Population genomics reveal that natural variation in PRDM16 contributes to cold tolerance in domestic cattle

Environmental temperature serves as a major driver for adaptive changes in wild organisms. To uncover the mechanisms of cold tolerance in domestic animals, we sequenced genomes of 28 cattle warm and cold areas across China. By characterizing the population structure and demographic history, we identified two genetic clusters, i.e., northern and southern cattle groups, and a common historic population peak at 30 kilo years ago. A genome scan of cold-tolerant breeds revealed potential candidate genes in thermogenesis-related pathways were under selection. Specifically, we functionally determined a substitution of PRDM16 (p.P779L) in northern cattle, which maintains the formation of brown adipocytes by boosting expression of thermogenic-related genes, indicating a vital role of this gene in cold tolerance. The findings provide a basis of genetic variation in domestic cattle shaped by temperature environments and highlight the role of reverse mutation in livestock species.