东帕米尔人群线粒体基因组学研究

Eastern Pamir, locating at western Xinjiang on the Silk Road, is an important place for studying human demographic history including migration and admixture. The high altitude (above 4000 m, on average) of Eastern Pamir makes the indigenous populations as the candidates for investigating adaptation to high altitude. The mitogenomic analyses based on mitochondrial DNA (mtDNA) complete sequences can provide valuable insights into both issues above. It is because that, the selection due to hypoxia aroused by high altitude may shape the pattern of mutational variation in mitogenome. Due to its hereditary characters such as lack of recombination and high mutation rate, mitogenome is widely used in tracing human population history. In this project, we propose to analyze mitogenome sequences for 298 samples from three ethnic groups living in Tashkurgan of Eastern Pamir: Sarikoli Tajiks (n=122), Wakhi Tajiks (n=75), and Kyrgyz (n=101). It is planned to perform parallel tagged sequencing of all 298 mitogenomes on the next-generation sequencing platform (Hiseq 2000, Illumina). According to some recent references, a series of efforts will be made to improve the sequencing accuracy and efficiency. The phylogenetic, population genetic as well as other evolutionary analyses will be performed for the sequence data. It is expected that, the information from 298 mitogenomes can discern the maternal genetic structure for the three populations in Eastern Pamir. Incorporating published data from other populations in Xinjiang as well as Central Asia, the origins and demographic histories of Sarikoli Tajiks, Wakhi Tajiks, and Kyrgyz will be inferred. Certain characteristic mtDNA lineages representing genetic evidence for the ancient settlements in Eastern Pamir will be uncovered. Meanwhile, the extensive analyses are able to reveal the specific mtDNA lineages or mutations associated with adaptation to high altitude. And the likely mechanisms and potential impacts will be discussed. As a result, this project will not only provide an essential piece to the Central Asian genetic jigsaw puzzle, but also extend the understanding of human genetic adaptation to high altitude, at least from a mitogenomic perspective.

位于我国西部边陲的东帕米尔平均海拔超过4000米，是历史上丝绸之路的必经之地。开展东帕米尔人群的遗传学研究可以增进对新疆以及中亚地区人群遗传多样性和群体历史的认识，并能拓展关于人群高原适应机制的了解。线粒体基因组已被运用在追溯人群进化历史和探讨人群高原适应机制的众多工作中。本项目旨在运用线粒体基因组学方法对东帕米尔人群（包括色勒库尔塔吉克、瓦罕塔吉克和柯尔克孜族三个族群）开展研究。本项目拟采用基于二代测序平台的多样本混合测序技术测定298份样本的线粒体基因组序列。通过系统发育、群体遗传学等多种进化分析手段，全面解析东帕米尔人群的母系遗传结构。结合已发表的线粒体DNA数据，本项目将从母系遗传角度阐明东帕米尔人群与其他新疆以及中亚人群的遗传关系，进而追溯和重建人类移居东帕米尔的历史。本项目还将尝试探讨东帕米尔人群中与其高原适应性存在相关的线粒体DNA世系和变异，并讨论其中可能的作用机制。

本项目运用二代测序方法对帕米尔及其周围地区的7个中亚群体382份样本的线粒体DNA（mtDNA）基因组进行了测定。遗传多样度计算结果说明中亚人群与东亚人群、南亚人群和西亚人群具有相近的水平。单倍型类群（haplogroup）划分结果显示所有样本的mtDNA均可以划分到欧亚东部和欧亚西部分布的单倍型类群内；没有发现M、N和R 超单倍型类群（macrohaplogroup）基部的古老世系。这表明中亚人群主要是由欧亚大陆东西方人群混合形成的。帕米尔人群96.07% mtDNA世系的溯主年龄（coalescent age）在距今一万九千年以内，提示现代人移居帕米尔高原的历史可以追溯到末次盛冰期（the Last Glacial Maximum）后的史前迁移活动。主成分分析结果显示讲突厥语的高原柯尔克孜群体与欧亚东部人群遗传关系较近而讲印欧语的高原塔吉克族群体与欧亚西部人群遗传关系较近。基于贝叶斯计算（Bayesian Skyline Plots和Approximate Bayesian Computation）的结果揭示各个群体具有不同的群体历史。进一步对帕米尔高原和周边平原人群的mtDNA数据的比较分析未能在高原人群中检出选择压力变化。