Several pathways in the cell can lead to gene conversion, but one of the most important arises from a particular consequence of recombination during meiosis. We have seen that both crossovers and non-crossovers produce heteroduplex regions of DNA. If the two strands that make up a heteroduplex region do not have identical nucleotide sequences, mismatched base pairs are formed, and these are often repaired by the cell’s mismatch repair system (see Figure 5–19). However, the mismatch repair system cannot distinguish between the paternal and maternal strands and will randomly choose the strand to be used as a template. As a consequence, one allele will be lost and the other duplicated (Figure 5–59), resulting in net “conversion” of one allele to the other. Thus, gene conversion, originally regarded as a mysterious deviation from the rules of genetics, can be seen as a straightforward consequence of the mechanisms of homologous recombination.
Homologous recombination describes a flexible set of reactions resulting in the exchange of DNA sequences between a pair of identical or nearly identical duplex DNA molecules. In all cells, this process is essential for the error-free repair of chromosome damage, particularly double-strand breaks and broken or stalled replication forks. Homologous recombination is also responsible for the crossing-over of chromosomes that occurs during meiosis. Homologous recombination takes place through a variety of pathways, but they have in common a strand-exchange step whereby a single strand from one DNA duplex invades a second duplex and base-pairs with one strand while displacing the other. This reaction, catalyzed by the RecA/Rad51 family of proteins, can only occur if the invading strand can form a short stretch of consecutive nucleotide pairs with one of the strands of the duplex. This requirement ensures that homologous recombination occurs only between identical or very similar DNA sequences.
DNA SYNTHESIS FILLS GAP, CREATING AN EXTRA COPY OF THE RED ALLELE OF
When used as a repair mechanism, homologous recombination occurs between a damaged DNA molecule and its recently duplicated sister molecule, with the undamaged duplex acting as a template to repair the damaged copy flawlessly.
In meiosis, homologous recombination is initiated by deliberate, carefully regulated double-strand breaks and occurs preferentially between the homologous chromosomes rather than the newly replicated sister chromatids. The outcome can be either two chromosomes that have crossed over (that is, chromosomes in which the DNA on either side of the site of DNA pairing originates from two different homo-logs) or two non-crossover chromosomes. In the latter case, the two chromosomes that result are identical to the original two homologs, except for relatively minor DNA sequence changes at the site of recombination.
We have seen that homologous recombination can result in the exchange of DNA sequences between chromosomes. However, the order of genes on the interacting chromosomes typically remains the same following homologous recombination, inasmuch as the recombining sequences must be very similar for the process to occur. In this section, we describe two very different types of recombination—transposition (also called transpositional recombination) and conservative site-specific recombination—that do not require substantial regions of DNA homology. These two types of recombination reactions can alter gene order along a chromosome and can cause unusual types of mutations that introduce whole blocks of DNA sequence into the genome.
Transposition and conservative site-specific recombination are largely dedicated to moving a wide variety of specialized segments of DNA—collectively termed mobile genetic elements—from one position in a genome to another. We will see that mobile genetic elements can range in size from a few hundred to tens of thousands of nucleotide pairs, and each typically carries a unique set of genes. Often, one of these genes encodes a specialized enzyme that catalyzes the movement of only that element, thereby making this type of recombination possible.