DNA Recombination:- Homologous Genetic Recombination Has Several Functions
In bacteria, homologous genetic recombination is primarily a DNA repair process and, in this context, (as noted in Section 25.2) is referred to as recombinational DNA repair. It is usually directed at the reconstruction of replication forks stalled at the site of DNA damage. Homologous genetic recombination can also occur during conjugation (mating), when chromosomal DNA is transferred from a donor to a recipient bacterial cell. Recombination during conjugation, although rare in wild bacterial populations, contributes to genetic diversity. In eukaryotes, homologous genetic recombination can have several roles in replication and cell division, including the repair of stalled replication forks. Recom bination occurs with the highest frequency during meiosis, the process by which diploid germ-line cells with two sets of chromosomes divide to produce haploid ga metes—sperm cells or ova in higher eukaryotes—each gamete having only one member of each chromosome pair (Fig. 1). Meiosis begins with replication of the DNA in the germ-line cell so that each DNA molecule is present in four copies. The cell then goes through two rounds of cell division without an intervening round of DNA replication. This reduces the DNA content to the haploid level in each gamete. After the DNA is replicated during prophase of the first meiotic division, the resulting sister chromatids remain associated at their centromeres. At this stage, each set of four homologous chromosomes exists as two pairs of chromatids. Genetic information is now exchanged between the closely associated homologous chromatids by homologous genetic recombination, a process in volving the breakage and rejoining of DNA (Fig. 2). This exchange, also referred to as crossing over, can be observed with the light microscope. Crossing over links the two pairs of sister chromatids together at points called chiasmata (singular, chiasma).
FIGURE 1 Meiosis in eukaryotic germ-line cells. The chromo somes of a hypothetical diploid germ-line cell (six chromosomes; three homologous pairs) replicate and are held together at their centromeres. Each replicated double-stranded DNA molecule is called a chromatid (sister chromatid). In prophase I, just before the first meiotic division, the three homologous sets of chromatids align to form tetrads, held together by covalent links at homologous junctions (chiasmata). Crossovers occur within the chiasmata (see Fig. 2). These transient associations between homologs ensure that the two tethered chromosomes segregate properly in the next step, when they migrate toward opposite poles of the dividing cell in the first meiotic division. The products of this division are two daughter cells, each with three pairs of chromatids. The pairs now line up across the equator of the cell in preparation for separation of the chromatids (now called chromosomes). The second meiotic division produces four haploid daughter cells that can serve as gametes. Each has three chromosomes, half the number of the diploid germ-line cell. The chromosomes have resorted and recombined.
FIGURE 2 Crossing over. (a) Crossing over often produces an exchange of genetic material. (b) The homologous chromosomes of a grasshopper are shown during prophase I of meiosis. Many points of joining (chiasmata) are evident between the two homologous pairs of chromatids. These chiasmata are the physical manifestation of prior homologous recombination (crossing over) events.
Crossing over effectively links together all four homologous chromatids, a linkage that is essential to the proper segregation of chromosomes in the subsequent meiotic cell divisions. Crossing over is not an entirely random process, and “hot spots” have been identified on many eukaryotic chromosomes. However, the assumption that crossing over can occur with equal prob ability at almost any point along the length of two homologous chromosomes remains a reasonable ap proximation in many cases, and it is this assumption that permits the genetic mapping of genes. The frequency of homologous recombination in any region separating two points on a chromosome is roughly proportional to the distance between the points, and this allows determination of the relative positions of and distances between different genes.
Homologous recombination thus serves at least three identifiable functions: (1) it contributes to the re pair of several types of DNA damage; (2) it provides, in eukaryotic cells, a transient physical link between chromatids that promotes the orderly segregation of chromosomes at the first meiotic cell division; and (3) it enhances genetic diversity in a population.
