Polintons: a hotbed of eukaryotic virus, transposon and plasmid evolution


Polintons (also known as Mavericks) are large DNA transposons that are widespread in the genomes of eukaryotes. We have recently shown that Polintons encode virus capsid proteins, which suggests that these transposons might form virions, at least under some conditions. In this Opinion article, we delineate the evolutionary relationships among bacterial tectiviruses, Polintons, adenoviruses, virophages, large and giant DNA viruses of eukaryotes of the proposed order 'Megavirales', and linear mitochondrial and cytoplasmic plasmids. We hypothesize that Polintons were the first group of eukaryotic double-stranded DNA viruses to evolve from bacteriophages and that they gave rise to most large DNA viruses of eukaryotes and various other selfish genetic elements.

Access options

Rent or Buy article

Get time limited or full article access on ReadCube.


All prices are NET prices.

Figure 1: Evolutionary relationships between Polintons and other mobile genetic elements.
Figure 2: Structural features of some viruses with double jelly-roll major capsid proteins.
Figure 3: Phylogenetic analysis of protein-primed type B DNA polymerases from mobile elements in archaea, bacteria and eukaryotes.
Figure 4: A hypothetical scenario for the evolution of various eukaryotic viruses and plasmids.

Accession codes


Protein Data Bank


  1. 1

    Koonin, E. V. & Dolja, V. V. A virocentric perspective on the evolution of life. Curr. Opin. Virol. 3, 546–557 (2013).

    PubMed  PubMed Central  Google Scholar 

  2. 2

    Krupovic, M. & Bamford, D. H. Order to the viral universe. J. Virol. 84, 12476–12479 (2010).

    CAS  PubMed  PubMed Central  Google Scholar 

  3. 3

    Koonin, E. V. & Dolja, V. V. Virus world as an evolutionary network of viruses and capsid-less selfish elements. Microbiol. Mol. Biol. Rev. 78, 278–303 (2014).

    CAS  PubMed  PubMed Central  Google Scholar 

  4. 4

    Krupovic, M., Prangishvili, D., Hendrix, R. W. & Bamford, D. H. Genomics of bacterial and archaeal viruses: dynamics within the prokaryotic virosphere. Microbiol. Mol. Biol. Rev. 75, 610–635 (2011).

    PubMed  PubMed Central  Google Scholar 

  5. 5

    Koonin, E. V., Senkevich, T. G. & Dolja, V. V. The ancient Virus World and evolution of cells. Biol. Direct 1, 29 (2006).

    PubMed  PubMed Central  Google Scholar 

  6. 6

    Holmes, E. C. What does virus evolution tell us about virus origins? J. Virol. 85, 5247–5251 (2011).

    CAS  PubMed  PubMed Central  Google Scholar 

  7. 7

    Kazazian, H. H. Jr. Mobile elements: drivers of genome evolution. Science 303, 1626–1632 (2004).

    CAS  PubMed  Google Scholar 

  8. 8

    Goodier, J. L. & Kazazian, H. H. Jr. Retrotransposons revisited: the restraint and rehabilitation of parasites. Cell 135, 23–35 (2008).

    CAS  PubMed  Google Scholar 

  9. 9

    Iyer, L. M., Aravind, L. & Koonin, E. V. Common origin of four diverse families of large eukaryotic DNA viruses. J. Virol. 75, 11720–11734 (2001).

    CAS  PubMed  PubMed Central  Google Scholar 

  10. 10

    Iyer, L. M., Balaji, S., Koonin, E. V. & Aravind, L. Evolutionary genomics of nucleo-cytoplasmic large DNA viruses. Virus Res. 117, 156–184 (2006).

    CAS  PubMed  Google Scholar 

  11. 11

    Koonin, E. V. & Yutin, N. Origin and evolution of eukaryotic large nucleo-cytoplasmic DNA viruses. Intervirology 53, 284–292 (2010).

    PubMed  PubMed Central  Google Scholar 

  12. 12

    Colson, P. et al. “Megavirales”, a proposed new order for eukaryotic nucleocytoplasmic large DNA viruses. Arch. Virol. 158, 2517–2521 (2013).

    PubMed  PubMed Central  Google Scholar 

  13. 13

    La Scola, B. et al. The virophage as a unique parasite of the giant mimivirus. Nature 455, 100–104 (2008).

    CAS  PubMed  Google Scholar 

  14. 14

    Claverie, J. M. & Abergel, C. Mimivirus and its virophage. Annu. Rev. Genet. 43, 49–66 (2009).

