Investigating the impact and patterns of homologous recombination and adaptive evolution on bacterial genomes

研究同源重组和适应性进化对细菌基因组的影响和模式

• 批准号: 10360686
• 负责人: Louis-Marie Bobay
• 金额: $ 28.86万
• 依托单位: UNIVERSITY OF NORTH CAROLINA GREENSBORO
• 依托单位国家: 美国
• 财政年份: 2020
• 资助国家: 美国
• 起止时间: 2020-04-01 至 2025-03-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10360686
• 关键词: Address; Affect; Animals; Antibiotic Resistance; Architecture; Automobile Driving; Bacteria; Bacterial Chromosomes; Bacterial Genome; Bacterial Infections; Bayesian Analysis; Biology; Chromosomes; Clustered Regularly Interspaced Short Palindromic Repeats; Contracts; DNA; Data Set; Ecology; Elements; Environment; Epidemic; Evolution; Fibrinogen; Frequencies; Gene Conversion; Genes; Genetic Models; Genetic Recombination; Genome; Genomics; Health; Hot Spot; Human; Individual; Knowledge; Laboratories; Maps; Mediating; Methodology; Methods; Modeling; Organism; Pathogenicity; Pathway interactions; Pattern; Phenotype; Plants; Play; Population; Population Genetics; Population Sizes; Process; Prokaryotic Cells; Recombinants; Role; Sampling; Shapes; Spottings; Stress; Structure; Testing; Time; Variant; Virulence; Virulent; Work; base; deep learning; gene function; genome analysis; genomic data; high throughput screening; homologous recombination; innovation; large datasets; microbial; novel strategies; resistance gene; tool; trait

Project summary In contract to sexual organisms, the mechanisms of population genetics in bacteria are far less understood. Two fundamental aspects of bacterial population genetics remain sorely understudied: i) the impact of DNA exchange on the evolution of bacterial genomes and populations is largely unknown. ii) the prominence of adaptive evolution has not been comprehensively assessed in bacteria. Determining how recombination and adaptive evolution impact bacteria is key to understand the biology of these organisms and to develop relevant models of their evolution. Although bacteria reproduce clonally, there is increasing evidence that the vast majority of these organisms are capable of homologous recombination by exchanging pieces of DNA in a process similar to gene conversion in animals and plants. This process enhances microbial capacity to adapt to stresses or changing environments and the exchange of DNA between bacterial strains is a major concern for human health as exemplified by the transfer of virulence and antibiotic resistance genes. Despite the central role of this process, the rates and patterns of recombination remain unresolved in bacteria. The extent of recombination often varies greatly from one study to another and, as a result, the same bacterial species can be perceived as clonal in one study and highly recombining in another. In this project, we propose to re-evaluate the landscape of recombination rates and patterns along the genomes of hundreds of bacterial species. Using new methodological frameworks based on Approximate Bayesian Computation and Deep Learning, we will identify the factors shaping the variation in recombination rate across bacteria. We will also uncover recombination rate variation across bacterial chromosomes (i.e. hot spots and cold spots). Our rate estimates will also allow us to study how recombination drives the evolution of genomic architecture of bacteria, including turnover in gene content. Finally, we will quantify the impact of adaptive evolution in bacteria, which may be substantially larger than in other organisms due to large bacterial effective population sizes. We will also investigate the relationship between adaptation and recombination, and identify the genes/pathways responsible for adaptation. In summary, this study will evaluate the rates and patterns of recombination across hundreds of species, determine the factors driving the evolution of the recombination process, reveal the role of adaptive evolution in bacteria, and the interplay between recombination and adaptation.

项目摘要 与有性生物相比，细菌中的群体遗传学机制要少得多 明白细菌群体遗传学的两个基本方面仍然令人痛苦 未充分研究：i）DNA交换对细菌基因组进化的影响， 人口大部分是未知的。（二）适应性进化的重要性并没有被 在细菌中进行全面评估。确定重组和适应性进化 影响细菌是了解这些生物的生物学和开发相关的 他们的进化模型。尽管细菌是克隆繁殖的，但越来越多的证据表明， 这些生物体中的绝大多数能够通过交换 这一过程类似于动物和植物的基因转换。这个过程 增强微生物适应压力或变化环境的能力， 细菌菌株之间的DNA是人类健康的主要关注点， 毒力和抗生素抗性基因的转移。尽管这一进程发挥着核心作用， 在细菌中重组的速率和模式仍然没有解决。重组的程度 在不同的研究中，不同的细菌种类往往会有很大的差异，因此，同一种细菌可以 在一项研究中被认为是克隆的，而在另一项研究中被认为是高度重组的。本课题 建议重新评估重组率和模式的景观沿着的基因组， 数百种细菌。使用基于近似值的新方法框架 贝叶斯计算和深度学习，我们将确定影响 细菌之间的重组率。我们还将揭示重组率的变化， 细菌染色体（即热点和冷点）。我们的利率估计也将允许我们 研究重组如何驱动细菌基因组结构的进化，包括 基因含量的转换。最后，我们将量化细菌适应性进化的影响， 由于大的细菌有效地抑制了细菌的生长， 人口规模。我们还将研究适应与 重组，并确定负责适应的基因/途径。总之，这 这项研究将评估数百个物种的重组率和模式， 确定驱动重组过程演变的因素，揭示 细菌的适应性进化，以及重组和适应之间的相互作用。