哺乳动物是恒温动物，它们需要恒定的体温来确保最佳的生活状态。这就给哺乳动物颤抖性产热和非颤抖性产热在内的产热系统带来了巨大的选择压力。在中国，由于南北方的纬度相差大，造成年平均气温相差较大，导致许多物种生活在不同的温度环境中，包括家养牛在内。在夏季，中国南方地区的温度明显高于北方地区，这使中国南方牛被暴露在极热的环境中，相反，北方牛的生活环境比较凉爽。在冬季，中国北方地区的温度比南方地区的温度低的很多，因此中国北方的牛暴露在极冷的生活环境中，相比中国北方牛，南方牛的生活环境相对温和。这些生活环境恰好驱动了北方牛可以抵抗急剧寒冷环境和南方牛可以抵抗炎热环境的特性。与牛耐热性研究相比，目前关于牛耐寒性调控机制的研究很少。然而，犊牛出生时的冷应激导致的新生犊牛死亡率是全世界寒冷地区养牛业关注的主要问题，它对畜牧业造成了巨大的经济损失，而且在畜牧业发展中带来了的一个主要的难题。因此，筛选与产热相关基因的SNP标记将为家养牛的遗传育种提供策略并减少寒冷暴露所引起的死亡率。为了探讨家养牛对环境温度的适应性机制，本研究利用全基因组重测序技术探索了家养牛产热相关候选基因，主要研究内容如下：

1. 对28头分布在中国寒冷地区和温暖地区牛（14头南方牛和14头北方牛）进行了全基因组重测序。通过群体遗传学分析（进化树构建，PCA分析，LD分析和群体结构分析）和种群历史重建（PSMC），确定了北方和南方牛可以分别组成两个遗传簇，并且，两种种群的祖先有效群体大小在5千年和7万年前呈现最高值，3千年和4万年前呈现出最小值。

2. 为了揭示耐寒品种的产热相关通路中潜在的选择候选基因，首先按50 kb窗口，25 kb步长进行划窗，计算每个窗口内的F_ST值，取前5%的F_ST值，识别为高度分化区域。高度分化区域中被识别出的基因外显子区域非同义SNPs进行Fisher’s精确检验，取q < 0.01为最终候选基因。通过对寒冷地区和温暖地区牛基因组进行选择性扫描获得了197个候选基因，并发现一些产热相关通路中的基因受到选择作用。其中，只有2个候选基因（PRDM16和CPT2）是与产热通路相关的，而且可以促进产热关键因子UCP1的候选基因—PRDM16为排名最靠前（F_ST = 0.52，Fisher’s exact test P = 3.76 × 10^-11）。

3. 通过PRDM16的SNPs 系统发育树分析揭示出耐寒牛和非耐寒牛PRDM16基因的不同进化历史，同时在耐寒牛和非耐寒牛之间发现了一共5个非同义SNVs，其中最高的突变率达到了93%（c.2336 T > C, p. L779P）。我们通过比较耐寒牛，非耐寒牛和不同物种PRDM16该位点的基因序列，得到了耐寒牛的基因型（PRDM16 779L）与拥有完整的棕色脂肪功能的物种相同（小鼠，大鼠和仓鼠），而非耐寒牛的基因型（PRDM16 779P）与不完整或者没有棕色脂肪功能的物种相同（羊，猪，鲸，马和人等），发现PRDM16基因的突变模式（c.2336 T > C, p. L779P）在全球范围的牛基因组中也是相同的。

4. 利用3T3-L1细胞构建了耐寒牛基因型PRDM16 和非耐寒牛基因型PRDM16 MU（c.2336 T > C, L779P mutation of PRDM16）过表达细胞系，并进行了棕色化分化。结果发现，虽然两组之间的形态学特征上没有差异，但PRDM16 MU组在棕色脂肪相关基因的mRNA水平（C/EBPb, PGC1-a, CIDEA, UCP1）与蛋白水平（UCP1）上明显低于PRDM16组；发现了PRDM16的突变（p.L779P）会导致基因功能受损，最终影响了非耐寒牛棕色脂肪细胞的形成，表明该基因在耐寒性方面发挥了重要作用。

总之，我们的结果为研究牛对环境温度变化的适应性机制提供了理论基础，为家养牛的遗传育种提供了更有效的策略。

Temperature is one of the most important environmental factors that drive evolutionary changes in diverse organisms. Mammals are endotherms; they require a constant body temperature to ensure optimal biological activity. This leads to strong selection pressure on the heat production system, including shivering and non-shivering thermogenesis.

In China, due to the large latitude difference between the South and north, the annual average temperature is greatly different. Therefore, there is a vast difference in the annual average temperature of the habitats among mammals and the domestication, including cattle. In summer, southern cattle are exposed to extreme heat environment compared to northern cattle, and in winter, northern cattle are exposed to extreme cold environment compared to southern cattle. These living conditions just drive the characteristics that resistance of northern cattle can tolerant extremely cold environment and southern cattle can tolerant extremely hot environment. Compared with the research on heat tolerance of cattle, there are few studies on the regulation mechanism of cold tolerance of cattle.

1. We sequenced genomes of 28 cattle, including 14 cold-tolerant cattle lineages (annual average temperature of habitat: 2–6℃) and 14 cold-intolerant cattle lineages (annual average temperature of habitat: 20–25℃). The Neighbor-joining trees, PCA, LD and population structure analysis were clearly indicated that cattle samples could be classified into northern and southern groups and PSMC analysis showed two bottlenecks and two expansions, with population peaks at ~50 and ~700 kilo years ago (Kya) and population bottlenecks at ~30 and 400 Kya, respectively.

2. Selective sweeps analyses were performed over whole genomes based on the distribution of population-differentiation statistic (F_ST) values. First, we identified highly differentiated regions using F_ST, and then determined the top 5% calculated in 50 kb windows in 25 kb steps. Then, final candidate genes were determined and ranked using Fisher’s exact test (q < 0.01). A total of 197 candidate genes had strong selective sweep signals and Among genes with signals of selective sweep, two candidate genes (PRDM16 and CPT2) were involved in thermogenesis; PRDM16 was of the most interest as it is known to increase thermogenesis by promoting the expression of the key gene UCP1. PRDM16 had the lowest P-value (Fisher’s exact test P = 3.8×10^-11) and the highest F_ST (0.52) among genes related to thermogenesis.

3. The PRDM16 genotypes found in northern and southern cattle were well-distinguished and consistent with the phylogenetic tree created using the SNPs of this gene. We discovered five nonsynonymous single nucleotide variants (SNVs), of which one (c.2336 T > C, p.L779P) was found at a higher level (93%) in southern cattle than northern cattle. we compared the PRDM16 protein sequences to other species, and found that the substitution that occurred at position Leu₇₇₉ of the PRDM16 gene in northern cattle is the same as that in species that have complete BAT function (e.g., mouse, rat, and hamster). Conversely, the substitution in southern cattle, which is proline, was the same as that in species with an incomplete or null BAT function (sheep, pig, whale, horse, platypus, elephant, sirenian, marsupial, human and rabbit). Moreover, we also explored the genetic pattern of these substitutions (c.2336 T > C, p.L779P) across cattle genomes worldwide, and found that cattle in cold regions have a high frequency of the c.2336 C > T mutation, consistent with the pattern in China.

4. In biochemical experiment, despite the similar differentiation efficiency between the two ectopic PRDM16-overexpressing groups, the mRNA expression levels of four BAT-selective genes (UCP1, C/EBPb, PGC1-a, and CIDEA) were significantly lower in the PRDM16 MU (c.2336 T > C, L779P mutation of PRDM16) group than in the PRDM16 group. Moreover, overexpression of PRDM16 increased UCP1 expression to a much greater degree than PRMD16 MU. In general, on the one hand, well-functioning PRDM16 in northern cattle is required to resist extreme cold, and on the other, the functional inactivation of PRDM16 impairs beige adipocyte formation, which is beneficial for the environmental adaptability of southern cattle. These results could improve understanding of adaptive genetic variations in cattle and other livestock species living in regions different temperatures.

[1] HAYES J P, GARLAND T, JR. The Evolution of Endothermy: Testing the Aerobic Capacity Model [J]. Evolution, 1995, 49(5): 836-47.
[2] RUF T, GEISER F. Daily torpor and hibernation in birds and mammals [J]. Biol Rev Camb Philos Soc, 2015, 90(3): 891-926.
[3] NAKAMURA K, MORRISON S F. A thermosensory pathway that controls body temperature [J]. Nat Neurosci, 2008, 11(1): 62-71.
[4] GEISER F. Metabolic rate and body temperature reduction during hibernation and daily torpor [J]. Annu Rev Physiol, 2004, 66: 239-74.
[5] SCHOLANDER P F, WALTERS V, HOCK R, et al. Body Insulation of Some Arctic and Tropical Mammals and Birds [J]. Biol Bull, 1950, 99(2): 225-36.
