Evolution of Gene Expression in Yeast

项目总结/摘要 基因表达的遗传差异是常见的，并有助于表型多样性 物种之间，同一物种的个体之间，有时甚至是细胞之间 同一个人的。这种多样性包括健康个体之间的“正常”变异， 以及引起疾病的“异常”变异。尽管它们很重要， 负责基因表达的差异和影响它们的进化过程 并没有得到很好的理解。其中一个原因是，人们对基因突变的输入知之甚少， 调节变异，选择和漂移作用于此，产生调节模式， 多态性和分歧在野外。本项目将通过以下方式帮助填补这一知识空白：（1） 收集和表征影响焦点基因活性的新突变，（2）鉴定和 将遗传变异分离表征为物种内的多态性，以及（3） 将这些突变的性质与适应性进行比较，并在突变集合之间进行比较， 多态性这些属性将包括：突变类型（编码或非编码）， 规模、网络位置、优势和多效性。利用这些信息， 将测试这些突变特性对新物种进化命运的影响。 调控突变这项工作将促进我们对分子机制的理解 潜在的监管（和可能的表型）差异，以及提供一个经验 为今后开发更现实的监管演变模型奠定了基础。

Project Summary/Abstract Heritable differences in gene expression are common and contribute to phenotypic diversity between species, between individuals of the same species, and sometimes even between cells of the same individual. This diversity includes "normal" variation among healthy individuals as well as "abnormal" variation causing disease. Despite their importance, the genetic changes responsible for difference in gene expression and the evolutionary processes that affect them are not well understood. One reason for this is that little is known about the mutational input for regulatory variation, upon which selection and drift act to produce patterns of regulatory polymorphism and divergence in the wild. This project will help fill this knowledge gap by (1) collecting and characterizing new mutations affecting activity of a focal gene, (2) identifying and characterizing genetic variants segregating as polymorphisms within a species, and (3) comparing properties of these mutations with fitness and between the sets of mutations and polymorphisms. These properties will include: the type of mutation (coding or noncoding), effect size, network position, dominance, and pleiotropy. Using this information, diverse hypotheses will be tested about the effects of these mutational properties on the evolutionary fate of new regulatory mutations. This work will advance our understanding of the molecular mechanisms underlying regulatory (and presumably phenotypic) differences, as well as provide an empirical foundation for developing more realistic models of regulatory evolution in the future.