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Gene conversion

Gene conversion

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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.[1]

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.

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.[2] 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.

Gene conversion is the process by which a DNA sequence replaces a homologous sequence such that the sequences become identical after the conversion event. Gene conversion may be allelic, which means that one allele of the same gene replaces another allele, or ectopic, meaning that one paralogous DNA sequence converts to another.

Conversion from one allele to another is often due to repair of the mismatch in homologous recombination: if one of the four chromatids during meiosis is paired with another chromatid, as may occur due to sequence homology, the Transfer of the DNA strand may occur. This can alter the sequence of one of the chromosomes, so that it is identical to the other.

The meiotic recombination is initiated through the formation of a double strand break (DSB). The 5 'ends of the tear are then degraded, leaving long 3' protrusions of several hundred nucleotides. One of these 3 'single-stranded DNA segments then invades a homologous sequence on the homologous chromosome, forming an intermediate that can be repaired through different pathways resulting in either crossovers (CO) or noncrossovers (NCO). At various stages of the recombination process, heteroduplex DNA is formed (double-stranded DNA consisting of individual strands of each of the two homologous chromosomes which may or may not be perfectly complementary). When mismatches occur in the heteroduplex DNA, the sequence of one strand will be repaired to join the other strand with perfect complementarity, leading to the conversion from one sequence to another. This repair process may follow any two alternative routes as illustrated in the figure. By one route, a structure called double bonding of Holliday (DHJ) is formed, which leads to the exchange of DNA strands. On the other hand, called Synthesis Dependent Chain Recovery (SDSA), there is information exchange but not physical exchange. Gene conversion will occur during SDSA if the two DNA molecules are heterozygous at the site of recombination repair. Gene conversion may also occur during recombination repair involving DHJ, and this gene conversion may be associated with the physical recombination of the DNA duplexes on both sides of the DHJ.

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