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Evolutionary entanglement of mobile genetic elements and host defence systems: guns for hire

Abstract

All cellular life forms are afflicted by diverse genetic parasites, including viruses and other types of mobile genetic elements (MGEs), and have evolved multiple, diverse defence systems that protect them from MGE assault via different mechanisms. Here, we provide our perspectives on how recent evidence points to tight evolutionary connections between MGEs and defence systems that reach far beyond the proverbial arms race. Defence systems incur a fitness cost for the hosts; therefore, at least in prokaryotes, horizontal mobility of defence systems, mediated primarily by MGEs, is essential for their persistence. Moreover, defence systems themselves possess certain features of selfish elements. Common components of MGEs, such as site-specific nucleases, are ‘guns for hire’ that can also function as parts of defence mechanisms and are often shuttled between MGEs and defence systems. Thus, evolutionary and molecular factors converge to mould the multifaceted, inextricable connection between MGEs and anti-MGE defence systems.

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Fig. 1: Distribution of mobile genetic elements and defence systems in the virtual space bounded by the axes of selfishness and mobility.
Fig. 2: Competition between mobile genetic elements as a host defence strategy.
Fig. 3: Domestication of transposases and integrases for ‘natural genome engineering’.
Fig. 4: Guns for hire: shuttling of components between MGEs and cellular organisms.

References

  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.

    Moreira, D. & Lopez-Garcia, P. Ten reasons to exclude viruses from the tree of life. Nat. Rev. Microbiol. 7, 306–311 (2009).

    CAS  PubMed  Google Scholar 

  3. 3.

    Edwards, R. A. & Rohwer, F. Viral metagenomics. Nat. Rev. Microbiol. 3, 504–510 (2005).

    CAS  PubMed  Google Scholar 

  4. 4.

    Koonin, E. V., Dolja, V. V. & Krupovic, M. Origins and evolution of viruses of eukaryotes: The ultimate modularity. Virology 479–480, 2–25 (2015).

    CAS  PubMed  PubMed Central  Google Scholar 

  5. 5.

    Koonin, E. V., Makarova, K. S. & Wolf, Y. I. Evolutionary genomics of defense systems in archaea and bacteria. Annu. Rev. Microbiol. 71, 233–261 (2017).

    CAS  PubMed  PubMed Central  Google Scholar 

  6. 6.

    Szathmary, E. & Demeter, L. Group selection of early replicators and the origin of life. J. Theor. Biol. 128, 463–486 (1987).

    CAS  PubMed  Google Scholar 

  7. 7.

    Szathmary, E. & Maynard Smith, J. From replicators to reproducers: the first major transitions leading to life. J. Theor. Biol. 187, 555–571 (1997).

    CAS  PubMed  Google Scholar 

  8. 8.

    Takeuchi, N. & Hogeweg, P. The role of complex formation and deleterious mutations for the stability of RNA-like replicator systems. J. Mol. Evol. 65, 668–686 (2007).

    CAS  PubMed  Google Scholar 

  9. 9.

    Takeuchi, N. & Hogeweg, P. Evolutionary dynamics of RNA-like replicator systems: a bioinformatic approach to the origin of life. Phys. Life Rev. 9, 219–263 (2012).

    PubMed  PubMed Central  Google Scholar 

  10. 10.

    Koonin, E. V., Wolf, Y. I. & Katsnelson, M. I. Inevitability of the emergence and persistence of genetic parasites caused by evolutionary instability of parasite-free states. Biol. Direct 12, 31 (2017).

    PubMed  PubMed Central  Google Scholar 

  11. 11.

    Berezovskaya, F., Karev, G. P., Katsnelson, M. I., Wolf, Y. I. & Koonin, E. V. Stable coevolutionary regimes for genetic parasites and their hosts: you must differ to coevolve. Biol. Direct 13, 27 (2018).

    PubMed  PubMed Central  Google Scholar 

  12. 12.

    Koonin, E. V. Viruses and mobile elements as drivers of evolutionary transitions. Phil. Trans. R. Soc. B Biol. Sci. 371, 20150442 (2016).

    PubMed  PubMed Central  Google Scholar 

  13. 13.

    Forterre, P. & Prangishvili, D. The great billion-year war between ribosome- and capsid-encoding organisms (cells and viruses) as the major source of evolutionary novelties. Ann. NY Acad. Sci. 1178, 65–77 (2009).

    CAS  PubMed  Google Scholar 

  14. 14.

    Forterre, P. & Prangishvili, D. The major role of viruses in cellular evolution: facts and hypotheses. Curr. Opin. Virol. 3, 558–565 (2013).

    CAS  PubMed  Google Scholar 

  15. 15.

    Koonin, E. V. Evolution of RNA- and DNA-guided antivirus defense systems in prokaryotes and eukaryotes: common ancestry vs convergence. Biol. Direct 12, 5 (2017).

    PubMed  PubMed Central  Google Scholar 

  16. 16.

    Iranzo, J., Puigbo, P., Lobkovsky, A. E., Wolf, Y. I. & Koonin, E. V. Inevitability of genetic parasites. Genome Biol. Evol. 8, 2856–2869 (2016).

    CAS  PubMed  PubMed Central  Google Scholar 

  17. 17.

    Iranzo, J., Cuesta, J. A., Manrubia, S., Katsnelson, M. I. & Koonin, E. V. Disentangling the effects of selection and loss bias on gene dynamics. Proc. Natl Acad. Sci. USA 114, E5616–E5624 (2017).

