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Open Access Research article

Evidence of host-virus co-evolution in tetranucleotide usage patterns of bacteriophages and eukaryotic viruses

David T Pride1*, Trudy M Wassenaar2, Chandrabali Ghose3 and Martin J Blaser4

Author Affiliations

1 Department of Medicine, Division of Infectious Diseases And Geographic Medicine, Stanford University School of Medicine, Stanford, CA, USA

2 Molecular Microbiology and Genomics Consultants, Zotzenheim, Germany

3 Department of Medicine, Division of Infectious Diseases, Harvard Medical School, Boston, MA, USA

4 Departments of Medicine and Microbiology, New York University School of Medicine and VA Medical Center, New York, NY4, USA

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BMC Genomics 2006, 7:8  doi:10.1186/1471-2164-7-8

Published: 18 January 2006



Virus taxonomy is based on morphologic characteristics, as there are no widely used non-phenotypic measures for comparison among virus families. We examined whether there is phylogenetic signal in virus nucleotide usage patterns that can be used to determine ancestral relationships. The well-studied model of tail morphology in bacteriophage classification was used for comparison with nucleotide usage patterns. Tetranucleotide usage deviation (TUD) patterns were chosen since they have previously been shown to contain phylogenetic signal similar to that of 16S rRNA.


We found that bacteriophages have unique TUD patterns, representing genomic signatures that are relatively conserved among those with similar host range. Analysis of TUD-based phylogeny indicates that host influences are important in bacteriophage evolution, and phylogenies containing both phages and their hosts support their co-evolution. TUD-based phylogeny of eukaryotic viruses indicates that they cluster largely based on nucleic acid type and genome size. Similarities between eukaryotic virus phylogenies based on TUD and gene content substantiate the TUD methodology.


Differences between phenotypic and TUD analysis may provide clues to virus ancestry not previously inferred. As such, TUD analysis provides a complementary approach to morphology-based systems in analysis of virus evolution.