    CAS  PubMed  Google Scholar 

  15. 15

    Desnues, C., Boyer, M. & Raoult, D. Sputnik, a virophage infecting the viral domain of life. Adv. Virus Res. 82, 63–89 (2012).

    CAS  PubMed  Google Scholar 

  16. 16

    Krupovic, M. & Cvirkaite-Krupovic, V. Virophages or satellite viruses? Nature Rev. Microbiol. 9, 762–763 (2011).

    CAS  Google Scholar 

  17. 17

    Fischer, M. G. & Suttle, C. A. A virophage at the origin of large DNA transposons. Science 332, 231–234 (2011).

    CAS  PubMed  Google Scholar 

  18. 18

    Yutin, N., Raoult, D. & Koonin, E. V. Virophages, polintons, and transpovirons: a complex evolutionary network of diverse selfish genetic elements with different reproduction strategies. Virol. J. 10, 158 (2013).

    CAS  PubMed  PubMed Central  Google Scholar 

  19. 19

    Krupovic, M., Bamford, D. H. & Koonin, E. V. Conservation of major and minor jelly-roll capsid proteins in Polinton (Maverick) transposons suggests that they are bona fide viruses. Biol. Direct 9, 6 (2014).

    PubMed  PubMed Central  Google Scholar 

  20. 20

    Kapitonov, V. V. & Jurka, J. Self-synthesizing DNA transposons in eukaryotes. Proc. Natl Acad. Sci. USA 103, 4540–4545 (2006).

    CAS  PubMed  Google Scholar 

  21. 21

    Pritham, E. J., Putliwala, T. & Feschotte, C. Mavericks, a novel class of giant transposable elements widespread in eukaryotes and related to DNA viruses. Gene 390, 3–17 (2007).

    CAS  PubMed  Google Scholar 

  22. 22

    Jurka, J., Kapitonov, V. V., Kohany, O. & Jurka, M. V. Repetitive sequences in complex genomes: structure and evolution. Annu. Rev. Genom. Hum. Genet. 8, 241–259 (2007).

    CAS  Google Scholar 

  23. 23

    Benson, S. D., Bamford, J. K., Bamford, D. H. & Burnett, R. M. Does common architecture reveal a viral lineage spanning all three domains of life? Mol. Cell 16, 673–685 (2004).

    CAS  PubMed  Google Scholar 

  24. 24

    Krupovic, M. & Bamford, D. H. Virus evolution: how far does the double β-barrel viral lineage extend? Nature Rev. Microbiol. 6, 941–948 (2008).

    CAS  Google Scholar 

  25. 25

    Krupovic, M. & Bamford, D. H. Double-stranded DNA viruses: 20 families and only five different architectural principles for virion assembly. Curr. Opin. Virol. 1, 118–124 (2011).

    CAS  PubMed  Google Scholar 

  26. 26

    Abrescia, N. G. et al. Insights into assembly from structural analysis of bacteriophage PRD1. Nature 432, 68–74 (2004).

    CAS  PubMed  Google Scholar 

  27. 27

    Abrescia, N. G. et al. Insights into virus evolution and membrane biogenesis from the structure of the marine lipid-containing bacteriophage PM2. Mol. Cell 31, 749–761 (2008).

    CAS  PubMed  Google Scholar 

  28. 28

    Veesler, D. et al. Atomic structure of the 75 MDa extremophile Sulfolobus turreted icosahedral virus determined by CryoEM and X-ray crystallography. Proc. Natl Acad. Sci. USA 110, 5504–5509 (2013).

    CAS  PubMed  Google Scholar 

  29. 29

    Zhang, X. et al. Structure of Sputnik, a virophage, at 3.5-Å resolution. Proc. Natl Acad. Sci. USA 109, 18431–18436 (2012).

    CAS  PubMed  Google Scholar 

  30. 30

    Zubieta, C., Schoehn, G., Chroboczek, J. & Cusack, S. The structure of the human adenovirus 2 penton. Mol. Cell 17, 121–135 (2005).

    CAS  PubMed  Google Scholar 

  31. 31

    Xiao, C. & Rossmann, M. G. Structures of giant icosahedral eukaryotic dsDNA viruses. Curr. Opin. Virol. 1, 101–109 (2011).

    CAS  PubMed  PubMed Central  Google Scholar 

  32. 32

    Dunigan, D. D. et al. Paramecium bursaria Chlorella virus 1 proteome reveals novel architectural and regulatory features of a giant virus. J. Virol. 86, 8821–8834 (2012).

