Natural selection on protein-coding genes in the human genome
Natural selection on protein-coding genes in the human genome
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DOI：
10.1038/nature04240
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发表时间：
2005-10-20
期刊：
影响因子：
64.8
通讯作者：
Clark, AG
中科院分区：
文献类型：
--
作者：
Bustamante, CD;Fledel-Alon, A;Clark, AG
物种内的DNA多态性与物种之间的差异的比较使得在进化限制的基因中发现了分子适应性，以及弱分化与强纯度选择的分化（1-4）。弱的负面和阳性达尔文人选择驱动不同物种的分子演变的程度差异很大（5-16），有些物种（例如果蝇Melanogaster），显示出广泛的阳性选择的有力证据（6-9）等等。 ，例如自我杂草拟南芥，在当地人群中表现出过多的有害变化（9,10）。在这里，我们对比编码序列多态性的模式通过直接测序39人对11,000多个基因进行直接测序与人类和黑猩猩之间的差异，并找到有力的证据，表明自然选择塑造了我们物种最近的分子进化。我们的分析发现3,377个潜在信息基因座中有304（9.0％），显示了快速氨基酸进化的证据。此外，在6,033个潜在信息的基因座中，有813（13.5％）显示了人类和黑猩猩之间的氨基酸差异很少，表明在这些基因座的突变上运行的负面选择和/或平衡选择。我们发现，在生物过程和分子函数之间进行负和正面选择的基因的分布差异很大，并且某些类别（例如转录因子）表现出过多的迅速发展的基因，而其他类别（例如细胞骨架蛋白）显示出过量的过量人类中具有广泛氨基酸多态性的基因，但人类和黑猩猩之间的氨基酸差异很小。
Comparisons of DNA polymorphism within species to divergence between species enables the discovery of molecular adaptation in evolutionarily constrained genes as well as the differentiation of weak from strong purifying selection(1-4). The extent to which weak negative and positive darwinian selection have driven the molecular evolution of different species varies greatly(5-16), with some species, such as Drosophila melanogaster, showing strong evidence of pervasive positive selection(6-9), and others, such as the selfing weed Arabidopsis thaliana, showing an excess of deleterious variation within local populations(9,10). Here we contrast patterns of coding sequence polymorphism identified by direct sequencing of 39 humans for over 11,000 genes to divergence between humans and chimpanzees, and find strong evidence that natural selection has shaped the recent molecular evolution of our species. Our analysis discovered 304 (9.0%) out of 3,377 potentially informative loci showing evidence of rapid amino acid evolution. Furthermore, 813 (13.5%) out of 6,033 potentially informative loci show a paucity of amino acid differences between humans and chimpanzees, indicating weak negative selection and/or balancing selection operating on mutations at these loci. We find that the distribution of negatively and positively selected genes varies greatly among biological processes and molecular functions, and that some classes, such as transcription factors, show an excess of rapidly evolving genes, whereas others, such as cytoskeletal proteins, show an excess of genes with extensive amino acid polymorphism within humans and yet little amino acid divergence between humans and chimpanzees.