[6] HAMMEL H T. Thermal properties of fur [J]. Am J Physiol, 1955, 182(2): 369-76.
[7] BALDWIN R L, SMITH N E, TAYLOR J, et al. Manipulating metabolic parameters to improve growth rate and milk secretion [J]. J Anim Sci, 1980, 51(6): 1416-28.
[8] ROLFE D F, BROWN G C. Cellular energy utilization and molecular origin of standard metabolic rate in mammals [J]. Physiol Rev, 1997, 77(3): 731-58.
[9] MCNAB B K. On the utility of uniformity in the definition of basal rate of metabolism [J]. Physiol Zool, 1997, 70(6): 718-20.
[10] COMMISSION FOR THERMAL PHYSIOLOGY OF THE INTERNATIONAL UNION OF PHYSIOLOGICAL S. Glossary of terms for thermal physiology : Second edition [J]. Pflugers Arch, 1987, 410(4-5): 567-87.
[11] STUART D G, KAWAMURA Y, HEMINGWAY A. Activation and suppression of shivering during septal and hypothalamic stimulation [J]. Exp Neurol, 1961, 4: 485-506.
[12] HALVORSON I, THORNHILL J. Posterior hypothalamic stimulation of anesthetized normothermic and hypothermic rats evokes shivering thermogenesis [J]. Brain Res, 1993, 610(2): 208-15.
[13] BENZINGER T H, PRATT A W, KITZINGER C. The Thermostatic Control of Human Metabolic Heat Production [J]. Proc Natl Acad Sci U S A, 1961, 47(5): 730-9.
[14] ASAMI A, ASAMI T, HORI T, et al. Thermally-induced activities of the mesencephalic reticulospinal and rubrospinal neurons in the rat [J]. Brain Res Bull, 1988, 20(3): 387-98.
[15] ASAMI T, HORI T, KIYOHARA T, et al. Convergence of thermal signals on the reticulospinal neurons in the midbrain, pons and medulla oblongata [J]. Brain Res Bull, 1988, 20(5): 581-96.
[16] CANNON B, NEDERGAARD J. Brown adipose tissue: function and physiological significance [J]. Physiol Rev, 2004, 84(1): 277-359.
[17] LANDSBERG L. Core temperature: a forgotten variable in energy expenditure and obesity? [J]. Obes Rev, 2012, 13 Suppl 2: 97-104.
[18] FOSTER D O. Quantitative contribution of brown adipose tissue thermogenesis to overall metabolism [J]. Can J Biochem Cell Biol, 1984, 62(7): 618-22.
[19] SOLER-VAZQUEZ M C, MERA P, ZAGMUTT S, et al. New approaches targeting brown adipose tissue transplantation as a therapy in obesity [J]. Biochemical Pharmacology, 2018, 155: 346-55.
[20] JACOBSSON A, MUHLEISEN M, CANNON B, et al. The uncoupling protein thermogenin during acclimation: indications for pretranslational control [J]. Am J Physiol, 1994, 267(4 Pt 2): R999-1007.
[21] BARTELT A, BRUNS O T, REIMER R, et al. Brown adipose tissue activity controls triglyceride clearance [J]. Nat Med, 2011, 17(2): 200-5.
[22] OUELLET V, LABBE S M, BLONDIN D P, et al. Brown adipose tissue oxidative metabolism contributes to energy expenditure during acute cold exposure in humans [J]. J Clin Invest, 2012, 122(2): 545-52.
[23] MORRISON S F, MADDEN C J, TUPONE D. Central neural regulation of brown adipose tissue thermogenesis and energy expenditure [J]. Cell Metab, 2014, 19(5): 741-56.
[24] NAUTIYAL K M, DAILEY M, BRITO N, et al. Energetic responses to cold temperatures in rats lacking forebrain-caudal brain stem connections [J]. Am J Physiol Regul Integr Comp Physiol, 2008, 295(3): R789-98.
[25] LOWELL B B, SPIEGELMAN B M. Towards a molecular understanding of adaptive thermogenesis [J]. Nature, 2000, 404(6778): 652-60.
[26] CRISTANCHO A G, LAZAR M A. Forming functional fat: a growing understanding of adipocyte differentiation [J]. Nat Rev Mol Cell Biol, 2011, 12(11): 722-34.
[27] CHAU Y Y, BANDIERA R, SERRELS A, et al. Visceral and subcutaneous fat have different origins and evidence supports a mesothelial source [J]. Nat Cell Biol, 2014, 16(4): 367-75.
[28] BILLON N, DANI C. Developmental origins of the adipocyte lineage: new insights from genetics and genomics studies [J]. Stem Cell Rev Rep, 2012, 8(1): 55-66.
[29] WANG Q A, TAO C, JIANG L, et al. Distinct regulatory mechanisms governing embryonic versus adult adipocyte maturation [J]. Nat Cell Biol, 2015, 17(9): 1099-111.
[30] SPALDING K L, ARNER E, WESTERMARK P O, et al. Dynamics of fat cell turnover in humans [J]. Nature, 2008, 453(7196): 783-7.
[31] TANG W, ZEVE D, SUH J M, et al. White fat progenitor cells reside in the adipose vasculature [J]. Science, 2008, 322(5901): 583-6.
[32] CHAWLA A, LAZAR M A. Peroxisome proliferator and retinoid signaling pathways co-regulate preadipocyte phenotype and survival [J]. Proc Natl Acad Sci U S A, 1994, 91(5): 1786-90.
[33] JIANG Y, BERRY D C, TANG W, et al. Independent stem cell lineages regulate adipose organogenesis and adipose homeostasis [J]. Cell Rep, 2014, 9(3): 1007-22.
[34] BERRY D C, JIANG Y, GRAFF J M. Mouse strains to study cold-inducible beige progenitors and beige adipocyte formation and function [J]. Nat Commun, 2016, 7: 10184.
[35] MIN S Y, KADY J, NAM M, et al. Human 'brite/beige' adipocytes develop from capillary networks, and their implantation improves metabolic homeostasis in mice [J]. Nat Med, 2016, 22(3): 312-8.
[36] ALTSHULER-KEYLIN S, SHINODA K, HASEGAWA Y, et al. Beige Adipocyte Maintenance Is Regulated by Autophagy-Induced Mitochondrial Clearance [J]. Cell Metab, 2016, 24(3): 402-19.
[37] ROH H C, TSAI L T Y, SHAO M, et al. Warming Induces Significant Reprogramming of Beige, but Not Brown, Adipocyte Cellular Identity [J]. Cell Metab, 2018, 27(5): 1121-37 e5.
[38] BONET M L, OLIVER P, PALOU A. Pharmacological and nutritional agents promoting browning of white adipose tissue [J]. Biochim Biophys Acta, 2013, 1831(5): 969-85.
[39] SHAN T, LIANG X, BI P, et al. Distinct populations of adipogenic and myogenic Myf5-lineage progenitors in white adipose tissues [J]. J Lipid Res, 2013, 54(8): 2214-24.
[40] SANCHEZ-GURMACHES J, GUERTIN D A. Adipocyte lineages: tracing back the origins of fat [J]. Biochim Biophys Acta, 2014, 1842(3): 340-51.
[41] LIU W, SHAN T, YANG X, et al. A heterogeneous lineage origin underlies the phenotypic and molecular differences of white and beige adipocytes [J]. J Cell Sci, 2013, 126(Pt 16): 3527-32.
[42] SANCHEZ-GURMACHES J, HUNG C M, SPARKS C A, et al. PTEN loss in the Myf5 lineage redistributes body fat and reveals subsets of white adipocytes that arise from Myf5 precursors [J]. Cell Metab, 2012, 16(3): 348-62.
[43] LONG J Z, SVENSSON K J, TSAI L, et al. A smooth muscle-like origin for beige adipocytes [J]. Cell Metab, 2014, 19(5): 810-20.
[44] HIMMS-HAGEN J, MELNYK A, ZINGARETTI M C, et al. Multilocular fat cells in WAT of CL-316243-treated rats derive directly from white adipocytes [J]. Am J Physiol Cell Physiol, 2000, 279(3): C670-81.
[45] CINTI S. Adipocyte differentiation and transdifferentiation: plasticity of the adipose organ [J]. J Endocrinol Invest, 2002, 25(10): 823-35.
[46] ROSENWALD M, PERDIKARI A, RULICKE T, et al. Bi-directional interconversion of brite and white adipocytes [J]. Nat Cell Biol, 2013, 15(6): 659-67.
[47] LEE Y H, PETKOVA A P, KONKAR A A, et al. Cellular origins of cold-induced brown adipocytes in adult mice [J]. Faseb J, 2015, 29(1): 286-99.
[48] LEE Y H, PETKOVA A P, MOTTILLO E P, et al. In vivo identification of bipotential adipocyte progenitors recruited by beta3-adrenoceptor activation and high-fat feeding [J]. Cell Metab, 2012, 15(4): 480-91.
