Evolution of Gene Expression in Yeast

酵母基因表达的进化

• 批准号: 8614566
• 负责人: Patricia Jean Wittkopp
• 金额: $ 28.9万
• 依托单位: UNIVERSITY OF MICHIGAN AT ANN ARBOR
• 依托单位国家: 美国
• 财政年份: 2013
• 资助国家: 美国
• 起止时间: 2013-09-30 至 2017-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8614566
• 关键词: Affect; Alleles; Biodiversity; Biological Assay; Biology; Cancerous; Cells; Code; Collection; Comparative Study; Congenital Abnormality; Data; Data Set; Diploid Cells; Disease; Dose; Evolution; Foundations; Future; Gene Expression; Generations; Genes; Genetic Polymorphism; Genome; Genomics; Genotype; Growth; Habitats; Haploid Cells; Haploidy; Individual; Knowledge; Malignant Neoplasms; Maps; Measures; Modeling; Molecular; Mutagenesis; Mutation; Natural Selections; Pattern; Phenotype; Population; Positioning Attribute; Process; Property; Relative (related person); Role; Saccharomyces cerevisiae; Site; Site-Directed Mutagenesis; Sorting - Cell Movement; Source; Testing; Variant; Work; Yeasts; fitness; genetic variant; mutant; pleiotropism; public health relevance; research study

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.

项目概要/摘要 基因表达的遗传差异很常见，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 属于同一个人。这种多样性包括健康个体之间的“正常”变异，例如 以及引起疾病的“异常”变异。尽管基因变化很重要， 负责基因表达的差异以及影响它们的进化过程 没有被很好地理解。造成这种情况的原因之一是人们对突变输入知之甚少。 监管变异，选择和漂移作用产生监管模式 野生环境中的多态性和分歧。该项目将通过 (1) 帮助填补这一知识空白 收集和表征影响焦点基因活性的新突变，(2) 识别和 表征物种内分离为多态性的遗传变异，以及 (3) 将这些突变的特性与适应度以及突变组之间进行比较 多态性。这些属性将包括：突变类型（编码或非编码）、效果 规模、网络地位、优势和多效性。利用这些信息，提出不同的假设 将测试这些突变特性对新物种进化命运的影响 调节突变。这项工作将增进我们对分子机制的理解 潜在的监管（以及可能的表型）差异，并提供经验 为未来开发更现实的监管演变模型奠定了基础。