title: Conserved Genetic Architecture Underlying Individual Recombination Rate Variation in a Wild Population of Soay Sheep (Ovis aries).
abstract: Meiotic recombination breaks down linkage disequilibrium (LD) 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 important in interpreting and predicting evolutionary phenomena and in understanding the potential of a population to respond to selection. However, despite attention in model systems, there remains little data on how recombination rate varies at the individual level in natural populations. Here we used extensive pedigree and high-density SNP information in a wild population of Soay sheep (Ovis aries) to investigate the genetic architecture of individual autosomal recombination rates. Individual rates were high relative to other mammal systems and were higher in males than in females (autosomal map lengths of 3748 and 2860 cM, respectively). The heritability of autosomal recombination rate was low but significant in both sexes (h(2) = 0.16 and 0.12 in females and males, respectively). In females, 46.7% of the heritable variation was explained by a subtelomeric region on chromosome 6; a genome-wide association study showed the strongest associations at locus RNF212, with further associations observed at a nearby ∼374-kb region of complete LD containing three additional candidate loci, CPLX1, GAK, and PCGF3 A second region on chromosome 7 containing REC8 and RNF212B explained 26.2% of the heritable variation in recombination rate in both sexes. Comparative analyses with 40 other sheep breeds showed that haplotypes associated with recombination rates are both old and globally distributed. Both regions have been implicated in rate variation in mice, cattle, and humans, suggesting a common genetic architecture of recombination rate variation in mammals.
authors.affiliation: Institute of Evolutionary Biology, School of Biological Sciences, University of Edinburgh, EH9 3FL, United Kingdom Susan.Johnston@ed.ac.uk.
authors.forename: Susan E
authors.identifier: 0000-0002-5623-8902
authors.initials: SE
authors.lastname: Johnston
authors.affiliation: Institute of Evolutionary Biology, School of Biological Sciences, University of Edinburgh, EH9 3FL, United Kingdom.
authors.forename: Camillo
authors.initials: C
authors.lastname: Bérénos
authors.affiliation: Department of Animal and Plant Sciences, University of Sheffield, S10 2TN, United Kingdom.
authors.forename: Jon
authors.identifier: 0000-0003-3356-5123
authors.initials: J
authors.lastname: Slate
authors.affiliation: Institute of Evolutionary Biology, School of Biological Sciences, University of Edinburgh, EH9 3FL, United Kingdom.
authors.forename: Josephine M
authors.identifier: 0000-0002-0075-1504
authors.initials: JM
authors.lastname: Pemberton
mesh_terms: D000818:Animals; D000835:Animals, Wild / Q000235:genetics; D017124:Conserved Sequence; D005260:Female; D056426:Genetic Loci; D055106:Genome-Wide Association Study; D006239:Haplotypes; D008297:Male; D020641:Polymorphism, Single Nucleotide; D011995:Recombination, Genetic; D012756:Sheep / Q000235:genetics*
keywords: genome-wide association study; genomic relatedness; heritability; meiotic recombination; natural population