Zhang Ya, Lv Wenjun, Yan Wen, Guo Boxiong, Yang Guang, Ren Wenhua
Jiangsu Key Laboratory for the Biodiversity Conservation and Sustainable Utilization in the Middle and Lower Reaches of the Yangtze River Basin, College of Life Sciences, Nanjing Normal University, Nanjing, 210023, China.
Institute of Entomology, College of Life Sciences, Nankai University, Tianjin, 300071, China.
BMC Genomics. 2025 Jun 5;26(1):562. doi: 10.1186/s12864-025-11751-2.
Cetaceans are a unique group of marine mammals that have evolved from terrestrial to fully aquatic life. During diving, they experience extreme physiological challenges, including lung collapse, limited gas exchange, and the risk of decompression-related injuries. The matrix metalloproteinase (MMP) gene family plays a central role in extracellular matrix (ECM) remodeling, vascular repair, and inflammatory responses, and is also involved in the formation and maintenance of elastic fibers-key components that contribute to lung elasticity. Enhanced lung elasticity is thought to facilitate reversible lung collapse and efficient blood shift during dives, ultimately reducing nitrogen uptake and the potential risk of decompression sickness (DCS). In this study, we analyzed 1,058 genes from 46 species, focusing on cetaceans and other diving marine mammals, with terrestrial mammals as a reference group. Our results reveal that the MMP gene family has undergone positive selection in cetaceans, with nine genes exhibiting accelerated evolution. Notably, we identified a cetacean-specific N319S mutation in the Fibronectin type-II domain of MMP9, which impairs collagen-binding and degradation, as confirmed by Western blot analysis. Mass spectrometry further revealed an increased number of post-translational modifications in cetacean MMP9 compared to terrestrial mammals, with several modifications overlapping the mutation sites. These findings suggest that adaptive changes in MMPs may enhance elastic fiber dynamics and vascular remodeling in cetaceans, contributing to physiological adaptations such as improved lung compliance and resilience to diving-related stress, including reduced susceptibility to DCS.
鲸类是一类独特的海洋哺乳动物，它们已从陆地生物进化为完全水生生物。在潜水过程中，它们面临极端的生理挑战，包括肺塌陷、气体交换受限以及减压相关损伤的风险。基质金属蛋白酶（MMP）基因家族在细胞外基质（ECM）重塑、血管修复和炎症反应中起核心作用，还参与弹性纤维的形成和维持，而弹性纤维是有助于肺弹性的关键成分。增强的肺弹性被认为有助于潜水过程中肺的可逆性塌陷和有效的血液转移，最终减少氮气摄取和减压病（DCS）的潜在风险。在本研究中，我们分析了46个物种的1058个基因，重点关注鲸类和其他潜水海洋哺乳动物，并以陆地哺乳动物作为参考组。我们的结果表明，MMP基因家族在鲸类中经历了正选择，有9个基因表现出加速进化。值得注意的是，我们在MMP9的纤连蛋白II型结构域中鉴定出一个鲸类特异性的N319S突变，Western印迹分析证实该突变损害了胶原蛋白结合和降解。质谱分析进一步显示，与陆地哺乳动物相比，鲸类MMP9的翻译后修饰数量增加，有几种修饰与突变位点重叠。这些发现表明，MMPs的适应性变化可能增强鲸类的弹性纤维动力学和血管重塑，有助于生理适应，如改善肺顺应性和对潜水相关应激的恢复力，包括降低对DCS的易感性。
