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Computational characterization of prokaryotic genomic islands

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Thesis type
(Thesis) Ph.D.
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Genomic islands, including pathogenicity islands, are commonly defined as clusters of genes in prokaryotic genomes that have probable horizontal origins. These genetic elements have been associated with rapid adaptations in prokaryotes that are of medical, economical or environmental importance, such as pathogen virulence, antibiotic resistance, symbiotic interactions with plants, and notable secondary metabolic capabilities. As the number of genomic sequences increases, the impact of genomic islands in prokaryotic evolution has become more apparent and detecting these regions using bioinformatics approaches has become an integral part of studying microbial evolution and function. I therefore constructed and analyzed a set of previously reported genomic islands, most of which are pathogenicity islands, to quantify features associated with islands as a prelude to improving their identification and characterization. I integrated some of the features associated with islands into a bioinformatics tool, named IslandPath, which aids visual detection and analysis of genomic islands. Features incorporated included %G+C of genes, dinucleotide bias of gene-clusters, occurrence of mobility genes, and presence of tRNA genes. Using IslandPath, and our knowledge of features of islands, I constructed sets of computationally predicted genomic islands and characterized the classes and functions of the gene products in these regions. I conducted the first large-scale analysis of genomic islands from over 60 prokaryotic genomes and showed that the distribution of genes in the islands versus the rest of a given genome is non-random for a wide range of phyla. Certain protein functional categories, including many virulence factors and novel hypothetical proteins, are significantly more prevalent in genomic islands. This study also led to the proposal that the horizontally-inherited gene pool is characteristically distinct from, and may be larger than, the vertically-inherited prokaryotic gene pool. I also carried out detailed analyses of genomic islands in the Rhodococcus sp. RHA1 genome to shed light on its evolutionary history. The results suggest that RHA1’s unusually large genome is not due to recent horizontal gene transfer, but rather formed through more ancient evolutionary processes. Overall, my studies offer new insights into the features associated with genomic islands and the significance of these regions in prokaryotic evolution.
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