    CAS  PubMed  Google Scholar 

  18. 18.

    Iranzo, J. & Koonin, E. V. How genetic parasites persist despite the purge of natural selection. Europhys. Lett. 122, 58001 (2018).

    Google Scholar 

  19. 19.

    Wolf, Y. I., Katsnelson, M. I. & Koonin, E. V. Physical foundations of biological complexity. Proc. Natl Acad. Sci. USA 115, E8678–E8687 (2018).

    CAS  PubMed  Google Scholar 

  20. 20.

    Puigbò, P., Makarova, K. S., Kristensen, D. M., Wolf, Y. I. & Koonin, E. V. Reconstruction of the evolution of microbial defense systems. BMC Evol. Biol. 17, 94 (2017).

    Google Scholar 

  21. 21.

    Makarova, K. S., Wolf, Y. I. & Koonin, E. V. Comprehensive comparative-genomic analysis of type 2 toxin-antitoxin systems and related mobile stress response systems in prokaryotes. Biol. Direct 4, 19 (2009).

    PubMed  PubMed Central  Google Scholar 

  22. 22.

    Van Melderen, L. Toxin-antitoxin systems: why so many, what for? Curr Opin Microbiol. 13, 781–785 (2010).

    PubMed  Google Scholar 

  23. 23.

    Van Melderen, L. & Saavedra De Bast, M. Bacterial toxin-antitoxin systems: more than selfish entities? PLOS Genet. 5, e1000437 (2009).

    PubMed  PubMed Central  Google Scholar 

  24. 24.

    Harms, A., Brodersen, D. E., Mitarai, N. & Gerdes, K. Toxins, targets, and triggers: an overview of toxin-antitoxin biology. Mol. Cell 70, 768–784 (2018).

    CAS  PubMed  Google Scholar 

  25. 25.

    Lehnherr, H., Maguin, E., Jafri, S. & Yarmolinsky, M. B. Plasmid addiction genes of bacteriophage P1: doc, which causes cell death on curing of prophage, and phd, which prevents host death when prophage is retained. J. Mol. Biol. 233, 414–428 (1993).

    CAS  PubMed  Google Scholar 

  26. 26.

    Hazan, R. & Engelberg-Kulka, H. Escherichia coli mazEF-mediated cell death as a defense mechanism that inhibits the spread of phage P1. Mol. Genet. Genomics 272, 227–234 (2004).

    CAS  PubMed  Google Scholar 

  27. 27.

    Fineran, P. C. et al. The phage abortive infection system, ToxIN, functions as a protein-RNA toxin-antitoxin pair. Proc. Natl Acad. Sci. USA 106, 894–899 (2009).

    CAS  PubMed  Google Scholar 

  28. 28.

    Dy, R. L., Przybilski, R., Semeijn, K., Salmond, G. P. & Fineran, P. C. A widespread bacteriophage abortive infection system functions through a Type IV toxin-antitoxin mechanism. Nucleic Acids Res. 42, 4590–4605 (2014).

    CAS  PubMed  PubMed Central  Google Scholar 

  29. 29.

    Brantl, S. & Jahn, N. sRNAs in bacterial type I and type III toxin-antitoxin systems. FEMS Microbiol. Rev. 39, 413–427 (2015).

    CAS  PubMed  Google Scholar 

  30. 30.

    Gerdes, K., Christensen, S. K. & Lobner-Olesen, A. Prokaryotic toxin-antitoxin stress response loci. Nat. Rev. Microbiol. 3, 371–382 (2005).

    CAS  PubMed  Google Scholar 

  31. 31.

    Mruk, I. & Kobayashi, I. To be or not to be: regulation of restriction-modification systems and other toxin-antitoxin systems. Nucleic Acids Res 42, 70–86 (2014).

    CAS  PubMed  Google Scholar 

  32. 32.

    Ichige, A. & Kobayashi, I. Stability of EcoRI restriction-modification enzymes in vivo differentiates the EcoRI restriction-modification system from other postsegregational cell killing systems. J. Bacteriol. 187, 6612–6621 (2005).

    CAS  PubMed  PubMed Central  Google Scholar 

  33. 33.

    Mochizuki, A., Yahara, K., Kobayashi, I. & Iwasa, Y. Genetic addiction: selfish gene's strategy for symbiosis in the genome. Genetics 172, 1309–1323 (2006).

    Google Scholar 

  34. 34.

    Orlowski, J. & Bujnicki, J. M. Structural and evolutionary classification of type II restriction enzymes based on theoretical and experimental analyses. Nucleic Acids Res. 36, 3552–3569 (2008).

    CAS  PubMed  PubMed Central  Google Scholar 

  35. 35.

    Makarova, K. S., Wolf, Y. I. & Koonin, E. V. Comparative genomics of defense systems in archaea and bacteria. Nucleic Acids Res. 41, 4360–4377 (2013).

    CAS  PubMed  PubMed Central  Google Scholar 

  36. 36.

    Soucy, S. M., Huang, J. & Gogarten, J. P. Horizontal gene transfer: building the web of life. Nat Rev Genet. 16, 472–482 (2015).

    CAS  PubMed  Google Scholar 

  37. 37.

    Martin, W. F. Too much eukaryote LGT. Bioessays 39, 1700115 (2017).

    Google Scholar 

  38. 38.

