Abstract
Meiotic recombination breaks down linkage disequilibrium and forms new haplotypes, meaning that it is an important driver of diversity in eukaryotic genomes. Understanding the causes of variation in recombination rate is not only important in interpreting and predicting evolutionary phenomena, but also for understanding the potential of a population to respond to selection. Yet, there remains little data on if, how and why recombination rate varies in natural populations. Here, we used extensive pedigree and high-density SNP information in a wild population of Soay sheep (Ovis aries) to determine individual crossovers in 3330 gametes from 813 individuals. Using these data, we investigated the recombination landscape and the genetic architecture of individual autosomal recombination rate. The population was strongly heterochiasmic (male to female linkage map ratio = 1.31), driven by significantly elevated levels of male recombination in sub-telomeric regions. Autosomal recombination rate was heritable in both sexes (h2 = 0.16 & 0.12 in females and males, respectively), but with different genetic architectures. In females, 46.7% of heritable variation was explained by a sub-telomeric region on chromosome 6; a genome-wide association study showed the strongest associations at RNF212, with further associations observed at a nearby ~374kb region of complete linkage disequilibrium containing three additional candidate loci, CPLX1, GAK and PCGF3. This region did not affect male recombination rate. A second region on chromosome 7 containing REC8 and RNF212B explained 26.2% of heritable variation in recombination rate in both sexes, with further single locus associations identified on chromosome 3. Our findings provide a key empirical example of the genetic architecture of recombination rate in a natural mammal population with male-biased crossover frequency.
Author Summary For almost 50 years we have known that genetic linkage can constrain responses to selection, while recombination can offer an escape from this constraint by forming new combinations of alleles. This increases the genetic variance for traits and hence the potential of a population to respond to selection. Therefore, understanding the causes and consequences of variation in the rate of recombination is important, not only in interpreting and predicting evolutionary phenomena, but for applications in genetic improvement of domesticated species. In our study, we used extensive genomic and pedigree information to identify genes underlying individual recombination rate variation in a wild population of Soay sheep on the St Kilda archipelago, NW Scotland. We show that the rate of recombination is partly inherited, that it is 30% higher in males than females, and that the majority of genetic variation in female sheep is likely to be explained by a genomic region containing the gene RNF212. This finding shows that recombination rate has the potential to evolve within wild populations.
