Thursday, August 7, 2008

fine-scale recombination and biased gene conversion

Two new papers mapping fine-scale recombination rates:

The first ( Mancera et al , see here for a commentary from Michael Lichten) maps recombination events in yeast tetrads using very high density genotyping. One of the most interesting points from an evolutionary perspective is that they claim to find direct evidence of biased gene conversion (repairing of G/C-A/T heterozygotes in gene conversion tracts in favour of GC). Biased gene conversion is a much discussed force that could potentially explain the patterns of base composition in genomes (e.g. in humans see Duret and Arndt, Spencer et al and Dreszer et al) and is a potential confounder of divergence based tests of selection ( Galtier and Duret ), but actually has relatively little experiment support (see Buard and De Massy for discussion). So it is nice to see it being confirmed. I do worry slightly about genotyping error as a confounder here, a genotyping error would look like a short gene conversion tract. Thus if genotyping errors were for some reason biased to call GC over AT they could result in this effect. I don't have any real sense of whether this could be a problem.

The second paper is a really nice application of sperm-typing in humans from Alec Jeffreys group (Webb et al), looking for meiotic recombination hotspots (1-2kb segments were recombination frequently happens) at places where Linkage Disequilibrium (LD) breaks down very rapidly. They confirm that all of these locations appear to be true hotspots, but that the intensity of the hotspots are not well predicted by inferences from LD (which is not too surprising). This futher confirms the utility of LD analyses in identifying hotspots of reocmbination in humans.
They find that some of the weaker hotspots are polymorphic between individuals (i.e. individuals varying in their intensity of the reocmbination in a hotspot), and that some of this polymorphism is experiencing biased gene conversion. Now this is a different type of biased gene conversion from that discussed above. This form of biased gene conversion occurs because the two different alleles simulate recombination (i.e. crossover accompanied by gene conversion) in cis at different rates (rather than a bias in the repair of gene conversion), thus the alleles are lost due to conversion at different rates. Because the chromosome that initiates recombination is the one repaired by gene conversion, an allele that stimulates recombination is cis is undertransmitted in heterozygotes. This means that alleles that promote hotspots are driven from the population, which leads to the paradox why are there hotspots (this was pointed by Rosy Redfield and colleagues, and termed the hotspot paradox she recently posted about this on her blog).

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