    Ku, C. & Martin, W. F. A natural barrier to lateral gene transfer from prokaryotes to eukaryotes revealed from genomes: the 70 % rule. BMC Biol. 14, 89 (2016).

    PubMed  PubMed Central  Google Scholar 

  39. 39.

    Hirt, R. P., Alsmark, C. & Embley, T. M. Lateral gene transfers and the origins of the eukaryote proteome: a view from microbial parasites. Curr. Opin. Microbiol. 23, 155–162 (2015).

    CAS  PubMed  PubMed Central  Google Scholar 

  40. 40.

    Aravind, L., Burroughs, A. M., Zhang, D. & Iyer, L. M. Protein and DNA modifications: evolutionary imprints of bacterial biochemical diversification and geochemistry on the provenance of eukaryotic epigenetics. Cold Spring Harb. Perspect. Biol. 6, a016063 (2014).

    CAS  PubMed  PubMed Central  Google Scholar 

  41. 41.

    Iyer, L. M., Abhiman, S. & Aravind, L. Natural history of eukaryotic DNA methylation systems. Prog. Mol. Biol. Transl. Sci. 101, 25–104 (2011).

    CAS  PubMed  Google Scholar 

  42. 42.

    Krishnan, A., Burroughs, A. M., Iyer, L. M. & Aravind, L. Unexpected evolution of lesion-recognition modules in eukaryotic NER and kinetoplast DNA dynamics proteins from bacterial mobile elements. iScience 9, 192–208 (2018).

    CAS  PubMed  PubMed Central  Google Scholar 

  43. 43.

    Anantharaman, V. & Aravind, L. New connections in the prokaryotic toxin-antitoxin network: relationship with the eukaryotic nonsense-mediated RNA decay system. Genome Biol. 4, R81 (2003).

    PubMed  PubMed Central  Google Scholar 

  44. 44.

    Koonin, E. V. & Zhang, F. Coupling immunity and programmed cell suicide in prokaryotes: life-or-death choices. Bioessays 39, 1–9 (2017).

    CAS  PubMed  Google Scholar 

  45. 45.

    Meeske, A. J., Nakandakari-Higa, S. & Marraffini, L. A. Cas13-induced cellular dormancy prevents the rise of CRISPR-resistant bacteriophage. Nature 570, 241–245 (2019).

    CAS  Google Scholar 

  46. 46.

    Mendoza, S. D. & Bondy-Denomy, J. Cas13 helps bacteria play dead when the enemy strikes. Cell Host Microbe 26, 1–2 (2019).

    CAS  PubMed  Google Scholar 

  47. 47.

    Bautista, M. A., Zhang, C. & Whitaker, R. J. Virus-induced dormancy in the archaeon Sulfolobus islandicus. mBio 6, e02565-14 (2015).

  48. 48.

    Shabalina, S. A. & Koonin, E. V. Origins and evolution of eukaryotic RNA interference. Trends Ecol. Evol. 23, 578–587 (2008).

    PubMed  PubMed Central  Google Scholar 

  49. 49.

    Swarts, D. C. et al. The evolutionary journey of Argonaute proteins. Nat. Struct. Mol. Biol. 21, 743–753 (2014).

    CAS  PubMed  PubMed Central  Google Scholar 

  50. 50.

    Petrova, Z. O., Broussard, G. W. & Hatfull, G. F. Mycobacteriophage-repressor-mediated immunity as a selectable genetic marker: Adephagia and BPs repressor selection. Microbiology 161, 1539–1551 (2015).

    CAS  PubMed  PubMed Central  Google Scholar 

  51. 51.

    Dedrick, R. M. et al. Prophage-mediated defence against viral attack and viral counter-defence. Nat. Microbiol. 2, 16251 (2017).

    CAS  PubMed  PubMed Central  Google Scholar 

  52. 52.

    Gentile, G. M. et al. More evidence of collusion: a new prophage-mediated viral defense system encoded by mycobacteriophage Sbash. mBio 10, e00196-19 (2019).

  53. 53.

    Montgomery, M. T., Guerrero Bustamante, C. A., Dedrick, R. M., Jacobs-Sera, D. & Hatfull, G. F. Yet more evidence of collusion: a new viral defense system encoded by Gordonia phage CarolAnn. mBio 10, e02417-18 (2019).

  54. 54.

    Faure, G. et al. CRISPR–Cas in mobile genetic elements: counter-defense and beyond. Nat. Rev. Microbiol. 17, 513–525 (2019).

    CAS  PubMed  Google Scholar 

  55. 55.

    Pawluk, A., Davidson, A. R. & Maxwell, K. L. Anti-CRISPR: discovery, mechanism and function. Nat. Rev. Microbiol. 16, 12–17 (2018).

    CAS  PubMed  Google Scholar 

  56. 56.

    Koonin, E. V. & Makarova, K. S. Anti-CRISPRs on the march. Science 362, 156–157 (2018).

    CAS  PubMed  Google Scholar 

  57. 57.

    Folimonova, S. Y. Superinfection exclusion is an active virus-controlled function that requires a specific viral protein. J. Virol. 86, 5554–5561 (2012).

    CAS  PubMed  PubMed Central  Google Scholar 

  58. 58.

    Bergua, M. et al. A viral protein mediates superinfection exclusion at the whole-organism level but is not required for exclusion at the cellular level. J. Virol. 88, 11327–11338 (2014).

    PubMed  PubMed Central  Google Scholar 

  59. 59.

    Zhang, X. F. et al. A New mechanistic model for viral cross protection and superinfection exclusion. Front. Plant Sci. 9, 40 (2018).

