Recombination as a driver of genome evolution : characterisation of biased gene conversion in mice

Abstract : During meiosis, recombination hotspots host the formation of DNA double-strand breaks (DSBs). DSBs are subsequently repaired through a process which, in a wide range of species, is biased towards the favoured transmission of G and C alleles: GC-biased gene conversion (gBGC). The intensity of this fundamental distorter of meiotic segregation strongly varies between species but the factors dictating its evolution are not known. We thus aimed at directly quantifying the transmission bias in mice and comparing the parameters on which it depends with other mammals. Here, we coupled capture-seq and bioinformatic techniques to implement an approach that proved 100 times more powerful than current methods to detect recombination. With it, we identified 18,821 crossing-over (CO) and non-crossover (NCO) events at very high resolution in single individuals and could thus precisely characterise patterns of recombination in mice. In this species, recombination hotspots are targeted by PRDM9 and are therefore subject to a second type of biased gene conversion (BGC): DSB-induced BGC (dBGC). Quantifying both dBGC and gBGC with our data brought to light the fact that, in cases of structured populations, past gBGC from the parental lineages is hitchhiked by dBGC when the populations cross. We next observed that, in male mice, only NCOs — and more particularly single-marker NCOs — contribute to the intensity of gBGC. In contrast, in humans, both NCOs and at least a portion of COs (those with complex conversion tracts) distort allelic frequencies. This suggests that the DSB repair machinery leading to gBGC varies across mammals. Our findings are also consistent with the hypothesis of a selective pressure restraining the intensity of the deleterious gBGC process at the population-scale: this would materialise through a multi-level compensation of the effective population size by the recombination rate, the length of conversion tracts and the transmission bias. Altogether, our work has allowed to better comprehend how recombination and biased gene conversion proceed in the mammalian clade
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Maud Gautier. Recombination as a driver of genome evolution : characterisation of biased gene conversion in mice. Genetics. Université de Lyon, 2019. English. ⟨NNT : 2019LYSE1184⟩. ⟨tel-02435079⟩

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