mtDNA Lineage Expansions in Sherpa Population Suggest Adaptive Evolution in Tibetan Highlands
mtDNA Lineage Expansions in Sherpa Population Suggest Adaptive Evolution in Tibetan Highlands
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夏尔巴人的线粒体DNA谱系扩张表明西藏高原的适应性进化。
DOI：
10.1093/molbev/mst147
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发表时间：
2013-12-01
影响因子：
10.7
通讯作者：
Jin, Li
中科院分区：
文献类型：
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作者：
Kang, Longli;Zheng, Hong-Xiang;Jin, Li
夏尔巴人是生活在喜马拉雅山南麓数百年的一个民族。他们以非凡的登山者和向导而闻名，被认为是成功适应西藏高原低氧环境的典范。线粒体DNA（mtDNA）的变化可能是重要的高原适应的作用，在编码核心亚基的氧化磷酸化线粒体。在这项研究中，我们对76个不相关的夏尔巴人的mtDNA全基因组进行了测序。夏尔巴人mtDNA单倍型群组成与藏族群体接近。然而，我们在夏尔巴人中发现了三个谱系扩展，其中两个（C4a3b1和A4e3a）是夏尔巴人特有的。这两种传承的扩张，都可能在最近数百年内开始。特别是，9个个体携带相同的单倍型群C4a3b1。根据夏尔巴人的历史和贝叶斯天际线图，我们构建了各种人口统计模型，发现这是不太可能发生的谱系扩展在中性模型，特别是对C4a3b1。C4 a3 b1（G3745 A）和A4 e3 a（T4216 C）中包含的非同义突变都是ND 1突变体（分别为A147 T和Y304 H）。二级结构预测表明，G3745A在结构上接近其他致病突变体，而T4216C本身被报道为Leber遗传性视神经病变的主要突变。因此，我们认为这些突变对复合体I的功能有一定的影响，可能在夏尔巴人的高原适应中起重要作用。
Sherpa population is an ethnic group living in south mountainside of Himalayas for hundreds of years. They are famous as extraordinary mountaineers and guides, considered as a good example for successful adaptation to low oxygen environment in Tibetan highlands. Mitochondrial DNA (mtDNA) variations might be important in the highland adaption given its role in coding core subunits of oxidative phosphorylation in mitochondria. In this study, we sequenced the complete mtDNA genomes of 76 unrelated Sherpa individuals. Generally, Sherpa mtDNA haplogroup constitution was close to Tibetan populations. However, we found three lineage expansions in Sherpas, two of which (C4a3b1 and A4e3a) were Sherpa-specific. Both lineage expansions might begin within the past hundreds of years. Especially, nine individuals carry identical Haplogroup C4a3b1. According to the history of Sherpas and Bayesian skyline plot, we constructed various demographic models and found out that it is unlikely for these lineage expansions to occur in neutral models especially for C4a3b1. Nonsynonymous mutations harbored in C4a3b1 (G3745A) and A4e3a (T4216C) are both ND1 mutants (A147T and Y304H, respectively). Secondary structure predictions showed that G3745A were structurally closing to other pathogenic mutants, whereas T4216C itself was reported as the primary mutation for Leber's hereditary optic neuropathy. Thus, we propose that these mutations had certain effect on Complex I function and might be important in the high altitude adaptation for Sherpa people.