title: mtDNA lineage expansions in Sherpa population suggest adaptive evolution in Tibetan highlands.
abstract: 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.
authors.affiliation: Key Laboratory of High Altitude Environment and Gene Related to Disease of Tibet Ministry of Education, Tibet University for Nationalities, Xianyang, Shaanxi, China.
authors.forename: Longli
authors.initials: L
authors.lastname: Kang
authors.forename: Hong-Xiang
authors.initials: HX
authors.lastname: Zheng
authors.forename: Feng
authors.initials: F
authors.lastname: Chen
authors.forename: Shi
authors.initials: S
authors.lastname: Yan
authors.forename: Kai
authors.initials: K
authors.lastname: Liu
authors.forename: Zhendong
authors.initials: Z
authors.lastname: Qin
authors.forename: Lijun
authors.initials: L
authors.lastname: Liu
authors.forename: Zhipeng
authors.initials: Z
authors.lastname: Zhao
authors.forename: Lei
authors.initials: L
authors.lastname: Li
authors.forename: Xiaofeng
authors.initials: X
authors.lastname: Wang
authors.forename: Yungang
authors.initials: Y
authors.lastname: He
authors.forename: Li
authors.initials: L
authors.lastname: Jin
mesh_terms: D000222:Adaptation, Physiological; D000531:Altitude; D001499:Bayes Theorem; D004272:DNA, Mitochondrial / Q000235:genetics* / Q000378:metabolism; D005006:Ethnicity / Q000235:genetics*; D019143:Evolution, Molecular; D014644:Genetic Variation; D005828:Genetics, Population; D054629:Genome, Mitochondrial; D006239:Haplotypes; D006801:Humans; D008928:Mitochondria / Q000235:genetics* / Q000378:metabolism; D009154:Mutation; D009245:NADH Dehydrogenase / Q000235:genetics*; D029242:Optic Atrophy, Hereditary, Leber / Q000235:genetics; D010085:Oxidative Phosphorylation; D010802:Phylogeny; D018609:Tibet
chemical_list: D004272:DNA, Mitochondrial; D009245:NADH Dehydrogenase; C515075:NADH dehydrogenase subunit 1, human
keywords: adaptive evolution; hypoxia adaption; mitochondrial DNA