1887

Abstract

The nucleocytoplasmic large DNA viruses (NCLDVs) are a diverse group that currently contain the largest known virions and genomes, also called giant viruses. The first giant virus was isolated and described nearly 20 years ago. Their genome sizes were larger than for any other known virus at the time and it contained a number of genes that had not been previously described in any virus. The origin and evolution of these unusually complex viruses has been puzzling, and various mechanisms have been put forward to explain how some NCLDVs could have reached genome sizes and coding capacity overlapping with those of cellular microbes. Here we critically discuss the evidence and arguments on this topic. We have also updated and systematically reanalysed protein families of the NCLDVs to further study their origin and evolution. Our analyses further highlight the small number of widely shared genes and extreme genomic plasticity among NCLDVs that are shaped via combinations of gene duplications, deletions, lateral gene transfers and creation of protein-coding genes. The dramatic expansions of the genome size and protein-coding gene capacity characteristic of some NCLDVs is now increasingly understood to be driven by environmental factors rather than reflecting relationships to an ancient common ancestor among a hypothetical cellular lineage. Thus, the evolution of NCLDVs is writ large viral, and their origin, like all other viral lineages, remains unknown.

Funding
This study was supported by the:
  • oskari huttunen foundation
    • Principle Award Recipient: HeliA. M. Mönttinen
  • jenny ja antti wihurin rahasto
    • Principle Award Recipient: HeliA. M. Mönttinen
  • This is an open-access article distributed under the terms of the Creative Commons Attribution License. This article was made open access via a Publish and Read agreement between the Microbiology Society and the corresponding author’s institution.
Loading

Article metrics loading...

/content/journal/mgen/10.1099/mgen.0.000649
2021-09-20
2021-10-23
Loading full text...

Full text loading...

/deliver/fulltext/mgen/7/9/mgen000649.html?itemId=/content/journal/mgen/10.1099/mgen.0.000649&mimeType=html&fmt=ahah

