Evolution of DNA ligases of nucleo-cytoplasmic large DNA viruses of eukaryotes: a case of hidden complexity

Abstract

Background: Eukaryotic Nucleo-Cytoplasmic Large DNA Viruses (NCLDV) encode most if not all of the enzymes involved in their DNA replication. It has been inferred that genes for these enzymes were already present in the last common ancestor of the NCLDV. However, the details of the evolution of these genes that bear on the complexity of the putative ancestral NCLDV and on the evolutionary relationships between viruses and their hosts are not well understood.

Results: Phylogenetic analysis of the ATP-dependent and NAD-dependent DNA ligases encoded by the NCLDV reveals an unexpectedly complex evolutionary history. The NAD-dependent ligases are encoded only by a minority of NCLDV (including mimiviruses, some iridoviruses and entomopoxviruses) but phylogenetic analysis clearly indicated that all viral NAD-dependent ligases are monophyletic. Combined with the topology of the NCLDV tree derived by consensus of trees for universally conserved genes suggests that this enzyme was represented in the ancestral NCLDV. Phylogenetic analysis of ATP-dependent ligases that are encoded by chordopoxviruses, most of the phycodnaviruses and Marseillevirus failed to demonstrate monophyly and instead revealed an unexpectedly complex evolutionary trajectory. The ligases of the majority of phycodnaviruses and Marseillevirus seem to have evolved from bacteriophage or bacterial homologs; the ligase of one phycodnavirus, Emiliana huxlei virus, belongs to the eukaryotic DNA ligase I branch; and ligases of chordopoxviruses unequivocally cluster with eukaryotic DNA ligase III.

Conclusions: Examination of phyletic patterns and phylogenetic analysis of DNA ligases of the NCLDV suggest that the common ancestor of the extant NCLDV encoded an NAD-dependent ligase that most likely was acquired from a bacteriophage at the early stages of evolution of eukaryotes. By contrast, ATP-dependent ligases from different prokaryotic and eukaryotic sources displaced the ancestral NAD-dependent ligase at different stages of subsequent evolution. These findings emphasize complex routes of viral evolution that become apparent through detailed phylogenomic analysis but not necessarily in reconstructions based on phyletic patterns of genes.

Reviewers: This article was reviewed by: Patrick Forterre, George V. Shpakovski, and Igor B. Zhulin.

Figure 1

A maximum-likelihood phylogenetic tree of NAD-dependent DNA ligases. The numbers indicate the statistical support (Expected-Likelihood Weights) of internal nodes. The support values are given as percentages (n = 1,000). Archaeal sequences are color-coded red, bacterial sequences green, eukaryotic sequences brown, and viral sequences blue. The NCLDV are shown in bold type. All proteins are denoted by their Genbank identification numbers (GIs). The truncated sequence of the NAD-dependent ligase of Crocodilepox virus was not used for phylogenetic analysis. Abbreviations: MSV, Melanoplus sanguinipes entomopoxvirus; AMV, Amsacta moorei entomopoxvirus; Acapo, Acanthamoeba polyphaga mimivirus; CIV, Chilo iridescent virus (Invertebrate iridescent virus 6); Aedta, Aedes taeniorhynchus iridescent virus (Invertebrate iridescent virus 3); Ralph, Ralstonia solanacearum phage RSL1; Lenar, Lentisphaera araneosa HTCC2155; Acife, Acidithiobacillus ferrooxidans ATCC 23270; Marsp, Marinobacter sp. ELB17; Desal, Desulfatibacillum alkenivorans AK-01; Desac, Desulfuromonas acetoxidans DSM 684; Natph, Natronomonas pharaonis DSM 2160; Halwa, Haloquadratum walsbyi DSM 16790; Ostlu, Ostreococcus lucimarinus CCE9901; Ricfe, Rickettsia felis URRWXCal2; Metin, Methylacidiphilum infernorum V4; Nitsp, Nitratiruptor sp. SB155-2; Aquae, Aquifex aeolicus VF5; CanBl, Candidatus Blochmannia floridanus; Brahy, Brachyspira hyodysenteriae WA1; Lepbu, Leptotrichia buccalis DSM 1135; Dicdi, Dictyostelium discoideum AX4; Borhe, Borrelia hermsii DAH; Bacth, Bacillus thuringiensis Bt407; Cloca, Clostridium carboxidivorans P7; Plepa, Plesiocystis pacifica SIR-1; Sorce, Sorangium cellulosum.

