Population and evolutionary dynamics of recombining genes and alleles in bacteria

项目摘要/摘要 传统上，物种被定义为相互繁殖并产生 有生育能力的后代，但不与其他物种的后代(根据恩斯特·迈尔的生物物种概念)。 然而，很难将这种真核物种的定义应用于微生物，因为即使它们繁殖 在克隆方面，DNA可以在菌株之间和物种之间获得。基因重组允许一种 细菌细胞通过将其他生物的DNA片段整合到自己的DNA片段中来获得新的特征 基因组。重组影响了无数的进化和种群过程，包括 林分多样性、生态位扩展、抗性和毒力决定因素的传播以及快速适应 对新的或变化的环境条件作出反应的变化。这些过程是基本的 对社会和公共健康至关重要的问题，例如新出现的疾病是否由新的 现有菌株的种类或变种，哪些因素使菌株具有抗药性或可传播性，以及病原体如何 会对临床干预和宿主免疫系统作出反应。人们通常认为所有的菌株都会在 在整个物种中以均匀且随机的频率传播。然而，私家侦探实验室最近的研究表明 同一物种的菌株的重组率沿着跨越几个数量级的连续统而变化 大小，不同品系和谱系具有独特的交换模式。原因和 物种内变异对重组的影响还知之甚少，因此我们仍然缺乏一个 整合了这种变异的基因组进化的连贯模型。填补了我们在知识上的空白 重组对于理解微生物中物种的形成和 一旦它们开始分化，就会有保持它们分离的机制。我们提出的研究的目标是 阐明菌株间重组率的差异如何影响种群结构和基因组进化 以及微生物中的物种形成。结合使用比较种群基因组学、实验室实验 和数学模型，我们将回答以下问题：(1)在多大程度上 亲本菌株的遗传距离和生态对重组的影响？(2)如何不同 不同物种的重组模式和遗传单位不同？(3)进化的结果是什么？ 基因组结构和分化的可变重组率？这项研究的成果将有所帮助 解决微生物学中的基本问题，即物种是否存在，如果存在，是什么过程使 它们是分开的、截然不同的。这项拟议的研究也将是朝着开发一种 基于进化的微生物分类框架和物种边界。这些研究的结果 在本申请中提出的建议，预计将带来其他机会，在以下方面进行富有成效的跨学科研究 进化生物学、微生物遗传学、计算生物学和流行病学的界限。

PROJECT SUMMARY/ABSTRACT Species are conventionally defined as groups of individuals that breed with each other and produce fertile offspring, but not with those of other species (according to Ernst Mayr's Biological Species Concept). However, it is difficult to apply this eukaryotic definition of species to microbes because, even if they reproduce clonally, DNA may be acquired between strains and between species. Genetic recombination allows a bacterial cell to acquire novel traits through incorporation of DNA fragments from other organisms into its own genome. Recombination influences a myriad of evolutionary and population processes, including levels of standing diversity, niche expansion, spread of resistance and virulence determinants, and rapid adaptive changes in response to new or fluctuating environmental conditions. These processes are fundamental to questions critical to society and public health, such as whether an emerging disease is caused by a new species or variants of existing ones, what factors make a strain resistant or transmissible, and how a pathogen will respond to clinical interventions and host immune system. It is often assumed that all strains recombine at a uniform frequency and randomly across the entire species. However, recent work from the PI's lab show that recombination rates of strains of the same species vary along a continuum spanning several orders of magnitude, with a unique pattern of exchange for different strains and lineages. The causes and consequences of within-species variation in recombination is poorly understood, and therefore we still lack a coherent model for genome evolution that incorporates this variation. Filling in this gap in our knowledge of recombination has important ramifications for understanding species formation in microbes and the mechanisms that keep them separate once they begin to diverge. The goal of our proposed research is to elucidate how variation in recombination rates between strains impact population structure, genome evolution and speciation in microbes. Using a combination of comparative population genomics, laboratory experiments and mathematical modeling, we will answer the following questions: (1) To what extent does the probability of recombination influenced by the genetic distance and ecology of the parental strains? (2) How do different modes and genetic units of recombination vary across a species? (3) What are the evolutionary consequences of variable recombination rates in genome structure and divergence? Output from this research will help address the fundamental question in microbiology of whether species exist and if so, what processes keep them separate and distinct. The proposed research will also be a significant step forward to developing an evolution-based taxonomical framework and species boundaries for microbes. The results of the studies proposed in this application are expected to lead to other opportunities for fruitful cross-disciplinary research at the boundary of evolutionary biology, microbial genetics, computational biology and epidemiology.