EVOLUTION IN MICROBES--POPULATION STRUCTURE AND GENETICS

这项建议的长期目标是了解 无性微生物种群的进化及其遗传 结构。丰富的遗传和生化信息 对于大肠杆菌和酿酒酵母，允许水平为 对许多其他生物进行分析是不可能的。 最近的研究表明，无性微生物种群表现出 广泛的“有趣的”和复杂的进化反应 类似于二倍体的进化现象，有性繁殖 高等真核生物。特别是，以单一的 克隆，并在简单的非结构化环境中生长，变得多态 在令人惊讶的短时间内。我们将继续，并 完成三组分稳定多态的分析，该多态具有 观察到在一群由单一的 克隆并在葡萄糖限制的连续培养中生长765代。 我们将，i)确定负责相互作用的机制 用于维持多态的组件，ii)确定 相互作用的遗传基础，通过作图、克隆和测序 负责地点，三)确定必要和充分的 建立多态的条件，以及iv)确定 多态在继续进化过程中的动态和命运 人口数量。 此外，我们将分析一个独特的样本库(大约每隔一段时间 10代)来自40多个进化种群的大肠杆菌和S 酿酒酵母，以确定遗传和生化基础的机制 这可能导致建立其他稳定的多态。 在这里，我们的目标将是确定进化变化的范围 它可以以简单的、非结构化的方式产生和维护遗传变异 环境。 除了对种群遗传学和进化很重要外，这些 研究将为人类进化和衰老提供重要信息。 不断增殖的细胞群。对细胞的全面了解 细胞的增殖和基因变化是至关重要的 对医学的许多方面都很重要，其中最重要的是癌症 治疗和衰老。

The long-term objectives of this proposal are to understand the process of evolution in asexual micro-organism populations, and their genetic structure. The wealth of genetic and biochemical information available for Escherichia coli and Saccharomyces cerevisiae permits a level of analysis not possible with many other organisms. Recent work has revealed that asexual micro-organism populations exhibit a wide-range of "interesting" and complex evolutionary responses that are analogous to evolutionary phenomena seen in diploid, sexually reproducing higher eukaryotes. In particular, populations initiated with a single clone, and grown in a simple unstructured environment, become polymorphic within a surprisingly short period of time. We will continue, and complete the analysis of a three component stable polymorphism that has been observed to develop in a population of E coli initiated with a single clone and grown in glucose-limited continuous culture for 765 generations. We will, i) determine the mechanisms responsible for interactions between the components, which serve to maintain the polymorphism, ii) determine the genetic bases for the interactions, by mapping, cloning and sequencing the loci responsible, iii) determine the necessary and sufficient conditions for the establishment of the polymorphism, and iv) determine the dynamics and fate of the polymorphism during continued evolution of the populations. In addition, we will analyze a unique "bank" of samples (taken every about 10 generations) from more that 40 evolving populations of E coli and S cerevisiae, to determine the genetic and biochemical bases for mechanisms which may result in the establishment of other stable polymorphisms. Here, our goal will be to determine the range of evolutionary changes which can generate and maintain genetic variation in simple, unstructured environments. As well as being important to population genetics and evolution, these studies will provide important information on the evolution and aging of proliferating cell populations. The complete understanding of cell proliferation and the genetic changes that cells undergo is critically important to many aspects of medicine, not the least of which are cancer therapy and aging.