Insights into the genetic determinism and evolution of recombination rates from combining multiple genome-wide datasets in Sheep

Recombinationis a complex biological process that results from a cascade of multiple events during meiosis. Understanding the genetic determinismof recombinationcan help to understand if and how these events are interacting. To tackle this question, we studied the patterns of recombinationin sheep, using multiple approaches and datasets. We constructed genetic maps in the Lacaune breed at a fine scale by combining meiotic recombinationrates from a large pedigree genotyped with a 50K SNP arrayand historical recombinationrates from a sample of unrelated individuals genotyped with a 600K SNP array. This analysis revealed recombinationpatterns in sheep similar to other mammals but also genome regions that have likely been affected by directional and diversifying selection. We estimated the average recombinationrate of Lacaune sheep at 1.5 cM/Mb, identified about 50,000 crossover hotspots on the genome and found a high correlation between population- and pedigree-based recombinationrate estimates. A genome-wide association study revealed three major loci affecting inter-individual variation in recombinationrate, including the RNF212, HEI10 and KCNJ15genes. Finally, we compared our results to those obtained previously in a distantly related population of domestic sheep, the Soay. This comparison revealed on one hand that Soay and Lacaune sheep have similar genetic determinantof total recombinationrate while confirming that Soay sheephave experienced strong selection greatly increasing their recombinationrate. Taken together these observations highlight that multiple genetically independent pathways affect recombinationrate.