    PubMed  PubMed Central  Google Scholar 

  60. 60.

    Nethe, M., Berkhout, B. & van der Kuyl, A. C. Retroviral superinfection resistance. Retrovirology 2, 52 (2005).

    PubMed  PubMed Central  Google Scholar 

  61. 61.

    Schaller, T. et al. Analysis of hepatitis C virus superinfection exclusion by using novel fluorochrome gene-tagged viral genomes. J. Virol. 81, 4591–4603 (2007).

    CAS  PubMed  PubMed Central  Google Scholar 

  62. 62.

    Zhang, X. F. et al. A self-perpetuating repressive state of a viral replication protein blocks superinfection by the same virus. PLOS Pathog. 13, e1006253 (2017).

    PubMed  PubMed Central  Google Scholar 

  63. 63.

    Biryukov, J. & Meyers, C. Superinfection exclusion between two high-risk human papillomavirus types during a coinfection. J. Virol. 92, e01993-17 (2018).

  64. 64.

    Kumar, N., Sharma, S., Barua, S., Tripathi, B. N. & Rouse, B. T. Virological and immunological outcomes of coinfections. Clin. Microbiol. Rev 31, e00111–e00117 (2018).

    CAS  PubMed  PubMed Central  Google Scholar 

  65. 65.

    Fillol-Salom, A. et al. Phage-inducible chromosomal islands are ubiquitous within the bacterial universe. ISME J. 12, 2114–2128 (2018).

    CAS  PubMed  PubMed Central  Google Scholar 

  66. 66.

    Penades, J. R. & Christie, G. E. The phage-inducible chromosomal islands: a family of highly evolved molecular parasites. Annu. Rev. Virol. 2, 181–201 (2015).

    CAS  PubMed  Google Scholar 

  67. 67.

    Novick, R. P. & Ram, G. Staphylococcal pathogenicity islands-movers and shakers in the genomic firmament. Curr. Opin. Microbiol. 38, 197–204 (2017).

    CAS  PubMed  PubMed Central  Google Scholar 

  68. 68.

    Duponchel, S. & Fischer, M. G. Viva lavidaviruses! Five features of virophages that parasitize giant DNA viruses. PLOS Pathog. 15, e1007592 (2019).

    PubMed  PubMed Central  Google Scholar 

  69. 69.

    Fischer, M. G. & Hackl, T. Host genome integration and giant virus-induced reactivation 1 of the virophage mavirus. Nature 540, 288–291 (2016).

    CAS  PubMed  Google Scholar 

  70. 70.

    Koonin, E. V. & Krupovic, M. Virology: a parasite's parasite saves host's neighbours. Nature 540, 204–205 (2016).

    CAS  Google Scholar 

  71. 71.

    Blanc, G., Gallot-Lavallee, L. & Maumus, F. Provirophages in the Bigelowiella genome bear testimony to past encounters with giant viruses. Proc. Natl Acad. Sci. USA 112, E5318–E5326 (2015).

    CAS  PubMed  Google Scholar 

  72. 72.

    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 

  73. 73.

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

    CAS  PubMed  Google Scholar 

  74. 74.

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

    CAS  Google Scholar 

  75. 75.

    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 

  76. 76.

    Krupovic, M. & Koonin, E. V. Polintons: a hotbed of eukaryotic virus, transposon and plasmid evolution. Nat. Rev. Microbiol. 13, 105–115 (2015).

    CAS  PubMed  Google Scholar 

  77. 77.

    Krupovic, M. & Koonin, E. V. Self-synthesizing transposons: unexpected key players in the evolution of viruses and defense systems. Curr. Opin. Microbiol. 31, 25–33 (2016).

    CAS  PubMed  PubMed Central  Google Scholar 

  78. 78.

    Sweere, J. M. et al. Bacteriophage trigger antiviral immunity and prevent clearance of bacterial infection. Science 363, eaat9691 (2019).

    CAS  PubMed  PubMed Central  Google Scholar 

  79. 79.

    Knezevic, P., Voet, M. & Lavigne, R. Prevalence of Pf1-like (pro)phage genetic elements among Pseudomonas aeruginosa isolates. Virology 483, 64–71 (2015).

    CAS  PubMed  Google Scholar 

  80. 80.

    Burgener, E. B. et al. Filamentous bacteriophages are associated with chronic Pseudomonas lung infections and antibiotic resistance in cystic fibrosis. Sci. Transl Med. 11, eaau9748 (2019).

    PubMed  Google Scholar 

  81. 81.

    Schmitt, M. J. & Breinig, F. Yeast viral killer toxins: lethality and self-protection. Nat. Rev. Microbiol. 4, 212–221 (2006).

    CAS  PubMed  Google Scholar 

  82. 82.

    Ghabrial, S. A., Caston, J. R., Jiang, D., Nibert, M. L. & Suzuki, N. 50-plus years of fungal viruses. Virology 479–480, 356–368 (2015).

    CAS  PubMed  Google Scholar 

  83. 83.

    Becker, B. & Schmitt, M. J. Yeast Killer Toxin K28: biology and unique strategy of host cell intoxication and killing. Toxins 9, E333 (2017).

    Google Scholar 

  84. 84.

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

    CAS  PubMed  Google Scholar 

  85. 85.

    Gnanasekaran, P. & Chakraborty, S. Biology of viral satellites and their role in pathogenesis. Curr. Opin. Virol. 33, 96–105 (2018).

