The Evolution of Specialists and Generalists

专家和通才的演变

• 批准号: 6526199
• 负责人: Antony M. DEAN
• 金额: $ 25.82万
• 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/6526199
• 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（由申请人提供）：对微生物进化的理解是 被认为对理解疾病和设计越来越重要 有效的疗法。因此，该建议旨在研究遗传， 生化和生理机制是微生物中进化的基础。的 特别的兴趣是评估自适应演化的程度 是可预测的。因为如果进化是可以预测的，则更有效的疗法 可能是设计的，不良的进化结果（例如，多药 避免抵抗，流行病的起源和演变更好地理解， 因此，实施了更好的公共卫生策略。 对微生物进化的理解仍然难以捉摸，因为研究是 要么被复杂性不知所措，要么还原为可预测的。 但是，大肠杆菌的乳糖途径代表了独特的平衡 复杂性和简单性。足够复杂的是多样性 自适应反应 - 专家，通才，共生 - 出现了，但这是 非常简单，可以详细分析每个。这之间的平衡 复杂性和简单性使自适应演变的可预测性达到 被调查。 强频率依赖性选择保持乳糖操纵子的变化 大肠杆菌在限制半乳糖苷混合物的竞争过程中。长期 化学稳定竞争实验表明，新的适应可能会加剧 频率依赖性，否则它们可能会将其减少到 多态性丢失了。平衡的多态性可能来自单个内部 克隆。专家向特定半乳糖剂的演变促进 多态性，表明分子水平的权衡控制 多样性的演变。通才的演变（能够 有效地代谢所有半乳糖剂）破坏了多态性和 证明权衡并不是不可避免的。 促进遗传，生理和生化机制 这些多态性的外观和损失将被确定。复制 实验将确定进化结果的可预测性。进化 将分析菌株以确定人口水平的相互作用 导致稳定或破坏多态性。生化研究 将确定专家发展的生理基础 通才，并确定贸易油的分子原因。突变 更改将进行测序以确定在 分子水平。