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

Area of Science:

• Marine Mammal Physiology
• Molecular Evolution
• Hemostasis and Thrombosis

Background:

• Cetaceans, or marine mammals, face a high risk of thromboembolism (blood clots) due to physiological challenges associated with deep diving and decompression.
• Despite these risks, cetaceans maintain normal blood circulation, indicating specialized adaptations to manage hemostatic challenges during dives.

Purpose of the Study:

• To investigate the molecular mechanisms cetaceans employ to mitigate diving-associated hemostatic challenges.
• To identify specific genes and proteins involved in anticoagulant pathways that have evolved in cetaceans.

Main Methods:

• Comparative genomic analysis of 39 anticoagulant genes and proteins across 18 cetacean species, 9 artiodactyls, and 19 other terrestrial mammals.
• Examination of conserved evolution, positive selection, and specific amino acid substitutions in these genes and proteins within cetaceans.
• Ancestral state reconstruction to infer the evolution of deep diving behavior and correlation analysis with gene evolution, such as the APOE gene.

Main Results:

• Identified 6 genes with conserved evolution (ANXA2, ANXA5, FGA, FGB, PLAUR, PLG) and 4 genes under positive selection (ANXA2, PDGFB, SH2B3, THBS1).
• Found 12 proteins with specific amino acid sites in cetaceans, including APOH, FGA, FGB, FGG, GP1BA, PLAU, PRKCD, PRKG1, SERPINF2, SERPING1, TMPRSS6, and TMX1.
• Linked the evolution of the APOE gene with diving depth, suggesting its role in adaptation to deep diving.

Conclusions:

• Cetaceans appear to mitigate thrombotic risk during diving by modulating platelet activity, enhancing fibrinolysis, and regulating the coagulation cascade.
• Specific genetic and protein adaptations, including conserved and positively selected genes and unique amino acid substitutions, contribute to hemostatic adaptation in cetaceans.
• This study provides candidate genes and molecular sites for future functional studies on cetacean hemostasis during diving.