References

  1. Koonin EV, Dolja VV, Krupovic M, Varsani A, Wolf YI et al. Global organization and proposed megataxonomy of the virus world. Microbiol Mol Biol Rev 2020; 84:e00061-19 [View Article] [PubMed]
    [Google Scholar]
  2. Aherfi S, Colson P, La Scola B, Raoult D. Giant Viruses of Amoebas: An Update. Front Microbiol 2016; 7:349 [View Article] [PubMed]
    [Google Scholar]
  3. La Scola B, Audic S, Robert C, Jungang L, Lamballerie de. A giant virus in amoebae. Science 2003; 299:2033 [View Article] [PubMed]
    [Google Scholar]
  4. Raoult D, Audic S, Robert C, Abergel C, Renesto P. The 1.2-megabase genome sequence of Mimivirus. Science 2004; 306:1344–1350 [View Article] [PubMed]
    [Google Scholar]
  5. Boyer M, Madoui MA, Gimenez G, La Scola B, Raoult D. Phylogenetic and phyletic studies of informational genes in genomes highlight existence of a fourth domain of life including giant viruses. PLoS One 2010; 5:e15530 [View Article] [PubMed]
    [Google Scholar]
  6. Moreira D, Brochier-Armanet C. Giant viruses, giant chimeras: the multiple evolutionary histories of Mimivirus genes. BMC Evol Biol 2008; 8:12 [View Article] [PubMed]
    [Google Scholar]
  7. Yutin N, Wolf YI, Koonin EV. Origin of giant viruses from smaller DNA viruses not from a fourth domain of cellular life. Virology 2014; 466:38–52 [View Article] [PubMed]
    [Google Scholar]
  8. Schulz F, Yutin N, Ivanova NN, Ortega DR, Lee TK. Giant viruses with an expanded complement of translation system components. Science 2017; 356:82–85 [View Article] [PubMed]
    [Google Scholar]
  9. Colson P, Lamballerie D, Yutin N, Asgari S, Bigot Y. Megavirales’, a proposed new order for eukaryotic nucleocytoplasmic large DNA viruses. Arch Virol 2013; 158:2517–2521 [View Article] [PubMed]
    [Google Scholar]
  10. Sharma V, Colson P, Chabrol O, Scheid P, Pontarotti P. Welcome to pandoraviruses at the ‘Fourth TRUC’ club. Front Microbiol 2015; 6:423 [View Article] [PubMed]
    [Google Scholar]
  11. Yutin N, Koonin EV. Pandoraviruses are highly derived phycodnaviruses. Biol Direct 2013; 8:25 [View Article] [PubMed]
    [Google Scholar]
  12. Reteno DG, Benamar S, Khalil JB, Andreani J, Armstrong N. Faustovirus, an asfarvirus-related new lineage of giant viruses infecting amoebae. J Virol 2015; 89:6585–6594 [View Article] [PubMed]
    [Google Scholar]
  13. Legendre M, Bartoli J, Shmakova L, Jeudy S, Labadie K. Thirty-thousand-year-old distant relative of giant icosahedral DNA viruses with a pandoravirus morphology. Proceedings of the National Academy of Sciences 2014; 111:4274–4279 [View Article]
    [Google Scholar]
  14. Legendre M, Lartigue A, Bertaux L, Jeudy S, Bartoli J et al. In-depth study of Mollivirus sibericum, a new 30,000-y-old giant virus infecting Acanthamoeba. P Natl Acad Sci USA 2015; 112:E5327–E5335 [View Article]
    [Google Scholar]
  15. Bajrai L, Benamar S, Azhar E, Robert C, Levasseur A. Kaumoebavirus, a new virus that clusters with faustoviruses and Asfarviridae. Viruses 2016; 8:278 [View Article]
    [Google Scholar]
  16. Wilson WH, Tarran GA, Schroeder D, Cox M, Oke J. Isolation of viruses responsible for the demise of an Emiliania huxleyi bloom in the English Channel. J Mar Biol Ass 2002; 82:369–377 [View Article]
    [Google Scholar]
  17. Delaroque N, Boland W. The genome of the brown alga Ectocarpus siliculosus contains a series of viral DNA pieces, suggesting an ancient association with large dsDNA viruses. Bmc Evol Biol 2008; 8:110 [View Article] [PubMed]
    [Google Scholar]
  18. Weynberg KD, Allen MJ, Gilg IC, Scanlan DJ, Wilson WH. Genome sequence of Ostreococcus tauri virus OtV-2 throws light on the role of picoeukaryote niche separation in the ocean. J Virol 2011; 85:4520–4529 [View Article] [PubMed]
    [Google Scholar]
  19. Hughes AL, Irausquin S, Friedman R. The evolutionary biology of poxviruses. Infect Genet Evol 2010; 10:50–59 [View Article] [PubMed]
    [Google Scholar]
  20. Sun T-W, Yang C-L, Kao T-T, Wang T-H, Lai M-W et al. Host range and coding potential of eukaryotic giant viruses. Viruses 2020; 12:1337 [View Article]
    [Google Scholar]
