GENOMIC ANALYSIS OF LAMBDOID, TB & OTHER BACTERIOPHAGES

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The dsDNA bacteriophages are the most numerous taxon of evolving organisms in the biosphere. However, their classification remains unclear and their inter-relationships are poorly understood. Characterization of these dsDNA phages by whole genome sequencing provide more detailed information of these relationships and provides an emerging picture in which essentially all dsDNA tailed bacteriophages have shared ancestry, even through they infect different hosts and have varied viral morphologies. Comparison of phage genomes also shows that they are constructed from a series of genetic modules that are joined into functional groups and they are essentially mosaic in nature. However, it is not known how many different modular segments there are, or how many variants exist of each module. Moreover, the mechanisms by which exchange occurs have yet to be clearly elucidated. We propose to investigate the process of phage evolution through the sequencing of phage genomes and comparisons of sequences, genome organization and function relationships. In addition, we propose to survey unselected phage populations in order to obtain a broader view of the diversity of bacteriophages that naturally exist in the environment. More sophisticated software systems will be developed that will greatly simplify the data analysis steps and provide automated methods for genome comparisons. These studies will not only lead to new insights into the mechanisms of viral evolution but will provide a valuable resource for other researchers, including those studying basic phage biology such as DNA replication, gene expression and macromolecular assembly as well as those interested in the application of phages to clinical problems, such as diagnosis and phage therapy.