The molecular basis of morphological evolution

描述（由申请人提供）：本项目的目标是鉴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所有可能突变的特殊集合。这项建议有三个具体目标。首先，我们将调查三个先前确定的增强子区域的shavenbaby/卵基因的所有转录因子结合位点，可以在体外检测。这一分析将充分利用这三个增强子在D. sechellia，推测是通过失去或获得转录因子结合位点。这项调查将提供基础的详细研究结合位点，已经演变成新的功能。特别地，我们将测试这些位点是否是D中基因功能所必需的。我们将进一步测试是否将它们改变为D。Sechellia序列足以以SVB功能进化的方式改变它们的功能。然后，我们将进行保守和进化的转录因子结合位点的群体遗传学分析，以测试进化的位点是否是通过自然选择进化的。其次，我们将继续发展一种新的方法，用于超高分辨率映射D。simulans、D. sechellia和D.毛里求斯。这种新的方法扩展了传统的减数分裂定位方法，通过采用侧翼进化区域的遗传标记来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，用于研究大量不同表型差异的进化，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部分是由遗传变异引起的。此外，使我们成为独特人类的特征在很大程度上是通过基因调控的变化而进化的，而不是通过新基因的进化。该项目包括详细研究果蝇中一种新的基因调控模式的进化。这种基因调控的详细分析有望提供新的见解，基因调控功能和自然物种的演变，可能导致适应性的形态变化。

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.