  21. Schulz F, Roux S, Paez-Espino D, Jungbluth S, Walsh DA. Giant virus diversity and host interactions through global metagenomics. Nature 2020; 578:432–436 [View Article] [PubMed]
    [Google Scholar]
  22. Novoa RR, Calderita G, Arranz R, Fontana J, Granzow H. Virus factories: associations of cell organelles for viral replication and morphogenesis. Biol Cell 2005; 97:147–172 [View Article] [PubMed]
    [Google Scholar]
  23. Mutsafi Y, Zauberman N, Sabanay I, Minsky A. Vaccinia-like cytoplasmic replication of the giant Mimivirus. Proceedings of the National Academy of Sciences 2010; 107:5978–5982 [View Article]
    [Google Scholar]
  24. Goorha R. Frog virus 3 DNA replication occurs in two stages. J Virol 1982; 43:519–528 [View Article] [PubMed]
    [Google Scholar]
  25. Yutin N, Wolf YI, Raoult D, Koonin EV. Eukaryotic large nucleo-cytoplasmic DNA viruses: clusters of orthologous genes and reconstruction of viral genome evolution. Virol J 2009; 6:223 [View Article] [PubMed]
    [Google Scholar]
  26. Yutin N, Koonin EV. Hidden evolutionary complexity of Nucleo-Cytoplasmic Large DNA viruses of eukaryotes. Virol J 2012; 9:161 [View Article] [PubMed]
    [Google Scholar]
  27. Elde NC, Child SJ, Eickbush MT, Kitzman JO, Rogers KS. Poxviruses deploy genomic accordions to adapt rapidly against host antiviral defenses. Cell 2012; 150:831–841 [View Article] [PubMed]
    [Google Scholar]
  28. Filée J. Genomic comparison of closely related giant viruses supports an accordion-like model of evolution. Front Microbiol 2015; 6:593 [View Article] [PubMed]
    [Google Scholar]
  29. Suhre K. Gene and genome duplication in Acanthamoeba polyphaga mimivirus. J Virol 2005; 79:14095–14101 [View Article] [PubMed]
    [Google Scholar]
  30. Landstein D, Burbank DE, Nietfeldt JW, VanEtten JL. Large deletions in antigenic variants of the Chlorella virus PBCV-1. Virology 1995; 214:413–420 [View Article] [PubMed]
    [Google Scholar]
  31. Filée J, Siguier P, Chandler M. I am what I eat and I eat what I am: acquisition of bacterial genes by giant viruses. Trends Genet 2007; 23:10–15 [View Article] [PubMed]
    [Google Scholar]
  32. Filée J, Pouget N, Chandler M. Phylogenetic evidence for extensive lateral acquisition of cellular genes by nucleocytoplasmic large DNA viruses. BMC Evol Biol 2008; 8:320 [View Article] [PubMed]
    [Google Scholar]
  33. Legendre M, Fabre E, Poirot O, Jeudy S, Lartigue A. Diversity and evolution of the emerging Pandoraviridae family. Nat Commun 2018; 9:2285 [View Article] [PubMed]
    [Google Scholar]
  34. Suttle CA. Marine viruses - major players in the global ecosystem. Nat Rev Microbiol 2007; 5:801–812 [View Article] [PubMed]
    [Google Scholar]
  35. Simmonds P, Adams MJ, Benkő M, Breitbart M, Brister JR. Virus taxonomy in the age of metagenomics. Nat Rev Microbiol 2017; 15:161–168 [View Article]
    [Google Scholar]
  36. Mokili JL, Rohwer F, Dutilh BE. Metagenomics and future perspectives in virus discovery. Curr Opin Virol 2012; 2:63–77 [View Article] [PubMed]
    [Google Scholar]
  37. Koonin EV, Senkevich TG, Dolja VV. The ancient Virus World and evolution of cells. Biol Direct 2006; 1:29 [View Article] [PubMed]
    [Google Scholar]
  38. Baltimore D. Expression of animal virus genomes. Bacteriol Rev 1971; 35:235–241 [View Article] [PubMed]
    [Google Scholar]
  39. Iranzo J, Krupovic M, Koonin EV. The double-stranded DNA virosphere as a modular hierarchical network of gene sharing. Mbio 2016; 7:e00978-16 [View Article] [PubMed]
    [Google Scholar]
  40. International Committee on Taxonomy of Viruses Executive Committee The new scope of virus taxonomy: Partitioning the virosphere into 15 hierarchical ranks. Nat Microbiol 2020; 5:668–674 [View Article]
    [Google Scholar]
  41. Lefkowitz EJ, Dempsey DM, Hendrickson RC, Orton RJ, Siddell SG. Virus taxonomy: the database of the International Committee on Taxonomy of Viruses (ICTV. Nucleic Acids Res 2018; 46:D708–D717 [View Article] [PubMed]
    [Google Scholar]
  42. Abrahão J, Silva L, Silva LS, Khalil JYB, Rodrigues R. Tailed giant Tupanvirus possesses the most complete translational apparatus of the known virosphere. Nat Commun 2018; 9:749 [View Article] [PubMed]
