The logic of DNA replication in double-stranded DNA viruses: insights from global analysis of viral genomes

Nucleic Acids Res. 2016 Jun 2;44(10):4551-64. doi: 10.1093/nar/gkw322. Epub 2016 Apr 25.


Genomic DNA replication is a complex process that involves multiple proteins. Cellular DNA replication systems are broadly classified into only two types, bacterial and archaeo-eukaryotic. In contrast, double-stranded (ds) DNA viruses feature a much broader diversity of DNA replication machineries. Viruses differ greatly in both completeness and composition of their sets of DNA replication proteins. In this study, we explored whether there are common patterns underlying this extreme diversity. We identified and analyzed all major functional groups of DNA replication proteins in all available proteomes of dsDNA viruses. Our results show that some proteins are common to viruses infecting all domains of life and likely represent components of the ancestral core set. These include B-family polymerases, SF3 helicases, archaeo-eukaryotic primases, clamps and clamp loaders of the archaeo-eukaryotic type, RNase H and ATP-dependent DNA ligases. We also discovered a clear correlation between genome size and self-sufficiency of viral DNA replication, the unanticipated dominance of replicative helicases and pervasive functional associations among certain groups of DNA replication proteins. Altogether, our results provide a comprehensive view on the diversity and evolution of replication systems in the DNA virome and uncover fundamental principles underlying the orchestration of viral DNA replication.

MeSH terms

  • DNA
  • DNA Helicases / genetics
  • DNA Helicases / metabolism
  • DNA Primase / genetics
  • DNA Primase / metabolism
  • DNA Replication*
  • DNA Topoisomerases / genetics
  • DNA Topoisomerases / metabolism
  • DNA Viruses / genetics*
  • Gene Transfer, Horizontal
  • Genome Size
  • Genome, Viral*
  • Host-Pathogen Interactions / genetics
  • Phylogeny
  • RNA-Dependent RNA Polymerase / genetics
  • RNA-Dependent RNA Polymerase / metabolism
  • Viral Proteins / genetics*
  • Viral Proteins / metabolism


  • Viral Proteins
  • DNA
  • DNA Primase
  • RNA-Dependent RNA Polymerase
  • DNA Helicases
  • DNA Topoisomerases