Evolution of ion channels in cetaceans: A natural experiment in the Tree of life

Cetaceans could be seen as a natural experiment within the tree of life in which a mammalian lineage changed from terrestrial to aquatic habitats. This shift involved extensive phenotypic modifications, which represent an opportunity to explore the genetic bases of phenotypic diversity. Furthermore, the availability of whole genome sequences in representative species of all main cetacean groups means that we are in a golden age for such studies. Among the different molecular systems that maintain cellular homeostasis, ion channels are crucial for the proper physiological functioning of all living species. This study aims to explore the evolution of ion channels during the evolutionary history of cetaceans. To do so, we created a bioinformatic pipeline to annotate the repertoire of ion channels in the genome of the species included in our sampling. Our main results show that cetaceans have on average, fewer protein-coding genes and a higher percentage of annotated ion channels than non-cetacean mammals. Signals of positive selection were detected in ion channels related to the heart, locomotion, visual and neurological phenotypes. Interestingly, we predict that the NaV1.5 ion channel of most toothed whales (odontocetes) is sensitive to tetrodotoxin (TTX), similar to NaV1.7, given the presence of tyrosine instead of cysteine, in a specific position of the ion channel. Finally, the gene turnover rate of the cetacean crown group is more than three times faster than non-cetacean mammals. ### Competing Interest Statement The authors have declared no competing interest.