    [Google Scholar]
  43. Moniruzzaman M, Martinez-Gutierrez CA, Weinheimer AR, Aylward FO. Dynamic genome evolution and complex virocell metabolism of globally-distributed giant viruses. Nat Commun 2020; 11:1710 [View Article] [PubMed]
    [Google Scholar]
  44. Yoshikawa G, Blanc-Mathieu R, Song C, Kayama Y, Mochizuki T. Medusavirus, a novel large DNA virus discovered from hot spring water. J Virol 2019; 93:e02130-18 [View Article] [PubMed]
    [Google Scholar]
  45. Valencia-Sánchez MI, Abini-Agbomson S, Wang M, Lee R, Vasilyev N. The structure of a virus-encoded nucleosome. Nat Struct Mol Biol 2021; 28:413–417 [View Article] [PubMed]
    [Google Scholar]
  46. Williams TA, Embley TM, Heinz E. Informational gene phylogenies do not support a fourth domain of life for nucleocytoplasmic large DNA viruses. PLoS One 2011; 6:e21080 [View Article] [PubMed]
    [Google Scholar]
  47. Jain S, Panda A, Colson P, Raoult D, Pontarotti P. MimiLook: A phylogenetic workflow for detection of gene acquisition in major orthologous groups of Megavirales. Viruses 2017; 9:72 [View Article]
    [Google Scholar]
  48. Li L, Stoeckert CJ, Roos DS. OrthoMCL: identification of ortholog groups for eukaryotic genomes. Genome Res 2003; 13:2178–2189 [View Article] [PubMed]
    [Google Scholar]
  49. Mistry J, Chuguransky S, Williams L, Qureshi M, Salazar GA. Pfam: The protein families database in 2021. Nucleic Acids Res 2021; 49:D412–D419 [View Article] [PubMed]
    [Google Scholar]
  50. Iyer LM, Aravind L, Koonin EV. Common origin of four diverse families of large eukaryotic DNA viruses. J Virol 2001; 75:11720–11734 [View Article] [PubMed]
    [Google Scholar]
  51. Bahar MW, Graham SC, Stuart DI, Grimes JM. Insights into the evolution of a complex virus from the crystal structure of vaccinia virus D13. Structure 2011; 19:1011–1020 [View Article] [PubMed]
    [Google Scholar]
  52. Sinclair RM, Ravantti JJ, Bamford DH. Nucleic and amino acid sequences support structure-based viral classification. J Virol 2017; 91:e02275-16 [View Article] [PubMed]
    [Google Scholar]
  53. Cock JM, Sterck L, Rouze P, Scornet D, Allen AE. The Ectocarpus genome and the independent evolution of multicellularity in brown algae. Nature 2010; 465:617–621 [View Article] [PubMed]
    [Google Scholar]
  54. Moniruzzaman M, Weinheimer AR, Martinez-Gutierrez CA, Aylward FO. Widespread endogenization of giant viruses shapes genomes of green algae. Nature 2020; 588:141–145 [View Article] [PubMed]
    [Google Scholar]
  55. Gilbert C, Feschotte C. Horizontal acquisition of transposable elements and viral sequences: patterns and consequences. Curr Opin Genet Dev 2018; 49:15–24 [View Article] [PubMed]
    [Google Scholar]
  56. Boratto PVM, Oliveira GP, Machado TB, Andrade ACSP, Baudoin J-P et al. Yaravirus: A novel 80-nm virus infecting Acanthamoeba castellanii. Proc Natl Acad Sci U S A 2020; 117:16579–16586 [View Article] [PubMed]
    [Google Scholar]
  57. Johnson RE, Klassen R, Prakash L, Prakash S. A major role of DNA polymerase δ in replication of both the leading and lagging DNA strands. Mol Cell 2015; 59:163–175 [View Article] [PubMed]
    [Google Scholar]
  58. Haller SL, Peng C, McFadden G, Rothenburg S. Poxviruses and the evolution of host range and virulence. Infect Genet Evol 2014; 21:15–40 [View Article] [PubMed]
    [Google Scholar]
  59. Boyer M, Azza S, Barrassi L, Klose T, Campocasso A. Mimivirus shows dramatic genome reduction after intraamoebal culture. Proceedings of the National Academy of Sciences 2011; 108:10296–10301 [View Article]
    [Google Scholar]
  60. Weynberg KD, Allen MJ, Wilson WH. Marine prasinoviruses and their tiny plankton hosts: A review. Viruses 2017; 9:43 [View Article]
    [Google Scholar]
  61. Kawachi M, Inouye I, Maeda O, Chihara M. The Haptonema as a food-capturing device - observations on Chrysochromulina hirta (Prymnesiophyceae. Phycologia 1991; 30:563–573 [View Article]
    [Google Scholar]
  62. Raven JA, Beardall J, Larkum AWD, Sanchez-Baracaldo P. Interactions of photosynthesis with genome size and function. Phil Trans R Soc B 2013; 368:20120264 [View Article]
