Analysis of human mitochondrial genome co-occurrence networks of Asian population at varying altitudes

Finding mechanisms behind high altitude adaptation in humans at the Tibetan plateau has been a subject of evolutionary research. Mitochondrial DNA (mt-DNA) variations have been established as one of the key players in understanding the biological mechanisms at the basis of adaptation to these extreme conditions. To explore cumulative effects and dynamics of the variations in mitochondrial genome at varying altitudes, we investigated human mt-DNA sequences from NCBI database at different altitudes by employing co-occurrence motifs framework. We constructed co-occurrence motifs by taking into account variable sites for each altitude group. Analysis of the co-occurrence motifs using similarity clustering revealed a clear distinction between a lower and a higher altitude region. In addition, the previously known high altitude markers 3394 and 7697 (which are definitive sites of haplogroup M9a1a1c1b) were found to co-occur within their own gene complexes indicating the impact of intra-genic constraint on co-evolution of nucleotides. Furthermore, an ancestral marker 10398 was found to co-occur only at higher altitudes supporting the fact that a separate root of colonization at these altitudes might have taken place. Overall, our analysis revealed the presence of co-occurrence motifs at a whole mitochondrial genome level. This study, combined with the classical haplogroups analysis is useful in understanding role of co-occurrence of mitochondrial variations in high altitude adaptation.