Gene expression levels are a target of recent natural selection in the human genome.
Gene expression levels are a target of recent natural selection in the human genome.
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DOI：
10.1093/molbev/msn289
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发表时间：
2009-03
影响因子：
10.7
通讯作者：
Pritchard JK
中科院分区：
文献类型：
--
作者：
Kudaravalli S;Veyrieras JB;Stranger BE;Dermitzakis ET;Pritchard JK
基因表达的变化可能代表了人类适应的一种重要模式。然而，迄今为止，有相对较少的已知的例子，其中选择已被证明直接作用于基因表达的水平或模式。为了测试影响顺式基因表达的单核苷酸多态性（SNP）是否是人类正自然选择的常见目标，我们分析了与国际人类基因组单体型图项目相关的细胞系的全基因组SNP和表达数据。使用单倍型为基础的测试选择，旨在检测不完全的选择性扫描，我们发现，显示选择信号的SNP比随机SNP更有可能与基因表达水平的顺式。这个信号在约鲁巴人中是显著的（约鲁巴人是总体上显示出最强选择信号的群体），并且在其他HapMap群体中显示出相同方向的趋势。我们的研究结果表明，基因表达水平的选择是人类适应的一种重要类型。最后，我们的工作提供了一个分析框架来解决一个更普遍的问题，这将变得越来越重要：即，测试选择信号是否与感兴趣的表型相关的SNP显著重叠。
Changes in gene expression may represent an important mode of human adaptation. However, to date, there are relatively few known examples in which selection has been shown to act directly on levels or patterns of gene expression. In order to test whether single nucleotide polymorphisms (SNPs) that affect gene expression in cis are frequently targets of positive natural selection in humans, we analyzed genome-wide SNP and expression data from cell lines associated with the International HapMap Project. Using a haplotype-based test for selection that was designed to detect incomplete selective sweeps, we found that SNPs showing signals of selection are more likely than random SNPs to be associated with gene expression levels in cis. This signal is significant in the Yoruba (which is the population that shows the strongest signals of selection overall) and shows a trend in the same direction in the other HapMap populations. Our results argue that selection on gene expression levels is an important type of human adaptation. Finally, our work provides an analytical framework for tackling a more general problem that will become increasingly important: namely, testing whether selection signals overlap significantly with SNPs that are associated with phenotypes of interest.
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影响因子：
4.5
作者：
Kim, Su Yeon;Pritchard, Jonathan K.
通讯作者：
Pritchard, Jonathan K.
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