[49] WANG W, KISSIG M, RAJAKUMARI S, et al. Ebf2 is a selective marker of brown and beige adipogenic precursor cells [J]. Proc Natl Acad Sci U S A, 2014, 111(40): 14466-71.
[50] WANG Q A, TAO C, GUPTA R K, et al. Tracking adipogenesis during white adipose tissue development, expansion and regeneration [J]. Nat Med, 2013, 19(10): 1338-44.
[51] SEALE P, BJORK B, YANG W, et al. PRDM16 controls a brown fat/skeletal muscle switch [J]. Nature, 2008, 454(7207): 961-7.
[52] SANCHEZ-GURMACHES J, GUERTIN D A. Adipocytes arise from multiple lineages that are heterogeneously and dynamically distributed [J]. Nat Commun, 2014, 5: 4099.
[53] WU J, BOSTROM P, SPARKS L M, et al. Beige adipocytes are a distinct type of thermogenic fat cell in mouse and human [J]. Cell, 2012, 150(2): 366-76.
[54] WHITTLE C A, KROCHKO J E. Transcript profiling provides evidence of functional divergence and expression networks among ribosomal protein gene paralogs in Brassica napus [J]. Plant Cell, 2009, 21(8): 2203-19.
[55] VISHVANATH L, MACPHERSON K A, HEPLER C, et al. Pdgfrbeta+ Mural Preadipocytes Contribute to Adipocyte Hyperplasia Induced by High-Fat-Diet Feeding and Prolonged Cold Exposure in Adult Mice [J]. Cell Metab, 2016, 23(2): 350-9.
[56] BARBATELLI G, MURANO I, MADSEN L, et al. The emergence of cold-induced brown adipocytes in mouse white fat depots is determined predominantly by white to brown adipocyte transdifferentiation [J]. Am J Physiol Endocrinol Metab, 2010, 298(6): E1244-53.
[57] FU L, ZHU X, YI F, et al. Regenerative medicine: transdifferentiation in vivo [J]. Cell Res, 2014, 24(2): 141-2.
[58] LOWELL B B, FLIER J S. Brown adipose tissue, beta 3-adrenergic receptors, and obesity [J]. Annu Rev Med, 1997, 48: 307-16.
[59] TEWS D, WABITSCH M. Renaissance of brown adipose tissue [J]. Horm Res Paediatr, 2011, 75(4): 231-9.
[60] OELKRUG R, POLYMEROPOULOS E T, JASTROCH M. Brown adipose tissue: physiological function and evolutionary significance [J]. J Comp Physiol B, 2015, 185(6): 587-606.
[61] ENERBACK S, JACOBSSON A, SIMPSON E M, et al. Mice lacking mitochondrial uncoupling protein are cold-sensitive but not obese [J]. Nature, 1997, 387(6628): 90-4.
[62] WU J, COHEN P, SPIEGELMAN B M. Adaptive thermogenesis in adipocytes: is beige the new brown? [J]. Genes Dev, 2013, 27(3): 234-50.
[63] ISHIBASHI J, SEALE P. Medicine. Beige can be slimming [J]. Science, 2010, 328(5982): 1113-4.
[64] SHABALINA I G, PETROVIC N, DE JONG J M, et al. UCP1 in brite/beige adipose tissue mitochondria is functionally thermogenic [J]. Cell Rep, 2013, 5(5): 1196-203.
[65] GOLOZOUBOVA V, HOHTOLA E, MATTHIAS A, et al. Only UCP1 can mediate adaptive nonshivering thermogenesis in the cold [J]. Faseb J, 2001, 15(11): 2048-50.
[66] FELDMANN H M, GOLOZOUBOVA V, CANNON B, et al. UCP1 ablation induces obesity and abolishes diet-induced thermogenesis in mice exempt from thermal stress by living at thermoneutrality [J]. Cell Metab, 2009, 9(2): 203-9.
[67] GOTO T, KIM M, TAKAHASHI H, et al. Food Intake and Thermogenesis in Adipose Tissue [J]. The Korean Journal of Obesity, 2016, 25(3): 109-14.
[68] ATIT R, SGAIER S K, MOHAMED O A, et al. Beta-catenin activation is necessary and sufficient to specify the dorsal dermal fate in the mouse [J]. Dev Biol, 2006, 296(1): 164-76.
[69] TIMMONS J A, WENNMALM K, LARSSON O, et al. Myogenic gene expression signature establishes that brown and white adipocytes originate from distinct cell lineages [J]. Proc Natl Acad Sci U S A, 2007, 104(11): 4401-6.
[70] LEPPER C, FAN C M. Inducible lineage tracing of Pax7-descendant cells reveals embryonic origin of adult satellite cells [J]. Genesis, 2010, 48(7): 424-36.
[71] HUDAK C S, GULYAEVA O, WANG Y, et al. Pref-1 marks very early mesenchymal precursors required for adipose tissue development and expansion [J]. Cell Rep, 2014, 8(3): 678-87.
[72] VIRTANEN K A, LIDELL M E, ORAVA J, et al. Functional brown adipose tissue in healthy adults [J]. N Engl J Med, 2009, 360(15): 1518-25.
[73] SEALE P, KAJIMURA S, YANG W, et al. Transcriptional control of brown fat determination by PRDM16 [J]. Cell Metab, 2007, 6(1): 38-54.
[74] KAJIMURA S, SEALE P, KUBOTA K, et al. Initiation of myoblast to brown fat switch by a PRDM16-C/EBP-beta transcriptional complex [J]. Nature, 2009, 460(7259): 1154-8.
[75] COHEN P, LEVY J D, ZHANG Y, et al. Ablation of PRDM16 and beige adipose causes metabolic dysfunction and a subcutaneous to visceral fat switch [J]. Cell, 2014, 156(1-2): 304-16.
[76] HARMS M, SEALE P. Brown and beige fat: development, function and therapeutic potential [J]. Nat Med, 2013, 19(10): 1252-63.
[77] SEALE P, CONROE H M, ESTALL J, et al. Prdm16 determines the thermogenic program of subcutaneous white adipose tissue in mice [J]. J Clin Invest, 2011, 121(1): 96-105.
[78] OHNO H, SHINODA K, SPIEGELMAN B M, et al. PPARgamma agonists induce a white-to-brown fat conversion through stabilization of PRDM16 protein [J]. Cell Metab, 2012, 15(3): 395-404.
[79] TSENG Y H, KOKKOTOU E, SCHULZ T J, et al. New role of bone morphogenetic protein 7 in brown adipogenesis and energy expenditure [J]. Nature, 2008, 454(7207): 1000-4.
[80] SCHULZ T J, HUANG T L, TRAN T T, et al. Identification of inducible brown adipocyte progenitors residing in skeletal muscle and white fat [J]. Proc Natl Acad Sci U S A, 2011, 108(1): 143-8.
[81] SCHULZ T J, HUANG P, HUANG T L, et al. Brown-fat paucity due to impaired BMP signalling induces compensatory browning of white fat [J]. Nature, 2013, 495(7441): 379-83.
[82] QIANG L, WANG L, KON N, et al. Brown remodeling of white adipose tissue by SirT1-dependent deacetylation of Ppargamma [J]. Cell, 2012, 150(3): 620-32.
[83] LIU W, BI P, SHAN T, et al. miR-133a regulates adipocyte browning in vivo [J]. Plos Genet, 2013, 9(7): e1003626.
[84] TRAJKOVSKI M, AHMED K, ESAU C C, et al. MyomiR-133 regulates brown fat differentiation through Prdm16 [J]. Nat Cell Biol, 2012, 14(12): 1330-5.
[85] YIN H, PASUT A, SOLEIMANI V D, et al. MicroRNA-133 controls brown adipose determination in skeletal muscle satellite cells by targeting Prdm16 [J]. Cell Metab, 2013, 17(2): 210-24.
[86] CASTRIOTA G, THOMPSON G M, LIN Y, et al. Peroxisome proliferator-activated receptor gamma agonists inhibit adipocyte expression of alpha1-acid glycoprotein [J]. Cell Biol Int, 2007, 31(6): 586-91.
[87] CHOI S S, KIM E S, JUNG J E, et al. PPARgamma Antagonist Gleevec Improves Insulin Sensitivity and Promotes the Browning of White Adipose Tissue [J]. Diabetes, 2016, 65(4): 829-39.
[88] BARBERA M J, SCHLUTER A, PEDRAZA N, et al. Peroxisome proliferator-activated receptor alpha activates transcription of the brown fat uncoupling protein-1 gene. A link between regulation of the thermogenic and lipid oxidation pathways in the brown fat cell [J]. J Biol Chem, 2001, 276(2): 1486-93.
[89] LIANG H, WARD W F. PGC-1alpha: a key regulator of energy metabolism [J]. Adv Physiol Educ, 2006, 30(4): 145-51.
[90] PUIGSERVER P, WU Z, PARK C W, et al. A cold-inducible coactivator of nuclear receptors linked to adaptive thermogenesis [J]. Cell, 1998, 92(6): 829-39.
