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

项目摘要 包括人类在内的动物在其生殖腺中含有少量的细胞，称为生殖干细胞 细胞（GSC）。这些细胞在整个生命周期中对制造精子或卵子至关重要。 动物分裂的干细胞更新为干细胞或分化的决定， 在GSC期间对早期分裂的调节是开发中最关键的决策。 对果蝇（Drosophilamelanogaster）的研究已经确定了许多相关的关键基因 GSC维持和分化的细胞信号传导。几个关键的GSC 调节基因在两个密切相关的物种中的适应性进化下迅速进化， 果蝇（D. melanogaster及其姊妹种D. simulans），但不是在几个额外的 近缘物种。GSC分化的关键“开关”基因，弹珠袋（bam） 在这两者之间积累了大量的氨基酸变化， 相关物种（13%）本建议的重点是确定以下方面的功能后果： 这些变化并深入了解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体的相互作用。这些知识是必不可少的 了解GSC在正常发育过程中如何调节，以及它们如何在 由于突变和与生殖系寄生虫的相互作用引起的失调可导致不育， 生殖系癌症和生殖隔离。我们提出的研究提供了一个框架， 测试这些进化的功能后果和进化力量， 果蝇和其他哺乳动物中控制干细胞命运决定的基因的变化 生物，包括人类。

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.