Environmental temperature serves as a major driver of adaptive changes in wild organisms. To discover the mechanisms underpinning cold tolerance in domestic animals, we sequenced the genomes of 28 cattle from warm and cold areas across China. By characterizing the population structure and demographic history, we identified two genetic clusters, i.e., northern and southern groups, as well as a common historic population peak at 30 kilo years ago. Genomic scan of cold-tolerant breeds determined potential candidate genes in the thermogenesis-related pathways that were under selection. Specifically, functional analysis identified a substitution of PRDM16 (p.P779L) in northern cattle, which maintains brown adipocyte formation by boosting thermogenesis-related gene expression, indicating a vital role of this gene in cold tolerance. These findings provide a basis for genetic variation in domestic cattle shaped by environmental temperature and highlight the role of reverse mutation in livestock species.
温度是推动多种生物进化和适应的重要的环境因素之一。为了探究家畜对环境温度的适应性机制，该研究首先对28头分布在中国寒冷地区和温暖地区黄牛进行了全基因组重测序。通过群体遗传学分析和种群历史重建，我们确定了北方和南方黄牛可以分别组成两个遗传簇，并且，大约在3万年前，黄牛的祖先有效种群大小有一个显著的增加。通过对寒冷地区和温暖地区黄牛基因组进行选择性扫描发现，一些与产热相关通路中的基因受到选择作用。尤其是与棕色脂肪生成密切相关的基因PRDM16在北方耐寒黄牛与南方黄牛种群之间产生一个非同义突变（p.P779L），且该位点在北方耐寒黄牛中的基因型和其他具有棕色脂肪功能的哺乳动物的基因型一致。进一步的诱变和细胞学实验发现与耐寒黄牛相同的基因型能够通过促进产热相关基因的表达来维持棕色脂肪细胞的形成，提示该突变在耐寒适应中发挥着重要作用。我们的结果为研究黄牛对环境温度变化的适应性机制提供了基础，并暗示一些回复性突变在家畜驯化可能起到重要作用。.
Keywords: Brown adipose tissue; Cattle; Cold tolerance; PRDM16; Population genomics.