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.

项目摘要/摘要自适应进化涉及同时优化多个适应性相关的特征。这些特征可以是投影到一个多维空间中，称为性状空间。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。一个生物的适应性环境通常取决于多个特征。对于酵母，这些特征包括发酵，呼吸和固定相性能。虽然在某些情况下可能有可能改进独立的多种健身性质，某些与健身相关的特征也可能受到限制其他与健身有关的特征的多效影响，导致了权衡。 Sherlock实验室的先前工作已经表明，在含葡萄糖的，碳限制的培养基中进化后，帕累托的前沿，指示基本的权衡，在固定阶段和呼吸之间以及呼吸之间出现和发酵，尽管不在固定相和发酵之间。在这里，我的目的是了解酵母增长周期中适应性的限制以及为什么这种与健身有关特征，但没有其他人。我将在不可发酵的碳源中进化的条形码酵母在固定阶段花费的时间。这种实验设计消除了完全发酵的选择，并且创建不同程度的呼吸和固定阶段性能的选择程度，例如两天转移制度主要选择呼吸表现，而在10天的转移方案中阶段性能将更重要。在这些条件下，固定相位性能可能是免费的为了增加发酵性能的不受约束，导致出现在这些有机健康的成分。免于发酵性能限制的自由也可能允许酵母同时提高呼吸和固定相表现。除表型分析，我还将表征出现的基本适应性突变的分子基础深入了解生物物理机制，以防止多种特征同时优化。最后，我将进一步发展特定的自适应突变体，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未来是否有限选择改善不同性状时的进化轨迹。