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Cited by 4Bacteriophages and microbial interactionsPlant and Fungal Interactions ResearchGenomics and Phylogenetic Studies

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Convergent evolution of viral-like Borg archaeal extrachromosomal elements and giant eukaryotic viruses

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Banfield, Jillian F., Valentin-Alvarado, Luis E., Shi, Ling-Dong, Robinson, Colin Michael, Bamert, Rebecca S., Coulibaly, Fasseli, Barth, Zachary K., Aylward, Frank O., Schoelmerich, Marie C., Lei, Shufei, Sachdeva, Rohan, Knott, Gavin J.·2025·Nature Communications
DOI 10.1038/s41467-025-65646-7PMC PMC12660748

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Abstract

Borgs are huge extrachromosomal elements of anaerobic methane-oxidizing archaea. They exist in exceedingly complex microbiomes, lack cultivated hosts and have few protein functional annotations, precluding their classification as plasmids, viruses or other. Here, we use in silico structure prediction methods to investigate potential roles for ~10,000 Borg proteins. Prioritizing analysis of multicopy genes that could signal importance for Borg lifestyles, we uncover highly represented de-ubiquitination-like Zn-metalloproteases that may counter host targeting of Borg proteins for proteolysis. Also prevalent are clusters of multicopy genes for production of diverse glycoconjugates that could contribute to decoration of the host cell surface, or of putative capsid proteins that we predict multimerize into pentagonal and hexagonal arrays. Features including megabase-scale linear genomes with inverted terminal repeats, genomic repertoires for energy metabolism, central carbon compound transformations and translation, and pervasive direct repeat regions are shared with giant viruses of eukaryotes, although analyses suggest that these parallels arose via convergent evolution. If Borgs are giant archaeal viruses they would fill the gap in the tri(um)virate of giant viruses of all three domains of life.

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Research works printed but not linked: 72

