Genetic Transfer in the Evolution of Infectious Disease

描述(由申请人提供)：普遍认为 细菌对外来DNA分子的获取起到了重要作用 新病原体的出现。事实上，人们相信，水平转移 是许多微生物进化的一个重要过程。已转接 基因可以提供一些特征，赋予病原体和 使非病原体具有致死性。抗生素耐药性、毒素等基因 产量和寄主专一性都可以水平获得。虽然很多 对水平转移的力学过程有所了解 细菌模型系统，对其历史动态知之甚少 水平转移及其对寄主表型和基因组的影响 有机体。 系统发育分析提供了一个强大的框架来识别水平 转移和检验关于其进化动力学和含义的假说。 我们建议采用现有的系统发育技术并开发新的技术来 在高分辨率下研究水平输送过程及其对大气的影响 对传染病进化的影响。我们还建议使用分子 实验室中的遗传学方法来检验基于系统发育的预测 水平转移。 要分析基因转移，关键是要检查一个可以 水平获取，分布广泛，并允许密集的分类群 取样。高度保守的广布殖民岛(WCI)呈现出 无与伦比的模型系统，用于测试假设和开发方法 更好地理解水平转移。WCI，最早是在 牙周病原菌伴生放线杆菌含有基因 对于细菌坚韧的、非特异性的黏附至关重要的 表面和原纤维的生物发生。序列分析表明，WCI是 分布在广泛的病原体和非病原体中 独特的利基市场。初步的系统发育分析和其他证据表明 WCI经历了多次水平转移事件。 WCI将作为一个模型系统来研究水平运动的过程 调职。我们的目标是：(1)测试和开发能够可靠地 确定历史转移事件，涉及的捐赠者和接受者血统， 以及它们的相对发生日期；(2)建立系统发育 基因组分析的技术和方法以了解病毒的出现 水平转移的致病性；(3)了解病毒的共同进化 遗传岛的组成部分彼此之间以及它们的细菌之间 宿主(S)；(4)确定转移的遗传或系统发育障碍 寄主之间的致病孤岛和；(5)设计可访问的、基于计算机的 水平转移和遗传分析的系统发育和基因组学方法 宿主/寄生虫的共同进化。 WCI系统提供了一个绝佳的机会来理解水平 大规模转移，并开发新的方法，可以 用于分析水平传播、传染病和 毒力在其他系统中的进化。

DESCRIPTION (provided by applicant): It is widely acknowledged that the acquisition of foreign DNA elements by Bacteria has contributed significantly to the emergence of new pathogens. Indeed, horizontal transfer of is believed to be an important process in the evolution of many microorganisms. Transferred genes can provide traits that confer a selective advantage to pathogens and confer virulence on non-pathogens. Genes for antibiotic resistance, toxin production, and host-specificity can all be acquired horizontally. Though much is understood about the mechanical processes of horizontal transfer in bacterial model systems, less is known about the historical dynamics of horizontal transfer and its impact on the phenotype and genomes of host organisms. Phylogenetic analysis offers a powerful framework to identify horizontal transfer and test hypotheses about its evolutionary dynamics and implications. We propose to adapt existing phylogenetic techniques and develop new ones to investigate at high resolution the process of horizontal transfer and its impact on the evolution of infectious disease. We also propose to use molecular genetic methods in the laboratory to test phylogeny-based predictions about horizontal transfer. To analyze gene transfer, it is critical to examine a system that can be horizontally acquired, is widely distributed, and allows for dense taxon sampling. The highly conserved Widespread Colonization Island (WCI) presents an unparalleled model system to test hypotheses and develop methodologies to better understand horizontal transfer. The WCI, first identified in the periodontal pathogen Actinobacillus actinomycetemcomitans, contains genes essential for the tenacious, nonspecific adherence of the bacterium to surfaces, and fibril biogenesis. Sequence analysis shows that the WCI is distributed in a wide array of pathogens and nonpathogens that inhabit very distinct niches. Preliminary phylogenetic analyses and other evidence suggest that the WCI has experienced multiple horizontal transfer events. The WCI will be used as a model system to study the process of horizontal transfer. Our objectives are: (1) to test and develop methods that can reliably identify historical transfer events, the donor and recipient lineages involved, and the relative dates of their occurrence; (2) to develop phylogenetic techniques and methods for genome analysis to understand the emergence of pathogenicity due to horizontal transfer; (3) to understand the co-evolution of the components of a genetic island with each other and with their bacterial host(s); (4) to identify genetic or phylogenetic barriers to the transfer of pathogenicity islands among hosts and; (5) to design accessible, computer-based phylogenetic and genomic methods for the analysis of horizontal transfer and host/parasite co-evolution. The WCI system offers an outstanding opportunity to understand horizontal transfer on a large scale and to develop new methodologies that can be generalized for the analysis of horizontal transfer, infectious disease, and the evolution of virulence in other systems.