Table 1.

The Viral Hallmark Genes and Proteins they Encode^a

Protein	Function	Virus groups	Homologs in cellular life forms	Comments
Jelly‐roll capsid protein (JRC)	Main capsid subunit of icosahedral virions	Picornaviruses, comoviruses, carmoviruses, dsRNA phage, NCLDV, herpesviruses, adenoviruses, papovaviruses, parvoviruses, icosahedral DNA phages, and archaeal viruses	Distinct jelly‐roll domains are present in eukaryotic nucleoplasmins and in protein‐protein interaction domains of certain enzymes	Certain icosahedral viruses, such as ssRNA phages and alphaviruses, have unrelated capsid proteins. In poxviruses, the JRC is not a virion protein but forms intermediate structures during virion morphogenesis
Superfamily 3 helicase (S3H)	Initiation and elongation of genome replication	Picornaviruses, comoviruses, eukaryotic RCR viruses, NCLDV, baculoviruses, some phages (e.g., P4), plasmids, particularly archaeal ones	S3H is a distinct, deep‐branching family of the AAA+ ATPase class	Fusion with primase in DNA viruses and plasmids
Archaeo‐eukaryotic DNA primase	Initiation of genome replication	NCLDV, herpesviruses, baculoviruses, some phages	All viral primases appear to form a clade within the archaeo‐eukaryotic primase family	Fusion with S3H in most NCLDV, some phages, and archaeal plasmids
UL9‐like superfamily 2 helicase	Initiation and elongation of genome replication	Herpesviruses, some NCLDV, some phages	Viral UL9‐like helicases form a distinct branch in the vast superfamily of DNA and RNA helicases	Fusion with primase in asfarviruses, mimiviruses
Rolling‐circle replication initiation endonuclease (RCRE)/origin‐binding protein	Initiation of genome replication	Small eukaryotic DNA viruses (parvo, gemini, circo, papova), phages, plasmids, and eukaryotic helitron transposons	No cellular RCRE or papovavirus‐type origin‐binding protein; however, these proteins have a derived form of the palm domain that is found in the majority of cellular DNA polymerases	Papovaviruses have an inactivated form of RCRE that functions as origin‐binding protein
Packaging ATPase of the FtsK family	DNA packaging into the virion	NCLDV, adenoviruses, polydnaviruses, some phages (e.g., P9, M13), nematode transposons	A distinct clade in the FtsK/HerA superfamily of P‐loop NTPases that includes DNA‐pumping ATPases of bacteria and archaea
ATPase subunit of terminase	DNA packaging into the virion	Herpesviruses, tailed phages	The terminases comprise a derived family of P‐loop NTPases that is distantly related to Superfamily I/II helicases and AAA+ ATPases
RNA‐dependent RNA polymerase (RdRp)/reverse transcriptase (RT)	Replication of RNA genomes	Positive‐strand RNA viruses and virus‐like elements, dsRNA viruses and virus‐like elements, retroid viruses/elements, possibly, negative‐strand RNA viruses	Another major group of palm‐fingers domains that are distinct from those in DNA polymerases; eukaryotic telomerase appears to be a RT derivative	The RdRps of dsRNA viruses are homologs of positive‐strand RNA virus polymerases. The provenance of negative‐strand RNA virus RdRp remains uncertain although sequence motif and, especially, structural analysis suggests their derivation from RdRps of positive‐strand RNA viruses.
B‐family DNA polymerase	Replication of large dsDNA genomes	Diverse bacteriophages with dsDNA genomes, NCLDV, adenoviruses, herpesviruses, baculoviruses, fungal dsDNA plasmids	A distinct family of palm‐finger domain polymerases	The hallmark status of this gene is somewhat uncertain as it is hard to demonstrate the monophyly of the viral polymerases; however, the polymerases of the viruses with genome‐linked terminal proteins do appear to be monophyletic.
Genome‐linked terminal protein		Adenoviruses, fungal dsDNA plasmids, several groups of bacteriophages	Protein involved in a distinct mechanism of DNA replication initiation

^aThe table is from Ref. 59, with modifications; see Ref. 59 for further details and references. The list of hallmark genes is not necessarily complete and is likely to grow with further sequencing of genomes from new groups of viruses, determination of structures of viral proteins, and comparative analysis.

Abbreviations: NCLDV, nucleo‐cytoplasmic large DNA viruses (of eukaryotes); RCR, rolling circle replication.