Figure 2

A maximum-likelihood phylogenetic tree of ATP-dependent DNA ligases. The designations are as in Figure 1. For a tree with an extended set of vertebrate sequences, see Additional File 4. Abbreviations: Acatu, Acanthocystis turfacea Chlorella virus 1; Acica, Acidobacterium capsulatum ATCC 51196; Aerph, Aeromonas phage; ASFV, African swine fever virus; Aquae, Aquifex aeolicus VF5; Arath, Arabidopsis thaliana; Arcfu, Archaeoglobus fulgidus DSM 4304; Argse, Agrotis segetum granulovirus; Artch, Arthrobacter chlorophenolicus A6; Bacph, Bacillus phage SPO1; Burph, Burkholderia phage BcepIL02; CanKo, Candidatus Korarchaeum cryptofilum OPF8; Chtfl, Chthoniobacter flavus Ellin428; Deevi, Deerpox virus W-848-83; Dicdi, Dictyostelium discoideum AX4; Drome, Drosophila melanogaster; EHV, Emiliania huxleyi virus 86; Enthi, Entamoeba histolytica HM-1:IMSS; Entph, Enterobacteria phage; Erwph, Erwinia phage; Escph, Escherichia phage rv5; FPV, Fowlpox virus; Gemob, Gemmata obscuriglobus UQM 2246; Goavi, Goatpox virus Pellor; Helze, Heliothis zea virus 1; Homsa, Homo sapiens; Lymdi, Lymantria dispar MNPV; Marvi, Marseillevirus; Metac, Methanosarcina acetivorans C2A; Metpe, Methylibium petroleiphilum PM1; Monbr, Monosiga brevicollis MX1; Myxvi, Myxoma virus; Naneq, Nanoarchaeum equitans Kin4-M; Nitma, Nitrosopumilus maritimus SCM1; Opite, Opitutus terrae PB90-1; Orgle, Orgyia leucostigma NPV; Ostvi, Ostreococcus virus OsV5; PBCV, Paramecium bursaria Chlorella virus 1; Plali, Planctomyces limnophilus DSM 3776; Pluxy, Plutella xylostella granulovirus; Proma, Prochlorococcus marinus; Pseph, Pseudomonas phage F8; Ralph, Ralstonia phage RSB1; Sphsp, Sphingobacterium spiritivorum ATCC 33300; Spoli, Spodoptera litura granulovirus; Staep, Staphylococcus epidermidis RP62A; Stama, Staphylothermus marinus F1; Stiau, Stigmatella aurantiaca DW4/3-1; Swivi, Swinepox virus; Tetth, Tetrahymena thermophila; Thepe, Thermofilum pendens Hrk 5; Thete, Thermobaculum terrenum ATCC BAA-798; VV, Vaccinia virus; Vibph, Vibrio phage; Xanph, Xanthomonas phage; Xylce, Xylanimonas cellulosilytica DSM 15894; Yeast, Saccharomyces cerevisiae.

Figure 3

Evolutionary scenario for the DNA ligases of the NCLDV. The underlying species tree is the consensus of maximum-likelihood phylogenetic trees of 4 universal NCLDV genes (see text)[6]. Filled circles denote presence (in extant viruses) or acquisition (in ancestral forms) and empty circles denote absence or loss of the respective ligases (blue: NAD-dependent ligase, red: ATP-dependent ligase). Abbreviations: Canvi, Canarypox virus; FPV, Fowlpox virus; Goavi, Goatpox virus Pellor; Shevi, Sheeppox virus 17077-99; Lumsk, Lumpy skin disease virus NI-2490; Deevi, Deerpox virus W-848-83; Myxvi, Myxoma virus; Rabfi, Rabbit fibroma virus; MCV, Molluscum contagiosum virus; VV, Vaccinia virus; Varvi, Variola virus (smallpox virus); Orfvi, Orf virus; Bovpa, Bovine papular stomatitis virus; Swivi, Swinepox virus; Tanvi, Tanapox virus; Yabmo, Yaba monkey tumor virus; Yabdi, Yaba-like disease virus; Crovi, Crocodilepox virus; AMV, Amsacta moorei entomopoxvirus; MSV, Melanoplus sanguinipes entomopoxvirus; Helvi, Heliothis virescens ascovirus 3e; Trini, Trichoplusia ni ascovirus 2c; Spofr, Spodoptera frugiperda ascovirus 1a; ASFV, African swine fever virus; Aedta, Aedes taeniorhynchus iridescent virus (Invertebrate iridescent virus 3); CIV, Invertebrate iridescent virus 6; Lymdi, Lymphocystis disease virus 1; LDV, Lymphocystis disease virus - isolate China; ISKNV, Infectious spleen and kidney necrosis virus; SGV, Singapore grouper iridovirus; FV3, Frog virus 3; ATSV, Ambystoma tigrinum virus; Acapo, Acanthamoeba polyphaga mimivirus; Mamav, Mamavirus; ParAR, Paramecium bursaria Chlorella virus AR158; ParNY, Paramecium bursaria Chlorella virus NY2A; ParMT, Paramecium bursaria chlorella virus MT325; Acatu, Acanthocystis turfacea Chlorella virus 1; ParFR, Paramecium bursaria Chlorella virus FR483; PBCV, Paramecium bursaria Chlorella virus 1; EHV, Emiliania huxleyi virus 86; Felsp, Feldmannia species virus; ESV, Ectocarpus siliculosus virus 1; Ostvi, Ostreococcus virus OsV5; Marvi, Marseille virus.