OPUS: CRS Integrating data and theory to understand the evolution of gene expression

OPUS：CRS 整合数据和理论来理解基因表达的进化

• 批准号: 1911322
• 负责人: Patricia Wittkopp
• 金额: $ 25.36万
• 依托单位: Regents of the University of Michigan - Ann Arbor
• 依托单位国家: 美国
• 项目类别: Standard Grant
• 财政年份: 2019
• 资助国家: 美国
• 起止时间: 2019-09-01 至 2023-08-31
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=1911322&HistoricalAwards=false
• 关键词: OPUS; CRS; Integrating; data; theory

Advances in biology are often the result of synthesizing findings from two different disciplines of research. This project combines 20 years of research in two areas: how genetic material is expressed to build organisms and how mutational changes in DNA sequence lead to changes in specific traits over time. The project combines data from experimental yeast populations measuring the effects of new mutations on gene expression with theory in evolutionary and quantitative genetics. The synthesis of this work will provide a more complete understanding of how differences in gene expression arise and persist over evolutionary time. This synthesis will be presented in a scholarly review paper expected to have a major influence on the field. It will also form the basis of a computational model that will enable new areas of interdisciplinary work. Finally, the importance of mutation as the origin of differences within and between species will be presented to the general public in an interactive museum exhibit developed in collaboration with the University of Michigan's Natural History Museum. Ultimately, this research provides insight into the general rules of life regarding how regulatory variation arises and persists, with potential insights into diverse problems in agriculture, medicine and other areas of societal interest. Gene expression is controlled by both cis- and trans-regulatory sequences. Variation in both types contributes to expression differences seen within and between species. As for all traits, this variation in gene expression reflects both the introduction of phenotypic variation by mutation (the "arrival of the fittest") as well as filtering of this variation by natural selection (the "survival of the fittest"). This project will take advantage of data produced by the laboratory's systematic study of properties of new regulatory mutations and comparisons with the properties of regulatory variants found in natural populations. These comparisons reveal both what can happen and what has happened in terms of regulatory evolution. More specifically, the relative frequency, effects, dominance, plasticity, gene-by-environment interactions, pleiotropy, and epistasis of cis- and trans-regulatory mutations affecting expression of a focal gene (the Saccharomyces cerevisiae TDH3 gene) have all been measured empirically. In addition, the fitness effects of changing TDH3 expression have also been determined in multiple environments, and cis- and trans-regulatory variation among strains of S. cerevisiae recently isolated from the wild have been characterized. Synthesizing these data and integrating them with evolutionary theory will result in a more complete picture of the evolutionary process than available for any other quantitative trait.This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.

生物学的进步往往是综合两个不同学科研究成果的结果。该项目结合了两个领域20年的研究：遗传物质如何表达以构建生物体，以及DNA序列的突变如何导致特定性状随时间的变化。该项目结合了实验酵母菌群的数据，测量新突变对基因表达的影响，以及进化和数量遗传学的理论。这项工作的综合将提供一个更完整的理解如何在基因表达的差异出现和持续进化的时间。这一综合将在一份学术评论文件中提出，预计将对该领域产生重大影响。它还将形成一个计算模型的基础，这将使跨学科工作的新领域。最后，突变作为物种内部和物种之间差异起源的重要性将在与密歇根大学自然历史博物馆合作开发的互动博物馆展览中向公众展示。最终，这项研究提供了关于调节变化如何产生和持续的一般生活规则的见解，并对农业，医学和其他社会感兴趣的领域的各种问题提供了潜在的见解。基因表达受顺式和反式调控序列控制。这两种类型的变异有助于在物种内和物种之间观察到的表达差异。就所有性状而言，基因表达的这种变异既反映了通过突变引入的表型变异（“适者生存”），也反映了通过自然选择过滤这种变异（“适者生存”）。该项目将利用实验室对新的调控突变特性的系统研究产生的数据，并与自然人群中发现的调控变异特性进行比较。这些比较揭示了在监管演变方面可能发生的事情和已经发生的事情。更具体地说，相对频率，效果，优势，可塑性，基因与环境的相互作用，多效性，和上位性的顺式和反式调节突变影响的焦点基因（酿酒酵母TDH 3基因）的表达都已被经验测量。此外，还在多种环境中确定了改变TDH 3表达的适应性效应，以及S.最近从野生分离的酿酒酵母已经被表征。综合这些数据并将其与进化理论相结合，将比任何其他数量性状更全面地了解进化过程。该奖项反映了NSF的法定使命，并通过使用基金会的知识价值和更广泛的影响审查标准进行评估，被认为值得支持。