The molecular basis of morphological evolution

描述(由申请人提供)：本项目的目标是确定导致近缘果蝇物种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。这项提议有三个具体目标。首先，我们将调查之前发现的shavenBaby/OVO基因的三个增强子区域，以寻找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，即所有三个增强子都在Sechellia中进化出新的功能，可能是通过失去或获得转录因子结合位点。这一调查将为详细研究已进化出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是黑腹盘藻基因功能所必需的，我们还将进一步测试将它们改变为D.sechellia序列是否足以改变它们的功能，以改变SVB功能的进化方式。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，以测试进化的位点是否通过自然选择进化。其次，我们将继续开发一种新的方法，用于超高分辨率地定位拟南虎、塞氏杜鹃和毛杜鹃之间的进化差异。这种新方法扩展了传统的减数分裂作图方法，利用进化区域两侧的遗传标记，允许自动识别具有信息重组事件的个体。这种方法有望为研究大量和多样化的表型差异的进化提供一种变革性的技术，特别是由多个基因控制的所谓数量性状。相关性：个体对疾病和药物治疗的反应差异在一定程度上是由遗传变异造成的。此外，使我们成为人类独一无二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来进化的。该项目详细研究了一种果蝇新的基因调控模式的进化。这一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发挥作用和进化，从而可能导致形态上的适应性变化提供新的见解。

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.