Evolution of ion channels in the water-to-land transition of vertebrates

Abstract

The transition of vertebrates from aquatic to terrestrial environments represents one of the most profound evolutionary events in their history, involving extensive physiological and morphological innovations. Key adaptations included the transformation of fins into limbs with digits to enable efficient terrestrial locomotion, the ability to perceive novel environmental stimuli, and the emergence of reproductive strategies suited to life on land, processes in which ion channels played fundamental roles. Accordingly, understanding the genetic basis of vertebrate terrestrialization requires investigating the evolution of this group of membrane proteins. Our analyses reveal that the proportion of ion channel genes is highly conserved, representing approximately 1.4% to 1.6% of total protein-coding genes in most lineages, with a notable increase to [~]1.9% in teleost fishes. Our natural selection analyses revealed an overrepresentation of specific ion channel gene families, including TRP, RyR, HTR3, and HCN. We identified 29 ion channel genes showing signatures of positive selection, many of which are associated with key physiological functions such as nociception and thermosensation. We also detected an elevated rate of gene turnover in the common ancestor of terrestrial vertebrates, indicative of substantial genomic remodeling through gene gain and loss. Together, these findings suggest that, despite overall conservation in the proportions of ion channel genes, specific gene families underwent changes that were likely critical to meeting the physiological demands of terrestrial life. These results provide a foundation for future comparative and functional studies aimed at elucidating the molecular mechanisms underlying major environmental transitions. SignificanceThe transition from water to land was one of the most important events in vertebrate evolution, requiring animals to detect new environmental cues, sense temperature, coordinate movement, and cope with unfamiliar pathogens and physical stresses. Because ion channels control many of these physiological processes, they provide an ideal system for investigating the molecular basis of vertebrate terrestrialization. By tracing their evolutionary history across vertebrates, we show that many ion channels underlying these functions underwent adaptive evolution during the transition from water to land. Our findings suggest that adaptive changes in ion channels helped vertebrates acquire the physiological capabilities needed to survive and diversify on land, providing new insight into the molecular basis of one of the greatest phenotypic transformations in vertebrate evolution.