    CAS  PubMed  PubMed Central  Google Scholar 

  33. 33

    Barrett, A. J. & Rawlings, N. D. Evolutionary lines of cysteine peptidases. Biol. Chem. 382, 727–733 (2001).

    CAS  PubMed  Google Scholar 

  34. 34

    San Martín, C. Latest insights on adenovirus structure and assembly. Viruses 4, 847–877 (2012).

    PubMed  PubMed Central  Google Scholar 

  35. 35

    Yutin, N., Wolf, Y. I., Raoult, D. & Koonin, E. V. Eukaryotic large nucleo-cytoplasmic DNA viruses: clusters of orthologous genes and reconstruction of viral genome evolution. Virol. J. 6, 223 (2009).

    PubMed  PubMed Central  Google Scholar 

  36. 36

    Andres, G., Alejo, A., Simon-Mateo, C. & Salas, M. L. African swine fever virus protease, a new viral member of the SUMO-1-specific protease family. J. Biol. Chem. 276, 780–787 (2001).

    CAS  PubMed  Google Scholar 

  37. 37

    Byrd, C. M. & Hruby, D. E. A conditional-lethal vaccinia virus mutant demonstrates that the I7L gene product is required for virion morphogenesis. Virol. J. 2, 4 (2005).

    PubMed  PubMed Central  Google Scholar 

  38. 38

    Gillis, A. & Mahillon, J. Phages preying on Bacillus anthracis, Bacillus cereus, and Bacillus thuringiensis: past, present and future. Viruses 6, 2623–2672 (2014).

    PubMed  PubMed Central  Google Scholar 

  39. 39

    Strömsten, N. J., Benson, S. D., Burnett, R. M., Bamford, D. H. & Bamford, J. K. The Bacillus thuringiensis linear double-stranded DNA phage Bam35, which is highly similar to the Bacillus cereus linear plasmid pBClin15, has a prophage state. J. Bacteriol. 185, 6985–6989 (2003).

    PubMed  PubMed Central  Google Scholar 

  40. 40

    Bao, W., Kapitonov, V. V. & Jurka, J. Ginger DNA transposons in eukaryotes and their evolutionary relationships with long terminal repeat retrotransposons. Mob DNA 1, 3 (2010).

    PubMed  PubMed Central  Google Scholar 

  41. 41

    Iyer, L. M., Makarova, K. S., Koonin, E. V. & 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. 32, 5260–5279 (2004).

    CAS  PubMed  PubMed Central  Google Scholar 

  42. 42

    Strömsten, N. J., Bamford, D. H. & Bamford, J. K. In vitro DNA packaging of PRD1: a common mechanism for internal-membrane viruses. J. Mol. Biol. 348, 617–629 (2005).

    PubMed  Google Scholar 

  43. 43

    Cassetti, M. C., Merchlinsky, M., Wolffe, E. J., Weisberg, A. S. & Moss, B. DNA packaging mutant: repression of the vaccinia virus A32 gene results in noninfectious, DNA-deficient, spherical, enveloped particles. J. Virol. 72, 5769–5780 (1998).

    CAS  PubMed  PubMed Central  Google Scholar 

  44. 44

    Burroughs, A. M., Iyer, L. M. & Aravind, L. Comparative genomics and evolutionary trajectories of viral ATP dependent DNA-packaging systems. Genome Dyn. 3, 48–65 (2007).

    CAS  PubMed  Google Scholar 

  45. 45

    Salas, M. Protein-priming of DNA replication. Annu. Rev. Biochem. 60, 39–71 (1991).

    CAS  PubMed  Google Scholar 

  46. 46

    Klassen, R. & Meinhardt, F. Linear protein-primed replicating plasmids in eukaryotic microbes. Microbiol. Monogr. 7, 188–216 (2007).

    Google Scholar 

  47. 47

    Krupovic, M. & Koonin, E. V. Evolution of eukaryotic single-stranded DNA viruses of the Bidnaviridae family from genes of four other groups of widely different viruses. Sci. Rep. 4, 5347 (2014).

    PubMed  PubMed Central  Google Scholar 

  48. 48

    Handa, H. Linear plasmids in plant mitochondria: peaceful coexistences or malicious invasions? Mitochondrion 8, 15–25 (2008).

    CAS  PubMed  Google Scholar 

  49. 49

    Filée, J. & Forterre, P. Viral proteins functioning in organelles: a cryptic origin? Trends Microbiol. 13, 510–513 (2005).

