Impact of modular mitochondrial epistatic interactions on the evolution of human subpopulations

• Published in: Mitochondrion Vol. 58; pp. 111 - 122
• Main Authors: Shinde, Pramod, Whitwell, Harry J., Verma, Rahul Kumar, Ivanchenko, Mikhail, Zaikin, Alexey, Jalan, Sarika
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier B.V 01.05.2021
• Subjects: Co-mutation network; Epistasis; Epistasis, Genetic; Evolution, Molecular; Genes, Mitochondrial; Genome evolution; Hierarchical modularity; Human mitochondria; Humans; Mutation; Population Groups - genetics; Human mitochondria; Epistasis; Hierarchical modularity; Genome evolution; Co-mutation network
• ISSN: 1567-7249; 1872-8278
• DOI: 10.1016/j.mito.2021.02.004

Investigation of human mitochondrial (mt) genome variation has been shown to provide insights to the human history and natural selection. By analyzing 24,167 human mt-genome samples, collected for five continents, we have developed a co-mutation network model to investigate characteristic human evolutionary patterns. The analysis highlighted richer co-mutating regions of the mt-genome, suggesting the presence of epistasis. Specifically, a large portion of COX genes was found to co-mutate in Asian and American populations, whereas, in African, European, and Oceanic populations, there was greater co-mutation bias in hypervariable regions. Interestingly, this study demonstrated hierarchical modularity as a crucial agent for these co-mutation networks. More profoundly, our ancestry-based co-mutation module analyses showed that mutations cluster preferentially in known mitochondrial haplogroups. Contemporary human mt-genome nucleotides most closely resembled the ancestral state, and very few of them were found to be ancestral-variants. Overall, these results demonstrated that subpopulation-based biases may favor mitochondrial gene specific epistasis.