Diving deep: understanding the genetic components of hypoxia tolerance in marine mammals

Marine mammals have highly specialized physiology, exhibited in many species by extreme breath-holding capabilities that allow deep dives and extended submergence. Cardiovascular control and cell-level hypoxia tolerance are key features of this phenotype. Identifying genomic signatures tied to physiology will be valuable in understanding these natural model species, which may generate translational opportunities to human diseases arising from hypoxic stress or tissue injury. Genomic analyses have now been conducted in dolphins, river dolphins, minke whales, bowhead whales, and polar bears, with multispecies studies exploring evolutionary signals across marine mammal lineages, encompassing extinct and extant divers. Single-species genome studies for sirenians do not yet exist. Extant marine mammals arose in three lineages from separate aquatic recolonizations. Their physiological specializations, along with these independent origins create an interesting case to examine convergent evolution. Although molecular mechanisms of hypoxia tolerance are not universally apparent across marine mammal genomic studies, altered evolutionary rates have been identified for genes linked to oxygen binding and transport (e.g., MB, HBA, and HBB), blood pressure control (e.g., endothelin pathway genes), and cell protection in multiple species. Despite convergent phenotypes across clades, instances of identical molecular convergence have been uncommon. Given the inherent logistical and regulatory difficulties associated with functional genetic experiments in marine mammals, several avenues of further investigation are suggested to enable validation of candidate genes for hypoxia tolerance: leveraging phylogeny to better understand convergent phenotypes; ontogenic studies to identify regulation of key genes underlying the elite, adult, hypoxia-tolerant physiology; and cell culture manipulations to understand gene function.