Genomics of Bacterium-Host Interactions: BIOMI/PLPA 6080 Lecture 10/6/10 Genome Structure 1. Genome sequencing has revealed surprising variations in pathogen genome structure (Bentley and Parkhill 2004). 2. Pathogen genome sizes reflect pathogen lifestyle (e.g., obligate versus facultative association with host) (Bentley and Parkhill 2004). 3. The percentage of regulatory genes increases with bacterial genome size (Stover et al. 2000). 4. Multiple processes enable the gain and loss of genes in a bacterial genome, and gene loss is also important in pathogen evolution, as exemplified by Yersinia pestis (Abby and Daubin 2007). 5. Multiple classes of mobile genetic elements carry virulence genes (Pallen and Wren 2007). 6. Genomic islands can be identified in multiple ways (Dobrindt et al. 2004; Langille et al. 2008). 7. Genomic islands have several typical structural features, and the subset of GIs known as pathogenicity islands may encode functional virulence system modules and possess additional structural complexities (Alfano et al. 2000; Dobrindt et al. 2004; Gal-Mor and Finlay 2006). 8. Excision of the PPHGI-1 genomic island from Pseudomonas syringae pv. phaseolicola in bean leaves carrying a resistance (R) gene that detects PPHGI-1-encoded AvrPphB provides an example of rapid pathogen evolution (Pitman et al. 2005). 9. Identification of genomic islands in a pathogen provides a roadmap to regions likely to harbor virulence genes (Lindeberg et al. 2008). 10. Simple sequence DNA repeats in contingency loci promote hypermutation through polymerase slippage and thereby generate high levels of phenotypic variation in pathogen populations in the face of host defenses (Medini et al. 2008; Moxon et al. 2006). 11. The pan-genome of some bacteria, such as Streptococcus agalactiae, may be extremely large (Medini et al. 2005). 12. Ecological and genetic diversity (driven largely by horizontal gene transfer) within bacterial species challenges the concept and convention of species designations, but genomics brings new perspectives and a new “gold standard” to this issue (Didelot and Maiden 2010; Doolittle and Papke 2006; Konstantinidis et al. 2006; Richter and Rossello-Mora 2009). References Abby, S., and Daubin, V. 2007. Comparative genomics and the evolution of prokaryotes. Trends Microbiol 15:135-41. Alfano, J. R., Charkowski, A. O., Deng, W.-L., Badel, J. L., Petnicki-Ocwieja, T., van Dijk, K., and Collmer, A. 2000. The Pseudomonas syringae Hrp pathogenicity island has a tripartite mosaic structure composed of a cluster of type III secretion genes bounded by exchangeable effector and conserved effector loci that contribute to parasitic fitness and pathogenicity in plants. Proc. Natl. Acad. Sci. 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R., Collmer, A., and Schneider, D. J. 2008. Roadmap to new virulence determinants in Pseudomonas syringae: Insights from comparative genomics and genome organization. Mol. Plant-Microbe Interact. 21:685-700. Medini, D., Donati, C., Tettelin, H., Masignani, V., and Rappuoli, R. 2005. The microbial pan-genome. Curr Opin Genet Dev 15:589-94. Medini, D., Serruto, D., Parkhill, J., Relman, D. A., Donati, C., Moxon, R., Falkow, S., and Rappuoli, R. 2008. Microbiology in the post-genomic era. Nat Rev Microbiol 6:419-30. Moxon, R., Bayliss, C., and Hood, D. 2006. Bacterial contingency loci: the role of simple sequence DNA repeats in bacterial adaptation. Annu Rev Genet 40:307-33. Pallen, M. J., and Wren, B. W. 2007. Bacterial pathogenomics. Nature 449:835-842. Pitman, A. R., Jackson, R. W., Mansfield, J. W., Kaitell, V., Thwaites, R., and Arnold, D. L. 2005. Exposure to host resistance mechanisms drives evolution of bacterial virulence in plants. Curr. Biol. 15:2230-2235. 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