Steux, C.; Szpiech, Z. A.

Understanding how deleterious variation is shaped and maintained in natural populations is of importance for both medical research and conservation biology. Various demographic processes can influence these patterns. For example, population bottlenecks and inbreeding increase the likelihood of inheriting identical-by-descent haplotypes from a recent common ancestor, creating long tracts of homozygous genotypes called runs of homozygosity (ROH). Long ROH (e.g., those created as a result of inbreeding) have been associated with an accumulation of mildly deleterious homozygotes. Counter intuitively, positive selection can also maintain deleterious variants in a population by increasing the frequency of a damaging allele tightly linked to an advantageous mutation (i.e., via genetic hitchhiking). Here we analyze whole genomes of 79 wild Chinese rhesus macaques across five sub-species and characterize patterns of deleterious variation with respect to ROH and signals of recent positive selection. We show that the fraction of deleterious homozygotes occurring in long ROH is significantly higher for deleterious homozygotes than tolerated ones (p = 3.4e-5) but not in short and medium ROH. This confirms that inbreeding, by generating these long tracts of homozygosity, is the main driver of the high burden of homozygous deleterious alleles in wild macaque populations. Furthermore, we show that small ROH have a lower proportion of homozygous loss-of-function variants than tolerated ones (p = 0.05), suggesting the purging of these variants through natural selection. Next, we identify regions putatively experiencing a recent or ongoing sweep and examine the presence of deleterious variants in these regions to find signals of genetic hitchhiking. We found 7 deleterious variants at high frequency in regions under selection containing genes involved with olfaction and other processes.