Adaptations to climate in candidate genes for common metabolic disorders.
Adaptations to climate in candidate genes for common metabolic disorders.
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适应常见代谢疾病的候选基因气候。
DOI：
10.1371/journal.pgen.0040032
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发表时间：
2008-02
期刊：
影响因子：
4.5
通讯作者：
Di Rienzo, Anna
中科院分区：
文献类型：
--
作者：
Hancock, Angela M.;Witonsky, David B.;Gordon, Adam S.;Eshel, Gidon;Pritchard, Jonathan K.;Coop, Graham;Di Rienzo, Anna
气候变化引起的进化压力在形成物种之间和物种内部的表型变异方面发挥着重要作用，并已被证明影响人类体型和大小等表型变异。参与能量代谢的基因可能是耐热性和耐寒性的核心。为了验证气候影响人类代谢基因变异的假设，我们使用基于网络理论的生物信息学方法选择了82个常见代谢疾病的候选基因。我们在全球54个人群（包括人类基因组多样性计划小组中的52个）中对这些基因的873个标签snp进行了基因分型，并使用等级相关分析和新开发的贝叶斯地理分析方法发现了与气候变量的相关性。此外，我们对210个精心匹配的对照snp进行了基因分型，为等位基因频率的空间格局提供了一个经验零分布，该空间格局仅受群体历史的影响。对于几乎所有的气候变量，我们发现与对照snp相比，在测试统计分布的尾部有过量的基因snp，这意味着代谢基因作为一个群体显示出空间变化选择的信号。在我们最强的信号中，有几个snp（例如，LEPR R109K, FABP2 A54T）先前与耐寒性直接相关的表型相关。由于气候变化可能与环境变化的其他方面相关，我们检测到的一些信号可能反映了气候以外的选择压力。然而，我们的结果与气候一直是一个重要的选择压力作用于常见代谢紊乱的候选基因的观点是一致的。人类居住的地理范围很广，气候也很多样，对这些气候的适应可能在形成种群间的遗传和表型变异中发挥了重要作用。我们假设，与气候相关的空间变化的选择压力塑造了能量代谢途径中遗传变异的频率。为了验证这一假设，我们研究了人类基因组多样性计划中52个全球分散人群中82个常见代谢疾病候选基因的遗传变异模式。我们采用统计方法的组合来测试这些变异的地理分布是否可以由不同的气候来解释，这与空间变化的积极选择的信号一致。对于一些气候变量，我们观察到的信号超出了仅从人口历史和偶然因素中预期的信号。值得注意的是，这些信号中有许多来自先前被证明影响耐寒性和疾病风险的基因。我们的研究结果提供了证据，表明人群中对常见代谢疾病易感性的差异可能部分归因于这些疾病途径中基因选择压力的不同历史。此外，我们的结果指出了其他基因和变异是后续疾病关联研究的合适目标。
Evolutionary pressures due to variation in climate play an important role in shaping phenotypic variation among and within species and have been shown to influence variation in phenotypes such as body shape and size among humans. Genes involved in energy metabolism are likely to be central to heat and cold tolerance. To test the hypothesis that climate shaped variation in metabolism genes in humans, we used a bioinformatics approach based on network theory to select 82 candidate genes for common metabolic disorders. We genotyped 873 tag SNPs in these genes in 54 worldwide populations (including the 52 in the Human Genome Diversity Project panel) and found correlations with climate variables using rank correlation analysis and a newly developed method termed Bayesian geographic analysis. In addition, we genotyped 210 carefully matched control SNPs to provide an empirical null distribution for spatial patterns of allele frequency due to population history alone. For nearly all climate variables, we found an excess of genic SNPs in the tail of the distributions of the test statistics compared to the control SNPs, implying that metabolic genes as a group show signals of spatially varying selection. Among our strongest signals were several SNPs (e.g., LEPR R109K, FABP2 A54T) that had previously been associated with phenotypes directly related to cold tolerance. Since variation in climate may be correlated with other aspects of environmental variation, it is possible that some of the signals that we detected reflect selective pressures other than climate. Nevertheless, our results are consistent with the idea that climate has been an important selective pressure acting on candidate genes for common metabolic disorders. The human species inhabits a wide geographical range encompassing a diversity of climates, and adaptation to these climates likely played an important role in shaping genetic and phenotypic variation among populations. We hypothesized that spatially varying selective pressures related to climate shaped the frequencies of genetic variants in the energy metabolic pathway. To test this hypothesis, we examined patterns of genetic variation in 82 candidate genes for common metabolic disorders across the 52 globally dispersed populations of the Human Genome Diversity Project. We applied a combination of statistical approaches to test whether the geographic distribution of these variants could be accounted for by differing climates, consistent with a signal of spatially varying positive selection. For several climate variables, we observed signals in excess of that expected from human population history and chance alone. Significantly, many of these signals were from genes previously shown to affect cold tolerance and disease risk. Our results provide evidence that variation among human populations in susceptibility to common metabolic diseases may be due, in part, to different histories of selective pressures on genes in these disease pathways. Furthermore, our results point to additional genes and variants that are suitable targets for follow-up disease association studies.
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影响因子：
15.9
作者：
BAIER, LJ;SACCHETTINI, JC;PROCHAZKA, M
通讯作者：
PROCHAZKA, M
DOI：
10.1098/rspb.1992.0128
发表时间：
1992-10-22
影响因子：
4.7
作者：
COSTA, R;PEIXOTO, AA;KYRIACOU, CP
通讯作者：
KYRIACOU, CP
影响因子：
2.8
作者：
Baum, L;Ng, HK;Wong, KS
通讯作者：
Wong, KS
影响因子：
7
作者：
Akey, JM;Zhang, G;Shriver, MD
通讯作者：
Shriver, MD
影响因子：
3
作者：
Donaldson, I;Martin, J;de Bruijn, B;Wolting, C;Lay, V;Tuekam, B;Zhang, SD;Baskin, B;Bader, GD;Michalickova, K;Pawson, T;Hogue, CWV
通讯作者：
Hogue, CWV