Molecular divergence of TRPA1 in cetaceans supports lineage-specific adaptation to aquatic life

Gene loss represents a powerful driver of adaptive evolution. Cetaceans, which underwent a profound transition from terrestrial to fully aquatic life, provide an excellent model for investigating this process. Comparative genomic analysis of the cold-sensitive ion channel transient receptor potential ankyrin 1 (TRPA1) revealed lineage-specific patterns of degeneration across cetaceans. In toothed whales, the ancestral lineage exhibited extensive exon loss within the TRPA1 locus, whereas baleen whales showed signatures consistent with markedly reduced or absent TRPA1 expression. These molecular alterations were inferred to disrupt or abolish TRPA1 protein function across cetaceans. Integration of these findings with established experimental evidence from human and murine TRPA1 studies supported several adaptive hypotheses for TRPA1 gene loss, including tolerance to abrupt thermal fluctuations, attenuation of nociceptive responses in aquatic environments, specialization of integumentary sensory systems, and the emergence of echolocation-associated sensory trade-offs in toothed whales. Collectively, these findings expand the gene loss repertoire of cetaceans and provide novel insights into the molecular underpinnings of secondary aquatic adaptation in mammals.