    CAS  PubMed  Google Scholar 

  86. 86.

    Murant, A. F. & Mayo, M. Satellites of plant viruses. Annu. Rev. Phytopathol. 20, 49–70 (1982).

    CAS  Google Scholar 

  87. 87.

    Qiu, W. & Scholthof, K. B. Defective interfering RNAs of a satellite virus. J. Virol. 75, 5429–5432 (2001).

    CAS  PubMed  PubMed Central  Google Scholar 

  88. 88.

    Ndunguru, J. et al. Two Novel DNAs that enhance symptoms and overcome cmd2 resistance to cassava mosaic disease. J. Virol. 90, 4160–4173 (2016).

    CAS  PubMed  PubMed Central  Google Scholar 

  89. 89.

    Makarova, K. S., Wolf, Y. I., Snir, S. & Koonin, E. V. Defense islands in bacterial and archaeal genomes and prediction of novel defense systems. J. Bacteriol. 193, 6039–6056 (2011).

    CAS  PubMed  PubMed Central  Google Scholar 

  90. 90.

    Doron, S. et al. Systematic discovery of antiphage defense systems in the microbial pangenome. Science 359, eaar4120 (2018).

    PubMed  PubMed Central  Google Scholar 

  91. 91.

    Novick, R. P. & Ram, G. The floating (pathogenicity) island: a genomic dessert. Trends Genet. 32, 114–126 (2016).

    Google Scholar 

  92. 92.

    Carraro, N., Rivard, N., Burrus, V. & Ceccarelli, D. Mobilizable genomic islands, different strategies for the dissemination of multidrug resistance and other adaptive traits. Mob. Genet. Elem. 7, 1–6 (2017).

    CAS  Google Scholar 

  93. 93.

    Oliveira Alvarenga, D., Moreira, L. M., Chandler, M. & Varani, A. M. A practical guide for comparative genomics of mobile genetic elements in prokaryotic genomes. Methods Mol. Biol. 1704, 213–242 (2018).

    PubMed  Google Scholar 

  94. 94.

    Shmakov, S. et al. Diversity and evolution of class 2 CRISPR-Cas systems. Nat. Rev. Microbiol. 15, 169–182 (2017).

    CAS  PubMed  PubMed Central  Google Scholar 

  95. 95.

    Makarova, K. S. et al. Predicted highly derived class 1 CRISPR-Cas system in Haloarchaea containing diverged Cas5 and Cas7 homologs but no CRISPR array. FEMS Microbiol. Lett. 366, fnz079 (2019).

    CAS  PubMed  Google Scholar 

  96. 96.

    Mohanraju, P. et al. Diverse evolutionary roots and mechanistic variations of the CRISPR-Cas systems. Science 353, aad5147 (2016).

    PubMed  Google Scholar 

  97. 97.

    Krupovic, M., Béguin, P. & Koonin, E. V. Casposons: mobile genetic elements that gave rise to the CRISPR-Cas adaptation machinery. Curr. Opin. Microbiol. 38, 36–43 (2017).

    CAS  PubMed  PubMed Central  Google Scholar 

  98. 98.

    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 

  99. 99.

    Koonin, E. V. & Krupovic, M. Evolution of adaptive immunity from transposable elements combined with innate immune systems. Nat. Rev. Genet. 16, 184–192 (2015).

    CAS  PubMed  Google Scholar 

  100. 100.

    Zhang, Y. et al. Transposon molecular domestication and the evolution of the RAG recombinase. Nature 569, 79–84 (2019).

    CAS  Google Scholar 

  101. 101.

    Nowacki, M., Shetty, K. & Landweber, L. F. RNA-mediated epigenetic programming of genome rearrangements. Annu. Rev. Genomics Hum. Genet. 12, 367–389 (2011).

    CAS  PubMed  PubMed Central  Google Scholar 

  102. 102.

    Bischerour, J. et al. Six domesticated PiggyBac transposases together carry out programmed DNA elimination in Paramecium. eLife 7, e37927 (2018).

    PubMed  PubMed Central  Google Scholar 

  103. 103.

    Maurer-Alcala, X. X. & Nowacki, M. Evolutionary origins and impacts of genome architecture in ciliates. Ann. NY Acad. Sci. 1447, 110–118 (2019).

    PubMed  PubMed Central  Google Scholar 

  104. 104.

    Yerlici, V. T. & Landweber, L. F. Programmed genome rearrangements in the ciliate oxytricha. Microbiol. Spectr. 2, MDNA3-0025-2014 (2014).

    Google Scholar 

  105. 105.

    Vogt, A., Goldman, A. D., Mochizuki, K. & Landweber, L. F. Transposon domestication versus mutualism in ciliate genome rearrangements. PLOS Genet. 9, e1003659 (2013).

    CAS  PubMed  PubMed Central  Google Scholar 

  106. 106.

    Midonet, C. & Barre, F. X. Xer site-specific recombination: promoting vertical and horizontal transmission of genetic information. Microbiol. Spectr. 2, MDNA3-0056-2014 (2014).

    Google Scholar 

  107. 107.

    Castillo, F., Benmohamed, A. & Szatmari, G. Xer site specific recombination: double and single recombinase systems. Front. Microbiol. 8, 453 (2017).

    PubMed  PubMed Central  Google Scholar 

  108. 108.

    Grindley, N. D., Whiteson, K. L. & Rice, P. A. Mechanisms of site-specific recombination. Annu. Rev Biochem. 75, 567–605 (2006).

