The molecular basis of morphological evolution

形态进化的分子基础

• 批准号: 7259668
• 负责人: DAVID L STERN
• 金额: $ 32.39万
• 依托单位: PRINCETON UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2001
• 资助国家: 美国
• 起止时间: 2001-08-01 至 2011-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7259668
• 关键词: Architecture; Behavior; Binding Sites; Biology; Chromosome Mapping; Development; Disease; Drosophila genus; Enhancers; Event; Evolution; Foundations; Funding; Gene Expression Regulation; Genes; Genetic; Genetic Markers; Genetic Recombination; Genetic Variation; Goals; Human; In Vitro; Individual; Larva; Maps; Meiosis; Methods; Molecular; Morphology; Mutation; Natural Selections; Nucleic Acid Regulatory Sequences; Nucleotides; Pattern; Pharmaceutical Preparations; Physiology; Population; Resolution; Site; Subgroup; Surveys; System; Technology; Testing; Trans-Activators; Variant; base; developmental genetics; gene function; genetic analysis; homologous recombination; insight; novel; response; species difference; trait; transcription factor; ultra high resolution

DESCRIPTION (provided by applicant): The goal of this project is to identify the nucleotide changes that have led to phenotypic differences between closely related Drosophila species. The larger goal is to determine whether these evolved changes reflect a special set of all possible mutations. There are three specific aims for this proposal. First, we will survey three previously identified enhancer regions of the shavenbaby/ovo gene for all transcription factor binding sites that can be detected in vitro. This analysis will leverage the fact that all three enhancers have evolved new functions in D. sechellia, presumably through the loss or gain of transcription factor binding sites. This survey will provide the foundation for detailed study of binding sites that have evolved new functions. In particular, we will test whether these sites are required for gene function in D. melanogaster and we will further test whether altering them to a D. sechellia sequence is sufficient to alter their function in the manner in which svb function has evolved. We will then perform a population genetic analysis of the conserved and evolved transcription factor binding sites to test whether the evolving sites have evolved by natural selection. Second, we will continue development of a novel method for ultra high-resolution mapping of evolved differences between D. simulans, D. sechellia and D. mauritiana. This new method extends traditional meiotic mapping approaches by employing genetic markers that flank an evolved region to allow automated identification of individuals with informative recombination events. This approach promises to provide a transformative technology for studying the evolution of a large and diverse set of phenotypic differences, especially so-called quantitative traits that are controlled by multiple genes. Relevance: Differences between the response of individuals to disease and drug treatment are caused in part by genetic variation. In addition, the traits that make us uniquely human evolved in large part through changes in gene regulation, rather than through the evolution of new genes. This project involves detailed study of the evolution of a new pattern of gene regulation in a species of Drosophila. This detailed analysis of gene regulation promises to provide new insights into how gene regulation functions and evolves in natural species to cause possibly adaptive changes in morphology.

描述（由申请人提供）：该项目的目标是确定导致密切相关的果蝇物种之间表型差异的核苷酸变化。更大的目标是确定这些进化的变化是否反映了一组特殊的所有可能的突变。这项建议有三个具体目标。首先，我们将调查先前确定的shavenbaby/ovo基因的三个增强子区域，以确定所有可以在体外检测到的转录因子结合位点。这一分析将利用这一事实，即所有三种增强子都在黑穗草中进化出了新的功能，可能是通过转录因子结合位点的丧失或获得。这项研究将为进一步深入研究具有新功能的结合位点提供基础。特别是，我们将测试这些位点是否为黑腹d.m anogaster基因功能所必需，我们将进一步测试将它们改变为d.s hellia序列是否足以以svb功能进化的方式改变它们的功能。然后，我们将对保守和进化的转录因子结合位点进行群体遗传分析，以测试进化位点是否通过自然选择进化而来。其次，我们将继续开发一种新的方法来超高分辨率绘制D. simulans， D. sechellia和D. mauritiana之间的进化差异。这种新方法扩展了传统的减数分裂作图方法，采用遗传标记，侧翼一个进化区域，允许自动识别具有信息重组事件的个体。这种方法有望提供一种变革性的技术，用于研究大量多样的表型差异的进化，特别是由多个基因控制的所谓的数量性状。相关性：个体对疾病和药物治疗反应的差异部分是由遗传变异引起的。此外，使我们人类独特的特征在很大程度上是通过基因调控的变化而不是通过新基因的进化而进化的。该项目涉及对果蝇一种新的基因调控模式的进化进行详细的研究。这种对基因调控的详细分析有望为基因调控如何在自然物种中起作用和进化以引起可能的形态学适应性变化提供新的见解。