Genetic Transfer in the Evolution of Infectious Disease

点击翻译按钮获取中文摘要

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.