Department of Biosciences and Biomedical Engineering, Indian Institute of Technology Indore, Khandwa Road, Simrol, Indore, 453552, India.
Department of Applied Mathematics and Centre of Bioinformatics, Lobachevsky State University of Nizhny Novgorod, Nizhny Novgorod, Russia.
Sci Rep. 2021 Jan 8;11(1):133. doi: 10.1038/s41598-020-80271-8.
Networks have been established as an extremely powerful framework to understand and predict the behavior of many large-scale complex systems. We studied network motifs, the basic structural elements of networks, to describe the possible role of co-occurrence of genomic variations behind high altitude adaptation in the Asian human population. Mitochondrial DNA (mtDNA) variations have been acclaimed as one of the key players in understanding the biological mechanisms behind adaptation to extreme conditions. To explore the cumulative effects of variations in the mitochondrial genome with the variation in the altitude, we investigated human mt-DNA sequences from the NCBI database at different altitudes under the co-occurrence motifs framework. Analysis of the co-occurrence motifs using similarity clustering revealed a clear distinction between lower and higher altitude regions. 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 'RSRS50' variant 10,398 was found to co-occur only at higher altitudes supporting the fact that a separate route of colonization at these altitudes might have taken place. Overall, our analysis revealed the presence of co-occurrence interactions specific to high altitude at a whole mitochondrial genome level. This study, combined with the classical haplogroups analysis is useful in understanding the role of co-occurrence of mitochondrial variations in high altitude adaptation.
网络已被确立为理解和预测许多大规模复杂系统行为的极其强大的框架。我们研究了网络基元，即网络的基本结构元素，以描述基因组变异共同发生在亚洲人群高海拔适应背后的可能作用。线粒体 DNA（mtDNA）变异被认为是理解适应极端条件的生物学机制的关键因素之一。为了探索线粒体基因组变异与海拔变化的累积效应，我们在共同发生基元框架下，研究了 NCBI 数据库中不同海拔高度的人类 mt-DNA 序列。使用相似性聚类对共同发生基元的分析显示，低海拔和高海拔区域之间存在明显区别。此外，先前已知的高海拔标记 3394 和 7697（是单倍群 M9a1a1c1b 的明确位点）被发现共同出现在它们自己的基因复合物中，表明核苷酸共同进化受到基因内约束的影响。此外，发现一个祖先的“RSRS50”变体 10,398 仅在高海拔处共同出现，支持了在这些海拔高度可能发生了单独的殖民化途径的事实。总的来说，我们的分析揭示了整个线粒体基因组水平上高海拔特有的共同发生相互作用的存在。这项研究结合经典的单倍群分析，有助于理解线粒体变异共同发生在高海拔适应中的作用。
