Polymorphic NumtS trace human population relationships
Polymorphic NumtS trace human population relationships
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DOI：
10.1007/s00439-011-1125-3
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发表时间：
2012-05-01
期刊：
影响因子：
5.3
通讯作者：
Gasparre, Giuseppe
中科院分区：
文献类型：
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作者：
Lang, Martin;Sazzini, Marco;Gasparre, Giuseppe
人类基因组不断受到进化力量的影响，这些力量塑造了它的结构。线粒体DNA序列插入核基因组（NumtS）已经在几个真核物种中描述，包括智人和其他灵长类动物。NumtS的生成过程正在进行，这使它们成为灵长类系统发育研究中有价值的标记，也是重建现代人类遗传史的潜在信息位点。在这里，我们报告了通过UCSC基因组浏览器的检查鉴定出的53个人类特异性NumtS，表明它们可能是人类-黑猩猩分裂后线粒体DNA直接插入到人类核DNA中。计算机模拟分析使我们能够鉴定14个NumtS，这些NumtS在不同祖先的个体中在人类基因组内的存在/不存在方面是多态的。这些多态性NumtS的等位基因频率计算1000基因组计划的序列数据，从全球13个人口，和主成分分析和层次聚类方法允许检测强信号的地理结构相关的这些位点的遗传多样性。所有鉴定的多态性人类特异性NumtS以及串联重复的NumtS也已通过PCR扩增在属于全球五个本地人群的60个样品的面板上进行验证，证实了预期的NumtS变异性。在此基础上，我们成功地描绘了一系列NumtS在几个民族中的变异景观，使其在人类群体遗传学研究中作为有用标记的鉴定取得了进展。
The human genome is constantly subjected to evolutionary forces which shape its architecture. Insertions of mitochondrial DNA sequences into nuclear genome (NumtS) have been described in several eukaryotic species, including Homo sapiens and other primates. The ongoing process of the generation of NumtS has made them valuable markers in primate phylogenetic studies, as well as potentially informative loci for reconstructing the genetic history of modern humans. Here, we report the identification of 53 human-specific NumtS by inspection of the UCSC genome browser, showing that they may be direct insertions of mitochondrial DNA into the human nuclear DNA after the human-chimpanzee split. In silico analyses allowed us to identify 14 NumtS which are polymorphic in terms of their presence/absence within the human genome in individuals of different ancestry. The allele frequencies of these polymorphic NumtS were calculated for 1000 Genomes Project sequence data from 13 populations worldwide, and principal components analysis and hierarchical clustering methods allowed the detection of strong signals of geographical structure related to the genetic diversity of these loci. All identified polymorphic human-specific NumtS together with a tandemly duplicated NumtS have also been validated by PCR amplification on a panel of 60 samples belonging to five native populations worldwide, confirming the expected NumtS variability. On the basis of these findings, we have succeeded in depicting the landscape of variation of a series of NumtS in several ethnic groups, making an advance in their identification as useful markers in the study on human population genetics.