Gene regulation in primates evolves under tissue-specific selection pressures.
Gene regulation in primates evolves under tissue-specific selection pressures.
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DOI：
10.1371/journal.pgen.1000271
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发表时间：
2008-11
期刊：
影响因子：
4.5
通讯作者：
Gilad Y
中科院分区：
文献类型：
--
作者：
Blekhman R;Oshlack A;Chabot AE;Smyth GK;Gilad Y
长期以来，人们一直认为调控变化在灵长类动物的进化中发挥着重要作用。为了确定人类的适应性调节变化，我们对调节可能在自然选择下进化的基因进行了全基因组调查。为此，我们使用多物种微阵列来测量六个人、黑猩猩和恒河猴肝脏、肾脏和心脏的基因表达水平。这种比较的基因表达数据使我们能够识别出大量的基因以及特定的途径，它们的物种间表达谱与稳定或定向选择对基因调控的作用是一致的。在后一组中，我们发现参与新陈代谢途径的基因丰富，这与饮食变化是人类许多调节适应的基础的假设一致。此外，我们发现了组织特定选择压力的证据，以及在自然选择下调节进化的基因的蛋白质进化速度较低的证据。这些观察结果与以下观点是一致的，即与蛋白质序列水平的变化相比，基因调节中的适应性限制性变化具有更少的有害多效性效应。长期以来，人们一直假设，除了蛋白质的结构变化外，基因调控的变化可能是人类与其他灵长类动物在解剖和行为上的许多差异的基础。然而，到目前为止，在人类身上进行监管适应的例子屈指可数。在这项工作中，我们对三个物种的肝脏、肾脏和心脏的基因表达水平进行了全基因组研究：人类、黑猩猩和恒河猴。这些数据使我们能够识别在自然选择下进化的调控的基因和整个途径，因此很可能具有重要的功能。我们的结果提供了一些特别在人类谱系中被重塑的路径的第一批例子。特别是，我们发现，参与代谢途径的大量基因的调节是在谱系特定的定向选择下进化的。这一结果很耐人寻味，因为除了人类和非人类类人猿之间明显的认知和语言差异外，我们的饮食中还可以发现人类和其他灵长类动物之间明显的生活方式变化。我们还发现了组织特异性选择压力对基因调节的证据，这一观察结果有力地支持了这样的观点，即与蛋白质序列水平的变化相比，基因调节中的适应性受限变化具有更少的有害多效性效应。
Regulatory changes have long been hypothesized to play an important role in primate evolution. To identify adaptive regulatory changes in humans, we performed a genome-wide survey for genes in which regulation has likely evolved under natural selection. To do so, we used a multi-species microarray to measure gene expression levels in livers, kidneys, and hearts from six humans, chimpanzees, and rhesus macaques. This comparative gene expression data allowed us to identify a large number of genes, as well as specific pathways, whose inter-species expression profiles are consistent with the action of stabilizing or directional selection on gene regulation. Among the latter set, we found an enrichment of genes involved in metabolic pathways, consistent with the hypothesis that shifts in diet underlie many regulatory adaptations in humans. In addition, we found evidence for tissue-specific selection pressures, as well as lower rates of protein evolution for genes in which regulation evolves under natural selection. These observations are consistent with the notion that adaptive circumscribed changes in gene regulation have fewer deleterious pleiotropic effects compared with changes at the protein sequence level. It has long been hypothesized that in addition to structural changes to proteins, changes in gene regulation might underlie many of the anatomic and behavioral differences between humans and other primates. However, to date, there are only a handful of examples of regulatory adaptations in humans. In this work, we present a genome-wide study of gene expression levels in livers, kidneys, and hearts from three species: humans, chimpanzees, and rhesus macaques. These data allowed us to identify genes and entire pathways in which regulation evolved under natural selection and therefore are likely to be functionally important. Our results provide some of the first examples of pathways that have been remodeled specifically in the human lineage. In particular, we find that the regulation of a large number of genes involved in metabolic pathways evolved under lineage-specific directional selection. This result is intriguing, because, in addition to the obvious cognitive and linguistic differences between humans and non-human apes, a clear lifestyle shift between us and other primates can be found in our diet. We also found evidence for tissue-specific selection pressures on gene regulation, an observation that provides strong support to the notion that adaptive circumscribed changes in gene regulation have fewer deleterious pleiotropic effects compared with changes at the protein sequence level.
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影响因子：
30.8
作者：
Enattah, NS;Sahi, T;Järvelä, I
通讯作者：
Järvelä, I
影响因子：
64.8
作者：
Bustamante, CD;Fledel-Alon, A;Clark, AG
通讯作者：
Clark, AG
DOI：
10.1111/j.2517-6161.1995.tb02031.x
发表时间：
1995-01-01
影响因子：
5.8
作者：
BENJAMINI, Y;HOCHBERG, Y
通讯作者：
HOCHBERG, Y
影响因子：
7
作者：
Gilad, Y;Rifkin, SA;White, KP
通讯作者：
White, KP
影响因子：
64.8
作者：
Gompel, N;Prud'homme, B;Carroll, SB
通讯作者：
Carroll, SB