title: A deep phylogeny of viral and cellular right-hand polymerases.
abstract: Right-hand polymerases are important players in genome replication and repair in cellular organisms as well as in viruses. All right-hand polymerases are grouped into seven related protein families: viral RNA-dependent RNA polymerases, reverse transcriptases, single-subunit RNA polymerases, and DNA polymerase families A, B, D, and Y. Although the evolutionary relationships of right-hand polymerases within each family have been proposed, evolutionary relationships between families remain elusive because their sequence similarity is too low to allow classical phylogenetic analyses. The structure of viral RNA-dependent RNA polymerases recently was shown to be useful in inferring their evolution. Here, we address evolutionary relationships between right-hand polymerase families by combining sequence and structure information. We used a set of 22 viral and cellular polymerases representing all right-hand polymerase families with known protein structure. In contrast to previous studies, which focused only on the evolution of particular families, the current approach allowed us to present the first robust phylogenetic analysis unifying evolution of all right-hand polymerase families. All polymerase families branched into discrete lineages, following a fairly robust adjacency pattern. Only single-subunit RNA polymerases formed an inner group within DNA polymerase family A. RNA-dependent RNA polymerases of RNA viruses and reverse transcriptases of retroviruses formed two sister groups and were distinguishable from all other polymerases. DNA polymerases of DNA bacteriophages did not form a monophyletic group and are phylogenetically mixed with cellular DNA polymerase families A and B. Based on the highest genetic variability and structural simplicity, we assume that RNA-dependent RNA polymerases are the most ancient group of right-hand polymerases, in agreement with the RNA World hypothesis, because RNA-dependent RNA polymerases are enzymes that could serve in replication of RNA genomes. Moreover, our results show that protein structure can be used in phylogenetic analyses of distantly related proteins that share only limited sequence similarity.
authors.affiliation: Institute of Parasitology, Biology Centre of the Czech Academy of Sciences, Branišovská 31, 370 05 České Budějovice, Czech Republic; Faculty of Science, University of South Bohemia in České Budějovice, Branišovská 31, 370 05 České Budějovice, Czech Republic. Electronic address: cerny@paru.cas.cz.
authors.forename: Jiří
authors.initials: J
authors.lastname: Černý
authors.affiliation: Faculty of Tropical AgriSciences, Czech University of Life Sciences Prague, Kamýcká 126, Suchdol, 165 21 Prague 6, Czech Republic.
authors.forename: Barbora
authors.initials: B
authors.lastname: Černá Bolfíková
authors.affiliation: Department of Microbiology, Biomedical Sciences Institute, ICB II University of Sao Paulo, 05508-000 Sao Paulo, Brazil.
authors.forename: Paolo M
authors.initials: PM
authors.lastname: de A Zanotto
authors.affiliation: Institute of Parasitology, Biology Centre of the Czech Academy of Sciences, Branišovská 31, 370 05 České Budějovice, Czech Republic; Faculty of Science, University of South Bohemia in České Budějovice, Branišovská 31, 370 05 České Budějovice, Czech Republic.
authors.forename: Libor
authors.initials: L
authors.lastname: Grubhoffer
authors.affiliation: Institute of Parasitology, Biology Centre of the Czech Academy of Sciences, Branišovská 31, 370 05 České Budějovice, Czech Republic; Veterinary Research Institute, Hudcova 296/70, 621 00 Brno, Czech Republic.
authors.forename: Daniel
authors.initials: D
authors.lastname: Růžek
mesh_terms: D000595:Amino Acid Sequence; D004254:DNA Nucleotidyltransferases / Q000737:chemistry / Q000145:classification / Q000235:genetics; D019143:Evolution, Molecular; D008958:Models, Molecular; D008969:Molecular Sequence Data; D010802:Phylogeny; D017434:Protein Structure, Tertiary; D012316:RNA Nucleotidyltransferases / Q000737:chemistry / Q000145:classification / Q000235:genetics; D016415:Sequence Alignment; D014764:Viral Proteins / Q000737:chemistry / Q000145:classification / Q000235:genetics
chemical_list: D014764:Viral Proteins; D004254:DNA Nucleotidyltransferases; D012316:RNA Nucleotidyltransferases
keywords: Polymerase evolution; Protein tertiary structure; Right-hand polymerase; Structural evolution; Virus evolution