Evolution of Gene Expression in Yeast

描述(由申请人提供)：基因表达的可遗传差异是常见的，并有助于物种之间、同一物种的个体之间、有时甚至同一个体的细胞之间的表型多样性。这种多样性既包括健康个体的“正常”变异，也包括导致疾病的“异常”变异。尽管它们很重要，但导致基因表达差异的基因变化以及影响它们的进化过程还没有被很好地理解。其中一个原因是，人们对调控变异的突变输入知之甚少，在此基础上进行选择和漂移 在野外产生调节多态和分化的模式。该项目将通过(1)收集和表征影响局部基因活性的新突变，(2)识别和表征分离为物种内的多态的遗传变异，以及(3)将这些突变的性质与适应度以及突变和多态集合之间的性质进行比较，来帮助填补这一知识空白。这些属性包括：突变类型(编码或非编码)、影响大小、网络位置、优势和多效性。利用这些信息，将测试关于这些突变属性对新调控突变的进化命运的影响的各种假设。这项工作将促进我们对调控(可能是表型)差异背后的分子机制的理解，并为未来开发更现实的调控进化模型提供经验基础。

DESCRIPTION (provided by applicant): 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.