phase of meiosis is fundamental to the success of this process, which maintains a correct haploid set of chromosomes in the germ cell. Recombination is an integral part of the pairing of homologous chromosomes. It occurs between non-sister chromatids during the pachytene stage of meiosis I (the first stage of meiosis) and possibly before, when the homologous chromosomes are aligned in zygotene (Figure 8.3). The crossovers of recombination are visible in the diplotene phase. During this phase, the homologous chromosomes partially separate, but they are still held together at joints called chiasmata; these are likely the actual crossovers between chromatids of homologous chromosomes. The chiasmata are progressively broken as meiosis I is completed, corresponding to resolution of the recombination intermediates. During anaphase and telophase of meiosis I, each homologous chromosome moves to a different cell, i.e. A and A’ in different cells, B and B’ in different cells in our example. Thus recombinations occur in every meiosis, resulting in at least one exchange between pairs of homologous chromosomes per meiosis.
Recent genetic evidence demonstrates that recombination is required for homologous pairing of chromosomes during meiosis. Genetic screens have revealed mutants of yeast and Drosophila that block pairing of homologous chromosomes. These are also defective in recombination. Likewise, mutants defective in some aspects of recombination are also defective in pairing. Indeed, the process of synapsis (or pairing) between homologous chromosomes in zygotene, crossing over between homologs in pachytene, and resolution of the crossovers in the latter phases of meiosis I (diakinesis, metaphase I, and anaphase I) correspond to the synapsis, formation of a recombinant joint and resolution that mark the progression of recombination, as will be explained below.
Figure 8.3.Homologous pairing and recombination during the first stage of meiosis (meiosis I). After DNA synthesis has been completed, two copies of each homologous chromosome are still connected at centromeres (yellow circles). This diagram starts with replicated chromosomes, referred to as the four-strand stage in the literature on meiosis and recombination. In this usage, each “strand” is a chromatid and is a duplex DNA molecule. In this diagram, each duplex DNA molecule is shown as a single line, brown for the two sister chromatids of chromosome derived from the mother (maternal) and pink for the sister chromatids from the paternal chromosome. Only one homologous pair is shown, but usually there are many more, e.g. 4 pairs of chromosomes in Drosophilaand 23 pairs in humans. During the meiosis I, the homologous chromosomes align and then separate. At the zygotene stage, the two homologous chromosomes, each with two sister chromatids, pair along their length in a process called synapsis. The resulting group of four chromatids is called a tetrad or bivalent. During pachytene, recombination occurs between a maternal and a paternal chromatid, forming crossovers between the homologous chromosomes. The two homologous chromosomes separate along much of their length at diplotene, but they continue to be held together at localized chiasmata, which appear as X-shaped structures in micrographs. These physical links are thought to be the positions of crossing over. During metaphase and anaphase of the first meiotic division, the crossovers are gradually broken (with those at the ends resolved last) and the two homologous chromosomes (each still with two chromatids joined at a centromere) are moved into separate cells. During the second meiotic division (meiosis II), the centromere of each chromosome separates, allowing the two chromatids to move to separate cells, thus finishing the reductive division and making four haploid germ cells.