  1. Prangishvili, D. et al. The enigmatic archaeal virosphere. Nat. Rev. Microbiol. 15, 724–739 (2017). · DOI
  2. Eme, L. et al. Inference and reconstruction of the heimdallarchaeial ancestry of eukaryotes. Nature 618, 992–999 (2023). · DOI
  3. Al-Shayeb, B. et al. Borgs are giant genetic elements with potential to expand metabolic capacity. Nature 610, 731–736 (2022). · DOI
  4. Wagenknecht, M. et al. Structural peculiarities of linear megaplasmid, pLMA1, from Micrococcus luteus interfere with pyrosequencing reads assembly. Biotechnol. Lett. 32, 1853–1862 (2010). · DOI
  5. Krupovic, M., Cvirkaite-Krupovic, V., Iranzo, J., Prangishvili, D. & Koonin, E. V. Viruses of archaea: Structural, functional, environmental and evolutionary genomics. Virus Res. 244, 181–193 (2018). · DOI
  6. Talbert, P. B., Henikoff, S. & Armache, K.-J. Giant variations in giant virus genome packaging. Trends Biochem. Sci. 48, 1071–1082 (2023). · DOI
  7. Chihara, A. et al. A novel capsid protein network allows the characteristic internal membrane structure of Marseilleviridae giant viruses. Sci. Rep. 12, 21428 (2022). · DOI
  8. Iyer, L. M., Balaji, S., Koonin, E. V. & Aravind, L. Evolutionary genomics of nucleo-cytoplasmic large DNA viruses. Virus Res. 117, 156–184 (2006). · DOI
  9. Mönttinen, H. A. M., Bicep, C., Williams, T. A. & Hirt, R. P. The genomes of nucleocytoplasmic large DNA viruses: viral evolution writ large. Microb. Genom. 7, 000649 (2021).
  10. Schoelmerich, M. C. et al. Borg extrachromosomal elements of methane-oxidizing archaea have conserved and expressed genetic repertoires. Nat. Commun. 15, 5414 (2024). · DOI · Paper page
  11. Mirdita, M. et al. ColabFold: making protein folding accessible to all. Nat. Methods 19, 679–682 (2022). · DOI · Paper page
  12. Holm, L. Dali server: structural unification of protein families. Nucleic Acids Res. 50, W210–W215 (2022). · DOI
  13. Suresh, H. G., Pascoe, N. & Andrews, B. The structure and function of deubiquitinases: lessons from budding yeast. Open Biol. 10, 200279 (2020). · DOI
  14. Darwin, K. H. & Hofmann, K. SAMPyling proteins in archaea. Trends Biochem. Sci. 35, 348–351 (2010). · DOI
  15. Humbard, M. A. et al. Ubiquitin-like small archaeal modifier proteins (SAMPs) in Haloferax volcanii. Nature 463, 54–60 (2010). · DOI
  16. Hör, J., Wolf, S. G. & Sorek, R. Bacteria conjugate ubiquitin-like proteins to interfere with phage assembly. Nature 631, 850–856 (2024). · DOI
  17. Kosakovsky Pond, S. L. et al. HyPhy 2.5-A customizable platform for evolutionary hypothesis testing using PHYlogenies. Mol. Biol. Evol. 37, 295–299 (2020). · DOI
  18. Gandini, R., Reichenbach, T., Tan, T.-C. & Divne, C. Structural basis for dolichylphosphate mannose biosynthesis. Nat. Commun. 8, 120 (2017). · DOI
  19. Ardiccioni, C. et al. Structure of the polyisoprenyl-phosphate glycosyltransferase GtrB and insights into the mechanism of catalysis. Nat. Commun. 7, 10175 (2016). · DOI
  20. Krupovic, M. & Koonin, E. V. Multiple origins of viral capsid proteins from cellular ancestors. Proc. Natl. Acad. Sci. USA 114, E2401–E2410 (2017). · DOI
  21. Shi, L.-D. et al. Methanotrophic Methanoperedens archaea host diverse and interacting extrachromosomal elements. Nat. Microbiol. 9, 2422–2433 (2024). · DOI
  22. Moniruzzaman, M. et al. Virus-host relationships of marine single-celled eukaryotes resolved from metatranscriptomics. Nat. Commun. 8, 16054 (2017). · DOI
  23. Parvez, M. K. Geometric architecture of viruses. World J. Virol. 9, 5–18 (2020). · DOI
  24. Bryant, P. et al. Predicting the structure of large protein complexes using AlphaFold and Monte Carlo tree search. Nat. Commun. 13, 6028 (2022). · DOI
  25. Kim, R. S., Levy Karin, E., Mirdita, M., Chikhi, R. & Steinegger, M. BFVD-a large repository of predicted viral protein structures. Nucleic Acids Res. 53, D340–D347 (2025). · DOI · Paper page
  26. Perkins, E. M. et al. Small capsid protein pORF65 is essential for assembly of Kaposi’s sarcoma-associated herpesvirus capsids. J. Virol. 82, 7201–7211 (2008). · DOI
  27. Rigou, S. et al. Nucleocytoviricotaviral factories are transient organelles made by phase separation. Preprint at https://doi.org/10.1101/2024.09.01.610734 (2024). · DOI
  28. Wilhelm, S. W. et al. A student’s guide to giant viruses infecting small eukaryotes: From Acanthamoeba to zooxanthellae. Viruses 9, 46 (2017). · DOI
  29. Wu, J. et al. Gene transfer among viruses substantially contributes to gene gain of giant viruses. Mol. Biol. Evol. 41, msae161 (2024). · DOI
  30. Moniruzzaman, M. et al. Virologs, viral mimicry, and virocell metabolism: the expanding scale of cellular functions encoded in the complex genomes of giant viruses. FEMS Microbiol. Rev. 47, https://doi.org/10.1093/femsre/fuad053 (2023). · DOI
  31. Osterman, I. et al. Phages reconstitute NAD+ to counter bacterial immunity. Nature 634, 1160–1167 (2024). · DOI
  32. Zhang, L., Villa, N. Y. & McFadden, G. Interplay between poxviruses and the cellular ubiquitin/ubiquitin-like pathways. FEBS Lett. 583, 607–614 (2009). · DOI
  33. M Iyer, L., Anantharaman, V., Krishnan, A., Burroughs, A. M. & Aravind, L. Jumbo. phages: A comparative genomic overview of core functions and adaptions for biological conflicts. Viruses 13, 63 (2021). · DOI
  34. Moniruzzaman, M., Martinez-Gutierrez, C. A., Weinheimer, A. R. & Aylward, F. O. Dynamic genome evolution and complex virocell metabolism of globally-distributed giant viruses. Nat. Commun. 11, 1710 (2020). · DOI
  35. Brandes, N. & Linial, M. Giant viruses-big surprises. Viruses 11, 404 (2019). · DOI
  36. Raoult, D. et al. The 1.2-megabase genome sequence of Mimivirus. Science 306, 1344–1350 (2004). · DOI
