Cross-Species Insights Into Genomic Adaptations to Hypoxia

Abstract

Over millions of years, vertebrate species populated vast environments spanning the globe. Among the most challenging habitats encountered were those with limited availability of oxygen, yet many animal and human populations inhabit and perform life cycle functions and/or daily activities in varying degrees of hypoxia today. Of particular interest are species that inhabit high-altitude niches, which experience chronic hypobaric hypoxia throughout their lives. Physiological and molecular aspects of adaptation to hypoxia have long been the focus of high-altitude populations and, within the past decade, genomic information has become increasingly accessible. These data provide an opportunity to search for common genetic signatures of selection across uniquely informative populations and thereby augment our understanding of the mechanisms underlying adaptations to hypoxia. In this review, we synthesize the available genomic findings across hypoxia-tolerant species to provide a comprehensive view of putatively hypoxia-adaptive genes and pathways. In many cases, adaptive signatures across species converge on the same genetic pathways or on genes themselves [i.e., the hypoxia inducible factor (HIF) pathway). However, specific variants thought to underlie function are distinct between species and populations, and, in most cases, the precise functional role of these genomic differences remains unknown. Efforts to standardize these findings and explore relationships between genotype and phenotype will provide important clues into the evolutionary and mechanistic bases of physiological adaptations to environmental hypoxia.

Intrauterine Hypoxia and Epigenetic Programming in Lung Development and Disease

“…Recent studies in certain animal models, including intrauterine hypoxia, unveiled significant changes in gene expression patterns in the placenta and fetal organs/tissues (such as the heart, brain, cerebral artery, liver, pulmonary artery, and lung). It has been demonstrated that both HIF-1α and hypoxia-derived reactive oxygen species (ROS) can significantly mediate hypoxia-induced epigenetic programming and developmental disorders [6,[118][119][120][121][122]. Although hypoxia-modulated epigenetics have been investigated in the placenta, fetal brain, and fetal heart, it remains unclear in the fetal lung.…”

Lifespan Extension in Long-Lived Vertebrates Rooted in Ecological Adaptation

“…Organisms that live in an environment with limited oxygen (hypoxic conditions), for instance, face persistent challenges of hypoxia and must develop physiological features that would aid in their survival in such a challenging environment. Evolutionary adaptations have largely converged across these species to address oxygen demand either by optimizing oxygen uptake or reducing oxygen requirement for metabolism ( Pamenter et al, 2020 ). Hypoxia-driven adaptation involves selection acting on pathways such as central metabolism, cellular respiration, hemoglobin-mediated oxygen transport, and hypoxia-inducible factor pathways ( Simonson, 2015 ; Ding et al, 2018 ), whereas other adaptive mechanisms in these species could be attributed to species physiology, ecological differences, lifestyle, and adaptive fitness ( Pamenter et al, 2020 ).…”

Phylogeny and evolution ofLasiopodomysin subfamily Arvivolinae based on mitochondrial genomics

“…Environmental stress caused a major driving on evolutionary process ( Parsons, 2005 ). In the species of rodents, limited oxygen availability resulted in evolutionary adaptation and appearance of various strategies ( Pamenter et al, 2020 ), such as different colonial habitats of life—subterranean ( L. mandarinus ) and plateau ( L. fuscus ); these strategies formed unique physiological and molecular adaptations to hypoxia ( Jiang et al, 2020 ; Dong, Wang & Jiang, 2020 ). Our study supports a history of rapid population expansion under positive selection via mitogenome sequences such as the ATP6 gene, which uses oxygen to create adenosine triphosphate.…”