Population and evolutionary dynamics of recombining genes and alleles in bacteria

细菌重组基因和等位基因的种群和进化动力学

• 批准号: 10276111
• 负责人: Cheryl Marie P Andam
• 金额: $ 30.32万
• 依托单位: STATE UNIVERSITY OF NEW YORK AT ALBANY
• 依托单位国家: 美国
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-08-09 至 2026-06-30
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10276111
• 关键词: Address; Alleles; Bacteria; Biological; Biology; Cells; Clinical; Computational Biology; DNA; Disease; Ecology; Epidemiology; Evolution; Fostering; Frequencies; Genes; Genetic; Genetic Recombination; Genome; Genomics; Goals; Health; Human; Immune system; Individual; Intervention; Knowledge; Lead; Microbe; Microbial Genetics; Microbiology; Mission; Modeling; National Institute of General Medical Sciences; Organism; Output; Pattern; Population; Population Process; Probability; Process; Public Health; Research; Resistance; Societies; Structure; Taxonomy; Variant; Virulence; Work; base; burden of illness; comparative; innovation; laboratory experiment; mathematical model; novel; offspring; pathogen; resistant strain; response; trait

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.

项目摘要/摘要 物种通常定义为彼此繁殖并产生的个体群体 肥沃的后代，但与其他物种的后代没有（根据恩斯特·梅尔（Ernst Mayr）的生物物种概念）。 但是，很难将这种物种的真核定义应用于微生物，因为即使它们繁殖 克隆地，可以在菌株和物种之间获得DNA。遗传重组允许 细菌细胞通过将来自其他生物的DNA片段纳入其自身而获得新的特征 基因组。重组会影响无数的进化和人口过程，包括 站立多样性，利基扩展，抵抗力和毒力决定因素的传播以及快速自适应 响应新或波动的环境条件的变化。这些过程对于 对社会和公共卫生至关重要的问题，例如新兴疾病是否是由新的 现有的物种或变体，哪些因素会产生抗应变或可传染的因素，以及病原体如何 将对临床干预措施做出反应和宿主免疫系统。通常认为所有菌株在 整个物种的均匀频率和随机的频率。但是，PI实验室的最新工作表明 同一物种菌株的重组率沿着几个顺序的连续体有所不同 大小，具有独特的交换不同菌株和谱系的模式。原因和 重组中种类内部变化的后果知之甚少，因此我们仍然缺乏 结合这种变异的基因组演化的相干模型。在我们的知识中填补了这一空白 重组具有了解微生物中物种形​​成和 一旦它们开始分歧，它们将它们分开的机制。我们提出的研究的目的是 阐明菌株之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。结合了比较种群基因组学，实验室实验 和数学建模，我们将回答以下问题：（1） 重组受父母菌株的遗传距离和生态学影响？ （2）如何不同 重组的模式和遗传单位因物种而异？ （3）进化后果是什么 基因组结构和差异的可变重组率的变化率？这项研究的输出将有所帮助 解决微生物学是否存在的基本问题，如果是，则保留哪些过程 它们分开而独特。拟议的研究也将是发展一个重要的一步 基于进化的分类框架和微生物的物种边界。研究结果 预计在本申请中提出的建议将为其他机会提供其他机会 进化生物学，微生物遗传学，计算生物学和流行病学的边界。