Adaptive Evolution of Energy Metabolism-Related Genes in Hypoxia-Tolerant Mammals

Abstract

Animals that are able to sustain life under hypoxic conditions have long captured the imagination of biologists and medical practitioners alike. Although the associated morphological modifications have been extensively described, the mechanisms underlying the evolution of hypoxia tolerance are not well understood. To provide such insights, we investigated genes in four major energy metabolism pathways, and provide evidence of distinct evolutionary paths to mammalian hypoxia-tolerance. Positive selection of genes in the oxidative phosphorylation pathway mainly occurred in terrestrial hypoxia-tolerant species; possible adaptations to chronically hypoxic environments. The strongest candidate for positive selection along cetacean lineages was the citrate cycle signaling pathway, suggestive of enhanced aerobic metabolism during and after a dive. Six genes with cetacean-specific amino acid changes are rate-limiting enzymes involved in the gluconeogenesis pathway, which would be expected to enhance the lactate removal after diving. Intriguingly, 38 parallel amino acid substitutions in 29 genes were observed between hypoxia-tolerant mammals. Of these, 76.3% were radical amino acid changes, suggesting that convergent molecular evolution drives the adaptation to hypoxic stress and similar phenotypic changes. This study provides further insights into life under low oxygen conditions and the evolutionary trajectories of hypoxia-tolerant species.

Natural Tolerance to Ischemia and Hypoxemia in Diving Mammals: A Review

“…In the case of myoglobin, an augmented net surface charge observed across all diving mammals might allow for high, functional muscle myoglobin concentrations, thereby increasing body oxygen stores (Mirceta et al, 2013). Several metabolic gene families are also under positive selection in cetaceans, including TCA cycle enzymes citrate synthase and pyruvate carboxylase (Tian et al, 2017). Cetacean-specific amino acid changes in and expansion of lactate dehydrogenase and monocarboxylate transporter 1 genes suggest an increased ability to metabolize lactate after dives exceeding aerobic limits (Yim et al, 2014; Tian et al, 2017).…”

The Role of RNA Editing in Cancer Development and Metabolic Disorders

“…APOBEC1-mediated editing of apoB, thus the production of apoB48, only occurs in mammals (82). Evolutionarily-aligned genetic alterations are thought to have important metabolic consequences (83). Such speculation is prevalent when debating the origins of human metabolic diseases, hence the proposal of the thrifty gene hypothesis (84).…”

Genomic divergence reveals unique populations among Indian Yaks

“…SNPs in the coding region were further grouped into missense, nonsense and silent SNPs. For gene wise annotation, the candidate genes for high altitude adaptation 11,12,32,33 were collected. The genomic location of the candidate genes were drawn from the NCBI database and the SNPs present in that region were captured from the annotated VCF file using VCFtools 34 .…”