Using Experimental Evolution to Evaluate Environmental Effects on Microbial Mutation and Adaptation

项目总结 在自然界和人类的微生物群中，由于可获得性的波动，微生物经常面临挑战 资源和营养--一种被称为盛宴/饥荒的生活方式。以前的研究调查了微生物对 盛宴/饥荒关注的是让微生物在极端饥饿中生存的特定适应，通常 忽视了资源的最终补充如何影响进化。然而，由于进化 在生长和生存之间的权衡，进化的分子、细胞和行为表型 对盛宴/饥荒的反应可能根据饥饿的持续时间和严重程度而有所不同。常见的适应于 资源限制包括通过营养能力扩大代谢能力和增加 通过向交叉饲喂生态型的多样化提高效率。因为微生物的新陈代谢会受到很多因素的制约 与生物相关的因素，包括氧气的存在，这可能会使进化复杂化，限制潜力 自适应轨迹。我实验室的研究重点是微生物如何适应和多样化新的复合体 通过将多组学、系统微生物学方法应用于实验进化来保护环境。我们计划 通过进行适应性研究，研究氧气供应如何影响微生物进化到丰盛/饥荒 两种细菌的实验室进化实验，兼性厌氧菌大肠杆菌和 挑剔的耐氧厌氧菌皱纹乳杆菌。我们将根据健康结果来描述人口的特征， 常见的适应突变和多样化模式，以确定氧气如何影响适应 盛宴/饥荒条件。我们将通过表征常见的适应性突变对 利用转录组学和高通量表型分析的微生物生理学。此外，由于氧气可以改变 地形的适应性通过影响突变的速率和光谱，我们还将执行 兼性厌氧、好氧厌氧和专性突变积累试验 在有氧和无氧条件下的厌氧细菌种类。对微生物进化的研究已经 由于相关挑战，历史上被忽视的挑剔微生物和厌氧环境 他们的文化。我们的研究将提供关于生物进化过程的基础知识 微生物生命树中被忽视的一部分，在人类中占很大比例 微生物组。

PROJECT SUMMARY In nature and human microbiomes, microbes regularly face challenges due to fluctuations in the availability of resources and nutrients - a lifestyle termed feast/famine. Previous studies investigating microbial adaptation to feast/famine have focused on the specific adaptations that allow microbes to survive extreme starvation, often overlooking how the eventual replenishment of resources affects evolution. However, due to evolutionary tradeoffs between growth and survival, the molecular, cellular, and behavioral phenotypes that evolve in response to feast/famine may vary based on the duration and severity of starvation. Common adaptations to resource limitation include expanding metabolic capability through nutritional competence and increasing efficiency by diversification into cross-feeding ecotypes. As microbial metabolism can be constrained by many biologically relevant factors, including the presence of oxygen, this can complicate evolution and limit potential adaptive trajectories. Research in my lab focuses on how microbes adapt and diversify in novel complex environments by applying multi-omic, systems microbiology approaches to experimental evolution. We plan to investigate how oxygen availability shapes microbial evolution to feast/famine by conducting an adaptive laboratory evolution experiment with two bacterial species, the facultative anaerobe Escherichia coli, and the fastidious aerotolerant anaerobe Lactobacillus crispatus. We will characterize populations for fitness outcomes, common adaptive mutations, and patterns of diversification to determine how oxygen influences adaptation to feast/famine conditions. We will follow up by characterizing the effects of common adaptive mutations on microbial physiology using transcriptomics and high-throughput phenotyping. Further, as oxygen can shift the topography of the adaptive landscape by affecting the rate and spectra of mutations, we will also perform mutation accumulation experiments on facultatively anaerobic, aerotolerant anaerobic, and obligately anaerobic bacterial species in the presence and absence of oxygen. Studies of microbial evolution have historically neglected fastidious microorganisms and anaerobic environments due to the challenges associated with their culture. Our research will provide fundamental knowledge about evolutionary processes in a neglected fraction of the microbial tree of life that accounts for a significant proportion of the human microbiome.