Cross-Species Insights Into Genomic Adaptations to Hypoxia

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.