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.

Agency
National Institute of Health (NIH)
Institute
National Institute of General Medical Sciences (NIGMS)
Type
Research Project (R01)
Project #
5R01GM051975-06
Application #
6180598
Study Section
Microbial Physiology and Genetics Subcommittee 2 (MBC)
Program Officer
Carter, Anthony D
Project Start
1995-01-01
Project End
2003-07-31
Budget Start
2000-08-01
Budget End
2001-07-31
Support Year
6
Fiscal Year
2000
Total Cost
$218,680
Indirect Cost
Name
University of Pittsburgh
Department
Biology
Type
Schools of Arts and Sciences
DUNS #
053785812
City
Pittsburgh
State
PA
Country
United States
Zip Code
15213
Pope, Welkin H; Bowman, Charles A; Russell, Daniel A et al. (2015) Whole genome comparison of a large collection of mycobacteriophages reveals a continuum of phage genetic diversity. Elife 4:e06416
Petrova, Zaritza O; Broussard, Gregory W; Hatfull, Graham F (2015) Mycobacteriophage-repressor-mediated immunity as a selectable genetic marker: Adephagia and BPs repressor selection. Microbiology 161:1539-51
Cresawn, Steven G; Pope, Welkin H; Jacobs-Sera, Deborah et al. (2015) Comparative genomics of Cluster O mycobacteriophages. PLoS One 10:e0118725
Casjens, Sherwood R; Jacobs-Sera, Deborah; Hatfull, Graham F et al. (2015) Genome Sequence of Salmonella enterica Phage Det7. Genome Announc 3:
Hendrix, Roger W; Ko, Ching-Chung; Jacobs-Sera, Deborah et al. (2015) Genome Sequence of Salmonella Phage ?. Genome Announc 3:
Hatfull, Graham F (2014) Molecular Genetics of Mycobacteriophages. Microbiol Spectr 2:
Pietilä, Maija K; Laurinmäki, Pasi; Russell, Daniel A et al. (2013) Structure of the archaeal head-tailed virus HSTV-1 completes the HK97 fold story. Proc Natl Acad Sci U S A 110:10604-9
Sen?ilo, Ana; Jacobs-Sera, Deborah; Russell, Daniel A et al. (2013) Snapshot of haloarchaeal tailed virus genomes. RNA Biol 10:803-16
Pope, Welkin H; Jacobs-Sera, Deborah; Best, Aaron A et al. (2013) Cluster J mycobacteriophages: intron splicing in capsid and tail genes. PLoS One 8:e69273
Hatfull, Graham F; Science Education Alliance Phage Hunters Advancing Genomics and Evolutionary Science Program; KwaZulu-Natal Research Institute for Tuberculosis and HIV Mycobacterial Genetics Course Students et al. (2012) Complete genome sequences of 138 mycobacteriophages. J Virol 86:2382-4

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