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

基本信息

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
项目类别：
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

项目摘要

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.

项目概要/摘要适应性进化涉及同时优化多个与适应性相关的特征。这些特征可以是投射到称为特征空间的多维空间。映射单个可访问的特征空间突变可以揭示对有机体适应性的限制。有机体在一定环境下的适应度环境往往取决于不止一种特征；对于酵母来说，这些特性包括发酵，呼吸和静止相性能。虽然在某些情况下可能会有所改善多个健身相关特征独立存在，某些健身相关特征也可能受到限制其他适应性相关特征的多效性效应，导致权衡。夏洛克实验室之前的工作已经表明，在帕累托前沿的含葡萄糖、碳限制介质中进化后，表明潜在的权衡，出现在静止相和呼吸之间以及呼吸之间和发酵，但不在固定期和发酵之间。在这里，我的目的是了解酵母生长周期中适应性的限制以及为什么在一些与适应性相关的因素中会出现这种权衡特征，但不是其他特征。我将在不可发酵的碳源中进化出带有不同数量的条形码的酵母处于稳定阶段的时间。该实验设计完全消除了发酵的选择，为呼吸和静止期的表现创建不同程度的选择，例如两天转移制度主要针对呼吸性能进行选择，而在 10 天转移制度中则为固定阶段表现将更加重要。在这些条件下，固定相性能可能是免费的提高不受发酵性能限制，从而导致之间出现帕累托前沿这些有机体健康的组成部分。不受发酵性能限制也可能允许酵母同时最大化呼吸和静止期性能。除了表型之外分析后，我还将描述潜在的适应性突变的分子基础，这些突变的出现是为了获得深入了解阻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某一特征的专家在未来是否受到限制当选择改善不同特征时的进化轨迹。