Evolutionary Genomics of Yeast

酵母的进化基因组学

• 批准号: 10217152
• 负责人: Hunter B Fraser
• 金额: $ 32.49万
• 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 2025-07-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10217152
• 关键词: Address; Affect; Alleles; Animal Model; Automobile Driving; Binding Sites; Biology; Characteristics; Code; Data; Environment; Evolution; Experimental Designs; Gene Frequency; Genes; Genetic; Genetic Polymorphism; Genetic Transcription; Genetic Variation; Genomics; Genotype; Goals; Human; Light; Measures; Minor; Molecular; Mutagenesis; Mutation; Natural Selections; Open Reading Frames; Organism; Pattern; Phenotype; Play; Point Mutation; Process; Property; Research; Resolution; Ribosomes; Role; Saccharomyces cerevisiae; Saccharomycetales; Shapes; Single base substitution; Source; Sum; System; Technology; Variant; Yeasts; base; experimental study; fitness; gene environment interaction; genetic variant; genome editing; genome-wide; human disease; insight; novel strategies; precise genome editing; promoter; rare variant; theories; transcription factor

Project summary A major goal of genetics and evolutionary biology is to understand how changes in genotype affect phenotype. Genetic variants affecting fitness are especially informative for investigating evolution, since natural selection acts exclusively on these variants. By identifying specific variants that influence fitness, we can begin to understand the molecular mechanisms driving the incredible adaptations of all organisms to their environments. We recently developed an approach that allows us to edit genomes with unprecedented efficiency (~100%) and throughput, and precisely measure each edit’s effect on fitness. In our initial screen, we measured the fitness effects of 16,000 natural genetic variants differing between two strains of Saccharomyces cerevisiae. In this pilot experiment, we measured the effects of each variant in isolation, in a single condition. We found that nearly all strong fitness effects were from promoter variants, rather than protein-coding regions, and these were especially enriched at transcription factor binding sites. Here we propose to utilize this powerful system to investigate two concepts of fundamental importance: the role of selection in shaping genetic variation in Aim 1, and gene-by-environment (GxE) interactions in Aim 2. This project will reveal key insights into the evolutionary process that would be unapproachable without our high-throughput precision genome editing technology.

项目摘要 遗传学和进化生物学的主要目标是了解基因型的变化如何影响 表型。影响健身的遗传变异对于研究进化特别有用，因为自然 选择仅作用于这些变体。通过确定影响健身的特定变体，我们可以开始 了解推动所有生物的令人难以置信的适应性的分子机制 环境。 我们最近开发了一种方法，该方法使我们能够以前所未有的效率编辑基因组 （〜100％）和吞吐量，并精确地衡量每个编辑对健身的影响。在我们的初始屏幕中，我们 测量了两种糖菌菌株之间不同的16,000种自然遗传变异的适应性影响 酿酒酵母。在这个试点实验中，我们在单个条件下分离地测量了每个变体的效果。 我们发现，几乎所有强大的健身效应都是来自启动子的变体，而不是蛋白质编码区域， 这些在转录因子结合位点特别丰富。 在这里，我们建议利用这个强大的系统来研究两个基本重要性的概念： 选择在AIM 1中塑造遗传变异的作用以及AIM基因相互作用（GXE）相互作用 2。该项目将揭示对没有我们的进化过程的关键见解 高通量精度基因组编辑技术。