Evolutionary Genomics of Yeast

项目总结 遗传学和进化生物学的一个主要目标是了解基因的变化如何影响 表型。影响适合度的遗传变异对于研究进化特别有用，因为 选择只作用于这些变种。通过识别影响适合度的特定变量，我们可以开始 为了了解推动所有有机体对其难以置信的适应的分子机制 环境。 我们最近开发了一种方法，使我们能够以前所未有的效率编辑基因组 (~100%)和吞吐量，并精确测量每个编辑对适应性的影响。在我们的初始屏幕中，我们 测量了两个酵母菌株之间16,000个不同的自然遗传变异的适合度效应 酿酒。在这项试点实验中，我们在单一条件下单独测量了每个变量的影响。 我们发现，几乎所有的强适应效应都来自启动子变体，而不是蛋白质编码区， 而且它们尤其在转录因子结合位点上富含。 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的概念： 选择在AIM 1中形成遗传变异中的作用，以及AIM中基因与环境(GxE)的相互作用 2.这个项目将揭示对进化过程的关键见解，如果没有我们的 高通量精准基因组编辑技术。

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.