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: 10588134
• 负责人: Louis-Marie Bobay
• 金额: --
• 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 2023-08-14
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10588134
• 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; 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; deep learning; gene conservation; gene function; genome analysis; genomic data; high throughput screening; homologous recombination; innovation; large datasets; microbial; novel strategies; resistance gene; tool; trait; virulence gene

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 在与性生物的合同中，细菌中种群遗传学的机制要少得多 理解。细菌种群遗传学的两个基本方面仍然如此 研究了：i）DNA交换对细菌基因组进化和 人口在很大程度上是未知的。 ii）自适应进化的突出尚未 在细菌中全面评估。确定重组和适应性进化如何 影响细菌是了解这些生物的生物学并发展相关的关键 它们的进化模型。尽管细菌在克隆上繁殖，但有越来越多的证据表明 这些生物中的绝大多数能够通过交换来同源重组 在类似于动物和植物基因转化的过程中的DNA部分。这个过程 增强微生物适应压力或不断变化的环境的能力以及交换 细菌菌株之间的DNA是人类健康的主要关注点，例如 毒力和抗生素抗性基因的转移。尽管这一过程的核心作用，但 在细菌中，重组的速率和模式仍未解决。重组程度 通常从一项研究到另一项研究都有很大不同，结果，相同的细菌物种可以 在一项研究中被认为是克隆的，并且在另一项研究中高度重组。在这个项目中，我们 建议重新评估沿着基因组的重组率和模式的景观 数百种细菌。根据大概使用新的方法论框架 贝叶斯计算和深度学习，我们将确定塑造变化的因素 跨细菌的重组率。我们还将发现整个重组率的变化 细菌染色体（即热点和冷点）。我们的费率估算还将使我们能够 研究重组如何驱动细菌基因组结构的演变，包括 基因含量的营业额。最后，我们将量化适应性进化对细菌的影响， 由于细菌有效的大量细菌，它可能大于其他生物 人口规模。我们还将调查适应与 重组，并确定负责适应的基因/途径。总而言之，这 研究将评估数百种物种重组的速率和模式， 确定推动重组过程演变的因素，揭示了 细菌的适应性进化以及重组与适应性之间的相互作用。