8.15:
Gene Conversion
Unlike mitosis where double-strand breaks are accidental, in meiosis, they are created by an enzyme called Spo11, which cleaves the phosphodiester backbone. The broken helical ends are trimmed by a protein complex called MRX and the damage is repaired by a process called gene conversion.
Here the damaged “acceptor” DNA strand invades a homologous “donor” DNA duplex to form a displacement loop. This creates regions of heteroduplex DNA where a strand from the donor DNA pairs with a complementary strand from the acceptor DNA.
DNA polymerase extends the invading strand, and the extended D-loop then pairs with the free 3′ tail. DNA synthesis at the newly captured strand, results in the formation of an intermediate with two four-strand structures called Holliday junctions.
This double Holliday junction intermediate is resolved by DNA repair enzymes called resolvases and there are two orientations in which the junctions can be cleaved. In the first, resolvase nicks each junction horizontally so that the parental strands are still intact.
This results in a non-crossover product, named because the strands after the break remain with their original partner, and there is no major crossing over of the donor and acceptor strands.
Alternatively, if cleavage occurs vertically the regions flanking the damage are switched leading to a crossover product, where the donor strand following the break recombines with the acceptor strand.
Gene conversion has a significant impact on genomic diversity. In sexually reproducing organisms the offspring inherits one set of genes from the father and one set from the mother.
The parental DNA sets recombine and the sister chromatids undergo gene conversion. This results in the offspring having novel chromosomes compared to those of the parents.
8.15:
Gene Conversion
Other than maintaining genome stability via DNA repair, homologous recombination plays an important role in diversifying the genome. In fact, the recombination of sequences forms the molecular basis of genomic evolution. Random and non-random permutations of genomic sequences create a library of new amalgamated sequences. These newly formed genomes can determine the fitness and survival of cells. In bacteria, homologous and non-homologous types of recombination lead to the evolution of new genomes that ultimately decide the adaptability of bacteria to varying environmental conditions.
During meiosis, when a single cell divides twice to produce four cells containing half the original number of chromosomes, HR leads to crossovers between genes. This means that two regions of the same chromosome with nearly identical sequences break and then reconnect but to a different end piece. The minor differences between the DNA sequences of the homologous chromosomes do not change the function of the gene but can change the allele or the phenotype of the gene. For example, if a gene codes for a trait such as hair color, its allele determines the specific phenotype, i.e. whether the hair would be black, blonde or red. Humans contain two alleles of the same gene, at each gene location, one from each parent. Recombination such as gene conversion changes this distribution, altering the gene’s form or manifestation in the offspring.
Suggested Reading
- Chen, Jian-Min, David N. Cooper, Nadia Chuzhanova, Claude Férec, and George P. Patrinos. "Gene conversion: mechanisms, evolution and human disease." Nature Reviews Genetics 8, no. 10 (2007): 762.
- Andersen, Sabrina L., and Jeff Sekelsky. "Meiotic versus mitotic recombination: Two different routes for double‐strand break repair: The different functions of meiotic versus mitotic DSB repair are reflected in different pathway usage and different outcomes." Bioessays 32, no. 12 (2010): 1058-1066.