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

果蝇生殖干细胞基因袋大理石的适应性蛋白质进化

• 批准号: 9509464
• 负责人: CHARLES F AQUADRO
• 金额: $ 32.27万
• 依托单位: CORNELL UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2011
• 资助国家: 美国
• 起止时间: 2011-08-01 至 2021-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9509464
• 关键词: Alleles; Amino Acid Sequence; Amino Acid Substitution; Amino Acids; Animals; Bacteria; Biological Assay; CRISPR/Cas technology; CSPG6 gene; Cell Differentiation process; Cell Maintenance; Cell physiology; Cells; Conflict (Psychology); Cytology; Development; Drosophila genus; Drosophila melanogaster; Evolution; Female; Fertility; Genes; Genetic; Geography; Germ Cells; Gonadal structure; Human; Infertility; Insecta; Knowledge; Lead; Life; Malignant Neoplasms; Marble; Molecular Evolution; Mutation; Natural Selections; Organism; Parasites; Plants; Population Genetics; Proteins; Recurrence; Regulation; Regulator Genes; Reproduction; Role; Sequence Analysis; Siblings; Signal Transduction; Site; Stem cells; Switch Genes; System; Technology; Testing; Variant; Virus; Wolbachia; cell type; comparative genomics; driving force; egg; female fertility; genetic approach; genome editing; germline stem cells; human pathogen; infancy; insight; life history; male; mutant; pressure; reproductive; reproductive function; self-renewal; sperm cell; stem cell differentiation; stem cell fate

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.

项目概要 包括人类在内的动物的性腺中含有少量称为生殖干的细胞 这些细胞对于在整个生命周期中产生精子或卵子至关重要。 动物分裂干细胞更新为干细胞或分化的决定，以及 GSC 期间早期分裂的监管是开发中最关键的决策之一。 对果蝇（Drosophila melanogaster）的研究已经确定了许多涉及的关键基因 GSC 维持和分化的细胞信号转导中的几个关键的 GSC。 调节基因在两个密切相关的物种的适应性进化下迅速进化 果蝇（D. melanogaster 及其兄弟物种 D. simulans），但其他几种果蝇中没有 GSC 分化的关键“开关”基因，弹珠袋 (bam) 密切相关的物种。 在这两者之间积累了非常显着过量的氨基酸变化 相关物种（13%）。 这些变化并深入了解驱动这些变化的可能的进化力量， 包括与内共生细菌沃尔巴克氏体的相互作用，这一知识至关重要。 了解 GSC 在正常发育过程中如何受到监管以及它们如何 由于突变和与种系寄生虫的相互作用而导致的失调可能导致不孕， 我们提出的研究提供了一个框架： 来测试功能后果和驱动这些进化的进化力量 控制果蝇和其他干细胞命运决定的基因的变化 有机体，包括人类。