    PubMed  Google Scholar 

  50. 50

    Shutt, T. E. & Gray, M. W. Bacteriophage origins of mitochondrial replication and transcription proteins. Trends Genet. 22, 90–95 (2006).

    CAS  PubMed  Google Scholar 

  51. 51

    Benson, S. D., Bamford, J. K., Bamford, D. H. & Burnett, R. M. Viral evolution revealed by bacteriophage PRD1 and human adenovirus coat protein structures. Cell 98, 825–833 (1999).

    CAS  PubMed  Google Scholar 

  52. 52

    Davison, A. J., Benko, M. & Harrach, B. Genetic content and evolution of adenoviruses. J. Gen. Virol. 84, 2895–2908 (2003).

    CAS  PubMed  Google Scholar 

  53. 53

    Merckel, M. C., Huiskonen, J. T., Bamford, D. H., Goldman, A. & Tuma, R. The structure of the bacteriophage PRD1 spike sheds light on the evolution of viral capsid architecture. Mol. Cell 18, 161–170 (2005).

    CAS  PubMed  Google Scholar 

  54. 54

    Hu, Z. Y., Li, G. H., Li, G. T., Yao, Q. & Chen, K. P. Bombyx mori bidensovirus: the type species of the new genus Bidensovirus in the new family Bidnaviridae. Chin. Sci. Bull. 58, 4528–4532 (2013).

    CAS  Google Scholar 

  55. 55

    Krupovic, M. Networks of evolutionary interactions underlying the polyphyletic origin of ssDNA viruses. Curr. Opin. Virol. 3, 578–586 (2013).

    CAS  PubMed  Google Scholar 

  56. 56

    Iyer, L. M., Abhiman, S. & Aravind, L. A new family of polymerases related to superfamily A DNA polymerases and T7-like DNA-dependent RNA polymerases. Biol. Direct 3, 39 (2008).

    PubMed  PubMed Central  Google Scholar 

  57. 57

    Jeske, S., Meinhardt, F. & Klassen, R. in Progress in Botany (eds Esser, K., Lüttge, U., Beyschlag, W. & Murata, J.) 98–129 (Springer, 2007).

    Google Scholar 

  58. 58

    Iyer, L. M., Koonin, E. V. & Aravind, L. Evolutionary connection between the catalytic subunits of DNA-dependent RNA polymerases and eukaryotic RNA-dependent RNA polymerases and the origin of RNA polymerases. BMC Struct. Biol. 3, 1 (2003).

    PubMed  PubMed Central  Google Scholar 

  59. 59

    Wilson, D. W. & Meacock, P. A. Extranuclear gene expression in yeast: evidence for a plasmid-encoded RNA polymerase of unique structure. Nucleic Acids Res. 16, 8097–8112 (1988).

    CAS  PubMed  PubMed Central  Google Scholar 

  60. 60

    Deng, L. & Shuman, S. Vaccinia NPH-I, a DExH-box ATPase, is the energy coupling factor for mRNA transcription termination. Genes Dev. 12, 538–546 (1998).

    CAS  PubMed  PubMed Central  Google Scholar 

  61. 61

    Larsen, M., Gunge, N. & Meinhardt, F. Kluyveromyces lactis killer plasmid pGKL2: evidence for a viral-like capping enzyme encoded by ORF3. Plasmid 40, 243–246 (1998).

    CAS  PubMed  Google Scholar 

  62. 62

    Kyrieleis, O. J., Chang, J., de la Pena, M., Shuman, S. & Cusack, S. Crystal structure of vaccinia virus mRNA capping enzyme provides insights into the mechanism and evolution of the capping apparatus. Structure 22, 452–465 (2014).

    CAS  PubMed  PubMed Central  Google Scholar 

  63. 63

    Shuman, S. What messenger RNA capping tells us about eukaryotic evolution. Nature Rev. Mol. Cell Biol. 3, 619–625 (2002).

    CAS  Google Scholar 

  64. 64

    Shuman, S. The mRNA capping apparatus as drug target and guide to eukaryotic phylogeny. Cold Spring Harb. Symp. Quant. Biol. 66, 301–312 (2001).

    CAS  PubMed  Google Scholar 

  65. 65

    Tiggemann, M., Jeske, S., Larsen, M. & Meinhardt, F. Kluyveromyces lactis cytoplasmic plasmid pGKL2: heterologous expression of Orf3p and proof of guanylyltransferase and mRNA-triphosphatase activities. Yeast 18, 815–825 (2001).

