Genetic diversity of ATP8 and ATP6 genes is associated with high-altitude adaptation in yak.

ATP synthase 8 (ATP8) and ATPase synthase 6 (ATP6) play an important role in mitochondrial ATPase assembly. Mutations in either of these units could affect the ATP processing and the respiration chain in mitochondria. To find out if there were differences in gene diversity between Tibetan yaks and domestic cattle, we sequenced the ATP8 and ATP6 genes in 66 Tibetan yaks and 81 domestic cattle. We identified 20 SNPs in the ATP8 gene and 60 SNPs in the ATP6 gene. Ten SNPs detected in ATP8 were probably positively associated with high-altitude adaptation, of which SNPs m.8164 G > A, m.8210 G > A, m.8231 C > T and m. 8249 C > T resulted in amino acid changes. Similarly, SNPs m.8308A > G, m.8370A > C, m.8514G > A of ATP6 also appeared to be associated with high-altitude adaptability. Specifically, m.8308 A > G, located in the overlap region, might bring in a conserved region found in cytochrome b561 which play an important role in iron regulation, thus it might help the Tibetan yaks with this mutation to utilize rare oxygen efficiently. Considering all mutations, three of eight haplotypes identified in gene ATP8 were present only in Tibetan yaks, and six (H3 to H8) out of 21 haplotypes (H1 to H21) in gene ATP6 were restricted to Tibetan yaks. Haplotypes present only in Tibetan yaks could be positively associated with high-altitude adaptation.