Selection signature analysis reveals RDH5 performed key function in vision during sheep domestication process.

As one of the most successful domesticated animals in the Neolithic age, sheep gradually migrated all over the world with human activities. During the domestication process, remarkable changes have taken place in morphology, physiology, and behavior, resulting in different breeds with different characters via artificial and natural selection. However, the genetic background responsible for these phenotypic variations remains largely unclear. Here, we used whole genome resequencing technology to compare and analyze the genome differences between Asiatic mouflon wild sheep (Ovis orientalis) and Hu sheep (Ovis aries). A total of 755 genes were positively selected in the process of domestication and selection, and the genes related to sensory perception had directional evolution in the autosomal region, such as OPRL1, LEF1, TAS1R3, ATF6, VSX2, MYO1A, RDH5, and some novel genes. A missense mutation of c.T722C/p.M241T in exon 4 of RDH5 existing in sheep were found, and the T allele was completely fixed in Hu sheep. In addition, the mutation with the C allele reduced the retinol dehydrogenase activity encoding by RDH5, which can impair retinoic acid metabolism and further influenced the visual cycle. Overall, our results showed significant enrichment for positively selected genes involved in sensory perception development during sheep domestication; RDH5 and its variants may be related to the retinal degeneration in sheep. We infer that the wild sheep ancestors with weaker visual sensitivity were weeded out by humans, and the mutation was selective, swept by the dual pressures of natural and artificial selection.