Evolution and function of vertebrate globins

珠蛋白是一种结合氧气的小铁血红蛋白，因此在动物的呼吸和氧化能生产中起着重要作用。血红蛋白和肌红蛋白是生物医学中研究得最好的蛋白质之一，是研究蛋白质功能和进化的模型系统。近年来，我们的研究在脊椎动物中发现了六种额外的珠蛋白类型（雄性红蛋白、神经红蛋白、细胞红蛋白、珠蛋白E、珠蛋白X和珠蛋白Y）。这些“新型”珠蛋白的功能仍然知之甚少，是目前应用的主题。分析珠蛋白的关系，珠蛋白基因库和基因顺序（synteny）允许描绘珠蛋白的进化史。我们将特别关注七鳃鳗的珠蛋白，它提供了脊椎动物珠蛋白的早期进化信息，以及海龟的珠蛋白，它们拥有所有八种珠蛋白类型，因此可以研究它们的亚功能化。对这些物种的表达分析将为这两个物种的组织和细胞特异性作用提供线索。功能分析将在稳定转染的脊椎动物细胞系中进行。不同珠蛋白增强线粒体呼吸的能力，调节对缺氧和活性氧（ROS）的耐受性，保护脂质，防止细胞凋亡及其在ROS和NO生成中的作用将被测试。这种比较方法将允许评估关于珠蛋白功能的不同假设，并有希望确定每种珠蛋白的生理作用。将获得所选珠蛋白的动力学和结构数据。系统发育和功能实验结果的结合将使我们能够追踪在进化过程中发生在脊椎动物珠蛋白家族的生理作用的变化。

Globins are small iron-heme proteins that bind oxygen and thus play an important role in the animal's respiration and oxidative energy production. Hemoglobin and myoglobin are among the best investigated proteins in biomedical sciences, and are a model system to study protein function and evolution. In recent years, our studies led to the identification of six additional globin types in vertebrate (androglobin, neuroglobin, cytoglobin, globin E, globin X and globin Y). The functions of these "novel" globins are still poorly understood and subject of the present application. Analyses of globin relationships, globin gene repertoire and gene order (synteny) allow delineating the evolutionary history of globins. We will specifically focus on the globins of the lamprey, which provide information on the early evolution of vertebrate globins, and of turtles, which possess all eight globin types and thus allow studying their sub-functionalisation. Expression analyses in these species will provide clues about the tissue- and cell-specific roles in both species. Functional analyses will be carried out in stably transfected vertebrate cell lines. The ability of different globins to augment mitochondrial respiration, to mediate tolerance towards hypoxia and reactive oxygen (ROS), to protect lipids, to protect from apoptosis and their roles in the generation of ROS and NO will be tested. This comparative approach will allow evaluating different hypothesis of globin functions and hopefully allow the identification the physiological role of each globin. Kinetic and structural data will be obtained for selected globins. The combination of the results from the phylogenetic and functional experiments will allow us to trace the changes of physiological roles that occurred in the vertebrate globin family during evolution.