Jiangsu Key Laboratory for Biodiversity and Biotechnology, College of Life Sciences, Nanjing Normal University, Nanjing, China.
Integr Zool. 2024 Sep;19(5):898-912. doi: 10.1111/1749-4877.12781. Epub 2023 Oct 27.
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.
海洋环境对鲸目动物的伤口愈合提出了挑战，尽管它们具有很强的恢复能力，感染或并发症很少。然而，这种高效伤口愈合的分子机制仍未得到充分探索。为了更好地理解鲸目动物伤口愈合的分子机制，我们研究了 37 个与伤口愈合相关的基因在代表性哺乳动物中的进化模式。我们发现，与伤口愈合相关的基因在鲸目动物中经历了适应性进化：（1）三个外在凝血途径相关基因——组织因子（F3）、凝血因子 VII（F7）和凝血因子 X（F10）——在鲸目动物中受到正选择，这可能促进受伤后有效的止血；转化生长因子-β2（TGF-β2）、转化生长因子-β3（TGF-β3）和血小板衍生生长因子 D（PDGFD）的正选择，它们在伤口愈合中发挥免疫作用，可能有助于鲸目动物增强炎症反应和组织清创。（2）凝血因子 XII（F12）是内在凝血途径的起始因子。它在鲸目动物中发生了提前终止密码子突变，并受到选择压力的松弛，表明 F12 的早期终止可能有助于鲸目动物避免潜水时血管阻塞的风险。（3）纤维蛋白原α链（FGA）和 FIII，它们在海洋哺乳动物中被检测到含有特定的氨基酸取代，这表明海洋哺乳动物中可能存在类似的进化机制来维持强大的伤口愈合能力。因此，我们的研究为进一步研究鲸目动物和其他海洋哺乳动物的伤口愈合系统进化提供了动力，扩展了人类预防凝血障碍和动脉粥样硬化的知识。