[91] ULDRY M, YANG W, ST-PIERRE J, et al. Complementary action of the PGC-1 coactivators in mitochondrial biogenesis and brown fat differentiation [J]. Cell Metab, 2006, 3(5): 333-41.
[92] LEONE T C, LEHMAN J J, FINCK B N, et al. PGC-1alpha deficiency causes multi-system energy metabolic derangements: muscle dysfunction, abnormal weight control and hepatic steatosis [J]. PLoS Biol, 2005, 3(4): e101.
[93] KLEINER S, MEPANI R J, LAZNIK D, et al. Development of insulin resistance in mice lacking PGC-1alpha in adipose tissues [J]. Proc Natl Acad Sci U S A, 2012, 109(24): 9635-40.
[94] FANELLI M, FILIPPI E, SENTINELLI F, et al. The Gly482Ser missense mutation of the peroxisome proliferator-activated receptor gamma coactivator-1 alpha (PGC-1 alpha) gene associates with reduced insulin sensitivity in normal and glucose-intolerant obese subjects [J]. Dis Markers, 2005, 21(4): 175-80.
[95] HANDSCHIN C, SPIEGELMAN B M. The role of exercise and PGC1alpha in inflammation and chronic disease [J]. Nature, 2008, 454(7203): 463-9.
[96] WENZ T, ROSSI S G, ROTUNDO R L, et al. Increased muscle PGC-1alpha expression protects from sarcopenia and metabolic disease during aging [J]. Proc Natl Acad Sci U S A, 2009, 106(48): 20405-10.
[97] SMAS C M, SUL H S. Control of adipocyte differentiation [J]. Biochem J, 1995, 309 ( Pt 3): 697-710.
[98] AUWERX J, MARTIN G, GUERRE-MILLO M, et al. Transcription, adipocyte differentiation, and obesity [J]. J Mol Med (Berl), 1996, 74(7): 347-52.
[99] REHNMARK S, ANTONSON P, XANTHOPOULOS K G, et al. Differential adrenergic regulation of C/EBP alpha and C/EBP beta in brown adipose tissue [J]. FEBS Lett, 1993, 318(3): 235-41.
[100] INOHARA N, KOSEKI T, CHEN S, et al. CIDE, a novel family of cell death activators with homology to the 45 kDa subunit of the DNA fragmentation factor [J]. EMBO J, 1998, 17(9): 2526-33.
[101] ZHOU Z, YON TOH S, CHEN Z, et al. Cidea-deficient mice have lean phenotype and are resistant to obesity [J]. Nat Genet, 2003, 35(1): 49-56.
[102] SMITH R E, HORWITZ B A. Brown fat and thermogenesis [J]. Physiol Rev, 1969, 49(2): 330-425.
[103] RICQUIER D, KADER J C. Mitochondrial protein alteration in active brown fat: a soidum dodecyl sulfate-polyacrylamide gel electrophoretic study [J]. Biochem Biophys Res Commun, 1976, 73(3): 577-83.
[104] HEATON G M, WAGENVOORD R J, KEMP A, JR., et al. Brown-adipose-tissue mitochondria: photoaffinity labelling of the regulatory site of energy dissipation [J]. Eur J Biochem, 1978, 82(2): 515-21.
[105] AQUILA H, LINK T A, KLINGENBERG M. The uncoupling protein from brown fat mitochondria is related to the mitochondrial ADP/ATP carrier. Analysis of sequence homologies and of folding of the protein in the membrane [J]. EMBO J, 1985, 4(9): 2369-76.
[106] BOUILLAUD F, WEISSENBACH J, RICQUIER D. Complete cDNA-derived amino acid sequence of rat brown fat uncoupling protein [J]. J Biol Chem, 1986, 261(4): 1487-90.
[107] BOSS O, SAMEC S, PAOLONI-GIACOBINO A, et al. Uncoupling protein-3: a new member of the mitochondrial carrier family with tissue-specific expression [J]. FEBS Lett, 1997, 408(1): 39-42.
[108] FLEURY C, NEVEROVA M, COLLINS S, et al. Uncoupling protein-2: a novel gene linked to obesity and hyperinsulinemia [J]. Nat Genet, 1997, 15(3): 269-72.
[109] GIMENO R E, DEMBSKI M, WENG X, et al. Cloning and characterization of an uncoupling protein homolog: a potential molecular mediator of human thermogenesis [J]. Diabetes, 1997, 46(5): 900-6.
[110] JASTROCH M. Uncoupling protein 1 controls reactive oxygen species in brown adipose tissue [J]. P Natl Acad Sci USA, 2017, 114(30): 7744-6.
[111] KLINGENBERG M, ECHTAY K S, BIENENGRAEBER M, et al. Structure-function relationship in UCP1 [J]. Int J Obes Relat Metab Disord, 1999, 23 Suppl 6: S24-9.
[112] PEBAY-PEYROULA E, DAHOUT-GONZALEZ C, KAHN R, et al. Structure of mitochondrial ADP/ATP carrier in complex with carboxyatractyloside [J]. Nature, 2003, 426(6962): 39-44.
[113] NEDERGAARD J, BENGTSSON T, CANNON B. Unexpected evidence for active brown adipose tissue in adult humans [J]. Am J Physiol Endocrinol Metab, 2007, 293(2): E444-52.
[114] BARTELT A, HEEREN J. Adipose tissue browning and metabolic health [J]. Nat Rev Endocrinol, 2014, 10(1): 24-36.
[115] ROWLATT U, MROSOVSKY N, ENGLISH A. A comparative survey of brown fat in the neck and axilla of mammals at birth [J]. Biol Neonate, 1971, 17(1): 53-83.
[116] HAYWARD J S, LISSON P A. Evolution of brown fat: its absence in marsupials and monotremes [J]. Canadian Journal of Zoology, 1992, 70(1): 171-9.
[117] JASTROCH M, WITHERS K W, TAUDIEN S, et al. Marsupial uncoupling protein 1 sheds light on the evolution of mammalian nonshivering thermogenesis [J]. Physiol Genomics, 2008, 32(2): 161-9.
[118] JASTROCH M, WUERTZ S, KLOAS W, et al. Uncoupling protein 1 in fish uncovers an ancient evolutionary history of mammalian nonshivering thermogenesis [J]. Physiol Genomics, 2005, 22(2): 150-6.
[119] TRZCIONKA M, WITHERS K W, KLINGENSPOR M, et al. The effects of fasting and cold exposure on metabolic rate and mitochondrial proton leak in liver and skeletal muscle of an amphibian, the cane toad Bufo marinus [J]. J Exp Biol, 2008, 211(Pt 12): 1911-8.
[120] SCHWARTZ T S, MURRAY S, SEEBACHER F. Novel reptilian uncoupling proteins: molecular evolution and gene expression during cold acclimation [J]. Proc Biol Sci, 2008, 275(1637): 979-85.
[121] GAUDRY M J, CAMPBELL K L. Evolution of UCP1 Transcriptional Regulatory Elements Across the Mammalian Phylogeny [J]. Front Physiol, 2017, 8: 670.
[122] MEREDITH R W, JANECKA J E, GATESY J, et al. Impacts of the Cretaceous Terrestrial Revolution and KPg extinction on mammal diversification [J]. Science, 2011, 334(6055): 521-4.
[123] O'LEARY M A, BLOCH J I, FLYNN J J, et al. The placental mammal ancestor and the post-K-Pg radiation of placentals [J]. Science, 2013, 339(6120): 662-7.
[124] JASTROCH M, OELKRUG R, KEIPERT S. Insights into brown adipose tissue evolution and function from non-model organisms [J]. J Exp Biol, 2018, 221(Pt Suppl 1).
[125] NICOL S C, PAVLIDES D, ANDERSEN N A. Nonshivering thermogenesis in marsupials: absence of thermogenic response to beta 3-adrenergic agonists [J]. Comp Biochem Physiol A Physiol, 1997, 117(3): 399-405.
[126] POLYMEROPOULOS E T, JASTROCH M, FRAPPELL P B. Absence of adaptive nonshivering thermogenesis in a marsupial, the fat-tailed dunnart (Sminthopsis crassicaudata) [J]. J Comp Physiol B, 2012, 182(3): 393-401.
[127] ROSE R W, WEST A K, YE J M, et al. Nonshivering thermogenesis in a marsupial (the tasmanian bettong Bettongia gaimardi) is not attributable to brown adipose tissue [J]. Physiol Biochem Zool, 1999, 72(6): 699-704.
[128] HUGHES D A, JASTROCH M, STONEKING M, et al. Molecular evolution of UCP1 and the evolutionary history of mammalian non-shivering thermogenesis [J]. Bmc Evol Biol, 2009, 9: 4.
[129] GAUDRY M J, JASTROCH M, TREBERG J R, et al. Inactivation of thermogenic UCP1 as a historical contingency in multiple placental mammal clades [J]. Sci Adv, 2017, 3(7): e1602878.
