基于线粒体ATP6及Cytb基因多态性研究藏山羊高原适应性

为了探究藏山羊ATP6和Cytb是否具有潜在的高海拔适应性突变，本研究利用藏山羊（n=157，来自西藏地区的8个群体，海拔高度>3 500 m）与低海拔山羊（n=104，来自欧亚大陆50个群体，海拔高度<1 000 m）两组261条ATP6和Cytb序列，对核苷酸组成、遗传多样性、单倍型网络以及基因突变对蛋白结构域功能影响进行比较分析。结果，在ATP6和Cytb中分别鉴定出33和67个单核苷酸多态性位点（SNPs），其中错义突变均为6个。值得注意的是，ATP6 m.8102A>G（Ile→Met；P=0.000 6）和Cytb m.14794A>G（Thr→Ala；P=0.007 7）是低海拔山羊群体特有的错义突变，由此形成的单倍体H27和Ha36与高原适应性呈显著负相关（H27，P=0.007 0；Ha36，P=0.012 3）。进一步分析推测，这两个突变阻碍了质子跨膜的正常功能，并影响了质子或电子在OXPHOS中的转移，从而导致了低海拔山羊和藏山羊之间呼吸作用效率的差异。本研究通过对线粒体ATP6和Cytb基因编码区多态性到功能的相关分析，初步推测了藏山羊高海拔低氧适应性机制，为高原适应性相关研究提供了一定的见解。

High Altitude Adaptation of Tibetan Goats Based on Polymorphisms of Mitochondrial ATP6 and Cytb Genes

This study was conducted to investigate whether Tibetan goat ATP6(ATP synthase F0 subunit 6) and Cytb(cytochrome b) genes had potential adaptive mutations in high altitude environments. In this study, by comparing 261 ATP6 and Cytb sequences of Tibetan goats (n=157, from 8 populations across Tibetan plateau with altitude>3 500 m) and low-altitude goats (n=104, from 50 populations across Eurasia with altitude<1 000 m), the nucleotide composition, genetic diversity, haplotype network map, and the effect of gene mutations on protein domain function were compared and analyzed. Thirty-three and 67 single nucleotide polymorphisms (SNPs) sites were identified in ATP6 and Cytb, respectively, in which, both genes contained 6 missense mutations. ATP6 m.8102A>G (Ile → Met; P=0.000 6) and Cytb m.14794A>G (Thr → Ala; P=0.007 7) were unique missense mutations in low-altitude goat populations, which formed haplotypes H27 and Ha36 that were significantly negatively related to high altitude adaptation (H27, P=0.007 0; Ha36, P=0.012 3). Further analysis speculated that the two mutations hindered the normal function of the proton transmembrane and affected the transfer of protons or electrons in OXPHOS(oxidative phosphorylation), which led to the difference in respiration efficiency between low-altitude goats and Tibetan goats. Based on the correlation analysis of polymorphism to function of mitochondrial ATP6 and Cytb coding regions, the high-altitude adaption mechanism of Tibetan goats was preliminarily explored, which provided certain insights for related research on altitude adaptability.