鲸类低氧适应的分子进化机制

Adaptive evolution is the result of long-term interaction between organisms and environment that is maintained and evolved by means of natural selection. Exploring genetic basis of the adaptation can contribute to understand its evolutionary history. Cetaceans are a highly specialized order of mammals that “returned” from the land to the sea approximately 53 million years ago (Ma) and they ultimately became a successful and highly diverse group of fully aquatic mammals. Cetaceans are confronted with enormous challenges from hypoxia because oxygen in the water is only 5% of that in the terrestrial. In order to adapt hypoxia, cetaceans have developed several anatomical and physiological adaptations in respiratory system, cardiovascular system, as well as energy metabolism, but their genetic and evolutionary bases remain poorly explored. In this project, approximately 30 hypoxia-tolerance related genes, including oxygen transmission, hypoxia - inducible genes, vasoconstriction, as well as energy metabolism related genes, will be examined in representative species of major cetacean lineages and compared with corresponding sequences from other mammals to determine its contribution to hypoxia adaptation during cetacean evolution. The aim of this project are 1) to test if the evolutionary pattern of cetacean hypoxia-tolerance related genes has been driven by positive selection, and if so 2) to detect whether functional changes of such genes under positive selection during the evolution of hypoxia adaptation in cetaceans, and 3) to evaluate whether different diving ability of cetaceans have experienced different selection pressure, and 4) to find whether cetaceans and other hypoxia-exposed mammals have similar or convergent adaptations at molecular level. From all the findings, we expect to illuminate the molecular evolution mechanism of adaptation to hypoxia in cetaceans. Thus, we can comprehensively insight into the genetic basis responsible for adaptation to extremely hypoxic environment in mammals living in different ecological niches.

适应性进化是在自然选择作用下，生物与环境长期相互作用的结果，阐明其遗传机制有助于揭示物种的演化历史。鲸类是一类特化的哺乳动物，其陆生祖先约5300万年前从陆地进入海洋。而水溶氧量仅为空气的5%，为了适应低氧环境，鲸类在呼吸、心血管和能量代谢等方面产生了解剖和生理的适应特征，然而，这一适应性的分子机制尚不清楚。鉴于此，本项目拟以不同潜水能力的鲸类物种为研究对象，筛选并测定一批低氧耐受相关基因（包括携氧、缺氧诱导、血管收缩以及能量代谢等），探讨1）鲸类低氧相关基因的进化模式如何？是否受正选择驱动？2）鲸类受正选择的基因是否产生了适应性功能改变？3）不同潜水能力的鲸类物种低氧耐受基因的进化模式是否不同？4）与栖于低氧环境的其他哺乳动物类群相比，鲸类是否存在相似或者趋同的适应机制？综合以上结果，以期阐明鲸类低氧适应的分子进化机制，全面理解不同生态类群适应低氧环境的遗传学基础。

为了适应水下低氧，鲸类在呼吸、心血管和能量代谢等方面产生了适应特征。为了探讨这一适应的分子机制，本项目在鲸类和近缘的陆生哺乳动物中比较分析了211个低氧耐受关键基因（4个携氧基因、13个血管收缩基因以及194个能量代谢基因）和2个基因家族（抗氧化基因家族GSTs和自由基捕获酶基因家族GPXs）。获得的主要结果如下：1）3个携氧基因（HBA、HBB和MB）在鲸类中受到显著正选择且鉴定了25个受正选择的位点，表明鲸类已进化出较强的携氧能力以应对低氧环境。长时间潜水鲸类主要通过提高血红蛋白氧气储存能力以满足长时间潜水对氧气的需要因为长时间潜水者HBB受到的选择压力强度显著高于短时间潜水者；2）鲸类的7个血管收缩基因的17个位点显著受正选择，为鲸类具有较强的血管调节策略将氧气优先供应给对氧气敏感组织而关闭对对氧气不敏感的组织提供了分子证据；3）通过对受正选择的能量代谢基因的分布和功能分析，揭示鲸类通过增强三羧酸循环中关键酶的活性以提高有氧代谢能力而获得能量；同时，低氧代谢产生的乳酸主要通过糖异生途径关键酶能力的增强快速代谢，且功能实验证实鲸类乳酸脱氢酶基因特异的氨基酸突变提高了该酶的活性，也加快了乳酸代谢，使其免受乳酸中毒的侵害；4）虽然鲸类抗氧化基因家族GSTs和自由基捕获酶基因家族GPXs基因数目显著减少，但GSTs保留了主效基因（GSTA1、GSTA4和GSTM1）以及GPX1和GPX5基因家族出现了多拷贝，是应对低氧应激的重要策略；5）低氧耐受不同生态类群鉴定了共享的正选择基因（如HBA、HBB在鲸类、牦牛、藏羚羊以及裸鼹鼠中均受正选择）以及平行／趋同进化位点（如不同类群在29个基因能量代谢基因中鉴定了38个平行位点），为趋同适应低氧提供了分子证据。综合以上结果，该项目较全面地揭示了鲸类低氧耐受分子机制。