[130] MZILIKAZI N, JASTROCH M, MEYER C W, et al. The molecular and biochemical basis of nonshivering thermogenesis in an African endemic mammal, Elephantulus myurus [J]. Am J Physiol Regul Integr Comp Physiol, 2007, 293(5): R2120-7.
[131] OELKRUG R, GOETZE N, EXNER C, et al. Brown fat in a protoendothermic mammal fuels eutherian evolution [J]. Nat Commun, 2013, 4: 2140.
[132] LOVEGROVE B G, LOBBAN K D, LEVESQUE D L. Mammal survival at the Cretaceous-Palaeogene boundary: metabolic homeostasis in prolonged tropical hibernation in tenrecs [J]. Proc Biol Sci, 2014, 281(1796): 20141304.
[133] OELKRUG R, HELDMAIER G, MEYER C W. Torpor patterns, arousal rates, and temporal organization of torpor entry in wildtype and UCP1-ablated mice [J]. J Comp Physiol B, 2011, 181(1): 137-45.
[134] LEVESQUE D L, LOVEGROVE B G. Increased homeothermy during reproduction in a basal placental mammal [J]. J Exp Biol, 2014, 217(Pt 9): 1535-42.
[135] LEVESQUE D L, LOBBAN K D, LOVEGROVE B G. Effects of reproductive status and high ambient temperatures on the body temperature of a free-ranging basoendotherm [J]. J Comp Physiol B, 2014, 184(8): 1041-53.
[136] BERG F, GUSTAFSON U, ANDERSSON L. The uncoupling protein 1 gene (UCP1) is disrupted in the pig lineage: a genetic explanation for poor thermoregulation in piglets [J]. Plos Genet, 2006, 2(8): e129.
[137] HOU L J, SHI J, CAO L B, et al. Pig has no uncoupling protein 1 [J]. Biochem Bioph Res Co, 2017, 487(4): 795-800.
[138] LIN J, CAO C, TAO C, et al. Cold adaptation in pigs depends on UCP3 in beige adipocytes [J]. J Mol Cell Biol, 2017, 9(5): 364-75.
[139] CADENAS S, BUCKINGHAM J A, SAMEC S, et al. UCP2 and UCP3 rise in starved rat skeletal muscle but mitochondrial proton conductance is unchanged [J]. FEBS Lett, 1999, 462(3): 257-60.
[140] CADENAS S, ECHTAY K S, HARPER J A, et al. The basal proton conductance of skeletal muscle mitochondria from transgenic mice overexpressing or lacking uncoupling protein-3 [J]. J Biol Chem, 2002, 277(4): 2773-8.
[141] DEL MAR GONZALEZ-BARROSO M, PECQUEUR C, GELLY C, et al. Transcriptional activation of the human ucp1 gene in a rodent cell line. Synergism of retinoids, isoproterenol, and thiazolidinedione is mediated by a multipartite response element [J]. J Biol Chem, 2000, 275(41): 31722-32.
[142] SHORE A, EMES R D, WESSELY F, et al. A comparative approach to understanding tissue-specific expression of uncoupling protein 1 expression in adipose tissue [J]. Front Genet, 2012, 3: 304.
[143] ADAMS A E, CARROLL A M, FALLON P G, et al. Mitochondrial uncoupling protein 1 expression in thymocytes [J]. Biochim Biophys Acta, 2008, 1777(7-8): 772-6.
[144] CARROLL A M, HAINES L R, PEARSON T W, et al. Immunodetection of UCP1 in rat thymocytes [J]. Biochem Soc Trans, 2004, 32(Pt 6): 1066-7.
[145] ROUSSET S, ALVES-GUERRA M C, OUADGHIRI-BENCHERIF S, et al. Uncoupling protein 2, but not uncoupling protein 1, is expressed in the female mouse reproductive tract [J]. J Biol Chem, 2003, 278(46): 45843-7.
[146] MCKUSICK V A, RUDDLE F H. A new discipline, a new name, a new journal [J]. Genomics, 1987, 1(1): 1-2.
[147] MIN JOU W, HAEGEMAN G, YSEBAERT M, et al. Nucleotide sequence of the gene coding for the bacteriophage MS2 coat protein [J]. Nature, 1972, 237(5350): 82-8.
[148] FIERS W, CONTRERAS R, DUERINCK F, et al. Complete nucleotide sequence of bacteriophage MS2 RNA: primary and secondary structure of the replicase gene [J]. Nature, 1976, 260(5551): 500-7.
[149] SANGER F, NICKLEN S, COULSON A R. DNA sequencing with chain-terminating inhibitors [J]. Proc Natl Acad Sci U S A, 1977, 74(12): 5463-7.
[150] EFSTRATIADIS A, POSAKONY J W, MANIATIS T, et al. The structure and evolution of the human beta-globin gene family [J]. Cell, 1980, 21(3): 653-68.
[151] MARGULIES M, EGHOLM M, ALTMAN W E, et al. Genome sequencing in microfabricated high-density picolitre reactors [J]. Nature, 2005, 437(7057): 376-80.
[152] GILLES A, MEGLECZ E, PECH N, et al. Accuracy and quality assessment of 454 GS-FLX Titanium pyrosequencing [J]. BMC Genomics, 2011, 12: 245.
[153] LOMAN N J, MISRA R V, DALLMAN T J, et al. Performance comparison of benchtop high-throughput sequencing platforms [J]. Nat Biotechnol, 2012, 30(5): 434-9.
[154] WOMMACK K E, BHAVSAR J, RAVEL J. Metagenomics: read length matters [J]. Appl Environ Microbiol, 2008, 74(5): 1453-63.
[155] BENTLEY D R, BALASUBRAMANIAN S, SWERDLOW H P, et al. Accurate whole human genome sequencing using reversible terminator chemistry [J]. Nature, 2008, 456(7218): 53-9.
[156] TURCATTI G, ROMIEU A, FEDURCO M, et al. A new class of cleavable fluorescent nucleotides: synthesis and optimization as reversible terminators for DNA sequencing by synthesis [J]. Nucleic Acids Res, 2008, 36(4): e25.
[157] METZKER M L. Sequencing technologies - the next generation [J]. Nat Rev Genet, 2010, 11(1): 31-46.
[158] SHENDURE J, PORRECA G J, REPPAS N B, et al. Accurate multiplex polony sequencing of an evolved bacterial genome [J]. Science, 2005, 309(5741): 1728-32.
[159] MILOS P M. Emergence of single-molecule sequencing and potential for molecular diagnostic applications [J]. Expert Rev Mol Diagn, 2009, 9(7): 659-66.
[160] HARRIS T D, BUZBY P R, BABCOCK H, et al. Single-molecule DNA sequencing of a viral genome [J]. Science, 2008, 320(5872): 106-9.
[161] BOWERS J, MITCHELL J, BEER E, et al. Virtual terminator nucleotides for next-generation DNA sequencing [J]. Nat Methods, 2009, 6(8): 593-5.
[162] EKBLOM R, WOLF J B. A field guide to whole-genome sequencing, assembly and annotation [J]. Evol Appl, 2014, 7(9): 1026-42.
[163] FUENTES-PARDO A P, RUZZANTE D E. Whole-genome sequencing approaches for conservation biology: Advantages, limitations and practical recommendations [J]. Mol Ecol, 2017, 26(20): 5369-406.
[164] LAMICHHANEY S, MARTINEZ BARRIO A, RAFATI N, et al. Population-scale sequencing reveals genetic differentiation due to local adaptation in Atlantic herring [J]. Proc Natl Acad Sci U S A, 2012, 109(47): 19345-50.
[165] DENNENMOSER S, VAMOSI S M, NOLTE A W, et al. Adaptive genomic divergence under high gene flow between freshwater and brackish-water ecotypes of prickly sculpin (Cottus asper) revealed by Pool-Seq [J]. Mol Ecol, 2017, 26(1): 25-42.
[166] NEVADO B, RAMOS-ONSINS S E, PEREZ-ENCISO M. Resequencing studies of nonmodel organisms using closely related reference genomes: optimal experimental designs and bioinformatics approaches for population genomics [J]. Mol Ecol, 2014, 23(7): 1764-79.
[167] GOODWIN S, MCPHERSON J D, MCCOMBIE W R. Coming of age: ten years of next-generation sequencing technologies [J]. Nat Rev Genet, 2016, 17(6): 333-51.
[168] GRIGORIEV I V, NIKITIN R, HARIDAS S, et al. MycoCosm portal: gearing up for 1000 fungal genomes [J]. Nucleic Acids Res, 2014, 42(Database issue): D699-704.
[169] SCIENTISTS G C O, BRACKEN-GRISSOM H, COLLINS A G, et al. The Global Invertebrate Genomics Alliance (GIGA): developing community resources to study diverse invertebrate genomes [J]. J Hered, 2014, 105(1): 1-18.
