Role of mitochondrial genetic interactions in determining adaptation to high altitude human population

Rahul K Verma,Alena Kalyakulina,Ankit Mishra,Mikhail Ivanchenko,Sarika Jalan

doi:10.1038/s41598-022-05719-5

Abstract

Physiological and haplogroup studies performed to understand high-altitude adaptation in humans are limited to individual genes and polymorphic sites. Due to stochastic evolutionary forces, the frequency of a polymorphism is affected by changes in the frequency of a near-by polymorphism on the same DNA sample making them connected in terms of evolution. Here, first, we provide a method to model these mitochondrial polymorphisms as “co-mutation networks” for three high-altitude populations, Tibetan, Ethiopian and Andean. Then, by transforming these co-mutation networks into weighted and undirected gene–gene interaction (GGI) networks, we were able to identify functionally enriched genetic interactions of CYB and CO3 genes in Tibetan and Andean populations, while NADH dehydrogenase genes in the Ethiopian population playing a significant role in high altitude adaptation. These co-mutation based genetic networks provide insights into the role of different set of genes in high-altitude adaptation in human sub-populations.

Highlights

Physiological and haplogroup studies performed to understand high-altitude adaptation in humans are limited to individual genes and polymorphic sites
Among Ethiopian highlanders, the positive genetic signatures are known for aryl-hydrocarbon receptor nuclear translocator 2 (ARNT2), basic HLH family member e41 (BHLHE41), vav 3 guanine nucleotide exchange factor (VAV3), mitochondrial calcium uptake 1 (MICU), and thyroid hormone receptor (THRB) genes[18]
Tibetan individuals showed the lowest oxygen saturation, followed by Andeans, and Ethiopians showed oxygen saturation values equivalent to sea level. These findings suggested that Andeans are less stressed by hypoxia than Tibetans, and Ethiopians can provide enough oxygen to their tissues even in a hypoxic environment

Summary

Introduction

Physiological and haplogroup studies performed to understand high-altitude adaptation in humans are limited to individual genes and polymorphic sites. The association and mutual role of polymorphisms in other regions of mtDNA as a complex system subject to investigation in establishing a conclusive role These three high-altitude populations can be viewed as an outcome of independent replications of a natural experiment of convergent evolution. Among Ethiopian highlanders, the positive genetic signatures are known for aryl-hydrocarbon receptor nuclear translocator 2 (ARNT2), basic HLH family member e41 (BHLHE41), vav 3 guanine nucleotide exchange factor (VAV3), mitochondrial calcium uptake 1 (MICU), and thyroid hormone receptor (THRB) genes[18] Among these three high-altitude populations, Andean and Tibetans represented similar set of genes for positive selection with specific attention to PHD2 gene than the Ethiopian p opulation[18]

Methods

Results

Conclusion