Gene conversion

[2] Allelic gene conversion occurs during meiosis when homologous recombination between heterozygotic sites results in a mismatch in base pairing.

[3] Recombination occurs not only during meiosis, but also as a mechanism for repair of double-strand breaks (DSBs) caused by DNA damage.

These DSBs are usually repaired using the sister chromatid of the broken duplex and not the homologous chromosome, so they would not result in allelic conversion.

By one pathway, a structure called a double Holliday junction (DHJ) is formed, leading to the exchange of DNA strands.

[6] In analyzed human DNA sequences, crossover rate has been found to correlate positively with GC-content.

The Fxy or Mid1 gene in some mammals closely related to house mice (humans, rats, and other Mus species) is located in the sex-linked region of the X chromosome.

However, in Mus musculus, it has recently translocated such that the 3’ end of the gene overlaps with the PAR region of the X-chromosome, which is known to be a recombination hotspot.

One possible explanation for the presence of GC-rich isochores is that they evolved due to GC-biased gene conversion in regions with high levels of recombination.

Detection of infrequent gene conversion events (e.g. 3:1 or 1:3 segregation patterns during individual meioses) provides insight into the alternate pathways of recombination leading either to crossover or non-crossover chromosomes.

Non-crossover gene conversion events are mainly produced by Synthesis Dependent Strand Annealing (SDSA).

However, the majority of meiotic recombination events can be explained by the proposal that they are an adaptation for repair of damage in the DNA that is to be passed on to gametes.

Lectin 11 (SIGLEC11), a human immunoglobulin that binds to sialic acid, can be considered an example of such a gene conversion event which has played a significant role in evolution.

While comparing the homologous genes of human SIGLEC11 and its pseudogene in the chimpanzee, gorilla and orangutan, it appears that there was gene conversion of the sequence of 5’ upstream regions and the exons that encode the sialic acid recognition domain, approximately 2kbp from the closely flanking hSIGLECP16 pseudogene (Hayakawa et al., 2005).

Of course the frequency of the contribution of this pseudogene-mediated gene conversion mechanism to functional and adaptive changes in evolution of human is still unknown and so far it has been scarcely explored.

[15] In spite of that, the introduction of positively selective genetic changes by such mechanism can be put forward for consideration by the example of SIGLEC11.

From various genome analyses, it was concluded that the double-strand breaks (DSB) can be repaired via homologous recombination by at least two different but related pathways.

[15][14] If the interlocus gene conversion events are compared, it will be frequently revealed that they exhibit biased directionality.

A current model of meiotic recombination, initiated by a double-strand break or gap, followed by pairing with a homologous chromosome and strand invasion to initiate the recombinational repair process. Repair of the gap can lead to crossover (CO) or non-crossover (NCO) of the flanking regions. CO recombination is thought to occur by the Double Holliday Junction (DHJ) model, illustrated on the right, above. NCO recombinants are thought to occur primarily by the Synthesis Dependent Strand Annealing (SDSA) model, illustrated on the left, above. Most recombination events appear to be the SDSA type.