Howard Hughes Medical Institute, Whitehead Institute, and Department of Biology, Massachusetts Institute of Technology, 9 Cambridge Center, Cambridge, MA 02142, USA.
Am J Hum Genet. 2009 Dec;85(6):923-8. doi: 10.1016/j.ajhg.2009.11.011.
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 no 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 approximately 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 approximately 100,000 years of human history. Thus our findings are at odds with prominent accounts of the human Y chromosome's imminent demise.
Y 连锁单核苷酸多态性（SNP）已成为重建人类 Y 染色体全球谱系以及阐明现代人类群体中父系关系的有力工具。然而，目前还没有对 Y 染色体蛋白编码基因内的序列变异进行系统的、全球性的调查。在这里，我们报告并分析了 Y 染色体上 16 个“X 退化”单拷贝基因中的编码序列变异。我们在来自世界各地的 105 名男性中检查了这些基因的变异情况，对每个人平均重新测序了 27kb 的编码 DNA、40kb 的内含子 DNA，以及为了进行比较而重新测序了 15kb 的 Y 染色体单拷贝假基因中的 DNA。X 退化蛋白序列的变异非常少：随机抽取的两条染色体平均只有一个氨基酸的差异，其中一半的差异来自于大约 5 万年前发生的单一保守的 Asp-->Glu 突变。进一步的分析表明，与同义位点、内含子或假基因相比，非同义位点的核苷酸多样性和变异位点的比例明显较低。这些差异意味着，在过去大约 10 万年的人类历史中，自然选择有效地作用于保护 Y 染色体 X 退化蛋白的氨基酸序列。因此，我们的发现与人类 Y 染色体即将灭绝的主要说法不一致。
