Yeast as a model for understanding gene expression adaptation

酵母作为理解基因表达适应的模型

• 批准号: 8417659
• 负责人: Hunter B Fraser
• 金额: $ 28.79万
• 依托单位: STANFORD UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2012
• 资助国家: 美国
• 起止时间: 2012-02-05 至 2016-01-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8417659
• 关键词: Address; Affect; Anabolism; Animal Model; Base Pairing; Cataloging; Catalogs; Collection; Data; Drosophila genus; Drug resistance; Engineering; Environment; Epidemic; Ergosterol; Evolution; Fruit; Gasterosteidae; Gene Expression; Gene Expression Regulation; Genes; Genetic Transcription; Genome; Human; Hybrids; Immunocompromised Host; Individual; Infection; Intuition; Life; Maps; Measures; Methods; Modeling; Molecular; Mutation; Nucleotides; Pathway interactions; Phenotype; Play; Population Sizes; Processed Genes; RNA Sequences; Regulation; Regulator Genes; Resources; Rest; Role; Saccharomyces; Saccharomycetales; Scanning; Site; System; Testing; Work; Yeasts; base; design; disease phenotype; fitness; functional group; genetic manipulation; genome analysis; genome-wide; innovation; pathogen; pressure; resistant strain; sample fixation; trait

DESCRIPTION (provided by applicant): To what extent changes in gene expression regulation drive the evolutionary innovations of life is an important unresolved question. In particular, the role of cis-regulation has been contentious. While some contend that changes in cis-regulation are responsible for the majority of morphological adaptations, others point out that only a few such cases have been demonstrated. The paucity of examples of adaptive regulatory divergence (cis-acting or otherwise) may be due in large part to the fact that no method for identifying such cases from genome-scale data has yet been developed. We have recently developed the first such method, which is based on analysis of genome-scale catalogs of regulatory differences between any pair of strains or species. We have demonstrated its ability to detect genes and even entire functional groups/pathways that have been subject to positive selection for changes in gene expression. What is now most needed is additional data from which to detect the signature of positive selection, as well as methods to pinpoint and functionally characterize the individual nucleotide changes responsible for these adaptations. Saccharomyces budding yeast represents an ideal model in which to study these questions. The end result of this work, in addition to a greatly increased understanding of how regulatory evolution occurs at the molecular level, will be a comprehensive catalog of cis-regulatory changes in yeast, as well as the first collection of strains (from any species) differing only by single adaptive mutations. We believe that this collection of results and resources will transform yeast into the leading model organism for studying gene expression adaptation.

描述（申请人提供）：基因表达调控的变化在多大程度上驱动生命的进化创新是一个重要的未解决的问题。特别是，顺式调节的作用一直存在争议。虽然有些人认为顺式调节的变化是负责大多数形态适应，其他人指出，只有少数这样的情况下已被证明。 缺乏适应性调节分歧（顺式作用或其他）的例子可能在很大程度上是由于这样一个事实，即没有方法来确定这种情况下，从基因组规模的数据尚未开发。我们最近开发了第一个这样的方法，它是基于对任何一对菌株或物种之间的调控差异的基因组规模目录的分析。我们已经证明了它能够检测基因，甚至整个功能组/途径，这些功能组/途径已经受到基因表达变化的正选择。现在最需要的是额外的数据，从中检测阳性选择的签名，以及确定和功能性地表征负责这些适应的单个核苷酸变化的方法。芽殖酵母是研究这些问题的理想模型。这项工作的最终结果，除了大大增加了对调控进化如何在分子水平上发生的理解外，还将是酵母中顺式调控变化的全面目录，以及第一批仅通过单一适应性突变而不同的菌株（来自任何物种）。我们相信，这些结果和资源的收集将使酵母成为研究基因表达适应的主要模式生物。