[170] I K C. The i5K Initiative: advancing arthropod genomics for knowledge, human health, agriculture, and the environment [J]. J Hered, 2013, 104(5): 595-600.
[171] ZHANG G, RAHBEK C, GRAVES G R, et al. Genomics: Bird sequencing project takes off [J]. Nature, 2015, 522(7554): 34.
[172] MACQUEEN D J, PRIMMER C R, HOUSTON R D, et al. Functional Annotation of All Salmonid Genomes (FAASG): an international initiative supporting future salmonid research, conservation and aquaculture [J]. BMC Genomics, 2017, 18(1): 484.
[173] FONTANESI L, DI PALMA F, FLICEK P, et al. LaGomiCs-Lagomorph Genomics Consortium: An International Collaborative Effort for Sequencing the Genomes of an Entire Mammalian Order [J]. J Hered, 2016, 107(4): 295-308.
[174] KOEPFLI K P, PATEN B, GENOME K C O S, et al. The Genome 10K Project: a way forward [J]. Annu Rev Anim Biosci, 2015, 3: 57-111.
[175] MANTHEY J D, CAMPILLO L C, BURNS K J, et al. Comparison of Target-Capture and Restriction-Site Associated DNA Sequencing for Phylogenomics: A Test in Cardinalid Tanagers (Aves, Genus: Piranga) [J]. Syst Biol, 2016, 65(4): 640-50.
[176] MCKINNEY G J, LARSON W A, SEEB L W, et al. RADseq provides unprecedented insights into molecular ecology and evolutionary genetics: comment on Breaking RAD by Lowry et al. (2016) [J]. Mol Ecol Resour, 2017, 17(3): 356-61.
[177] CATCHEN J M, HOHENLOHE P A, BERNATCHEZ L, et al. Unbroken: RADseq remains a powerful tool for understanding the genetics of adaptation in natural populations [J]. Mol Ecol Resour, 2017, 17(3): 362-5.
[178] HOBAN S, KELLEY J L, LOTTERHOS K E, et al. Finding the Genomic Basis of Local Adaptation: Pitfalls, Practical Solutions, and Future Directions [J]. Am Nat, 2016, 188(4): 379-97.
[179] GENOMES PROJECT C, ABECASIS G R, ALTSHULER D, et al. A map of human genome variation from population-scale sequencing [J]. Nature, 2010, 467(7319): 1061-73.
[180] AUER P L, LETTRE G. Rare variant association studies: considerations, challenges and opportunities [J]. Genome Med, 2015, 7(1): 16.
[181] FIELD Y, BOYLE E A, TELIS N, et al. Detection of human adaptation during the past 2000 years [J]. Science, 2016, 354(6313): 760-4.
[182] BOSSDORF O, RICHARDS C L, PIGLIUCCI M. Epigenetics for ecologists [J]. Ecol Lett, 2008, 11(2): 106-15.
[183] FRACASSETTI M, GRIFFIN P C, WILLI Y. Validation of Pooled Whole-Genome Re-Sequencing in Arabidopsis lyrata [J]. PLoS One, 2015, 10(10): e0140462.
[184] WANG J, SKOOG T, EINARSDOTTIR E, et al. Investigation of rare and low-frequency variants using high-throughput sequencing with pooled DNA samples [J]. Sci Rep, 2016, 6: 33256.
[185] MARTINEZ BARRIO A, LAMICHHANEY S, FAN G, et al. The genetic basis for ecological adaptation of the Atlantic herring revealed by genome sequencing [J]. Elife, 2016, 5.
[186] PATEN B, NOVAK A M, EIZENGA J M, et al. Genome graphs and the evolution of genome inference [J]. Genome Res, 2017, 27(5): 665-76.
[187] SHAFER A B, WOLF J B, ALVES P C, et al. Genomics and the challenging translation into conservation practice [J]. Trends Ecol Evol, 2015, 30(2): 78-87.
[188] GARNER B A, HAND B K, AMISH S J, et al. Genomics in Conservation: Case Studies and Bridging the Gap between Data and Application [J]. Trends Ecol Evol, 2016, 31(2): 81-3.
[189] QUICK J, LOMAN N J, DURAFFOUR S, et al. Real-time, portable genome sequencing for Ebola surveillance [J]. Nature, 2016, 530(7589): 228-32.
[190] CUCCHI T, HULME-BEAMAN A, YUAN J, et al. Early Neolithic pig domestication at Jiahu, Henan Province, China: clues from molar shape analyses using geometric morphometric approaches [J]. J Archaeol Sci, 2011, 38(1): 11-22.
[191] LARSON G, DOBNEY K, ALBARELLA U, et al. Worldwide phylogeography of wild boar reveals multiple centers of pig domestication [J]. Science, 2005, 307(5715): 1618-21.
[192] LARSON G, LIU R, ZHAO X, et al. Patterns of East Asian pig domestication, migration, and turnover revealed by modern and ancient DNA [J]. Proc Natl Acad Sci U S A, 2010, 107(17): 7686-91.
[193] FRACHETTI M. Pastoralist landscapes and social interaction in bronze age Eurasia [J]. Pastoralist Landscapes and Social Interaction in Bronze Age Eurasia, 2009.
[194] JAANG L. The Landscape of China’s Participation in the Bronze Age Eurasian Network [J]. Journal of World Prehistory, 2015, 28(3): 179-213.
[195] BRADLEY D G, MACHUGH D E, CUNNINGHAM P, et al. Mitochondrial diversity and the origins of African and European cattle [J]. Proc Natl Acad Sci U S A, 1996, 93(10): 5131-5.
[196] BRADLEY D G, MAGEE D A. Genetics and the origins of domestic cattle [J]. Documenting Domestication: New Genetic and Archaeological Paradigms, 2006: 317-28.
[197] HELMER D, GOURICHON L, MONCHOT H, et al. Identifying early domestic cattle from Pre-Pottery Neolithic sites on the Middle Euphrates using sexual dimorphism [M]//JEAN-DENIS V, JORIS P, DANIEL H. New methods and the first steps of mammal domestication. Oxford; Oxbow Books. 2005: 86-95.
[198] MEADOW R H. Origins And Spread Of Agriculture And Pastoralism In Northwestern South Asia [M]. Origins And Spread Of Agriculture And Pastoralism In Eurasia. London; UCL Press. 1996: 390-412.
[199] CAI D W, SUN Y, TANG Z W, et al. The origins of Chinese domestic cattle as revealed by ancient DNA analysis [J]. J Archaeol Sci, 2014, 41: 423-34.
[200] FLAD R K, YUAN J 袁, LI S 李. Zooarcheological evidence for animal domestication in northwest China [M]. Late Quaternary Climate Change and Human Adaptation in Arid China. 2007: 167-203.
[201] ZHANG R, CHENG M, LI X, et al. Y-SNPs haplotype diversity in four Chinese cattle breeds [J]. Anim Biotechnol, 2013, 24(4): 288-92.
[202] CHEN S, LIN B Z, BAIG M, et al. Zebu cattle are an exclusive legacy of the South Asia neolithic [J]. Mol Biol Evol, 2010, 27(1): 1-6.
[203] ACHILLI A, BONFIGLIO S, OLIVIERI A, et al. The multifaceted origin of taurine cattle reflected by the mitochondrial genome [J]. PLoS One, 2009, 4(6): e5753.
[204] MANNEN H, KOHNO M, NAGATA Y, et al. Independent mitochondrial origin and historical genetic differentiation in North Eastern Asian cattle [J]. Mol Phylogenet Evol, 2004, 32(2): 539-44.
[205] TROY C S, MACHUGH D E, BAILEY J F, et al. Genetic evidence for Near-Eastern origins of European cattle [J]. Nature, 2001, 410(6832): 1088-91.
[206] LOFTUS R T, ERTUGRUL O, HARBA A H, et al. A microsatellite survey of cattle from a centre of origin: the Near East [J]. Mol Ecol, 1999, 8(12): 2015-22.
[207] LOFTUS R T, MACHUGH D E, NGERE L O, et al. Mitochondrial genetic variation in European, African and Indian cattle populations [J]. Anim Genet, 1994, 25(4): 265-71.
[208] LAI S J, LIU Y P, LIU Y X, et al. Genetic diversity and origin of Chinese cattle revealed by mtDNA D-loop sequence variation [J]. Mol Phylogenet Evol, 2006, 38(1): 146-54.
[209] LENSTRA J, AJMONE-MARSAN P, BEJA-PEREIRA A, et al. Meta-Analysis of Mitochondrial DNA Reveals Several Population Bottlenecks during Worldwide Migrations of Cattle [J]. Diversity, 2014, 6(1): 178-87.
[210] CAI X, CHEN H, LEI C, et al. mtDNA diversity and genetic lineages of eighteen cattle breeds from Bos taurus and Bos indicus in China [J]. Genetica, 2007, 131(2): 175-83.
[211] LI R, XIE W M, CHANG Z H, et al. Y chromosome diversity and paternal origin of Chinese cattle [J]. Mol Biol Rep, 2013, 40(12): 6633-6.
