The Evolution of Specialists and Generalists

专家和通才的演变

• 批准号: 6630488
• 负责人: Antony M. DEAN
• 金额: $ 25.77万
• 依托单位: UNIVERSITY OF MINNESOTA
• 依托单位国家: 美国
• 财政年份: 2001
• 资助国家: 美国
• 起止时间: 2001-08-01 至 2005-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6630488
• 关键词: Escherichia coli; SDS polyacrylamide gel electrophoresis; biochemical evolution; gene frequency; gene mutation; genetic polymorphism; genetic strain; hydrolysis; lac operon; microarray technology; microorganism population study; molecular genetics; natural selections; nuclear magnetic resonance spectroscopy; nucleic acid sequence; population genetics; statistics /biometry; systematic biology

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.

描述(申请人提供)：对微生物进化的理解是 被认为对了解疾病和设计 有效的治疗方法。因此，这项提议的目的是研究基因， 支持微生物进化的生化和生理机制。的 尤其令人感兴趣的是对适应性进化的程度的评估 是可以预测的。因为如果进化是可预测的，那么更有效的治疗方法 可能是设计好的、不受欢迎的进化结果(例如多种药物 抗药性)避免，更好地了解流行病的起源和演变， 因此，实施了更好的公共卫生战略。 对微生物进化的理解仍然难以捉摸，因为研究 要么被复杂性压倒，要么沦落到微不足道的可预测性。 然而，大肠杆菌的乳糖途径代表了一种独特的平衡 复杂性和简单性。它足够复杂，以至于各种各样的 适应性反应--专家、多面手、共同点--出现了，但它是 足够简单，每一个都可以被详细分析。这两者之间的平衡 复杂性和简单性使自适应进化的可预测性 被调查。 强烈的频率依赖性选择保持乳糖操纵子的变异 在竞争限制半乳糖苷混合物的过程中，大肠杆菌。长期的 恒化器竞争实验表明，新的适应可能会加剧 频率依赖性，否则它们可能会将其降低到这样的程度 多态就消失了。平衡的多态可能产生于单个 克隆人。专家对特定半乳糖苷的进化促进了 多态，并表明分子水平上的权衡决定了 多样性的进化。多面手的进化(品系能够 有效代谢所有半乳糖苷)会破坏多态和 表明权衡并不是不可避免的。 基因、生理和生化机制促进了 这些多态的出现和丢失将被确定。复制 实验将决定进化结果的可预测性。进化的 将对菌株进行分析以确定种群水平的相互作用 导致多态稳定或不稳定。生化研究 将决定专家进化的生理基础和 多面手，并确定贸易的分子原因--油。突变 将对变化进行排序，以确定在 分子水平。