Adaptive protein evolution of the Drosophila germline stem cell gene bag of marbles

项目摘要 动物，包括人类，在他们的性腺中含有少量的称为生殖系干细胞的细胞。 细胞(GSC)。这些细胞是在整个生命周期中制造精子或卵子所必需的 动物。决定将分裂的干细胞更新为干细胞还是分化，以及 在GSC期间对早期部门进行管理是发展中最关键的决定之一。 对果蝇黑腹果蝇的研究已经确定了许多与之相关的关键基因 在细胞信号转导中维持和分化GSC。几个关键的GSC 在两个密切相关的物种中，调节基因在适应性进化下快速进化 果蝇(黑腹果蝇及其近亲种拟果蝇)，但不存在于其他几种 亲缘关系密切的物种。GSC分化的关键“开关”基因--大理石袋(Bam) 在这两者之间积累了非常显著的过量氨基酸变化 近缘种(13%)。本提案侧重于确定以下功能后果： 这些变化，并洞察推动这些变化的可能进化力量， 包括与内共生细菌沃尔巴克氏菌的相互作用。这些知识是必不可少的。 为了了解GSC在正常发育过程中是如何受到调节的，以及它们的 由于突变和与生殖系寄生虫的相互作用而导致的调控不当可能导致不育， 生殖系癌症和生殖隔离。我们建议的研究提供了一个框架， 以测试推动这些进化的功能后果和进化力量 控制果蝇和其他动物干细胞命运的基因的变化 包括人类在内的有机体。

Project Summary Animals, including humans, contain a small number of cells in their gonads called germline stem cells (GSCs). These cells are essential for making sperm or eggs throughout the lifetime of the animal. The decision for a dividing stem cell to renew as a stem cell or to differentiate, and the regulation of early divisions during GSC are some of the most critical decisions in development. Studies in the fruit fly, Drosophila melanogaster, have identified many of the key genes involved in the cellular signaling for GSC maintenance and differentiation. Several of the key GSC regulatory genes are rapidly evolving under adaptive evolution in two closely related species of Drosophila (D. melanogaster and its sibling species D. simulans) but not in several additional closely related species. The key “switch” gene for GSC differentiation, bag of marbles (bam) has accumulated a highly significant excess of amino-acid changes between these two closely related species (13%). This proposal focuses on identifying the functional consequences of these changes and gaining insight into possible evolutionary forces driving these changes, including interactions with the endosymbiotic bacteria Wolbachia. This knowledge is essential for understanding how GSCs are regulated during normal development and how their misregulation due to mutation and interaction with germline parasites can lead to infertility, germline cancers, and reproductive isolation. Our proposed studies provide a framework with which to test the functional consequences and evolutionary forces driving these evolutionary changes in genes controlling stem cell fate decisions in Drosophila as well as in other organisms, including humans.