Remarkably Little Variation in Proteins Encoded by the Y Chromosome's Single-Copy Genes, Implying Effective Purifying Selection
Remarkably Little Variation in Proteins Encoded by the Y Chromosome's Single-Copy Genes, Implying Effective Purifying Selection
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DOI：
10.1016/j.ajhg.2009.11.011
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发表时间：
2009-12-11
影响因子：
9.8
通讯作者：
Page, David C.
中科院分区：
文献类型：
--
作者：
Rozen, Steve;Marszalek, Janet D.;Page, David C.
Y连锁单核苷酸多态性（SNPs）已成为重建人类Y染色体全球谱系和阐明现代人类群体中父系关系的有力工具。然而，已经有110个系统的，世界范围内的Y染色体的蛋白质编码基因的序列变异的调查。在这里，我们报告和分析编码序列的变异之间的16个单拷贝的“X-简并”基因的Y染色体。我们研究了这些基因的变异在105名男子代表世界各地的多样性，在每个人的平均27 kb的编码DNA，40 kb的内含子DNA，并进行比较，15 kb的DNA在单拷贝Y染色体假基因重测序。X简并蛋白质序列的变异非常小：随机抽取的两条染色体平均相差一个氨基酸，其中一半的差异来自一个保守的Asp -> Glu突变，这种突变发生在5万年前。进一步的分析表明，核苷酸多样性和变异位点的比例显着低于非同义位点的同义位点，内含子，或假基因。这些差异意味着自然选择在过去10万年的人类历史中有效地保留了Y染色体X-简并蛋白的氨基酸序列。因此，我们的发现与关于人类Y染色体即将消亡的著名说法不一致。
Y-linked single-nucleotide polymorphisms (SNPs) have served as powerful tools for reconstructing the worldwide genealogy of human Y chromosomes and for illuminating patrilineal relationships among modern human populations. However, there has been 110 systematic, worldwide survey of sequence variation within the protein-coding genes of the Y chromosome. Here we,report and analyze coding sequence variation among the 16 single-copy "X-degenerate" genes of the Y chromosome. We examined variation in these genes in 105 men representing worldwide diversity, resequencing in each man an average of 27 kb of coding DNA, 40 kb of intronic DNA and, for comparison, 15 kb of DNA in single-copy Y-chromosomal pseudogenes. There is remarkably little variation in X-degenerate protein sequences: two chromosomes drawn at random differ on average by a single amino acid, with half of these differences arising from a single, conservative Asp -> Glu mutation that occurred similar to 50,000 years ago. Further analysis showed that nucleotide diversity and the proportion of variant sites are significantly lower for nonsynonymous sites than for synonymous sites, introns, or pseudogenes. These differences imply that natural selection has operated effectively in preserving the amino acid sequences of the Y chromosome's X-degenerate proteins during the last similar to 100,000 years of human history. Thus our findings are at odds with prominent accounts of the human Y chromosome's imminent demise.