Introduction
Temperature is one of the most important environmental factors that drives evolutionary changes in diverse organisms [1]. Mammals are endotherms and they request a constant body temperature to ensure optimal biological activity [2,3], leading to a strong selection pressure on the heat production system, i.e, shivering and non-shivering thermogenesis [4]. In particular, shivering thermogenesis produces heat in short term [5] and non-shivering thermogenesis is a non-contractile process that able to compensate the defects of shivering thermogenesis and maintain body temperature effectively [4]. Though white adipose tissue (WAT) stores excessive energy as triglycerides, the brown adipose tissue (BAT) which activated by cold exposure has been recognized as a major source of adaptive non-shivering thermogenesis [6-9].For example, the uncoupling protein-1 (UCP1) in BAT dissipates energy into heat through uncoupled respiration, resulting in increased fatty acid oxidation and heat production [10]. The thermogenic capacity of BAT is particularly effective in maintaining the core body temperature of small mammals and infants [4]. Nevertheless, the thermogenic program in adipose tissue is a complex transcriptional regulation process that has not been fully dissected. The widely reported transcriptional regulators of adipocytes include the peroxisome proliferator-activated receptor-gamma (PPARγ), peroxisome proliferator activated receptor-gamma coactivator 1α (PGC1-α), Forkhead box C2 (FoxC2) and PRD1-BF-1-RIZ1 homologous domain-containing protein-16 (PRDM16) [11]. Among these genes, PPARγ plays a leading role in the differentiation of all adipocytes [12-14]. It is also known that PGC1-α acts together with PPARγ or the thyroid hormone receptor adaptive thermogenesis [15-16]. FoxC2 can increase the BAT amount to enhance the insulin sensitivity [17] and PRDM16 can induce the browning of WAT and fibroblasts through driving a brown adipogenesis program while suppressing the white fat adipogenesis program [17] .
Cattle are intimately associated with human civilization and culture worldwide. Currently, there are 53 cattle breeds in China, and two species are recognized: Bos taurus and Bos indicus [18-19]. Archaeological studies supports the claim that B. taurus was imported into northern China and north-east Asia from north Eurasia between 5000–4000 BP [20], and B. indicus migrated from the Indian subcontinent to East Asia around 3000 BP [21]. Intriguingly, there is a vast difference in the annual average temperature of the habitats among those cattle along with the domestication. Here, to detect the molecular footprints underlying the cold adaptations in domestic cattle, we sequenced genomes of 28 cattle, including 14 cold-tolerant cattle (annual average temperature of habitat: 2–6℃) and 14 cold-intolerant cattle (annual average temperature of habitat: 20–25℃). By characterizing the population history and selective sweeps, we identified a candidate gene PRDM16 that was under selection and responsible for the modification of the BAT function, which underpin the cold-tolerance in northern cattle.