Takezaki Naoko, Nei Masatoshi
Life Science Research Center, Kagawa University, Japan.
Mol Biol Evol. 2009 Aug;26(8):1835-40. doi: 10.1093/molbev/msp091. Epub 2009 Apr 30.
In recent years, copy number variation (CNV) of DNA segments has become a hot topic in the study of genetic variation, and a large amount of CNVs has been uncovered in human populations. The CNVs involving the smallest units of DNA segments are microsatellite DNAs, and the evolutionary change of microsatellite DNAs is believed to occur mostly by the increase or decrease of one repeat unit at a time in a more or less neutral fashion. If we note that eukaryotic genomes contain millions of microsatellite loci, this pattern of nucleotide change is expected to generate random changes of genome size, that is, genomic drift, and will provide a neutral model of CNV evolution. We therefore investigated the amount of variation of the total number of repeats (TNR) per individual concerned with 145 microsatellite loci in three human populations, Africans, Europeans, and Asians. It was shown that the TNR follows the normal distribution in all three populations and that the extent of variation of TNR is more than 50% greater in Africans than in Europeans and Asians as expected from the hypothesis of African origin of modern humans. If we consider all microsatellite loci in the human genome and compute the variation of the total number of nucleotides involved (TNN), it is possible to study the contribution of microsatellite loci to the genome size variation. This study has shown that the genome sizes of human individuals are affected considerably by genomic drift of microsatellite DNA alone. This pattern of evolution is similar to that of olfactory receptor (OR) genes previously studied in human populations and support the idea that the number of OR genes has evolved in a more or less neutral fashion. However, this conclusion does not necessarily apply to the genomewide CNVs of various DNA segments, and it appears that long variant DNA fragments are deleterious and under purifying selection.
近年来，DNA片段的拷贝数变异（CNV）已成为遗传变异研究中的一个热点话题，并且在人类群体中发现了大量的CNV。涉及最小DNA片段单位的CNV是微卫星DNA，人们认为微卫星DNA的进化变化大多是以或多或少中性的方式一次增加或减少一个重复单位而发生的。如果我们注意到真核生物基因组包含数百万个微卫星位点，那么这种核苷酸变化模式预计会产生基因组大小的随机变化，即基因组漂变，并将提供一种CNV进化的中性模型。因此，我们研究了非洲人、欧洲人和亚洲人这三个人类群体中与145个微卫星位点相关的每个个体的重复总数（TNR）的变异量。结果表明，TNR在所有三个人类群体中均呈正态分布，并且正如现代人类起源于非洲这一假说所预期的那样，非洲人群中TNR的变异程度比欧洲人和亚洲人高出50%以上。如果我们考虑人类基因组中的所有微卫星位点并计算所涉及的核苷酸总数（TNN）的变异，就有可能研究微卫星位点对基因组大小变异的贡献。这项研究表明，人类个体的基因组大小仅受微卫星DNA的基因组漂变的显著影响。这种进化模式与先前在人类群体中研究的嗅觉受体（OR）基因的模式相似，并支持OR基因数量是以或多或少中性的方式进化的观点。然而，这一结论不一定适用于各种DNA片段的全基因组CNV，并且似乎长的变异DNA片段是有害的且处于纯化选择之下。
