title: Comparative genomics of four closely related Clostridium perfringens bacteriophages reveals variable evolution among core genes with therapeutic potential.
abstract: BACKGROUND
  Because biotechnological uses of bacteriophage gene products as alternatives to conventional antibiotics will require a thorough understanding of their genomic context, we sequenced and analyzed the genomes of four closely related phages isolated from Clostridium perfringens, an important agricultural and human pathogen.
  
  
  RESULTS
  Phage whole-genome tetra-nucleotide signatures and proteomic tree topologies correlated closely with host phylogeny. Comparisons of our phage genomes to 26 others revealed three shared COGs; of particular interest within this core genome was an endolysin (PF01520, an N-acetylmuramoyl-L-alanine amidase) and a holin (PF04531). Comparative analyses of the evolutionary history and genomic context of these common phage proteins revealed two important results: 1) strongly significant host-specific sequence variation within the endolysin, and 2) a protein domain architecture apparently unique to our phage genomes in which the endolysin is located upstream of its associated holin. Endolysin sequences from our phages were one of two very distinct genotypes distinguished by variability within the putative enzymatically-active domain. The shared or core genome was comprised of genes with multiple sequence types belonging to five pfam families, and genes belonging to 12 pfam families, including the holin genes, which were nearly identical.
  
  
  CONCLUSIONS
  Significant genomic diversity exists even among closely-related bacteriophages. Holins and endolysins represent conserved functions across divergent phage genomes and, as we demonstrate here, endolysins can have significant variability and host-specificity even among closely-related genomes. Endolysins in our phage genomes may be subject to different selective pressures than the rest of the genome. These findings may have important implications for potential biotechnological applications of phage gene products.
authors.affiliation: Poultry Microbiological Research Unit, Richard B. Russell Agricultural Research Center, Agricultural Research Service, USDA, Athens, GA 30605, USA. brian.oakley@ars.usda.gov
authors.forename: Brian B
authors.initials: BB
authors.lastname: Oakley
authors.forename: Eldin
authors.initials: E
authors.lastname: Talundzic
authors.forename: Cesar A
authors.initials: CA
authors.lastname: Morales
authors.forename: Kelli L
authors.initials: KL
authors.lastname: Hiett
authors.forename: Gregory R
authors.initials: GR
authors.lastname: Siragusa
authors.forename: Nikolay V
authors.initials: NV
authors.lastname: Volozhantsev
authors.forename: Bruce S
authors.initials: BS
authors.lastname: Seal
mesh_terms: D000581:Amidohydrolases / Q000737:chemistry; D000595:Amino Acid Sequence; D001483:Base Sequence; D002874:Chromosome Mapping; D003016:Clostridium perfringens / Q000821:virology*; D019295:Computational Biology; D003198:Computer Simulation; D010450:Endopeptidases / Q000737:chemistry; D019143:Evolution, Molecular; D023281:Genomics; D005838:Genotype; D008390:Markov Chains; D008958:Models, Molecular; D008969:Molecular Sequence Data; D010802:Phylogeny; D017434:Protein Structure, Tertiary; D016415:Sequence Alignment; D017422:Sequence Analysis, DNA; D017385:Sequence Homology; D017906:Siphoviridae / Q000235:genetics*
chemical_list: D010450:Endopeptidases; C001143:endolysin; D000581:Amidohydrolases