Adaptation, Tradeoffs and Specialized Metabolism in Experimental and Natural Populations

生物体对环境的适应与导致专业化的祖先能力的丧失之间的关系是什么？一种可能性是，当前生态位中缺乏对某些能力的选择，因此，退化未使用系统的突变可以中性地积累(即。“你不使用它，你就会失去它”)。或者，可能存在具有多重（即多效性）效应的特定突变：它们可能在一种环境中增加适应性，但在另一种环境中具有拮抗的生理副作用，降低性能。该项目将结合实验室进化和自然种群的使用，以解决细菌适应不同生长环境的机制基础。这个为期一年的项目的主要方法是检查在甲醇和/或琥珀酸盐上进化的甲基细菌AM1的实验种群，这两种底物需要非常不同的代谢途径。对许多细菌的观察表明，获得在单碳（C1）化合物（如甲醇）上生长的能力反复且独立地与在许多或所有多碳化合物上生长能力的丧失有关，这使其成为研究此类权衡的自然相关系统。根据竞争适应度分析，已经繁殖了1200多代的实验室种群已经明显适应并专门适应了各自的生长基质。该项目的第一个目标是利用生理、分析和功能基因组学方法，扩展和整合对各种全系统表型水平的适应和专业化的研究。其次，将采用一种新的超低成本重测序技术来全面识别基因型变化（点突变和/或基因组重排），然后对其对适应和/或专业化的贡献进行严格测试。最后，C1和多碳代谢之间的权衡将通过对甲基杆菌属分离物的检查扩展到自然种群。该项目将提供一个模型，将进化的实验研究与跨自然分离株的相同过程的比较分析结合起来。这项工作的广泛影响包括增加了对细菌种群适应和专门适应其环境的过程的理解。这对于在微生物水平上理解生物多样性的起源和维持至关重要。鉴于微生物在介导生化循环、有毒化合物降解以及它们与多细胞生物的各种积极和消极相互作用中的关键作用，这些信息具有重要的实际意义。最后，这个正在进行的项目将为研究生和本科生提供宝贵的机会，让他们接触并参与到进化、生态学、微生物学和系统生物学交叉的高度跨学科的研究中。这种广泛的训练和经验对于解决超越传统学术领域界限的重要但困难的问题至关重要。

What underlies the relationship between adaptation of organisms to their environment and loss of ancestral capacities that result in specialization? One possibility is an absence of selection for certain capacities in the current niche such that mutations that degrade unused systems can accumulate neutrally (i.e. "you don't use it you lose it"). Alternatively, there may be particular mutations that have multiple (i.e. pleiotropic) effects: they may increase fitness in one environment but have antagonistic physiological side-effects that decrease performance in another environment. This project will combine the use of laboratory-evolved and natural populations to address the mechanistic bases that underlie tradeoffs in the adaptation of bacteria to different growth environments.The primary approach of this one-year project is to examine experimental populations of Methylobacterium extorquens AM1 that have been evolved on methanol and/or succinate, two substrates that require very different metabolic pathways. The observation across numerous bacteria that acquisition of the ability to grow on single-carbon (C1) compounds such as methanol has repeatedly and independently been associated with loss of the ability to grow on many or all multiple-carbon compounds makes this a naturally relevant system to examine such tradeoffs. Based upon competitive fitness assays the laboratory populations, already propagated for over 1200 generations, have clearly adapted and specialized to their respective growth substrate. The first aim of this project is to extend and integrate the examination of adaptation and specialization across a variety of system-wide phenotypic levels using physiological, analytical and functional genomics approaches. Second, a new ultra-low-cost resequencing technique will be employed to comprehensively identify the genotypic changes (point mutations and/or genome rearrangements) that will then be rigorously tested for their contribution to adaptation and/or specialization. Finally, tradeoffs between C1 and multi-carbon metabolism will be extended to natural population through an examination of isolates from across the Methylobacterium genus.This project will provide a model for the integration of experimental studies of evolution with a comparative analysis of the same processes across natural isolates. Broader impacts of this work include increased understanding of the processes through which bacterial populations adapt and specialize to their environment. This is critical for understanding the origin and maintenance of biological diversity at the microbial level. Given the key role of microbes in mediating biochemical cycling, degradation of toxic compounds, and their diverse positive and negative interactions with multi-cellular organisms, this information has significant practical benefit. Finally, this ongoing project will provide valuable opportunities for both graduate and undergraduate students to be exposed to and involved in highly interdisciplinary research at the intersection of evolution, ecology, microbiology, and systems biology. Such broad training and experience is critical for tackling important but difficult questions that transcend the boundaries of traditional academic fields.