Population genetic analysis of the uncoupling proteins supports a role for UCP3 in human cold resistance.
Population genetic analysis of the uncoupling proteins supports a role for UCP3 in human cold resistance.
复制标题
解偶联蛋白的群体遗传分析支持 UCP3 在人类抗寒性中的作用。
DOI：
10.1093/molbev/msq228
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发表时间：
2011-01
影响因子：
10.7
通讯作者：
Di Rienzo A
中科院分区：
文献类型：
--
作者：
Hancock AM;Clark VJ;Qian Y;Di Rienzo A
通过非寒颤产热（NST）产生热量对哺乳动物的温度稳态至关重要。解偶联蛋白UCP1通过解偶联线粒体内膜产生的质子梯度来产生热量，在NST中发挥核心作用；然而，UCP1的同系物UCP2和UCP3在多大程度上参与了NST，这是一个持续争论的主题。我们使用进化方法来验证与这些基因（UCP1−3826A、UCP2−866A和UCP3−55T）表达增加相关的变异对冬季气候的适应性。为此，我们计算了这些单核苷酸多态性（snp）的等位基因频率与冬季气候变量之间的相关性，并在全球52个人群中进行了基因分型。结果表明，UCP1−3826G/A和UCP3−55C/T与冬季气候存在显著相关。此外，通过分析先前发表的这些snp的基因型数据，我们发现UCP1区域的相关性峰值出现在与疾病相关的- 3826A/G变体上，UCP3区域总体上具有显著的信号，其中几个单个snp显示出有趣的模式，包括- 55C/T变体。对三组不同人群样本的区域重新排序有助于澄清我们在基因型数据中发现的信号。在UCP1，重测序数据显示了适度的证据，即携带- 3826A变体的单倍型通过选择被驱动到高频。在UCP3区域，结合气候分析和重测序调查的结果，提出了一个更复杂的模型，其中多个单倍型的变异可能独立地与温度相关。汉族人群中UCP3区域中频变异的过量进一步支持了这一点。综上所述，我们的研究结果表明，气候适应影响了UCP1和UCP3等位基因频率的全球分布，并为UCP3在抗寒性中的作用提供了独立的证据来源。
Production of heat via nonshivering thermogenesis (NST) is critical for temperature homeostasis in mammals. Uncoupling protein UCP1 plays a central role in NST by uncoupling the proton gradients produced in the inner membranes of mitochondria to produce heat; however, the extent to which UCP1 homologues, UCP2 and UCP3, are involved in NST is the subject of an ongoing debate. We used an evolutionary approach to test the hypotheses that variants that are associated with increased expression of these genes (UCP1 −3826A, UCP2 −866A, and UCP3 −55T) show evidence of adaptation with winter climate. To that end, we calculated correlations between allele frequencies and winter climate variables for these single-nucleotide polymorphisms (SNPs), which we genotyped in a panel of 52 worldwide populations. We found significant correlations with winter climate for UCP1 −3826G/A and UCP3 −55C/T. Further, by analyzing previously published genotype data for these SNPs, we found that the peak of the correlation for the UCP1 region occurred at the disease-associated −3826A/G variant and that the UCP3 region has a striking signal overall, with several individual SNPs showing interesting patterns, including the −55C/T variant. Resequencing of the regions in a set of three diverse population samples helped to clarify the signals that we found with the genotype data. At UCP1, the resequencing data revealed modest evidence that the haplotype carrying the −3826A variant was driven to high frequency by selection. In the UCP3 region, combining results from the climate analysis and resequencing survey suggest a more complex model in which variants on multiple haplotypes may independently be correlated with temperature. This is further supported by an excess of intermediate frequency variants in the UCP3 region in the Han Chinese population. Taken together, our results suggest that adaptation to climate influenced the global distribution of allele frequencies in UCP1 and UCP3 and provide an independent source of evidence for a role in cold resistance for UCP3.
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影响因子：
4.5
作者：
Hancock, Angela M.;Witonsky, David B.;Gordon, Adam S.;Eshel, Gidon;Pritchard, Jonathan K.;Coop, Graham;Di Rienzo, Anna
通讯作者：
Di Rienzo, Anna
DOI：
10.1073/pnas.0914625107
发表时间：
2010-05-11
影响因子：
11.1
作者：
Hancock, Angela M.;Witonsky, David B.;Di Rienzo, Anna
通讯作者：
Di Rienzo, Anna
影响因子：
30.8
作者：
Fleury, C;Neverova, M;Warden, CH
通讯作者：
Warden, CH
影响因子：
3.5
作者：
Hagen, T;Zhang, CY;Lowell, BB
通讯作者：
Lowell, BB
影响因子：
3.3
作者：
Coop, Graham;Witonsky, David;Pritchard, Jonathan K.
通讯作者：
Pritchard, Jonathan K.