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

项目摘要/摘要 适应性进化涉及同时优化多个与适应度相关的性状。这些特征可能是 投射到称为特征空间的多维空间中。绘制单个人可访问的特征空间 突变可以揭示对生物体健康施加的限制。生物体在生物体中的适合性 环境通常依赖于不止一种特性；对于酵母来说，这些特性包括发酵， 呼吸作用，和静止期表现。虽然在某些情况下可能会改进 多个与健康相关的性状独立存在，某些与健康相关的性状也可能受到限制，因为 其他与健康相关的特征的多效性效应，导致了一种权衡。福尔摩斯实验室之前的工作 已经表明，在含葡萄糖、碳有限的介质中进化后，帕累托面临着， 指示潜在的权衡，出现在静止期和呼吸之间，以及呼吸之间 和发酵，虽然不是在固定相和发酵之间。在这里，我的目的是理解 在酵母生长周期中对适合度的限制以及为什么在一些与适合度相关的 特征，而不是其他。我将在非发酵碳源中进化条形码酵母，其中含有不同数量的 停留在静止阶段的时间。这种实验设计完全取消了对发酵的选择，并且 为呼吸和静止阶段的表现创造不同程度的选择，例如，两天 转移区主要根据呼吸性能进行选择，而在10天转移区是固定的 阶段性能将变得更加重要。在这些条件下，固定相性能可能是自由的 不受发酵性能的限制而增加，导致出现帕累托前沿 这些是身体健康的组成部分。不受发酵性能限制的自由也可以允许 酵母菌以最大限度地提高呼吸作用和静止相性能的同时。除了表型外 分析，我还将描述潜在的适应性突变的分子基础 对生物物理机制的洞察(S)防止多个性状同时优化。 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性状的专家在未来是否受到限制 当被选择用于改进不同的特征时，进化轨迹。

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.