    [Google Scholar]
  63. Chartier F, Laine B, Sautiere P. Characterization of the chromosomal protein MC1 from the thermophilic archaebacterium Methanosarcina sp. CHTI 55 and its effect on the thermal stability of DNA. Biochim Biophys Acta 1988; 951:149–156 [View Article] [PubMed]
    [Google Scholar]
  64. Odom MR, Hendrickson RC, Lefkowitz EJ. Poxvirus protein evolution: family wide assessment of possible horizontal gene transfer events. Virus Res 2009; 144:233–249 [View Article] [PubMed]
    [Google Scholar]
  65. Theze J, Takatsuka J, Nakai M, Arif B, Herniou EA. Gene acquisition convergence between entomopoxviruses and baculoviruses. Viruses 2015; 7:1960–1974 [View Article] [PubMed]
    [Google Scholar]
  66. Gallot-Lavallee L, Blanc G. A glimpse of nucleo-cytoplasmic large DNA virus biodiversity through the eukaryotic genomics window. Viruses 2017; 9:17 [View Article]
    [Google Scholar]
  67. Krupovic M, Koonin EV. Polintons: a hotbed of eukaryotic virus, transposon and plasmid evolution. Nat Rev Microbiol 2015; 13:105–115 [View Article] [PubMed]
    [Google Scholar]
  68. Fischer MG, Suttle CA. A virophage at the origin of large DNA transposons. Science 2011; 332:231–234 [View Article] [PubMed]
    [Google Scholar]
  69. Campbell S, Aswadl A, Katzourakis A. Disentangling the origins of virophages and polintons. Curr Opin Virol 2017; 25:59–65 [View Article] [PubMed]
    [Google Scholar]
  70. Krupovic M, Bamford DH, Koonin EV. Conservation of major and minor jelly-roll capsid proteins in polinton (Maverick) transposons suggests that they are bona fide viruses. Biol Direct 2014; 9:6 [View Article] [PubMed]
    [Google Scholar]
  71. Yutin N, Shevchenko S, Kapitonov V, Krupovic M, Koonin EV. A novel group of diverse Polinton-like viruses discovered by metagenome analysis. BMC Biol 2015; 13:95 [View Article] [PubMed]
    [Google Scholar]
  72. Krupovic M, Kuhn JH, Fischer MG. A classification system for virophages and satellite viruses. Arch Virol 2016; 161:233–247 [View Article] [PubMed]
    [Google Scholar]
  73. Iyer LM, Makarova KS, Koonin EV, Aravind L. Comparative genomics of the FtsK-HerA superfamily of pumping ATPases: implications for the origins of chromosome segregation, cell division and viral capsid packaging. Nucleic Acids Res 2004; 32:5260–5279 [View Article] [PubMed]
    [Google Scholar]
  74. Yutin N, Raoult D, Koonin EV. Virophages, polintons, and transpovirons: a complex evolutionary network of diverse selfish genetic elements with different reproduction strategies. Virol J 2013; 10:158 [View Article] [PubMed]
    [Google Scholar]
  75. Ravantti J, Bamford D, Stuart DI. Automatic comparison and classification of protein structures. J Struct Biol 2013; 183:47–56 [View Article] [PubMed]
    [Google Scholar]
  76. Fischer MG, Hackl T. Host genome integration and giant virus-induced reactivation of the virophage mavirus. Nature 2016; 540:288 [View Article] [PubMed]
    [Google Scholar]
  77. Köhsler M, Leitsch D, Furnkranz U, Duchene M, Aspock H. Acanthamoeba strains lose their abilities to encyst synchronously upon prolonged axenic culture. Parasitol Res 2008; 102:1069–1072 [View Article] [PubMed]
    [Google Scholar]
  78. Koehsler M, Leitsch D, Duchene M, Nagl M, Walochnik J. Acanthamoeba castellanii: growth on human cell layers reactivates attenuated properties after prolonged axenic culture. Fems Microbiol Lett 2009; 299:121–127 [View Article] [PubMed]
    [Google Scholar]
  79. Moliner C, Fournier PE, Raoult D. Genome analysis of microorganisms living in amoebae reveals a melting pot of evolution. FEMS Microbiol Rev 2010; 34:281–294 [View Article] [PubMed]
    [Google Scholar]
  80. Sanjuán R, Nebot MR, Chirico N, Mansky LM, Belshaw R. Viral mutation rates. J Virol 2010; 84:9733–9748 [View Article]
    [Google Scholar]
  81. Langland JO, Jacobs BL. The role of the PKR-inhibitory genes, E3L and K3L, in determining vaccinia virus host range. Virology 2002; 299:133–141 [View Article] [PubMed]
    [Google Scholar]
  82. Li J, Mahajan A, Tsai MD. Ankyrin repeat: a unique motif mediating protein-protein interactions. Biochemistry 2006; 45:15168–15178 [View Article] [PubMed]
