Molecular and functional evolution of IL-1 superfamily genes in cetacean species

Cetacea is a mammalian order that contains entirely aquatic species. The evolutionary transition of cetaceans from a terrestrial common ancestor to an aquatic environment exposed them to distinct microbial communities, likely requiring adaptations in barrier tissues and immune function. To investigate molecular changes associated with cetacean adaptation to the new habitat and differentiation between long-lived Mysticeti and shorter-lived Odontoceti, we examined the evolution of the IL-1 superfamily genes, a group of cytokines and receptors implicated in immune and inflammatory defensive functions. Multiple genes involved in immune response and signaling, including IL-1 superfamily genes, showed signatures of positive selection associated with the transition to marine environments and freshwater colonization. Although many of the IL-1 superfamily genes are conserved, our results show that the IL36A gene and IL-1α nuclear localizing sequence were lost in the Odontoceti common ancestor, while the anti-inflammatory IL1RN gene was positively selected and correlated with longevity. Together, these findings suggest that cetacean adaptation to aquatic environments was accompanied by changes that reshaped the functional landscape of IL-1 superfamily genes and support the concept that longevity is linked to optimal immunity coupled with efficient control of inflammation.