We have discussed how DNA in chromosomes is rearranged via genetic recombination during the meiotic process. However, genetic recombination occurs not only in meiosis but also in somatic cell division and viral infection. The resulting DNA rearrangement brings about genetic diversity, allowing organisms to survive in various environments. In this section, genetic recombination is more broadly discussed, including general recombination and site-specific recombination.
General recombination occurs between homologous DNA regions, and includes the type that takes place between homologous chromosomes during meiosis. In recombination between such chromosomes, a double-strand break occurs in one of the paired homologous DNA strands followed by the initiation of partial degradation of the 5’ ends at the break point, thereby exposing the 3’ ends (Fig. 12-7). The 3’ ends recognize the similar DNA sequence in the paired DNA strand, and bind to it through the action of proteins that mediate recombination. The partial synthesis of complementary DNA then proceeds, and DNA recombination is finally completed after the breaking of the DNA strands and the repair of the chromosomes.
Site-specific recombination is caused by specific short sequences. These sequences are known as movable genetic elements, and move not only within the same chromosome but also to other chromosomes, where they cause recombination. Figure 12-8 shows the movement of a movable genetic element called transposon and the rearrangement of chromosomes that accompanies it. In this figure, the deletion of the movable genetic element and its insertion to a new site are shown. There are many types of movable genetic element, which are roughly classified into those that move as DNA and those that move as RNA (despite being incorporated into chromosomes as DNA). All organisms have large amounts of movable genetic elements in their chromosomes, although element types vary by organism. As an example, in the human genome, regions that encode proteins account for less than 5% of the total, whereas the proportion of movable-genetic-elements-like sequences is 45%. Although it is thought that many of the sequences have been mutated and are no longer transposable, some are capable of movement. On the other hand, as confirmed in a number of viruses, foreign genes can enter host chromosomes using site-specific recombination.
Fig. 12-8. Molecular process of site-specific recombination by transposition
Transposase recognizes and binds to short repetitive sequences in transposons. Transposases that bind to the repetitive sequences at both ends are paired to form a complex consisting of a dimer and a DNA loop. This DNA region is cut out from donor chromosome A and is incorporated randomly into target chromosome B. In chromosome B, two DNA strands are nicked at separate sites, forming a gap through which the transposon enters. This gap is then repaired using the complementary strand as a template, thus creating short parallel repetitive sequences. Chromosome A, broken by the removal of the transposon, is reconnected.