[212] 国家畜禽遗传资源委员会. 中国畜禽遗传资源志:牛志 [Animal Genetic Resources in China Bovines] [M]. 中国农业出版社, 2011.
[213] QIU H, QING Z, CHEN Y-C, et al. Bovine breeds in China [J]. Shanghai Scientific and Technical Publishers, Shanghai, 1988: 31-117.
[214] LEI C Z, CHEN H, ZHANG H C, et al. Origin and phylogeographical structure of Chinese cattle [J]. Anim Genet, 2006, 37(6): 579-82.
[215] YUE X P, LI R, LIU L, et al. When and how did Bos indicus introgress into Mongolian cattle? [J]. Gene, 2014, 537(2): 214-9.
[216] PAYNE W J A, HODGES J. Tropical cattle : origins, breeds, and breeding policies [M]. Oxford ; Malden, MA, USA: Blackwell Science, 1997.
[217] CHEN N, CAI Y, CHEN Q, et al. Whole-genome resequencing reveals world-wide ancestry and adaptive introgression events of domesticated cattle in East Asia [J]. Nat Commun, 2018, 9(1): 2337.
[218] MEI C, WANG H, LIAO Q, et al. Genetic Architecture and Selection of Chinese Cattle Revealed by Whole Genome Resequencing [J]. Mol Biol Evol, 2018, 35(3): 688-99.
[219] QIU Q, WANG L, WANG K, et al. Yak whole-genome resequencing reveals domestication signatures and prehistoric population expansions [J]. Nat Commun, 2015, 6: 10283.
[220] LAN D, XIONG X, MIPAM T D, et al. Genetic Diversity, Molecular Phylogeny, and Selection Evidence of Jinchuan Yak Revealed by Whole-Genome Resequencing [J]. G3 (Bethesda), 2018, 8(3): 945-52.
[221] CHOI J W, CHOI B H, LEE S H, et al. Whole-Genome Resequencing Analysis of Hanwoo and Yanbian Cattle to Identify Genome-Wide SNPs and Signatures of Selection [J]. Mol Cells, 2015, 38(5): 466-73.
[222] LEE Y S, SHIN D. Estimation of the Genetic Substitution Rate of Hanwoo and Holstein Cattle Using Whole Genome Sequencing Data [J]. Genomics Inform, 2018, 16(1): 14-20.
[223] KAWAGUCHI F, KIGOSHI H, NAKAJIMA A, et al. Pool-based genome-wide association study identified novel candidate regions on BTA9 and 14 for oleic acid percentage in Japanese Black cattle [J]. Anim Sci J, 2018, 89(8): 1060-6.
[224] KAWAGUCHI F, KIGOSHI H, FUKUSHIMA M, et al. Whole-genome resequencing to identify candidate genes for the QTL for oleic acid percentage in Japanese Black cattle [J]. Anim Sci J, 2019, 90(4): 467-72.
[225] ZENG L, CHEN N, NING Q, et al. PRLH and SOD1 gene variations associated with heat tolerance in Chinese cattle [J]. Anim Genet, 2018, 49(5): 447-51.
[226] RONG Y, ZENG M, GUAN X, et al. Association of HSF1 Genetic Variation with Heat Tolerance in Chinese Cattle [J]. Animals (Basel), 2019, 9(12).
[227] LIU S, YUE T, AHMAD M J, et al. Transcriptome Analysis Reveals Potential Regulatory Genes Related to Heat Tolerance in Holstein Dairy Cattle [J]. Genes (Basel), 2020, 11(1).
[228] BAHBAHANI H, AFANA A, WRAGG D. Genomic signatures of adaptive introgression and environmental adaptation in the Sheko cattle of southwest Ethiopia [J]. PLoS One, 2018, 13(8): e0202479.
[229] RADONS J. The human HSP70 family of chaperones: where do we stand? [J]. Cell Stress Chaperones, 2016, 21(3): 379-404.
[230] KAMPINGA H H, CRAIG E A. The HSP70 chaperone machinery: J proteins as drivers of functional specificity [J]. Nat Rev Mol Cell Biol, 2010, 11(8): 579-92.
[231] OLSON T A, LUCENA C, CHASE C C, JR., et al. Evidence of a major gene influencing hair length and heat tolerance in Bos taurus cattle [J]. J Anim Sci, 2003, 81(1): 80-90.
[232] MARIASEGARAM M, CHASE C C, JR., CHAPARRO J X, et al. The slick hair coat locus maps to chromosome 20 in Senepol-derived cattle [J]. Anim Genet, 2007, 38(1): 54-9.
[233] PARSONS P A. Environments and evolution: interactions between stress, resource inadequacy and energetic efficiency [J]. Biol Rev Camb Philos Soc, 2005, 80(4): 589-610.
[234] HAIM A, LEVI G. Role of Body-Temperature in Seasonal Acclimatization - Photoperiod-Induced Rhythms and Heat-Production in Meriones-Crassus [J]. J Exp Zool, 1990, 256(3): 237-41.
[235] NICHOLLS D G, LOCKE R M. Thermogenic Mechanisms in Brown Fat [J]. Physiological Reviews, 1984, 64(1): 1-64.
[236] SAITO S, SAITO C T, SHINGAI R. Adaptive evolution of the uncoupling protein 1 gene contributed to the acquisition of novel nonshivering thermogenesis in ancestral eutherian mammals [J]. Gene, 2008, 408(1-2): 37-44.
[237] KLINGENBERG M. Uncoupling protein - A useful energy dissipator [J]. J Bioenerg Biomembr, 1999, 31(5): 419-30.
[238] TONTONOZ P, HU E, SPIEGELMAN B M. Stimulation of adipogenesis in fibroblasts by PPAR gamma 2, a lipid-activated transcription factor [J]. Cell, 1994, 79(7): 1147-56.
[239] BARAK Y, NELSON M C, ONG E S, et al. PPAR gamma is required for placental, cardiac, and adipose tissue development [J]. Mol Cell, 1999, 4(4): 585-95.
[240] NEDERGAARD J, PETROVIC N, LINDGREN E M, et al. PPARgamma in the control of brown adipocyte differentiation [J]. Biochim Biophys Acta, 2005, 1740(2): 293-304.
[241] WU Z, PUIGSERVER P, ANDERSSON U, et al. Mechanisms controlling mitochondrial biogenesis and respiration through the thermogenic coactivator PGC-1 [J]. Cell, 1999, 98(1): 115-24.
[242] ROSEN E D, HSU C H, WANG X, et al. C/EBPalpha induces adipogenesis through PPARgamma: a unified pathway [J]. Genes Dev, 2002, 16(1): 22-6.
[243] HANDSCHIN C, SPIEGELMAN B M. Peroxisome proliferator-activated receptor gamma coactivator 1 coactivators, energy homeostasis, and metabolism [J]. Endocr Rev, 2006, 27(7): 728-35.
[244] CARSTENS G E. Cold Thermoregulation in the Newborn Calf [J]. Vet Clin N Am-Food A, 1994, 10(1): 69-106.
[245] BOVINE HAPMAP C, GIBBS R A, TAYLOR J F, et al. Genome-wide survey of SNP variation uncovers the genetic structure of cattle breeds [J]. Science, 2009, 324(5926): 528-32.
[246] CHEN F H, DONG G H, ZHANG D J, et al. Agriculture facilitated permanent human occupation of the Tibetan Plateau after 3600 B.P [J]. Science, 2015, 347(6219): 248-50.
[247] VERDUGO M P, MULLIN V E, SCHEU A, et al. Ancient cattle genomics, origins, and rapid turnover in the Fertile Crescent [J]. Science, 2019, 365(6449): 173-6.
[248] LI H, DURBIN R. Fast and accurate short read alignment with Burrows-Wheeler transform [J]. Bioinformatics, 2009, 25(14): 1754-60.
[249] MCKENNA A, HANNA M, BANKS E, et al. The Genome Analysis Toolkit: a MapReduce framework for analyzing next-generation DNA sequencing data [J]. Genome Res, 2010, 20(9): 1297-303.
[250] WANG K, LI M, HAKONARSON H. ANNOVAR: functional annotation of genetic variants from high-throughput sequencing data [J]. Nucleic Acids Res, 2010, 38(16): e164.
[251] PRICE A L, PATTERSON N J, PLENGE R M, et al. Principal components analysis corrects for stratification in genome-wide association studies [J]. Nat Genet, 2006, 38(8): 904-9.
[252] PLOTREE D, PLOTGRAM D. PHYLIP-Phylogeny inference package (version 3.2) [M]. 1989.
[253] JUNIER T, ZDOBNOV E M. The Newick utilities: high-throughput phylogenetic tree processing in the UNIX shell [J]. Bioinformatics, 2010, 26(13): 1669-70.
[254] ALEXANDER D H, NOVEMBRE J, LANGE K. Fast model-based estimation of ancestry in unrelated individuals [J]. Genome Res, 2009, 19(9): 1655-64.