  37. Al-Shayeb, B. et al. Clades of huge phages from across Earth’s ecosystems. Nature 578, 425–431 (2020). · DOI
  38. Aylward, F. O., Moniruzzaman, M., Ha, A. D. & Koonin, E. V. A phylogenomic framework for charting the diversity and evolution of giant viruses. PLoS Biol. 19, e3001430 (2021). · DOI
  39. Liu, Y. et al. Virus-encoded histone doublets are essential and form nucleosome-like structures. Cell 184, 4237–4250.e19 (2021). · DOI
  40. Gaïa, M. et al. Mirusviruses link herpesviruses to giant viruses. Nature 616, 783–789 (2023). · DOI · Paper page
  41. Dominski, Z., Yang, X.-C., Kaygun, H., Dadlez, M. & Marzluff, W. F. A 3′ exonuclease that specifically interacts with the 3′ end of histone mRNA. Mol. Cell 12, 295–305 (2003). · DOI
  42. Da Cunha, V. et al. Giant viruses encode actin-related proteins. Mol. Biol. Evol. 39, msac022 (2022). · DOI
  43. Chaikeeratisak, V., Birkholz, E. A. & Pogliano, J. The Phage Nucleus and PhuZ spindle: Defining features of the subcellular organization and speciation of nucleus-forming jumbo phages. Front. Microbiol. 12, 641317 (2021). · DOI
  44. Filée, J. Lateral gene transfer, lineage-specific gene expansion and the evolution of Nucleo Cytoplasmic Large DNA viruses. J. Invertebr. Pathol. 101, 169–171 (2009). · DOI
  45. Erazo-Garcia, M. P. et al. Cryptic infection of a giant virus in a unicellular green alga. Science 388, eads6303 (2025). · DOI
  46. Subirana, J. A. & Messeguer, X. Unique features of tandem repeats in bacteria. J. Bacteriol. 202, https://doi.org/10.1128/jb.00229-20 (2020). · DOI
  47. Schoelmerich, M. C., Sachdeva, R., West-Roberts, J., Waldburger, L. & Banfield, J. F. Tandem repeats in giant archaeal Borg elements undergo rapid evolution and create new intrinsically disordered regions in proteins. PLoS Biol. 21, e3001980 (2023). · DOI
  48. Mier, P. et al. Disentangling the complexity of low complexity proteins. Brief. Bioinform. 21, 458–472 (2020). · DOI
  49. Kumar, A. & Balbach, J. Folding and stability of ankyrin repeats control biological protein function. Biomolecules 11, 840 (2021). · DOI
  50. Aftab, A., Sil, S., Nath, S., Basu, A. & Basu, S. Intrinsic disorder and other malleable arsenals of evolved protein multifunctionality. J. Mol. Evol. 1, 16 (2024).
  51. Prichard, A., Sy, A., Meyer, J., Villa, E. & Pogliano, J. Erwinia phage Asesino is a nucleus-forming phage that lacks PhuZ. Sci. Rep. 15, 1692 (2025). · DOI
  52. Machado, T. B. et al. Gene duplication as a major force driving the genome expansion in some giant viruses. J. Virol. 97, e0130923 (2023). · DOI
  53. Van Etten, J. L. Unusual life style of giant chlorella viruses. Annu. Rev. Genet. 37, 153–195 (2003). · DOI
  54. Elde, N. C. et al. Poxviruses deploy genomic accordions to adapt rapidly against host antiviral defenses. Cell 150, 831–841 (2012). · DOI
  55. Koonin, E. V. & Yutin, N. Evolution of the large nucleocytoplasmic DNA viruses of eukaryotes and convergent origins of viral gigantism. Adv. Virus Res. 103, 167–202 (2019). · DOI
  56. Moreira, D. & Brochier-Armanet, C. Giant viruses, giant chimeras: the multiple evolutionary histories of Mimivirus genes. BMC Evol. Biol. 8, 12 (2008). · DOI
  57. Claverie, J.-M. & Abergel, C. Open questions about giant viruses. Adv. Virus Res. 85, 25–56 (2013). · DOI
  58. Schoelmerich, M. C. et al. A widespread group of large plasmids in methanotrophic Methanoperedens archaea. Nat. Commun. 13, 7085 (2022). · DOI · Paper page
  59. Koonin, E. V. & Yutin, N. Multiple evolutionary origins of giant viruses. F1000Res. 7, 1840 (2018). · DOI
  60. Koonin, E. V. et al. Global organization and proposed megataxonomy of the virus world. Microbiol. Mol. Biol. Rev. 84, https://doi.org/10.1128/mmbr.00061-19 (2020). · DOI
  61. Takemura, M., Yokobori, S.-I. & Ogata, H. Evolution of eukaryotic DNA polymerases via interaction between cells and large DNA viruses. J. Mol. Evol. 81, 24–33 (2015). · DOI
  62. Villarreal, L. P. & DeFilippis, V. R. A hypothesis for DNA viruses as the origin of eukaryotic replication proteins. J. Virol. 74, 7079–7084 (2000). · DOI
  63. Zhang, Y. & Skolnick, J. TM-align: a protein structure alignment algorithm based on the TM-score. Nucleic Acids Res. 33, 2302–2309 (2005). · DOI · Paper page
  64. Mistry, J. et al. Pfam: The protein families database in 2021. Nucleic Acids Res. 49, D412–D419 (2021). · DOI · Paper page
  65. Katoh, K. & Standley, D. M. MAFFT multiple sequence alignment software version 7: improvements in performance and usability. Mol. Biol. Evol. 30, 772–780 (2013). · DOI · Paper page
  66. Hallgren, J. et al. DeepTMHMM predicts alpha and beta transmembrane proteins using deep neural networks. Preprit at https://doi.org/10.1101/2022.04.08.487609 (2022). · DOI
  67. Teufel, F. et al. SignalP 6.0 predicts all five types of signal peptides using protein language models. Nat. Biotechnol. 40, 1023–1025 (2022). · DOI
  68. Nguyen, L.-T., Schmidt, H. A., von Haeseler, A. & Minh, B. Q. IQ-TREE: a fast and effective stochastic algorithm for estimating maximum-likelihood phylogenies. Mol. Biol. Evol. 32, 268–274 (2015). · DOI · Paper page
  69. Kazlauskas, D., Krupovic, M., Guglielmini, J., Forterre, P. & Venclovas Diversity and evolution of B-family DNA polymerases. Nucleic Acids Res. 48, 10142–10156 (2020). · DOI
  70. Capella-Gutiérrez, S., Silla-Martínez, J. M. & Gabaldón, T. trimAl: a tool for automated alignment trimming in large-scale phylogenetic analyses. Bioinformatics 25, 1972–1973 (2009). · DOI
  71. Eddy, S. R. Accelerated Profile HMM Searches. PLoS Comput. Biol. 7, e1002195 (2011). · DOI · Paper page
  72. Kopylova, E., Noé, L. & Touzet, H. SortMeRNA: fast and accurate filtering of ribosomal RNAs in metatranscriptomic data. Bioinformatics 28, 3211–3217 (2012). · DOI

