Fig 4. Long-term consequences of recombination activity.

In addition to allele reshuffling between distant loci generated by crossovers, recurrent recombination events in PRDM9-defined hotspots influence locally the evolution of genome sequences within populations. The first consequence is the result of the molecular mechanism of recombination that leads to gene conversion of the region surrounding the initiating DSB in the allele of the noninitiating chromosome [104, 136] (Fig 7). Therefore, when a polymorphism that alters the initiation rate is within the frequently converted interval of a recombination hotspot, the allele associated with a higher initiation rate is undertransmitted. This phenomenon, called dBGC, might act against the emergence of new hotspots in the population and also favor the fixation of the less active alleles at existing hotspots, eventually leading to their extinction. It has been demonstrated that dBGC drives the erosion of PRDM9-binding motifs at hotspots (discussed in section 3.1) and might influence the base composition at the center of hotspots depending on the PRDM9-binding motif sequence. gBGC is the consequence of a bias of the recombinational repair of meiotic DSBs that favors the transmission of GC over AT alleles [137]. gBGC results in a rise in the frequency of GC alleles at polymorphic sites in populations and promotes their fixation. This bias in favor of the fixation of GC alleles is a signature of recombination hotspots, detectable as a local increase in the equilibrium GC–content. gBGC has been described in several species in which PRDM9 specifies recombination hotspots [59, 65, 107, 138, 139]. It has been proposed that the mechanism of recombination, because it involves some DNA synthesis, could increase locally the mutation rate [140, 141]. Support for increased mutagenesis at recombination hotspots comes from the higher diversity [142], from base compositions skews observed at DSB hotspots in mice and humans [65, 72, 138], and from direct measurement at one human hotspot [143]. dBGC, DSB-induced biased gene conversion; DSB, DNA double strand break; gBGC, GC-biased gene conversion; GC, gene conversion; PRDM9, PR domain-containing protein 9.