Jiangsu Key Laboratory for Biodiversity and Biotechnology, College of Life Sciences, Nanjing Normal University, Nanjing, China.
Southern Marine Science and Engineering Guangdong Laboratory (Guangzhou), Guangzhou, Guangdong, China.
Mol Biol Evol. 2022 Nov 3;39(11). doi: 10.1093/molbev/msac230.
Uncoupling protein 1 (UCP1) is an essential protein in the mitochondrial inner membrane that mediates nonshivering thermogenesis (NST) and plays an important role in thermoregulation and fat deposition. However, the relationship between the evolution of UCP1 and fat deposition in the blubber layer in cetaceans remains unclear. Here, frameshift mutations, premature termination, and relaxed selection pressure (ω = 0.9557, P < 0.05) were detected in UCP1 in cetaceans, suggesting that UCP1 was inactivated during cetacean evolution. By time estimation, it was found that the inactivation of UCP1 in cetaceans occurred between 53.1 and 50.2 Ma. However, combined with findings from immunohistochemical analysis of the blubber layer of the Yangtze finless porpoise and in vitro functional assays, a premature termination of cetacean UCP1 resulted in a reduction of UCP1-mediated NST capacity (about 50%) and lipolytic capacity (about 40%), both of which were beneficial to maintain blubber layer and body temperature without excessive fat consumption. This study provides new insights into the molecular mechanisms of the blubber thickening in cetaceans and highlights the importance of UCP1 attenuation in cetaceans for secondary aquatic adaptation.
解偶联蛋白 1（UCP1）是线粒体内膜中的一种必需蛋白，介导非颤抖性产热（NST），在体温调节和脂肪沉积中发挥重要作用。然而，UCP1 的进化与鲸目动物的鲸脂层脂肪沉积之间的关系尚不清楚。在这里，在鲸目动物的 UCP1 中检测到移码突变、提前终止和松弛的选择压力（ω = 0.9557，P < 0.05），表明 UCP1 在鲸类进化过程中失活。通过时间估计，发现鲸类 UCP1 的失活发生在 53.1 到 50.2 百万年前之间。然而，结合对长江江豚鲸脂层的免疫组织化学分析和体外功能测定的结果，发现鲸目动物 UCP1 的提前终止导致 UCP1 介导的 NST 能力（约 50%）和脂肪分解能力（约 40%）降低，这两者都有利于在不消耗过多脂肪的情况下维持鲸脂层和体温。本研究为鲸目动物鲸脂层增厚的分子机制提供了新的见解，并强调了 UCP1 衰减在鲸类动物中对二次水生适应的重要性。