    CAS  PubMed  Google Scholar 

  109. 109.

    Hickman, A. B. & Dyda, F. Mechanisms of DNA transposition. Microbiol. Spectr. 3, MDNA3-0034-2014 (2015).

    Google Scholar 

  110. 110.

    Meinke, G., Bohm, A., Hauber, J., Pisabarro, M. T. & Buchholz, F. Cre recombinase and other tyrosine recombinases. Chem. Rev. 116, 12785–12820 (2016).

    CAS  PubMed  Google Scholar 

  111. 111.

    De Ste Croix, M. et al. Phase-variable methylation and epigenetic regulation by type I restriction-modification systems. FEMS Microbiol. Rev. 41, S3–S15 (2017).

    Google Scholar 

  112. 112.

    Kwun, M. J., Oggioni, M. R., De Ste Croix, M., Bentley, S. D. & Croucher, N. J. Excision-reintegration at a pneumococcal phase-variable restriction-modification locus drives within- and between-strain epigenetic differentiation and inhibits gene acquisition. Nucleic Acids Res. 46, 11438–11453 (2018).

    CAS  PubMed  PubMed Central  Google Scholar 

  113. 113.

    Wang, J. et al. A novel family of tyrosine integrases encoded by the temperate pleolipovirus SNJ2. Nucleic Acids Res. 46, 2521–2536 (2018).

    CAS  PubMed  PubMed Central  Google Scholar 

  114. 114.

    Makarova, K. S. et al. An updated evolutionary classification of CRISPR-Cas systems. Nat. Rev. Microbiol. 13, 722–736 (2015).

    CAS  PubMed  PubMed Central  Google Scholar 

  115. 115.

    Koonin, E. V. & Makarova, K. S. Origins and evolution of CRISPR-Cas systems. Phil. Trans. R. Soc. B Biol. Sci. 374, 20180087 (2019).

    CAS  PubMed  PubMed Central  Google Scholar 

  116. 116.

    Burroughs, A. M., Zhang, D., Schaffer, D. E., Iyer, L. M. & Aravind, L. Comparative genomic analyses reveal a vast, novel network of nucleotide-centric systems in biological conflicts, immunity and signaling. Nucleic Acids Res. 43, 10633–10654 (2015).

    CAS  PubMed  PubMed Central  Google Scholar 

  117. 117.

    Harrington, L. B. et al. Programmed DNA destruction by miniature CRISPR-Cas14 enzymes. Science 362, 839–842 (2018).

    CAS  PubMed  PubMed Central  Google Scholar 

  118. 118.

    Yan, W. X. et al. Functionally diverse type V CRISPR-Cas systems. Science eeav7271 (2018).

  119. 119.

    Makarova, K. S., Aravind, L., Wolf, Y. I. & Koonin, E. V. Unification of Cas protein families and a simple scenario for the origin and evolution of CRISPR-Cas systems. Biol. Direct 6, 38 (2011).

    CAS  PubMed  PubMed Central  Google Scholar 

  120. 120.

    Koonin, E. V. & Makarova, K. S. Mobile genetic elements and evolution of Crispr-Cas systems: all the way there and back. Genome Biol. Evol. 9, 2812–2825 (2017).

    CAS  PubMed  PubMed Central  Google Scholar 

  121. 121.

    AlShayeb, B. et al. Clades of huge phage from across Earth’s ecosystems. bioRxiv, https://doi.org/10.1101/572362 (2019).

  122. 122.

    Krupovic, M. et al. Integrated mobile genetic elements in Thaumarchaeota. Environ. Microbiol. 21, 2056–2078 (2019).

    CAS  Google Scholar 

  123. 123.

    Seed, K. D., Lazinski, D. W., Calderwood, S. B. & Camilli, A. A bacteriophage encodes its own CRISPR/Cas adaptive response to evade host innate immunity. Nat. 494, 489–491 (2013).

    CAS  Google Scholar 

  124. 124.

    McKitterick, A. C., LeGault, K. N., Angermeyer, A., Alam, M. & Seed, K. D. Competition between mobile genetic elements drives optimization of a phage-encoded CRISPR-Cas system: insights from a natural arms race. Phil. Trans. R. Soc. B Biol. Sci. 374, 20180089 (2019).

    CAS  PubMed  PubMed Central  Google Scholar 

  125. 125.

    Peters, J. E., Makarova, K. S., Shmakov, S. & Koonin, E. V. Recruitment of CRISPR-Cas systems by Tn7-like transposons. Proc. Natl Acad. Sci. USA 114, E7358–E7366 (2017).

    CAS  PubMed  Google Scholar 

  126. 126.

    Klompe, S. E., Vo, P. L. H., Halpin-Healy, T. S. & Sternberg, S. H. Transposon-encoded CRISPR-Cas systems direct RNA-guided DNA integration. Nature 571, 219–225 (2019).

    CAS  Google Scholar 

  127. 127.

    Strecker, J. et al. RNA-guided DNA insertion with CRISPR-associated transposases. Science 365, 48–53 (2019).

    CAS  PubMed  PubMed Central  Google Scholar 

  128. 128.

    Bernheim, A., Bikard, D., Touchon, M. & Rocha, E. P. Co-occurrence of multiple CRISPRs and cas clusters suggests epistatic interactions. Preprint at bioRxiv https://www.biorxiv.org/content/10.1101/592600v1 (2019).