Metadata

Authors
Banfield, J. F., Valentin-Alvarado, L. E., Shi, L.-D., Robinson, C. M., Bamert, R. S., Coulibaly, F., Barth, Z. K., Aylward, F. O., Schoelmerich, M. C., Lei, S., Sachdeva, R., & Knott, G. J.
Affiliations
  • Innovative Genomics Institute (US)
  • University of California, Berkeley (US)
  • Monash University (AU)
  • Virginia Tech (US)
  • ETH Zurich (CH)
Corresponding author
  • Banfield, Jillian F.
  • Knott, Gavin J.
ORCID
Venue
Nature Communications
Publisher
Springer Science and Business Media LLC
Published
2025-11-27
Volume
16
Issue
1
Pages
10641-10641
ISSN
2041-1723 (ISSN-L)
DOI
10.1038/s41467-025-65646-7
PMC
PMC12660748
OpenAlex
W4416758670
Cited by
4
References
5
Citations by year
2026: 2 · 2025: 2
FWCI
2.12
Type
journal article
Language
en
Open access
Licence
Locations
  • Nature Communications (publishedVersion, cc-by)
  • bioRxiv (Cold Spring Harbor Laboratory) (acceptedVersion)
  • Europe PMC (PubMed Central) (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • PubMed Central (submittedVersion)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
Funders
National Institute of General Medical Sciences (R35GM147290)
Topics
  • Life Sciences › Immunology and Microbiology › Virology › Bacteriophages and microbial interactions
  • Life Sciences › Immunology and Microbiology › Virology › Plant and Fungal Interactions Research
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Genomics and Phylogenetic Studies
Keywords
giant viruses, convergent evolution, anaerobic methane-oxidizing archaea, archaeal viruses, deubiquitination, multi-copy genes, glycoconjugates, capsid protein, inverted terminal repeats, direct repeat region, energy metabolism genes, translation genes

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