Widespread purifying selection at polymorphic sites in human protein-coding loci
Widespread purifying selection at polymorphic sites in human protein-coding loci
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DOI：
10.1073/pnas.2536718100
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发表时间：
2003-12-23
影响因子：
11.1
通讯作者：
Yeager, M
中科院分区：
文献类型：
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作者：
Hughes, AL;Packer, B;Yeager, M
对不同种族人类样本中 1,442 个单核苷多态性 (SNP) 位点的基因多样性（杂合性）进行估计，发现 SNP 位点的基因多样性持续减少，导致氨基酸变化，特别是那些导致预计会破坏蛋白质结构的氨基酸变化的变化。与不影响蛋白质结构的相同基因中的 SNP 相比，这些 SNP 位点基因多样性的减少证明负向自然选择（纯化选择）降低了有害 SNP 等位基因的群体频率。这反过来表明，轻微有害的突变在人群中广泛存在，即使在适度规模的样本中，对基因多样性的估计也可以帮助指导寻找与疾病相关的基因。
Estimation of gene diversity (heterozygosity) at 1,442 single-nucleoticle polymorphism (SNP) loci in an ethnically diverse sample of humans revealed consistently reduced gene diversities at SNP loci causing amino acid changes, particularly those causing amino acid changes predicted to be disruptive to protein structure. The reduction of gene diversity at these SNP loci, in comparison to SNPs in the same genes not affecting protein structure, is evidence that negative natural selection (purifying selection) has reduced the population frequencies of deleterious SNP alleles. This, in turn, suggests that slightly deleterious mutations are widespread in the human population and that estimation of gene diversity even in a sample of modest size can help guide the search for disease-associated genes.