Differences in mtDNA whole sequence between Tibetan and Han populations suggesting adaptive selection to high altitude

We performed a mitochondrial whole-genome comparison study in 40 Tibetan and 50 Han Chinese. All subjects could be classified into 13 haplogroups pertained to the Macrohaplogroup M and N that pitched different quadrants by principal component analysis. We observed a difference in the M9 haplogroup and identified 18 significant variants by comparing whole sequences between Tibetan and Han populations. Variants in ND2, COX2, tRNA alanine and 12S rRNA were predicted to confer increased protein stability in Tibetans. We compared the base substitutions of nonsynonymous (NS) versus synonymous (S) of 13 protein-encoding genes and found the NS/S values of the ATP6, ATP8, and Cyt b genes were larger (> 1) in Tibetans than that in Han population. Our findings provide clues for the existence of adaptive selection for the ATP6, ATP8, Cyt b, ND2, COX2, tRNA alanine and 12S rRNA genes in Tibetans which likely contributed to adaptation to their specific geographic environment, such as high altitude.