  129. 129.

    Newire, E., Aydin, A., Juma, S., Enne, V. & Roberts, A. P. Identification of a type IV CRISPR-Cas system located exclusively on IncHI1B/ IncFIB plasmids in Enterobacteriaceae. Preprint at bioRxiv https://doi.org/10.1101/536375 (2019).

  130. 130.

    Hudaiberdiev, S. et al. Phylogenomics of Cas4 family nucleases. BMC Evol. Biol. 17, 232 (2017).

    PubMed  PubMed Central  Google Scholar 

  131. 131.

    Zhang, Z., Pan, S., Liu, T., Li, Y. & Peng, N. Cas4 nucleases can effect specific integration of CRISPR spacers. J. Bacteriol. 201, e00747-18 (2019).

    CAS  PubMed  PubMed Central  Google Scholar 

  132. 132.

    Oliveira, P. H., Touchon, M. & Rocha, E. P. The interplay of restriction-modification systems with mobile genetic elements and their prokaryotic hosts. Nucleic Acids Res. 42, 10618–10631 (2014).

    CAS  PubMed  PubMed Central  Google Scholar 

  133. 133.

    Murphy, J., Mahony, J., Ainsworth, S., Nauta, A. & van Sinderen, D. Bacteriophage orphan DNA methyltransferases: insights from their bacterial origin, function, and occurrence. Appl. Env. Microbiol. 79, 7547–7555 (2013).

    CAS  Google Scholar 

  134. 134.

    Samson, J. E., Magadan, A. H., Sabri, M. & Moineau, S. Revenge of the phages: defeating bacterial defences. Nat. Rev. Microbiol. 11, 675–687 (2013).

    CAS  PubMed  Google Scholar 

  135. 135.

    Miller, E. S. et al. Bacteriophage T4 genome. Microbiol. Mol. Biol. Rev. 67, 86–156 (2003).

    CAS  PubMed  PubMed Central  Google Scholar 

  136. 136.

    Sternberg, N. & Coulby, J. Cleavage of the bacteriophage P1 packaging site (pac) is regulated by adenine methylation. Proc. Natl Acad. Sci. USA 87, 8070–8074 (1990).

    CAS  PubMed  Google Scholar 

  137. 137.

    Song, H. K., Sohn, S. H. & Suh, S. W. Crystal structure of deoxycytidylate hydroxymethylase from bacteriophage T4, a component of the deoxyribonucleoside triphosphate-synthesizing complex. EMBO J. 18, 1104–1113 (1999).

    CAS  PubMed  PubMed Central  Google Scholar 

  138. 138.

    Bryson, A. L. et al. Covalent modification of bacteriophage T4 DNA inhibits CRISPR-Cas9. mBio 6, e00648 (2015).

    CAS  PubMed  PubMed Central  Google Scholar 

  139. 139.

    Vlot, M. et al. Bacteriophage DNA glucosylation impairs target DNA binding by type I and II but not by type V CRISPR-Cas effector complexes. Nucleic Acids Res. 46, 873–885 (2018).

    CAS  PubMed  Google Scholar 

  140. 140.

    Kutter, E. M. & Wiberg, J. S. Degradation of cytosin-containing bacterial and bacteriophage DNA after infection of Escherichia coli B with bacteriophage T4D wild type and with mutants defective in genes 46, 47 and 56. J. Mol. Biol. 38, 395–411 (1968).

    CAS  PubMed  Google Scholar 

  141. 141.

    Weigele, P. & Raleigh, E. A. Biosynthesis and function of modified bases in bacteria and their viruses. Chem. Rev. 116, 12655–12687 (2016).

    CAS  PubMed  Google Scholar 

  142. 142.

    Weynberg, K. D., Allen, M. J. & Wilson, W. H. Marine prasinoviruses and their tiny plankton hosts: a review. Viruses 9, E43 (2017).

    PubMed  Google Scholar 

  143. 143.

    Yamada, T., Onimatsu, H. & Van Etten, J. L. Chlorella viruses. Adv. Virus Res. 66, 293–336 (2006).

    CAS  PubMed  PubMed Central  Google Scholar 

  144. 144.

    Agarkova, I. V., Dunigan, D. D. & Van Etten, J. L. Virion-associated restriction endonucleases of chloroviruses. J. Virol. 80, 8114–8123 (2006).

    CAS  PubMed  PubMed Central  Google Scholar 

  145. 145.

    Ranjit, D. K., Endres, J. L. & Bayles, K. W. Staphylococcus aureus CidA and LrgA proteins exhibit holin-like properties. J. Bacteriol. 193, 2468–2476 (2011).

    CAS  PubMed  PubMed Central  Google Scholar 

  146. 146.

    Ghequire, M. G. & De Mot, R. Ribosomally encoded antibacterial proteins and peptides from Pseudomonas. FEMS Microbiol. Rev. 38, 523–568 (2014).

    CAS  PubMed  Google Scholar 

  147. 147.

    Lien, Y. W., Lai, E. M. & Type, V. I. Secretion effectors: methodologies and biology. Front. Cell Infect. Microbiol. 7, 254 (2017).

    PubMed  PubMed Central  Google Scholar 

  148. 148.

    Basler, M. Type VI secretion system: secretion by a contractile nanomachine. Phil. Trans. R. Soc. B Biol. Sci. 370, 20150021 (2015).

    Google Scholar 

  149. 149.

