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.