Computational analysis of DNA replicases in double-stranded DNA viruses: relationship with the genome size

Nucleic Acids Res. 2011 Oct;39(19):8291-305. doi: 10.1093/nar/gkr564. Epub 2011 Jul 8.


Genome duplication in free-living cellular organisms is performed by DNA replicases that always include a DNA polymerase, a DNA sliding clamp and a clamp loader. What are the evolutionary solutions for DNA replicases associated with smaller genomes? Are there some general principles? To address these questions we analyzed DNA replicases of double-stranded (ds) DNA viruses. In the process we discovered highly divergent B-family DNA polymerases in phiKZ-like phages and remote sliding clamp homologs in Ascoviridae family and Ma-LMM01 phage. The analysis revealed a clear dependency between DNA replicase components and the viral genome size. As the genome size increases, viruses universally encode their own DNA polymerases and frequently have homologs of DNA sliding clamps, which sometimes are accompanied by clamp loader subunits. This pattern is highly non-random. The absence of sliding clamps in large viral genomes usually coincides with the presence of atypical polymerases. Meanwhile, sliding clamp homologs, not accompanied by clamp loaders, have an elevated positive electrostatic potential, characteristic of non-ring viral processivity factors that bind the DNA directly. Unexpectedly, we found that similar electrostatic properties are shared by the eukaryotic 9-1-1 clamp subunits, Hus1 and, to a lesser extent, Rad9, also suggesting the possibility of direct DNA binding.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • DNA Viruses / enzymology
  • DNA Viruses / genetics*
  • DNA-Directed DNA Polymerase / chemistry*
  • DNA-Directed DNA Polymerase / classification
  • DNA-Directed DNA Polymerase / genetics
  • Genome Size
  • Genome, Viral*
  • Genomics
  • Molecular Sequence Data
  • Sequence Alignment
  • Static Electricity
  • Viral Proteins / chemistry*
  • Viral Proteins / classification
  • Viral Proteins / genetics


  • Viral Proteins
  • DNA replicase
  • DNA-Directed DNA Polymerase