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: 8187760
• 负责人: CHARLES F AQUADRO
• 金额: $ 31.02万
• 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/8187760
• 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. PUBLIC HEALTH RELEVANCE: Germline stem cells (GSCs) are arguably the most fundamental cell type required for animal reproduction because these cells both maintain the germline throughout the animal's life, and produce the cells that go on to form either sperm or eggs. Remarkably, several key GSC regulatory genes are under strong natural selection to change at the protein sequence level between species. Our proposed study is aimed at identifying the functional consequences of GSC gene evolution and to test the germline endosymbiont conflict hypothesis as a key evolutionary driver of these changes.

描述(由申请人提供)： 包括人类在内的动物的性腺中含有少量被称为生殖系干细胞(GSCs)的细胞。这些细胞在动物一生中制造精子或卵子是必不可少的。决定将分裂的干细胞更新为干细胞还是分化，以及调节生殖系的早期分裂，都是发育过程中最关键的决定。对果蝇黑腹果蝇这一过程的细胞信号的研究发现了许多涉及的关键基因。在所有动物物种中适当调控这一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，最近发现一些关键的GSC调节分子在两个密切相关的果蝇物种(黑腹果蝇及其近缘物种拟态果蝇)的适应性进化下快速进化，但在另外几个密切相关的物种中没有。与中性进化的基因相比，这些适应性进化的基因积累了非常显著的过量氨基酸变化。识别GSC基因进化的功能后果和推动这些变化的进化力量对于了解GSC在正常发育过程中是如何调控的以及它们的错误调控如何导致不孕不育、生殖系癌症和生殖隔离至关重要。这项建议侧重于评估导致两个关键GSC调节基因bam和bgcn蛋白质高度分化的功能后果和进化力量。GSC调节基因的进化模式也将在其他果蝇物种中进行研究。许多假说被提出来解释驱动先前发现的其他生殖基因的快速蛋白质进化的进化机制。基于初步的功能和进化数据，这一建议侧重于检验这样一种假设，即调节或防御生殖系内共生菌的影响的自然选择是bam和bgcn适应性进化的关键驱动因素。这些研究提供了一个框架，用来测试控制果蝇和包括人类在内的其他生物的干细胞命运决定的其他基因中类似的选择性驱动的功能变化，并为理解推动这些进化变化的进化力量提供了一个框架。 公共卫生相关性： 生殖系干细胞(GSCs)可以说是动物繁殖所需的最基本的细胞类型，因为这些细胞既在动物一生中维持生殖系，又产生继续形成精子或卵子的细胞。值得注意的是，几个关键的GSC调控基因处于强烈的自然选择之下，在物种之间的蛋白质序列水平上发生变化。我们提出的研究旨在确定GSC基因进化的功能后果，并检验生殖系内共生体冲突假说是这些变化的关键进化驱动因素。