Deep Dive into Evolution: How Cetaceans Adapt Their Anticoagulant Genes for Underwater Survival.

Cetaceans face the risk of thromboembolism due to diving and decompression responses. However, cetaceans maintain normal blood circulation. This study explores the molecular mechanisms cetaceans use to mitigate diving-associated hemostatic challenges during diving. Forty-six species were analyzed, including 18 cetaceans, 9 artiodactyls, and 19 other terrestrial mammals. Thirty-nine anticoagulant genes and proteins were examined, identifying 6 genes (ANXA2, ANXA5, FGA, FGB, PLAUR, and PLG) with conserved evolution, 4 genes (ANXA2, PDGFB, SH2B3, THBS1) with positive selection, and 12 proteins (APOH, FGA, FGB, FGG, GP1BA, PLAU, PRKCD, PRKG1, SERPINF2, SERPING1, TMPRSS6, and TMX1) with specific amino acid sites in cetaceans. Ancestral state reconstruction revealed independent evolution of deep diving behavior in different cetacean lineages, particularly within Odontoceti. Correlation analysis linked the evolution of the APOE gene with diving depth, suggesting its role in diving adaptation. These analyses suggest that cetaceans may help reduce the risk of thrombosis during diving by lowering platelet activity, enhancing fibrinolysis, and modulating the coagulation cascade. These analyses suggest that cetaceans may mitigate diving-associated thrombotic risk by modulating platelet activity, fibrinolysis, and the coagulation cascade. Overall, this study identifies candidate anticoagulant-related genes and amino acid substitutions for future functional validation of hemostatic adaptation in cetaceans.