Adaptation, Tradeoffs and Specialized Metabolism in Experimental and Natural Populations

生物体对其环境的适应和祖先能力的丧失之间的关系是什么？一种可能性是，在当前的利基市场中，缺乏对某些能力的选择，从而使未使用的系统降级的突变可以中性地积累(即“你不使用它，你就会失去它”)。或者，可能有特定的突变具有多种(即多效性)效应：它们可能在一个环境中提高适应性，但具有拮抗的生理副作用，从而降低在另一个环境中的表现。这个项目将结合使用实验室进化的种群和自然种群来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/或琥珀酸这两种需要非常不同的代谢途径的底物上进化的实验种群。对许多细菌的观察表明，获得在单碳(C1)化合物(如甲醇)上生长的能力一再独立地与丧失在许多或所有多碳化合物上生长的能力有关，这使这成为一个自然相关的系统来检查这种权衡。根据竞争适合度分析，实验室种群已经繁殖了1200多代，显然已经适应并专门适合它们各自的生长基质。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，在各种全系统表型水平上扩展和整合适应和专业化审查。其次，将采用一种新的超低成本重新测序技术来全面识别基因类型变化(点突变和/或基因组重排)，然后将严格测试这些变化对适应和/或专业化的贡献。最后，通过对甲氧半乳杆菌属菌株的研究，将把C1和多碳代谢之间的权衡扩展到自然种群。这个项目将提供一个模型，用于将进化的实验研究与自然菌株之间相同过程的比较分析相结合。这项工作的更广泛的影响包括增加对细菌群体适应和专门化其环境的过程的理解。这对于在微生物层面上理解生物多样性的起源和维持至关重要。鉴于微生物在调节生化循环、有毒化合物的降解以及它们与多细胞生物体的不同正负相互作用方面的关键作用，这一信息具有重大的实际意义。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，让他们接触和参与进化论、生态学、微生物学和系统生物学交叉学科的高度交叉研究。这种广泛的培训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.