Comparative Genomics Uncovers Molecular Adaptations for Cetacean Deep-Sea Diving

Cetaceans show remarkable diversity in diving capability, implying a range of adaptive strategies to hazards such as hydrostatic pressure and oxidative stress, but few studies have considered the evolution of extreme diving. Here, we first examined the relationship between morphological and physiological factors and diving capability and then considered the molecular evolution of candidate deep-sea diving traits in a genomic dataset of cetaceans. Our dataset included six super-divers, sperm whales (families Physeteridae and Kogiidae) and beaked whales (Ziphiidae), species that can dive deeper than 1000 m for about an hour or longer. We found a positive association between diving capability and oxygen-linked globins, and super-diver myoglobin (MB) is under positive selection and harbours a reported functional amino acid change. Blubber thickness was positively associated, likely to provide thermal insulation and hydrostatic pressure resistance. Super-divers have gene changes that may contribute to differences in the composition of outer blubber neutral lipids (triacylglycerols and wax esters), fatty acids and cholesterol. Total lung capacity relative to body mass showed a negative association, ostensibly to limit gas bubbles that can cause decompression sickness. A functional assay suggests that an ATP8B1 amino acid substitution may reduce lung injury in super-divers. Super-diver XDH has two unique amino acids and a decreased ability to produce uric acid under hypoxia when its ROS-generating XO isoform is prevalent, suggesting that it reduces cell damage from oxidative stress and uric acid accumulation in species with prolonged dives. Our study deepens the understanding of how deep-sea diving emerged in the cetacean lineage.