Gene conversion



Gene conversion is an event in DNA genetic recombination, which occurs at high frequencies during meiotic division but which also occurs in somatic cells. It is a process by which DNA sequence information is transferred from one DNA helix (which remains unchanged) to another DNA helix, whose sequence is altered. It is one of the ways a gene may be mutated. Gene conversion may lead to non-Mendelian inheritance and has often been recorded in fungal crosses.

Mechanism
This conversion of one allele to the other is due to base mismatch repair during recombination: if one of the four strands during meiosis pairs up with one of the four strands of a different chromosome, as can occur if there is sequence homology, mismatch repair can alter the sequence of one of the chromosomes, so that it is identical to the other.

Gene conversion can result from the repair of damaged DNA as described by the Double Strand Break Repair Model. Here a break in both strands of DNA is repaired from an intact homologous region of DNA. Resection (degradation) of the DNA strands near the break site leads to stretches of single stranded DNA that can invade the homologous DNA strand. The intact DNA can then function as a template to copy the lost DNA. During this repair process a structure called a double Holliday structure is formed. Depending on how this structure is resolved (taken apart) either cross-over or gene conversion products result.

Effect
Normally, an organism that has inherited different copies of a gene from each of its parents is called heterozygous. This is generically represented as genotype: Aa (i.e. one copy of variant (allele) 'A', and one copy of allele 'a'). When a heterozygote creates gametes by meiosis, the alleles normally split, and end up in a 1:1 ratio in the resulting cells. However, in gene conversion, a ratio other than the expected 1A:1a is observed, in which A and a are the two alleles. Such examples are 3A:1a, 1A:3a, 5A:3a or 3A:5a. In other words there can, for example, be three times as many A alleles as a alleles expressed in the daughter cells, as is the case in 3A:1a.

Importance of gene conversion in the cohesiveness of the gene pool
Gene conversion acts to homogenize the DNA sequences composing the gene pool of a species. Every gene conversion event takes as its substrate two DNA sequences that are homologous but not identical, because of sequence mismatches, and yields two identical DNA sequences. Gene conversion forms the cohesive force that links DNA sequences within different organisms of a species. Over time, gene conversion events yield a homogenous set of DNA sequences, both for allelic forms of a gene and for multi gene families. Interspersed repeats act to block gene conversion events, thus catalyzing evolution of new genes and species.

Medical relevance
Gene conversion resulting in mutation of the CYP21A2 gene is a common underlying genetic cause of congenital adrenal hyperplasia.

Somatic gene conversion is one of the mechanisms that can result in familial retinoblastoma, a congenital cancer of the retina.

It is theorized that gene conversion may play a role in the development of Huntington's Disease