Adaptive protein evolution of_Drosophila_germline stem cell genes_bam_and_bgcn_

果蝇生殖干细胞基因的适应性蛋白质进化bam_and_bgcn_

• 批准号: 8512742
• 负责人: CHARLES F AQUADRO
• 金额: $ 29.91万
• 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 2015-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8512742
• 关键词: Affect; Amino Acid Sequence; Amino Acids; Animals; Attention; Automobile Driving; Bacteria; Benign; Biological Assay; Cell Count; Cells; Conflict (Psychology); Data; Development; Disease; Drosophila genus; Drosophila melanogaster; Ensure; Environment; Eukaryota; Evolution; Female; Fertility; Fertilization; Gametogenesis; Genes; Genetic; Genomics; Genotype; Germ Cells; Gonadal structure; Human; Infection; Infertility; Inherited; Investments; Lead; Life; Malignant Neoplasms; Marble; Medical; Molecular; Molecular Evolution; Molecular Genetics; Natural Selections; Neoplasms; Organism; Parasites; Partner in relationship; Pattern; Peptide Sequence Determination; Phenotype; Plants; Population; Population Genetics; Process; Proteins; RNA Interference; Regulation; Regulator Genes; Regulatory Pathway; Reproduction; Reproductive Physiology; Sampling; Shapes; Siblings; Spiroplasma; Staging; Stem cells; System; Technology; Testing; Transgenic Organisms; Viral; Wolbachia; Work; base; cell type; computerized data processing; driving force; egg; fitness; follow-up; genetic analysis; knock-down; life history; male; mutant; reproductive; research study; self-renewal; sex; sperm cell; stem cell differentiation; stem cell fate; trait; transmission process

DESCRIPTION (provided by applicant): 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 in the germline are some of the most critical decisions in development. Studies of the cellular signaling for this process in the fruit fly, Drosophila melanogaster, have discovered many of the key genes involved. The importance of proper regulation of this process in all animal species would lead one to predict that these functions are highly conserved. However, several of the key GSC regulatory molecules have recently been discovered to be 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. These adaptively evolving genes have accumulated a highly significant excess of amino-acid changes compared to neutrally evolving genes. Identifying the functional consequences of GSC gene evolution and the evolutionary forces driving these changes is essential for understanding how GSCs are regulated during normal development and how their misregulation can lead to infertility, germline cancers, and reproductive isolation. This proposal focuses on evaluating both the functional consequences and the evolutionary forces responsible for driving high rates of protein divergence at two key GSC regulator genes, bam and bgcn. Evolutionary patterns of GSC regulatory genes will also be examined in other Drosophila species. Numerous hypotheses have been proposed to explain the evolutionary mechanisms driving the previously discovered rapid protein evolution of other reproductive genes. Based on preliminary functional and evolutionary data, this proposal focuses on testing the hypothesis that natural selection to modulate the effects of or defend against germline endosymbionts is a key driver of adaptive evolution of bam and bgcn. These studies provide a framework with which to test for similar selectively driven functional changes in other genes controlling stem cell fate decisions in Drosophila as well as in other organisms including humans, and for understanding the evolutionary forces driving these evolutionary changes.

描述（由申请人提供）： 包括人在内的动物在其性腺中包含少数细胞，称为种系干细胞（GSC）。这些细胞对于在动物的整个生命周期中生产精子或卵是必不可少的。决定将干细胞更新为干细胞或分化的决定，以及对种系中早期分裂的调节是发育中最关键的决定。果蝇果蝇（Drosophila Melanogaster）在果蝇中的细胞信号传导的研究发现了许多关键基因。在所有动物物种中，适当调节该过程的重要性将导致人们预测这些功能是高度保守的。然而，最近发现，在两个密切相关的果蝇（D. melanogaster及其兄弟姐妹种类d。Inmulans）中，几种关键的GSC调节分子在适应性进化下正在迅速发展，但在几个其他密切相关的物种中没有。与中性不断发展的基因相比，这些适应性发展的基因已经积累了极大的氨基酸变化。确定GSC基因演化的功能后果和推动这些变化的进化力对于理解正常发育过程中如何调节GSC以及它们的正常调节如何导致不育，种系癌和生殖隔离至关重要。该提案的重点是评估功能后果和负责在两个关键GSC调节剂基因BAM和BGCN上驱动高蛋白质差异的进化力。 GSC调节基因的进化模式也将在其他果蝇物种中进行检查。已经提出了许多假设来解释驱动其他生殖基因的先前发现的快速蛋白进化的进化机制。基于初步功能和进化数据，该提案重点是检验以下假设：自然选择调节或防御生殖线内共生菌的影响是BAM和BGCN自适应演化的关键驱动力。这些研究提供了一个框架，可以通过该框架测试控制果蝇中的干细胞命运决策以及包括人类在内的其他生物的其他基因的类似驱动的功能变化，并了解驱动这些进化变化的进化力。