[255] LI H, DURBIN R. Inference of human population history from individual whole-genome sequences [J]. Nature, 2011, 475(7357): 493-6.
[256] ZHAO S, ZHENG P, DONG S, et al. Whole-genome sequencing of giant pandas provides insights into demographic history and local adaptation [J]. Nat Genet, 2013, 45(1): 67-71.
[257] ZHOU X, WANG B, PAN Q, et al. Whole-genome sequencing of the snub-nosed monkey provides insights into folivory and evolutionary history [J]. Nat Genet, 2014, 46(12): 1303-10.
[258] MURRAY C, HUERTA-SANCHEZ E, CASEY F, et al. Cattle demographic history modelled from autosomal sequence variation [J]. Philos Trans R Soc Lond B Biol Sci, 2010, 365(1552): 2531-9.
[259] DANECEK P, AUTON A, ABECASIS G, et al. The variant call format and VCFtools [J]. Bioinformatics, 2011, 27(15): 2156-8.
[260] PURCELL S, NEALE B, TODD-BROWN K, et al. PLINK: a tool set for whole-genome association and population-based linkage analyses [J]. Am J Hum Genet, 2007, 81(3): 559-75.
[261] ATSHAVES B P, STOREY S M, MCINTOSH A L, et al. Sterol carrier protein-2 expression modulates protein and lipid composition of lipid droplets [J]. J Biol Chem, 2001, 276(27): 25324-35.
[262] ATSHAVES B P, STARODUB O, MCINTOSH A, et al. Sterol carrier protein-2 alters high density lipoprotein-mediated cholesterol efflux [J]. J Biol Chem, 2000, 275(47): 36852-61.
[263] LEE J, ELLIS J M, WOLFGANG M J. Adipose fatty acid oxidation is required for thermogenesis and potentiates oxidative stress-induced inflammation [J]. Cell Rep, 2015, 10(2): 266-79.
[264] LEE J, CHOI J, AJA S, et al. Loss of Adipose Fatty Acid Oxidation Does Not Potentiate Obesity at Thermoneutrality [J]. Cell Rep, 2016, 14(6): 1308-16.
[265] ZHENG X Y, YU B L, XIE Y F, et al. Apolipoprotein A5 regulates intracellular triglyceride metabolism in adipocytes [J]. Mol Med Rep, 2017, 16(5): 6771-9.
[266] ISHIHARA M, KUJIRAOKA T, IWASAKI T, et al. A sandwich enzyme-linked immunosorbent assay for human plasma apolipoprotein A-V concentration [J]. J Lipid Res, 2005, 46(9): 2015-22.
[267] HUANG X S, ZHAO S P, HU M, et al. Decreased apolipoprotein A5 is implicated in insulin resistance-related hypertriglyceridemia in obesity [J]. Atherosclerosis, 2010, 210(2): 563-8.
[268] NICULESCU L S, FRUCHART-NAJIB J, FRUCHART J C, et al. Apolipoprotein A-V gene polymorphisms in subjects with metabolic syndrome [J]. Clin Chem Lab Med, 2007, 45(9): 1133-9.
[269] PAMIR N, MCMILLEN T S, LI Y I, et al. Overexpression of apolipoprotein A5 in mice is not protective against body weight gain and aberrant glucose homeostasis [J]. Metabolism, 2009, 58(4): 560-7.
[270] QUAN L H, ZHANG C, DONG M, et al. Myristoleic acid produced by enterococci reduces obesity through brown adipose tissue activation [J]. Gut, 2019.
[271] HEEREN J, SCHEJA L. Brown adipose tissue and lipid metabolism [J]. Curr Opin Lipidol, 2018, 29(3): 180-5.
[272] LI Z, YI C X, KATIRAEI S, et al. Butyrate reduces appetite and activates brown adipose tissue via the gut-brain neural circuit [J]. Gut, 2018, 67(7): 1269-79.
[273] ZECHNER R, MADEO F, KRATKY D. Cytosolic lipolysis and lipophagy: two sides of the same coin [J]. Nat Rev Mol Cell Biol, 2017, 18(11): 671-84.
[274] DE VADDER F, KOVATCHEVA-DATCHARY P, GONCALVES D, et al. Microbiota-generated metabolites promote metabolic benefits via gut-brain neural circuits [J]. Cell, 2014, 156(1-2): 84-96.
[275] GUIRGUIS E, HOCKMAN S, CHUNG Y W, et al. A role for phosphodiesterase 3B in acquisition of brown fat characteristics by white adipose tissue in male mice [J]. Endocrinology, 2013, 154(9): 3152-67.
[276] CHUNG Y W, AHMAD F, TANG Y, et al. White to beige conversion in PDE3B KO adipose tissue through activation of AMPK signaling and mitochondrial function [J]. Sci Rep, 2017, 7: 40445.
[277] GERST F, JAGHUTRIZ B A, STAIGER H, et al. The Expression of Aldolase B in Islets Is Negatively Associated With Insulin Secretion in Humans [J]. J Clin Endocrinol Metab, 2018, 103(12): 4373-83.
[278] LYNES M D, SCHULZ T J, PAN A J, et al. Disruption of Insulin Signaling in Myf5-Expressing Progenitors Leads to Marked Paucity of Brown Fat but Normal Muscle Development [J]. Endocrinology, 2015, 156(5): 1637-47.
[279] MONTANARI T, POSCIC N, COLITTI M. Factors involved in white-to-brown adipose tissue conversion and in thermogenesis: a review [J]. Obes Rev, 2017, 18(5): 495-513.
[280] PARK U H, SEONG M R, KIM E J, et al. Reciprocal regulation of LXRalpha activity by ASXL1 and ASXL2 in lipogenesis [J]. Biochem Biophys Res Commun, 2014, 443(2): 489-94.
[281] KAJIMURA S, SEALE P, TOMARU T, et al. Regulation of the brown and white fat gene programs through a PRDM16/CtBP transcriptional complex [J]. Genes Dev, 2008, 22(10): 1397-409.
[282] SCARPACE P J, MATHENY M, BORST S, et al. Thermoregulation with age: role of thermogenesis and uncoupling protein expression in brown adipose tissue [J]. Proc Soc Exp Biol Med, 1994, 205(2): 154-61.
[283] KIROV S A, TALAN M I, KOSHELEVA N A, et al. Nonshivering thermogenesis during acute cold exposure in adult and aged C57BL/6J mice [J]. Exp Gerontol, 1996, 31(3): 409-19.
[284] ALEXANDER G, BELL A W. Quantity and calculated oxygen consumption during summit metabolism of brown adipose tissue in new-born lambs [J]. Biol Neonate, 1975, 26(3-4): 214-20.
[285] LIDELL M E, BETZ M J, DAHLQVIST LEINHARD O, et al. Evidence for two types of brown adipose tissue in humans [J]. Nat Med, 2013, 19(5): 631-4.
[286] KEANE M, SEMEIKS J, WEBB A E, et al. Insights into the evolution of longevity from the bowhead whale genome [J]. Cell Rep, 2015, 10(1): 112-22.
[287] REYNE Y, NOUGUES J, CAMBON B, et al. Expression of c-erbA alpha, c-erbA beta and Rev-erbA alpha mRNA during the conversion of brown adipose tissue into white adipose tissue [J]. Mol Cell Endocrinol, 1996, 116(1): 59-65.
[288] FISCHER A W, SHABALINA I G, MATTSSON C L, et al. UCP1 inhibition in Cidea-overexpressing mice is physiologically counteracted by brown adipose tissue hyperrecruitment [J]. Am J Physiol Endocrinol Metab, 2017, 312(1): E72-E87.
[289] SMITH S B, CARSTENS G E, RANDEL R D, et al. Brown adipose tissue development and metabolism in ruminants [J]. J Anim Sci, 2004, 82(3): 942-54.
[290] HIMMS-HAGEN J. Brown adipose tissue thermogenesis: interdisciplinary studies [J]. Faseb J, 1990, 4(11): 2890-8.
[291] HORSCROFT C, ENNIS S, PENGELLY R J, et al. Sequencing era methods for identifying signatures of selection in the genome [J]. Brief Bioinform, 2019, 20(6): 1997-2008.
[292] OBERKOFLER H, DALLINGER G, LIU Y M, et al. Uncoupling protein gene: quantification of expression levels in adipose tissues of obese and non-obese humans [J]. J Lipid Res, 1997, 38(10): 2125-33.
[293] DIETZ R E, HALL J B, WHITTIER W D, et al. Effects of feeding supplemental fat to beef cows on cold tolerance in newborn calves [J]. Journal of Animal Science, 2003, 81(4): 885-94.
[294] LANDIS M D, CARSTENS G E, MCPHAIL E G, et al. Ontogenic development of brown adipose tissue in Angus and Brahman fetal calves [J]. Journal of Animal Science, 2002, 80(3): 591-601.