    CAS  PubMed  Google Scholar 

  66. 66

    Yutin, N. & Koonin, E. V. Hidden evolutionary complexity of nucleo-cytoplasmic large DNA viruses of eukaryotes. Virol. J. 9, 161 (2012).

    CAS  PubMed  PubMed Central  Google Scholar 

  67. 67

    Sandmeyer, S. B. & Menees, T. M. Morphogenesis at the retrotransposon-retrovirus interface: gypsy and copia families in yeast and Drosophila. Curr. Top. Microbiol. Immunol. 214, 261–296 (1996).

    CAS  PubMed  Google Scholar 

  68. 68

    Yutin, N., Wolf, Y. I. & Koonin, E. V. Origin of giant viruses from smaller DNA viruses not from a fourth domain of cellular life. Virology 466–467, 38–52 (2014).

    PubMed  Google Scholar 

  69. 69

    Legendre, M. et al. Thirty-thousand-year-old distant relative of giant icosahedral DNA viruses with a pandoravirus morphology. Proc. Natl Acad. Sci. USA 111, 4274–4279 (2014).

    CAS  PubMed  Google Scholar 

  70. 70

    Rixon, F. J. & Schmid, M. F. Structural similarities in DNA packaging and delivery apparatuses in Herpesvirus and dsDNA bacteriophages. Curr. Opin. Virol. 5, 105–110 (2014).

    CAS  PubMed  Google Scholar 

  71. 71

    Philippe, N. et al. Pandoraviruses: amoeba viruses with genomes up to 2.5 Mb reaching that of parasitic eukaryotes. Science 341, 281–286 (2013).

    CAS  PubMed  Google Scholar 

  72. 72

    Keeling, P. J. et al. The tree of eukaryotes. Trends Ecol. Evol. 20, 670–676 (2005).

    PubMed  Google Scholar 

  73. 73

    Desnues, C. et al. Provirophages and transpovirons as the diverse mobilome of giant viruses. Proc. Natl Acad. Sci. USA 109, 18078–18083 (2012).

    CAS  PubMed  Google Scholar 

  74. 74

    Nandhagopal, N. et al. The structure and evolution of the major capsid protein of a large, lipid-containing DNA virus. Proc. Natl Acad. Sci. USA 99, 14758–14763 (2002).

    CAS  PubMed  Google Scholar 

  75. 75

    Rux, J. J., Kuser, P. R. & Burnett, R. M. Structural and phylogenetic analysis of adenovirus hexons by use of high-resolution x-ray crystallographic, molecular modeling, and sequence-based methods. J. Virol. 77, 9553–9566 (2003).

    CAS  PubMed  PubMed Central  Google Scholar 

  76. 76

    Guindon, S. et al. New algorithms and methods to estimate maximum-likelihood phylogenies: assessing the performance of PhyML 3.0. Syst. Biol. 59, 307–321 (2010).

    CAS  PubMed  Google Scholar 

  77. 77

    Krupovic, M., Makarova, K. S., Forterre, P., Prangishvili, D. & Koonin, E. V. Casposons: a new superfamily of self-synthesizing DNA transposons at the origin of prokaryotic CRISPR-Cas immunity. BMC Biol. 12, 36 (2014).

    PubMed  PubMed Central  Google Scholar 

Download references


E.V.K. is supported by the intramural funds of the US Department of Health and Human Services (to the National Library of Medicine).

Author information



Corresponding authors

Correspondence to Mart Krupovic or Eugene V. Koonin.

Ethics declarations

Competing interests

The authors declare no competing financial interests.

Related links


Protein Data Bank

PowerPoint slides

Supplementary information

Supplementary information S1 (figure)

Multiple sequence alignment of the putative penton proteins of polintoviruses with uncharacterized proteins of phycodnaviruses. (PDF 136 kb)

Supplementary information S2 (figure)

Relationship between the ATPases of the Polintovirus 2 from Alligator mississippiensis (P2_AMi) and human adenovirus 4. (PDF 152 kb)

Supplementary information S3 (figure)

Phylogenetic analysis of pPolBs from prokaryotic and eukaryotic mobile elements. (PDF 167 kb)

Supplementary information S4 (table)

Key polinton proteins with homologs in Reticulomyxa filosa. (PDF 129 kb)

Rights and permissions

Reprints and Permissions

About this article

Verify currency and authenticity via CrossMark

Cite this article

Krupovic, M., Koonin, E. Polintons: a hotbed of eukaryotic virus, transposon and plasmid evolution. Nat Rev Microbiol 13, 105–115 (2015). https://doi.org/10.1038/nrmicro3389

Download citation

Further reading