Persisting viral sequences shape microbial CRISPR-based immunity

Ariel D. Weinberger, Christine L. Sun, Mateusz M. Pluciński, Vincent J. Denef, Brian C. Thomas, Philippe Horvath, Rodolphe Barrangou, Michael S. Gilmore, Wayne M. Getz, Jillian F. Banfield

Research output: Contribution to journalArticle

80 Citations (Scopus)

Abstract

Well-studied innate immune systems exist throughout bacteria and archaea, but a more recently discovered genomic locus may offer prokaryotes surprising immunological adaptability. Mediated by a cassette-like genomic locus termed Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR), the microbial adaptive immune system differs from its eukaryotic immune analogues by incorporating new immunities unidirectionally. CRISPR thus stores genomically recoverable timelines of virus-host coevolution in natural organisms refractory to laboratory cultivation. Here we combined a population genetic mathematical model of CRISPR-virus coevolution with six years of metagenomic sequencing to link the recoverable genomic dynamics of CRISPR loci to the unknown population dynamics of virus and host in natural communities. Metagenomic reconstructions in an acid-mine drainage system document CRISPR loci conserving ancestral immune elements to the base-pair across thousands of microbial generations. This 'trailer-end conservation' occurs despite rapid viral mutation and despite rapid prokaryotic genomic deletion. The trailer-ends of many reconstructed CRISPR loci are also largely identical across a population. 'Trailer-end clonality' occurs despite predictions of host immunological diversity due to negative frequency dependent selection (kill the winner dynamics). Statistical clustering and model simulations explain this lack of diversity by capturing rapid selective sweeps by highly immune CRISPR lineages. Potentially explaining 'trailer-end conservation,' we record the first example of a viral bloom overwhelming a CRISPR system. The polyclonal viruses bloom even though they share sequences previously targeted by host CRISPR loci. Simulations show how increasing random genomic deletions in CRISPR loci purges immunological controls on long-lived viral sequences, allowing polyclonal viruses to bloom and depressing host fitness. Our results thus link documented patterns of genomic conservation in CRISPR loci to an evolutionary advantage against persistent viruses. By maintaining old immunities, selection may be tuning CRISPR-mediated immunity against viruses reemerging from lysogeny or migration.

Original languageEnglish (US)
Article numbere1002475
JournalPLoS computational biology
Volume8
Issue number4
DOIs
StatePublished - Apr 1 2012

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Clustered Regularly Interspaced Short Palindromic Repeats
Immunity
immunity
Viruses
Locus
virus
Virus
genomics
Light trailers
Genomics
trailers
loci
viruses
Conservation
algal bloom
Immune system
coevolution
immune system
Coevolution
Immune System

All Science Journal Classification (ASJC) codes

  • Ecology, Evolution, Behavior and Systematics
  • Modeling and Simulation
  • Ecology
  • Molecular Biology
  • Genetics
  • Cellular and Molecular Neuroscience
  • Computational Theory and Mathematics

Cite this

Weinberger, A. D., Sun, C. L., Pluciński, M. M., Denef, V. J., Thomas, B. C., Horvath, P., ... Banfield, J. F. (2012). Persisting viral sequences shape microbial CRISPR-based immunity. PLoS computational biology, 8(4), [e1002475]. https://doi.org/10.1371/journal.pcbi.1002475
Weinberger, Ariel D. ; Sun, Christine L. ; Pluciński, Mateusz M. ; Denef, Vincent J. ; Thomas, Brian C. ; Horvath, Philippe ; Barrangou, Rodolphe ; Gilmore, Michael S. ; Getz, Wayne M. ; Banfield, Jillian F. / Persisting viral sequences shape microbial CRISPR-based immunity. In: PLoS computational biology. 2012 ; Vol. 8, No. 4.
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Weinberger, AD, Sun, CL, Pluciński, MM, Denef, VJ, Thomas, BC, Horvath, P, Barrangou, R, Gilmore, MS, Getz, WM & Banfield, JF 2012, 'Persisting viral sequences shape microbial CRISPR-based immunity', PLoS computational biology, vol. 8, no. 4, e1002475. https://doi.org/10.1371/journal.pcbi.1002475

Persisting viral sequences shape microbial CRISPR-based immunity. / Weinberger, Ariel D.; Sun, Christine L.; Pluciński, Mateusz M.; Denef, Vincent J.; Thomas, Brian C.; Horvath, Philippe; Barrangou, Rodolphe; Gilmore, Michael S.; Getz, Wayne M.; Banfield, Jillian F.

In: PLoS computational biology, Vol. 8, No. 4, e1002475, 01.04.2012.

Research output: Contribution to journalArticle

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Weinberger AD, Sun CL, Pluciński MM, Denef VJ, Thomas BC, Horvath P et al. Persisting viral sequences shape microbial CRISPR-based immunity. PLoS computational biology. 2012 Apr 1;8(4). e1002475. https://doi.org/10.1371/journal.pcbi.1002475