Comparative Genomic Analysis of 60 Mycobacteriophage Genomes: Genome Clustering, Gene Acquisition, and Gene Size

Graham F. Hatfull*, Deborah Jacobs-Sera, Jeffrey G. Lawrence, Welkin H. Pope, Daniel A. Russell, Ching Chung Ko, Rebecca J. Weber, Manisha C. Patel, Katherine L. Germane, Robert H. Edgar, Natasha N. Hoyte, Charles A. Bowman, Anthony T. Tantoco, Elizabeth C. Paladin, Marlana S. Myers, Alexis L. Smith, Molly S. Grace, Thuy T. Pham, Matthew B. O'Brien, Amy M. VogelsbergerAndrew J. Hryckowian, Jessica L. Wynalek, Helen Donis-Keller, Matt W. Bogel, Craig L. Peebles, Steven G. Cresawn, Roger W. Hendrix

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

246 Scopus citations

Abstract

Mycobacteriophages are viruses that infect mycobacterial hosts. Expansion of a collection of sequenced phage genomes to a total of 60-all infecting a common bacterial host-provides further insight into their diversity and evolution. Of the 60 phage genomes, 55 can be grouped into nine clusters according to their nucleotide sequence similarities, 5 of which can be further divided into subclusters; 5 genomes do not cluster with other phages. The sequence diversity between genomes within a cluster varies greatly; for example, the 6 genomes in Cluster D share more than 97.5% average nucleotide similarity with one another. In contrast, similarity between the 2 genomes in Cluster I is barely detectable by diagonal plot analysis. In total, 6858 predicted open-reading frames have been grouped into 1523 phamilies (phams) of related sequences, 46% of which possess only a single member. Only 18.8% of the phams have sequence similarity to non-mycobacteriophage database entries, and fewer than 10% of all phams can be assigned functions based on database searching or synteny. Genome clustering facilitates the identification of genes that are in greatest genetic flux and are more likely to have been exchanged horizontally in relatively recent evolutionary time. Although mycobacteriophage genes exhibit a smaller average size than genes of their host (205 residues compared with 315), phage genes in higher flux average only 100 amino acids, suggesting that the primary units of genetic exchange correspond to single protein domains.

Original languageEnglish (US)
Pages (from-to)119-143
Number of pages25
JournalJournal of Molecular Biology
Volume397
Issue number1
DOIs
StatePublished - Mar 19 2010

Funding

This work was supported in part by a grant to the University of Pittsburgh by the Howard Hughes Medical Institute in support of G.F.H. under the institution's Professors Program. Support was also provided by grants from the National Institutes of Health to R.W.H. ( GM51975 ) and G.F.H. ( AI28927 ). We thank Christina Ferreira for superb technical assistance. We also acknowledge the following students and teachers who contributed to genome annotation and analysis: (1) Anand Naranbhai and Melisha Sukkhu (Brujita), Natasha Pillay and Reevanan Naidoo (Gumball), and Fortunate Ndlandla, Karnishree Govender, and Mantha Makume (Butterscotch), all of whom were participants in the 2008 KwaZulu-Natal Research Institute for TB and HIV (K-RITH) Phage Discovery Workshop at the Nelson R. Mandela School of Medicine led by G.F.H., D.J.S., William R. Jacobs, Jr., Michelle Larsen, and A. Wilhelm Sturm; (2) Tom Bogen, Gary Osowick, and Greg King (Fruitloop), Rachael Becker, Beth Smyder, and Sandy Breitenbach (Pacc40), Sue Glennon, Susan Offner, Carol Seemuller, and Sandy Wardell (Ramsey), Kathy VanHoeck, Jen Gordinier, Chris Bogiages, and Blair Buck (Solon), Jerry Fuelling, Joan-Beth Gow, Sue Lentz, and Bill Welch (Troll4), all of whom participated in a teacher phagehunting workshop (2008) at the University of Pittsburgh; (3) Roger Chambers and Dalton Paluzzi (Lockley) and Chris Lyons and Dan Altman (Adjutor), who participated in the Science Education Alliance Pilot Course (2008) at the University of Pittsburgh; and (4) Sam Miake-Lye and Dr. Susan Offner (KBG) at Lexington High School, Lexington, MA.

Keywords

  • bacteriophage
  • evolution
  • genomics
  • mycobacteriophage
  • tuberculosis

ASJC Scopus subject areas

  • Molecular Biology
  • Biophysics
  • Structural Biology

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