Understanding Horizontal Gene Transfer in Bacteria and Archaea: Units of Transfer and Modes of Integration

微生物进化最重要但知之甚少的驱动因素之一是水平基因转移(HGT)，即整个基因或大基因片段在两个细菌细胞之间传递，有时代表不同的物种。了解HGT是如何发生的，可能有助于揭示微生物对新的生态位的适应、抗生素耐药基因的进化和传播、新兴病原体的兴起以及微生物之间的竞争。拟议研究的结果将包括用于分析HGT事件的新计算方法和技术、供生物学家使用的开源软件工具，以及对海洋细菌中不同类型的HGT事件的有价值的新见解。该项目将培训三名博士生和至少三名本科生掌握跨学科研究技能。该项目还将向几名高中生介绍生物信息学研究，并为几名高中科学教师提供计算分子进化方面的培训。研究成果也将被整合到研究生和本科生水平的课堂教学中。该项目侧重于HGTS的两个基本特性。第一个属性涉及HGT事件的“模式”，它定义了转移的基因是“相加的”还是“替换的”，即它是将自己作为新基因添加到受体基因组中还是替换现有的同源基因。第二个属性涉及HGT事件的单位，即HGT事件是否涉及一个基因片段、整个基因、几个基因或整个操纵子。该项目需要开发新的、广泛适用的计算方法来推断HGT事件的模式和单位，将这些方法应用于微生物基因组数据集以调查HGT事件的不同模式和单位在不同进化情景中的频率和作用，以及测试将HGT事件的这些属性与进化差异、HGT整合机制和基因功能联系起来的具体假设。

One of the most important, but poorly understood, drivers of microbial evolution is horizontal gene transfer (HGT), when whole genes or large gene fragments are passed along between two bacterial cells, sometimes representing different species. Understanding how HGT occurs may shed light on the adaptation of microbes to new ecological niches, evolution and spread of antibiotic resistance genes, the rise of emerging pathogens, and competition between microbes. The outcomes of the proposed research will include new computational methods and techniques for analyzing HGT events, open-source software tools for use by biologists, and valuable new insights into different types of HGT events in oceanic bacteria. The project will train three PhD students and at least three undergraduate students in interdisciplinary research skills. The project will also introduce several high-school students to bioinformatics research and provide training to several high-school science teachers on computational molecular evolution. Research results will also be integrated into graduate and undergraduate level classroom teaching.The project focuses on two fundamental properties of HGTs. The first property deals with the 'mode' of an HGT event, which defines whether the transferred gene is 'additive' or 'replacing', i.e., whether it adds itself as a new gene to the recipient genome or replaces an existing homologous gene. The second property concerns the units of HGT events, i.e., whether the HGT event involved a gene fragment, entire gene, several genes, or entire operons. The project entails development of new, broadly applicable, computational methods to infer the modes and units of HGT events, application of these methods to microbial genome datasets to investigate the frequencies and roles of the different modes and units of HGT events in various evolutionary scenarios, and testing of specific hypotheses relating these properties of HGT events to evolutionary divergence, HGT integration mechanism, and gene function.