Mitochondrial DNA genomes revealed different patterns of high-altitude adaptation in high-altitude Tajiks compared with Tibetans and Sherpas

Abstract

High-altitude Tajiks (HA-Tajiks), Tibetans and Sherpas are three groups of high-altitude native people in China. The differences in the mtDNA genome between the three populations and the role of the mtDNA genome in the high-altitude adaptation of HA-Tajiks were seldom investigated. In this study, 80 HA-Tajiks were enrolled, and their whole mtDNA genomes were sequenced. The haplogroup of each subject was determined by comparison to the revised Cambridge Reference Sequence (rCRS). Ten additional populations from East Asia and Central Asia, including Tibetans and Sherpas, were selected as references. The top haplogroup was U, followed by H, T and J. Principle component analysis and genetic distance analysis indicated that HA-Tajiks showed a close relationship with Wakhi Tajiks, pamiri tajiks and Sarikoli tajiks, indicating that they should be considered one nation scattered around the Pamirs. The difference in the mtDNA genome between HA-Tajiks and Sherpas was significantly greater than that between HA-Tajiks and Tibetans. Among the 13 genes related to the OXPHOS pathway encoded by the mtDNA genome, HA-Tajiks showed more significant differences in ND3 and CYTB compared to Tibetans. Compared to Sherpas, HA-Tajiks showed more significant differences in ND1, ND2, COX1, ATP8, ATP6, ND3, ND4L, ND4, ND5 and CYTB. The associated functional changes and underlying molecular mechanisms should be explored by molecular and biochemical investigations in further studies. When humans spread throughout the Earth, high-altitude environments presented a significant challenge to the people living within them. Low air pressure, hypoxia, strong solar radiation and low temperature exert great pressure on the survival of local people. Genetic factors in both the nuclear genome and mitochondrial DNA (mtDNA) genome play great roles in the adaptation to high-altitude environments, which was considered as natural impacts on human evolution and adaptation 1. In the past few years, an increasing number of genetic studies on the nuclear genome have shown that a series of genes have been involved in high-altitude adaptation in Tibetans 2-8 , Andeans 8,9 and Ethiopians 10,11 , and these genes are mainly distributed in the hypoxia-inducible factor signaling pathway and the TP53 pathway. However, the role of the mtDNA genome in high-altitude adaptation are still in discussion and should receive more attention. Mitochondria are known as the cell's power plant, where cellular fuel is oxidized to provide energy for metabolism. Mitochondrial function is dependent on mtDNA, and mtDNA is well established as a genetic marker. A high mutation rate, small genome size, maternal inheritance, and lack of recombination make mtDNA an important tool for studying genetic structure in different populations. Besides, analyses of mtDNA sequences provide clues for exploring the genetic relationships between different populations, which contributes to deep understanding the role of mtDNA variations in human evolution. In addition to 2 rRNAs and 22 tRNAs, mtDNA encodes 1...

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