Positive Selection in East Asians for an EDAR Allele that Enhances NF-κB Activation
Positive Selection in East Asians for an EDAR Allele that Enhances NF-κB Activation
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DOI：
10.1371/journal.pone.0002209
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发表时间：
2008-05-21
期刊：
影响因子：
3.7
通讯作者：
Myles, Sean
中科院分区：
文献类型：
--
作者：
Bryk, Jaroslaw;Hardouin, Emilie;Myles, Sean
全基因组扫描人类正选择提供了一个有前途的方法来建立遗传变异和适应性表型之间的联系。通过这种方法，已经组装了数百个用于正选择的候选基因组区域的列表。这些候选区域预计包含有助于适应性表型的变体，但这些区域中很少有与表型效应相关的。在这里，我们提出的证据表明，一个衍生的非同义替换（370 A）在EDAR，参与外胚层发育的基因，是驱动到高频率在东亚的积极选择之前，10,000年前。通过体外转染试验，我们证明370 A增强NF-κ B活性。我们的研究结果表明，370 A是一个积极选择的功能性遗传变异的基础上的适应性人类表型。
Genome-wide scans for positive selection in humans provide a promising approach to establish links between genetic variants and adaptive phenotypes. From this approach, lists of hundreds of candidate genomic regions for positive selection have been assembled. These candidate regions are expected to contain variants that contribute to adaptive phenotypes, but few of these regions have been associated with phenotypic effects. Here we present evidence that a derived nonsynonymous substitution (370A) in EDAR, a gene involved in ectodermal development, was driven to high frequency in East Asia by positive selection prior to 10,000 years ago. With an in vitro transfection assay, we demonstrate that 370A enhances NF-kappa B activity. Our results suggest that 370A is a positively selected functional genetic variant that underlies an adaptive human phenotype.