Molecular evolution of wound healing‐related genes during cetacean secondary aquatic adaptation

Abstract The marine environment presents challenges for wound healing in cetaceans, despite their remarkable recovery abilities with minimal infections or complications. However, the molecular mechanism underlying this efficient wound healing remains underexplored. To better understand the molecular mechanisms behind wound healing in cetaceans, we investigated the evolutionary patterns of 37 wound healing‐related genes in representative mammals. We found wound healing‐related genes experience adaptive evolution in cetaceans: (1) Three extrinsic coagulation pathway‐related genes—tissue factor ( F3 ), coagulation factor VII ( F7 ), and coagulation factor X ( F10 )—are subject to positive selection in cetaceans, which might promote efficient hemostasis after injury; positive selection in transforming growth factor‐beta 2 ( TGF‐β2) , transforming growth factor‐beta 3 ( TGF‐β3 ), and platelet‐derived growth factor D ( PDGFD ), which play immunological roles in wound healing, may help cetaceans enhance inflammatory response and tissue debridement. (2) Coagulation factor XII ( F12 ) is the initiation factor in the intrinsic coagulation pathway. It had a premature stop codon mutation and was subjected to selective stress relaxation in cetaceans, suggesting that the early termination of F12 may help cetaceans avoid the risk of vascular blockage during diving. (3) Fibrinogen alpha chain (FGA) and FIII, which were detected to contain the specific amino acid substitutions in marine mammals, indicating similar evolutionary mechanisms might exist among marine mammals to maintain strong wound‐healing ability. Thus, our research provides further impetus to study the evolution of the wound healing system in cetaceans and other marine mammals, extending knowledge of preventing coagulation disorder and atherosclerosis in humans.