    [Google Scholar]
  83. Cheng CH, Shuman S. Recombinogenic flap ligation pathway for intrinsic repair of topoisomerase IB-induced double-strand breaks. Mol Cell Biol 2000; 20:8059–8068 [View Article] [PubMed]
    [Google Scholar]
  84. Mohamed MR, Rahman MM, Lanchbury JS, Shattuck D, Neff C. Proteomic screening of variola virus reveals a unique NF-kappa B inhibitor that is highly conserved among pathogenic orthopoxviruses. Proceedings of the National Academy of Sciences 2009; 106:9045–9050 [View Article]
    [Google Scholar]
  85. Upton C, Slack S, Hunter AL, Ehlers A, Roper RL. Poxvirus orthologous clusters: toward defining the minimum essential poxvirus genome. J Virol 2003; 77:7590–7600 [View Article] [PubMed]
    [Google Scholar]
  86. Esteban DJ, Hutchinson AP. Genes in the terminal regions of orthopoxvirus genomes experience adaptive molecular evolution. Bmc Genomics 2011; 12:261 [View Article] [PubMed]
    [Google Scholar]
  87. Arslan D, Legendre M, Seltzer V, Abergel C, Claverie JM. Distant mimivirus relative with a larger genome highlights the fundamental features of Megaviridae. Proc Natl Acad Sci USA 2011; 108:17486–17491 [View Article] [PubMed]
    [Google Scholar]
  88. Blanca L, Christo-Foroux E, Rigou S, Legendre M. Comparative analysis of the circular and highly asymmetrical Marseilleviridae genomes. Viruses 2020; 12:1270 [View Article]
    [Google Scholar]
  89. Nishida K, Kimura Y, Kawasaki T, Fujie M, Yamada T. Genetic variation of Chlorella viruses: Variable regions localized on the CVK2 genomic DNA. Virology 1999; 255:376–384 [View Article] [PubMed]
    [Google Scholar]
  90. Lu Z, Li Y, Zhang Y, Kutish GF, Rock DL et al. Analysis of 45 kb of DNA located at the left end of the chlorella virus PBCV-1 genome. Virology 1995; 206:339–352 [View Article] [PubMed]
    [Google Scholar]
  91. Songsri P, Hamazaki T, Ishikawa Y, Yamada T. Large deletions in the genome of Chlorella virus CVK1. Virology 1995; 214:405–412 [View Article] [PubMed]
    [Google Scholar]
  92. Chuchird N, Nishida K, Kawasaki T, Fujie M, Usami S. A variable region on the chlorovirus CVK2 genome contains five copies of the gene for Vp260, a viral-surface glycoprotein. Virology 2002; 295:289–298 [View Article] [PubMed]
    [Google Scholar]
  93. Vigerust DJ, Shepherd VL. Virus glycosylation: role in virulence and immune interactions. Trends Microbiol 2007; 15:211–218 [View Article] [PubMed]
    [Google Scholar]
  94. Holmes EC. What does virus evolution tell us about virus origins. J Virol 2011; 85:5247–5251 [View Article] [PubMed]
    [Google Scholar]
  95. Tavaré S. Some probabilistic and statistical problems in the analysis of DNA sequences. In In American Mathematical Society: Lectures on Mathematics in the Life Sciences 1986 pp 57–86
    [Google Scholar]
  96. Lewis PO. A likelihood approach to estimating phylogeny from discrete morphological character data. Syst Biol 2001; 50:913–925 [View Article] [PubMed]
    [Google Scholar]
  97. Hoang DT, Chernomor O, von Haeseler A, Minh BQ, Vinh LS. UFBoot2: Improving the ultrafast bootstrap approximation. Mol Biol Evol 2018; 35:518–522 [View Article] [PubMed]
    [Google Scholar]
  98. Nguyen L-. T, Schmidt HA, von Haeseler A, Minh BQ. IQ-TREE: a fast and effective stochastic algorithm for estimating maximum-likelihood phylogenies. Mol Biol Evol 2015; 32:268–274 [View Article] [PubMed]
    [Google Scholar]
  99. Smoot ME, Ono K, Ruscheinski J, Wang PL, Ideker T. Cytoscape 2.8: new features for data integration and network visualization. Bioinformatics 2011; 27:431–432 [View Article] [PubMed]
    [Google Scholar]
http://instance.metastore.ingenta.com/content/journal/mgen/10.1099/mgen.0.000649
Loading
/content/journal/mgen/10.1099/mgen.0.000649
Loading

Data & Media loading...

Supplements

Supplementary material 1

PDF

Most cited this month Most Cited RSS feed

This is a required field
Please enter a valid email address
Approval was a Success
Invalid data
An Error Occurred
Approval was partially successful, following selected items could not be processed due to error