Genetic Transfer in the Evolution of Infectious Disease

描述（由申请人提供）：人们普遍认为， 细菌获得外源DNA成分的作用 新病原体的出现。事实上，人们认为， 是许多微生物进化的重要过程。转移 基因可以提供赋予病原体选择优势的性状， 赋予非病原体毒性。抗生素抗性基因、毒素基因 生产和宿主特异性都可以水平获得。尽管还很 了解水平转移的机械过程， 细菌模型系统中，对细菌的历史动力学知之甚少。 水平转移及其对宿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，以确定水平 转移和测试有关其进化动力学和影响的假设。 我们建议调整现有的系统发育技术，并开发新的系统发育技术， 研究在高分辨率的水平转移过程及其 对传染病演变的影响。我们还建议使用分子 实验室中的遗传学方法来测试基于遗传学的预测， 横向转移 为了分析基因转移，关键是要检查一个系统， 水平获得，广泛分布，并允许密集的分类单元 取样.高度保守的广泛殖民岛（WCI）是一个 无与伦比的模型系统，以测试假设和开发方法， 更好地理解横向迁移。WCI，首先在 牙周致病菌伴放线放线杆菌，含有基因 对于细菌的顽强的、非特异性的粘附至关重要， 表面和纤维生物发生。序列分析表明，WCI是 分布在广泛的病原体和非病原体中， 不同的壁龛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的过程， 转移我们的目标是：（1）测试和开发能够可靠地 识别历史转移事件，所涉及的供体和受体谱系， 及其发生的相对年代;（2）发展系统发育 基因组分析的技术和方法，以了解 水平转移引起的致病性;（3）了解 一个基因岛的组成部分彼此之间以及它们的细菌 （4）确定转移的遗传或系统发育障碍; 致病岛的主机之间;（5）设计可访问的，基于计算机的 水平转移分析的系统发育和基因组学方法， 宿主/寄生虫共同进化 WCI系统提供了一个很好的机会来了解水平 大规模转让，并开发新的方法， 一般用于分析水平转移、传染病和 在其他系统中的毒力进化。

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.