Revisiting the matrilineal lineages and hypoxic adaptation of highland Tibetans

Abstract

The mitochondrial DNA (mtDNA) plays a vital role in forensic, anthropological, biogeographical and genealogical studies. In the present study, we sequenced 59 mitochondrial genomes of Tibetan individuals settling in Muli Tibetan Autonomous County of Sichuan Province using the Precision ID mtDNA Whole Genome Panel and Ion S5 XL system. Meanwhile, 192 published complete mitogenomes from five Tibetan populations were included for further analysis. All 251 investigated Tibetan participants were assigned to 98 unique subclades pertained to the macrohaplogroups M and N, and 17 subhaplogroups were considered as major haplogroups of Tibetans since these subhaplogroups accounted for considerably high frequencies in randomly selected Tibetans. It was noteworthy that M9a1a1c1b1a was the predominant subhaplogroup in the Tibetans collectively. Furthermore, the nonsynonymous substitutions and synonymous substitutions ratios (N/S) of Tibetans, Tibetan highlanders (Monpas, Lhobas, Dengs and Sherpas), non-Tibetan highlanders and general populations were estimated to evaluate the potential selective constraints. The N/S ratio in the Tibetan groups (0.503) is higher than that in Tibetan highlanders (0.465), non-Tibetan highlanders (0.430) and general populations (0.415). The distributions of N/S ratio in 13 protein-coding genes revealed that significant differences were existed in COX2, ATP8 genes, which likely contributed to hypoxic adaptation.