The Evolution of Specialists and Generalists

描述（由申请人提供）：了解微生物进化， 被认为对理解疾病和设计 有效的治疗。因此，这项建议旨在研究遗传， 微生物进化的生化和生理机制。的 特别令人感兴趣的是对适应性进化 是可以预测的因为如果进化是可预测的， 可能是设计的，不希望的进化结果（例如，多药 耐药性），更好地了解流行病的起源和演变， 因此，更好的公共卫生战略得以实施。 对微生物进化的理解仍然是难以捉摸的，因为研究 要么被复杂性淹没，要么被简化为微不足道的可预测性。 然而，E.大肠杆菌代表了一种独特的平衡， 复杂和简单。它是足够复杂的， 适应性反应-专家，通才，专家-出现，但它是 简单到每个都可以详细分析。之间的平衡 复杂性和简单性使适应性进化的可预测性， 追究 强频率依赖性选择维持了乳糖操纵子的变异， E.大肠杆菌在竞争限制混合物的半乳糖苷。长期 恒化器竞争实验表明，新的适应可能会加强 频率依赖性，或者它们可以将其减少到 多态性丢失。平衡的多态性可以产生于单个 分身专家对特定半乳糖苷的进化促进了 多态性，并表明，在分子水平上的权衡支配 多样性的演变。多面手的进化（能够 有效代谢所有半乳糖苷）使多态性不稳定， 这表明权衡并非不可避免。 基因，生理和生化机制，促进 将确定这些多态性的出现和丧失。复制 实验将决定进化结果的可预测性。演变 将对菌株进行分析，以确定群体水平的相互作用， 导致多态性的稳定或不稳定。生化研究 将决定专家进化的生理基础， 通才，并确定贸易油的分子原因。突变 将对变化进行排序，以确定 分子水平。

DESCRIPTION (provided by applicant): An understanding of microbial evolution is seen as increasingly important to an understanding of disease and the design of effective therapies. As such, this proposal aims to investigate the genetic, biochemical and physiological mechanisms underpinning evolution in microbes. Of particular interest is an assessment of the degree to which adaptive evolution is predictable. For if evolution is predictable, more efficacious therapies might be designed, undesirable evolutionary outcomes (e.g. multi-drug resistance) avoided, the origin and evolution of epidemics better understood, and as a consequence better strategies in public health implemented. An understanding of microbial evolution remains elusive because studies are either overwhelmed by complexity or reduced to the trivially predictable. However, the lactose pathway of E. coli represents a unique balance between complexity and simplicity. It is sufficiently complex that a diversity of adaptive responses - specialists, generalists, commensals - arise, yet it is sufficiently simple that each can be analyzed in detail. This balance between complexity and simplicity enables the predictability of adaptive evolution to be investigated. Strong frequency dependent selection maintains variation in lactose operons of E. coli during competition for limiting mixtures of galactosides. Long-term chemostat competition experiments reveal that new adaptations may intensify the frequency dependence or they may diminish it to the point whereby the polymorphism is lost. Balanced polymorphisms can arise from within a single clone. The evolution of specialists towards particular galactosides promotes polymorphism and suggests that trade-offs at the molecular level govern the evolution of diversity. The evolution of generalists (strains capable of efficiently metabolizing all galactosides) destabilizes polymorphisms and demonstrates that trade-offs are not inevitable. The genetic, physiological and biochemical mechanisms that promote the appearance, and loss, of these polymorphisms will be determined. Replicate experiments will determine the predictability of evolutionary outcomes. Evolved strains will be analyzed to determine the population level interactions that result in stabilizing or destabilizing the polymorphisms. Biochemical studies will determine the physiological basis for the evolution of specialists and generalists, and to determine the molecular causes of trade-oils. Mutational changes will be sequenced to determine the predictably of evolution at the molecular level.