Evolutionary Mechanisms Governing Gene Regulation

描述(申请人提供)：破译非编码的组织 参与真核基因表达调控的序列，两者 在结构和功能上，是后基因组序列的主要挑战。我们 相信发展对进化过程作用于 这些序列，并建立管理关系的进化规则 结构/功能和进化约束之间的关系，将对 迎接这一挑战。我们的建议是实验性地解剖进化 模型顺式调控元件的变化，果蝇甚至跳过了条纹2 在所有真核细胞增强子中，功能最好的增强子之一 序列。我们的实验将使我们能够确定功能重要性 体内调节蛋白结合位点序列的进化变化 要素，装订之间的间距变化的功能重要性 以及两者可能的共同进化相互作用。此外，我们 描述进行这些进化遗传的技术能力 各物种遗传背景的种间差异分析 正在调查中，这提供了第一个机会来批判性地审查 反式作用因子协同进化在基因进化中的重要性 监管。这些实验将有助于真核生物基因组的分析。 结构/功能，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.