Mutations and Biased Gene Conversion drive the evolution of human meiotic recombination hotspots
Sprache des Vortragstitels:
Meiotic recombination occurs in localized regions that are rapidly evolving and have been associated with high sequence diversity and divergence. The factors that drive this evolution are still highly debated, but recombination hotspots are recurrent targets of double strand breaks that lead during their repair to biased gene conversion and possibly more mutations. In order to explore the mechanisms of sequence evolution at hotspots, we characterized experimentally the frequency of de novo mutations and the variation in allelic transmission in recombination products by collecting and sequencing a large number of single crossovers of six donors at two hotspots. Our results show that human recombination hotspots harbor a higher mutation rate compared to the genome average. We measured 0.0029 new mutations per crossover, with a striking asymmetry in the rate of CG to TA transitions favoring a higher TA content and a 46.7 fold higher transition rate for CpG sites than non-CpG sites. We also identified rare conversion events within crossovers with the majority of the conversions favoring the GC allele over the TA allele. Another identified source of allelic bias was the significant overtransmission of simple crossovers with a higher GC content that likely resulted also from biased gene conversion. This first evidence about the opposite directionality in terms of weak to strong substitutions of two processes affecting the sequence evolution of recombination hotspots, supports the idea that biased gene conversion could be an adaptation to counteract the mutational load of recombination.