Evolution and function of vertebrate globins

球蛋白是小的铁血红素蛋白，其结合氧并且因此在动物的呼吸和氧化能量产生中起重要作用。血红蛋白和肌红蛋白是生物医学领域研究最多的蛋白质之一，是研究蛋白质功能和进化的模型系统。近年来，我们的研究导致在脊椎动物中鉴定出另外六种珠蛋白类型（雄珠蛋白、脑珠蛋白、细胞珠蛋白、珠蛋白E、珠蛋白X和珠蛋白Y）。这些“新型”球蛋白的功能仍然知之甚少，并且是本申请的主题。珠蛋白的关系，珠蛋白基因库和基因顺序（同线性）的分析允许描绘珠蛋白的进化历史。我们将特别关注七鳃鳗的球蛋白，它提供了脊椎动物球蛋白和海龟的早期进化信息，海龟拥有所有八种球蛋白类型，从而可以研究它们的亚功能。在这些物种中的表达分析将提供线索的组织和细胞特异性的作用，在这两个物种。将在稳定转染的脊椎动物细胞系中进行功能分析。将测试不同球蛋白增强线粒体呼吸、介导对缺氧和活性氧（ROS）的耐受性、保护脂质、防止细胞凋亡的能力以及它们在ROS和NO产生中的作用。这种比较的方法将允许评估不同的珠蛋白功能的假设，并希望允许识别每个珠蛋白的生理作用。将获得选定球蛋白的动力学和结构数据。系统发育和功能实验的结果相结合，将使我们能够跟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.