Characterizing Pareto fronts: Trade-offs in the yeast growth cycle constrain adaptation

表征帕累托前沿：酵母生长周期的权衡限制了适应

• 批准号: 10749856
• 负责人: JASON Alexander TARKINGTON
• 金额: $ 7.43万
• 依托单位: STANFORD UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2024
• 资助国家: 美国
• 起止时间: 2024-01-17 至 2025-01-16
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10749856
• 关键词: Antineoplastic Agents; Bar Codes; Biological Assay; Biophysical Process; Carbon; Communicable Diseases; DNA; Data; Dimensions; Drug resistance; Drug usage; Environment; Ethanol; Evolution; Experimental Designs; Extinction; Fermentation; Freedom; Future; Genetic; Genetic Epistasis; Genotype; Glucose; Glycerol; Growth; Heterogeneity; Lead; Maps; Measurement; Measures; Microbe; Molecular; Mutation; Natural Selections; Organism; Outcome; Pattern; Performance; Pharmaceutical Preparations; Phase; Phenotype; Population; Population Pressures; Process; Recording of previous events; Research Personnel; Respiration; Role; Route; Sampling; Seasonal Variations; Shapes; Source; Specialist; Stochastic Processes; Time; Work; Yeasts; antimicrobial drug; cancer cell; cost; design; experience; fitness; genome sequencing; global health; improved; insight; mutant; pleiotropism; prevent; response; trait; tumor progression; whole genome; yeast genome

Project Summary/Abstract Adaptive evolution involves optimizing multiple fitness related traits simultaneously. These traits can be projected into a multidimensional space known as trait space. Mapping the trait space accessible by single mutations can reveal the constraints imposed on organismal fitness. The fitness of an organism in an environment is often dependent on more than one trait; for yeast these traits include fermentation, respiration, and stationary phase performance. While in some cases it may be possible to improve multiple fitness related traits independently, certain fitness-related traits can also be constrained due to the pleiotropic effects of other fitness related traits, resulting in a trade-off. Previous work from the Sherlock lab has shown that following evolution in a glucose-containing, carbon-limited medium, that Pareto fronts, indicative of underlying trade-offs, emerge between stationary phase and respiration, and between respiration and fermentation, though not between stationary phase and fermentation. Here, I aim to understand the constraints on fitness in the yeast growth cycle and why such trade-offs emerge among some fitness-related traits but not others. I will evolve barcoded yeast in a non-fermentable carbon source with varying amounts of time spent in stationary phase. This experimental design eliminates selection for fermentation entirely and creates varying degrees of selection for performance in respiration and stationary phase e.g., the two-day transfer regime selects primarily for respiration performance, while in the 10-day transfer regime stationary phase performance will be more important. Under these conditions stationary phase performance may be free to increase unconstrained by fermentation performance resulting in the emergence of a pareto front between these components of organismal fitness. Freedom from fermentation performance constraints may also allow yeast to maximize respiration and stationary phase performances simultaneously. In addition to phenotypic analysis, I will also characterize the molecular basis of the underlying adaptive mutations that emerge to gain insight into the biophysical mechanism(s) preventing multiple traits from being optimized simultaneously. Finally, I will further evolve specific adaptive mutants to gain insight into the role of contingency in determining adaptive outcomes and determine whether specialists for one trait are limited in their future evolutionary trajectories when selected for improvement of a different trait.

项目总结/摘要 适应性进化涉及同时优化多个适应度相关性状。这些特征可以是 投射到一个被称为特质空间的多维空间中。映射单个可访问的特征空间 突变可以揭示对生物体适应性的限制。一个有机体在一个 环境通常取决于一种以上的性状;对于酵母，这些性状包括发酵， 呼吸和固定相性能。虽然在某些情况下， 多个适应度相关性状独立，某些适应度相关性状也可以受到约束，由于 其他健身相关性状的多效性效应，导致权衡。夏洛克实验室之前的工作 已经表明，在含葡萄糖、碳限制的培养基中进化后，帕累托前沿， 指示潜在权衡，在稳定期和呼吸之间以及在呼吸之间出现 和发酵，但不是在稳定期和发酵之间。在这里，我的目的是了解 限制健身在酵母生长周期，为什么这种权衡出现在一些健身相关 而不是其他的。我将在不可发酵的碳源中进化出条形码酵母， 停留在静止期的时间。这种实验设计完全消除了对发酵的选择， 为呼吸和稳定阶段的性能创建不同程度的选择，两天的 在10天的转移制度下，主要选择呼吸性能，而在10天的转移制度下， 阶段性能将更加重要。在这些条件下，固定相性能可能是自由的 不受发酵性能约束地增加，导致在 这些有机体适应性的组成部分。不受发酵性能限制也可以允许 酵母，以最大限度地提高呼吸和固定相性能的同时。除了表型 分析，我也将描述潜在的适应性突变的分子基础，出现获得 深入了解防止多个性状同时优化的生物物理机制。 最后，我将进一步进化特定的适应性突变体，以深入了解偶然性在 确定适应性结果，并确定一个特征的专家在未来是否有限 进化轨迹时，选择改善不同的性状。