Evolutionary Mechanisms Governing Gene Regulation

描述（由申请人提供）：解密非编码的组织 参与真核基因表达调控的序列， 在结构和功能上，是一个主要的后基因组测序挑战。我们 我相信，发展对进化过程的理解， 这些序列，并建立进化规则的关系 结构/功能和进化约束之间的关系，将是至关重要的， 迎接这一挑战。我们的建议是实验性地解剖 在一个模型顺式调节元件的变化，果蝇甚至跳过条纹2 元件，所有真核增强子中功能最好的元件之一 序列的我们的实验将使我们能够确定 调节蛋白结合位点序列的进化变化， 元素，功能的重要性，在装订间距的变化 网站，以及两者可能的共同进化的相互作用。另外我们 描述进行这些进化遗传学的技术能力， 分析每个物种遗传背景的种间差异 在调查中，提供了第一次机会，以批判性地审查 反式作用因子协同进化在基因进化中重要性 调控这些实验将有助于真核生物基因组的分析 结构/功能，并将有助于破译人类基因的控制 表情

DESCRIPTION (provided by applicant): Deciphering the organization of noncoding sequences involved in the regulation of eukaryotic gene expression, both structurally and functionally, is a major, post-genome sequence challenge. We believe that developing an understanding of evolutionary processes acting on these sequences, and establishing evolutionary rules governing the relationship between structure/function and evolutionary constraint, will be critical to meeting this challenge. Our proposal is to experimentally dissect evolved changes in a model cis-regulatory element, the Drosophila even-skipped stripe 2 element, one of the best functionally characterized of all eukaryotic enhancer sequences. Our experiments will allow us to determine the functional importance of evolved changes in the sequences of regulatory protein binding sites within the element, the functional importance of changes in spacing between binding sites, and the possible co-evolutionary interaction of the two. In addition, we describe the technical capability to conduct these evolutionary genetic analyses of interspecific differences in the genetic background of each species under investigation, providing the first opportunity to critically examine the importance of trans-acting factor coevolution in the evolution of gene regulation. These experiments will benefit the analysis of eukaryotic genome structure/function and will aid work to decipher the controls of human gene expression.