Population and evolutionary dynamics of recombining genes and alleles in bacteria

项目总结/摘要 物种通常被定义为相互繁殖并生产的个体群体 繁殖后代，但不能与其他物种（根据恩斯特·迈尔的生物物种概念）。 然而，将这种真核生物的物种定义应用于微生物是困难的，因为即使它们繁殖， 克隆地，DNA可以在菌株之间和物种之间获得。基因重组允许 细菌细胞通过将其他生物体的DNA片段整合到自己的DNA片段中而获得新的特性 基因组进化影响着无数的进化和种群过程，包括 现存多样性、生态位扩展、抗性和毒力决定因素的传播以及快速适应性 对新的或波动的环境条件作出反应的变化。这些过程对于 对社会和公共卫生至关重要的问题，例如新出现的疾病是否由新的 物种或现有物种的变种，什么因素使菌株具有抗性或可传播性，以及病原体如何 将对临床干预和宿主免疫系统作出反应。通常假设所有菌株在 在整个物种中是均匀的随机的。然而，PI实验室最近的研究表明， 相同物种的菌株的重组率沿着跨越几个数量级的连续体变化， 规模，与不同的菌株和血统交换的独特模式。的原因和 重组中种内变异的后果知之甚少，因此我们仍然缺乏一个 基因组进化的一个连贯的模型，包括这种变化。填补了我们知识上的空白 重组对于理解微生物中的物种形成具有重要的分支， 一旦它们开始分离，我们研究的目标是 阐明菌株间重组率的变化如何影响种群结构、基因组进化 和微生物的物种形成。利用比较群体基因组学、实验室实验 和数学模型，我们将回答以下问题：（1）在多大程度上的概率， 重组的遗传距离和生态的亲本菌株的影响？(2)如何做不同的 重组的模式和遗传单位在不同物种之间是不同的？(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助于 解决微生物学中的一个基本问题，即物种是否存在，如果存在，是什么过程保持 他们是分开的，是不同的。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。研究结果 在此应用中提出的，预计将导致其他富有成效的跨学科研究的机会， 进化生物学、微生物遗传学、计算生物学和流行病学的边界。

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.