    Taylor, N. M. I., van Raaij, M. J. & Leiman, P. G. Contractile injection systems of bacteriophages and related systems. Mol. Microbiol. 108, 6–15 (2018).

    CAS  PubMed  Google Scholar 

  150. 150.

    Makarova, K. S. et al. Antimicrobial peptides, polymorphic toxins and self-nonself recognition systems in archaea: an untapped armory deployed in microbial conflicts. mBio https://doi.org/10.1128/mBio.00715-19 (2019).

  151. 151.

    Ghequire, M. G. K. & De Mot, R. The tailocin tale: peeling off phage tails. Trends Microbiol. 23, 587–590 (2015).

    CAS  PubMed  Google Scholar 

  152. 152.

    Ghequire, M. G. et al. Different ancestries of R tailocins in rhizospheric pseudomonas isolates. Genome Biol. Evol. 7, 2810–2828 (2015).

    CAS  PubMed  PubMed Central  Google Scholar 

  153. 153.

    Krupovic, M., Forterre, P. & Bamford, D. H. Comparative analysis of the mosaic genomes of tailed archaeal viruses and proviruses suggests common themes for virion architecture and assembly with tailed viruses of bacteria. J. Mol. Biol. 397, 144–160 (2010).

    CAS  PubMed  Google Scholar 

  154. 154.

    Pope, W. H. et al. Genome sequences of Gordonia terrae phages Attis and SoilAssassin. Genome Announc. 4, e00591-16 (2016).

    Google Scholar 

  155. 155.

    Garcia-Pino, A. et al. Doc of prophage P1 is inhibited by its antitoxin partner Phd through fold complementation. J Biol. Chem. 283, 30821–30827 (2008).

    CAS  PubMed  PubMed Central  Google Scholar 

  156. 156.

    Nichols, D. B., De Martini, W. & Cottrell, J. Poxviruses utilize multiple strategies to inhibit apoptosis. Viruses 9, E215 (2017).

    Google Scholar 

  157. 157.

    Seet, B. T. et al. Poxviruses and immune evasion. Annu. Rev. Immunol. 21, 377–423 (2003).

    CAS  PubMed  Google Scholar 

  158. 158.

    Brune, W. & Andoniou, C. E. Die another day: inhibition of cell death pathways by cytomegalovirus. Viruses 9, E249 (2017).

    PubMed  Google Scholar 

  159. 159.

    Koonin, E. V. & Krupovic, M. A movable defense. Scientist 29, 46–53 (2015).

  160. 160.

    Kapitonov, V. V., Makarova, K. S. & Koonin, E. V. ISC, a novel group of bacterial and archaeal DNA transposons that encode Cas9 homologs. J. Bacteriol. 198, 797–807 (2015).

    PubMed  Google Scholar 

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Acknowledgements

E.V.K. thanks U. Gophna (Tel Aviv University) and E. Westra (University of Exeter) for inspiring discussions. E.V.K., K.S.M. and Y.I.W. are supported by the Intramural Research Program funds of the US National Institutes of Health (US Department of Health and Human Services). M.K. was supported by the Agence Nationale de la Recherche (France) project ENVIRA (no. ANR-17-CE15-0005-01).

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E.V.K. and M.K. wrote the manuscript. All authors researched data for the article and contributed to discussion of the content and reviewing/editing of the manuscript before submission.

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Glossary

Abortive infection systems

Toxin–antitoxin systems that abrogate virus infection by inducing cell dormancy or death.

Autoimmunity

Immune reaction to self (that is, components of the organism itself instead of components of mobile genetic elements). Autoimmunity stems from failure of self versus non-self discrimination mechanisms.

CRISPR–Cas

Prokaryotic adaptive immunity systems that create an immune memory bank by integrating fragments of foreign genomes into CRISPR arrays and use them to recognize and inactivate the cognate foreign nucleic acid.

Exapted

Pertaining to exaptation, which is recruitment of a biological feature for a function that is different from the function it had been selected for.

Horizontal gene transfer

(HGT). Transfer of genes between organisms by any means other than vertical transmission from parents to offspring.

Integrative conjugative elements

(ICEs). A diverse class of mobile genetic elements present in numerous bacteria that are integrated into bacterial chromosomes and are inherited vertically but retain the capacity to excise and move horizontally by conjugation.

Lytic viruses

Viruses that, at the end of their reproduction cycle, lyse and kill the infected cell.

Mobile genetic elements

(MGEs). Genetic elements that are prone to changing locations within the same genome (e.g. transposons) or to horizontal transfer between host cells (e.g. viruses and plasmids). Many MGEs encompass genes mediating self-replication.

Restriction–modification systems

(RM systems). A variety of prokaryotic defence systems that contain distinct modification components (typically DNA methyltransferases) that modify and thus protect the self DNA, and restriction endonucleases that cleave unmodified, foreign DNA.

Temperate viruses

Viruses that integrate into the host genome, forming proviruses, but retain the capacity of induction followed by a lytic cycle.

Toxin–antitoxin modules

(TA modules). Genetic elements that consist of a toxin component (often a nuclease) and an antitoxin component that binds and transiently inactivates the toxin. When the antitoxin is inactivated, typically under stress, the toxin induces cell dormancy or death.

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Koonin, E.V., Makarova, K.S., Wolf, Y.I. et al. Evolutionary entanglement of mobile genetic elements and host defence systems: guns for hire. Nat Rev Genet 21, 119–131 (2020). https://doi.org/10.1038/s41576-019-0172-9

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