Skip to main content
SpringerLink
Log in

Intervening Sequences of Regularly Spaced Prokaryotic Repeats Derive from Foreign Genetic Elements

  • Published:
Journal of Molecular Evolution Aims and scope Submit manuscript

Abstract

Prokaryotes contain short DNA repeats known as CRISPR, recognizable by the regular spacing existing between the recurring units. They represent the most widely distributed family of repeats among prokaryotic genomes, suggesting a biological function. The origin of the intervening sequences, at present unknown, could provide clues about their biological activities. Here we show that CRISPR spacers derive from preexisting sequences, either chromosomal or within transmissible genetic elements such as bacteriophages and conjugative plasmids. Remarkably, these extrachromosomal elements fail to infect the specific spacer-carrier strain, implying a relationship between CRISPR and immunity against targeted DNA. Bacteriophages and conjugative plasmids are involved in prokaryotic population control, evolution, and pathogenicity. All these biological traits could be influenced by the presence of specific spacers. CRISPR loci can be visualized as mosaics of a repeated unit, separated by sequences at some time present elsewhere in the cell.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Figure 1

Similar content being viewed by others

References

  • SF Altschul TL Madden AA Schaffer J Zhang Z Zhang W Miller DJ Lipman (1997) ArticleTitleGapped BLAST and PSI-BLAST: A new generation of protein database search programs Nucleic Acids Res 25 3389–3402 Occurrence Handle1:CAS:528:DyaK2sXlvFyhu7w%3D Occurrence Handle9254694

    CAS  PubMed  Google Scholar 

  • DJ Banks SB Beres JM Musser (2002) ArticleTitleThe fundamental contribution of phages to GAS evolution, genome diversification and strain emergence Trends Microbiol 10 515–521

    Google Scholar 

  • SB Beres GL Sylva KD Barbian BF Lei JS Hoff ND Mammarella MY Liu JC Smoot SF Porcella LD Parkins DS Campbell TM Smith JK McCormick DYM Leung PM Schlievert JM Musser (2002) ArticleTitleGenome sequence of a serotype M3 strain of group A Streptococcus: Phage-encoded toxins, the high-virulence phenotype, and clone emergence Proc Natl Acad Sci USA 99 10078–10083

    Google Scholar 

  • RP Birkenbihl K Neef D Prangishvili B Kemper (2001) ArticleTitleHolliday junction resolving enzymes of archaeal viruses SIRV1 and SIRV2 J Mol Biol 309 1067–1076

    Google Scholar 

  • Y Boucher CJ Douady RT Papke DA Walsh ME Boudreau CL Nesbo RJ Case WF Doolittle (2003) ArticleTitleLateral gene transfer and the origins of prokaryotic groups Annu Rev Genet 37 283–328

    Google Scholar 

  • EF Boyd H Brussow (2002) ArticleTitleCommon themes among bacteriophage-encoded virulence factors and diversity among the bacteriophages involved Trends Microbiol 10 521–529

    Google Scholar 

  • E Cabezón JI Sastre F la Cruz Particlede (1997) ArticleTitleGenetic evidence of a coupling role for the TraG protein family in bacterial conjugation Mol Gen Genet 254 400–406

    Google Scholar 

  • C Canchaya C Proux G Fournous A Bruttin H Brq/4ssow (2003) ArticleTitleProphage genomics Microbiol Mol Biol Rev 67 38–276

    Google Scholar 

  • MW Cunningham (2000) ArticleTitlePathogenesis of group A streptococcal infections Clin Microbiol Rev 13 470–511

    Google Scholar 

  • CL Easter PA Sobecky DR Helinski (1997) ArticleTitleContribution of different segments of the par region to stable maintenance of the broad-host-range plasmid RK2 J Bacteriol 179 6472–6479 Occurrence Handle1:CAS:528:DyaK2sXmslOmtbw%3D Occurrence Handle9335298

    CAS  PubMed  Google Scholar 

  • JJ Ferretti WM McShan D Ajdic et al. (2001) ArticleTitleComplete genome sequence of an M1 strain of Streptococcus pyogenes Proc Natl Acad Sci USA 98 4658–4663

    Google Scholar 

  • N Firth R Skurray (1992) ArticleTitleCharacterization of the F plasmid bifunctional conjugation gene traG Mol Gen Genet 232 145–153

    Google Scholar 

  • P Glaser L Frangeul C Buchrieser et al. (2001) ArticleTitleComparative genomics of Listeria species Science 294 849–852 Occurrence Handle10.1126/science.1063447 Occurrence Handle1:CAS:528:DC%2BD3MXotVChtL0%3D Occurrence Handle11679669

    Article  CAS  PubMed  Google Scholar 

  • S Iida MB Streiff TA Bickle W Arber (1987) ArticleTitleTwo DNA antirestriction systems of bacteriophage P1, darA, and darB: Characterization of darA↓ phages Virology 157 156–166

    Google Scholar 

  • R Jansen JD Embden W Gaastra LM Schouls (2002) ArticleTitleIdentification of genes that are associated with DNA repeats in prokaryotes Mol Microbiol 43 1565–1575

    Google Scholar 

  • Y Kawarabayasi Y Hino H Horikawa et al. (2001) ArticleTitleComplete genome sequence of an aerobic thermoacidophilic crenarchaeon, Sulfolobus tokodaii strain7 DNA Res 8 123–140 Occurrence Handle1:CAS:528:DC%2BD3MXms1Snt7s%3D Occurrence Handle11572479

    CAS  PubMed  Google Scholar 

  • D Lane R Feyter Particlede M Kennedy SH Phua D Semon (1986) ArticleTitleD protein of miniF plasmid acts as a repressor of transcription and as a site-specific resolvase Nucleic Acids Res 14 9713–9728

    Google Scholar 

  • YN Luo P Pfister T Leisinger A Wasserfallen (2001) ArticleTitleThe genome of archaeal prophage Ψ M100 encodes the lytic enzyme responsible for autolysis of Methanothermobacter wolfeii J Bacteriol 183 5788–5792

    Google Scholar 

  • KA Martin MA Davis S Austin (1991) ArticleTitleFine-structure analysis of the P1 plasmid partition site J Bacteriol 173 3630–3634

    Google Scholar 

  • JL Martínez F Baquero (2002) ArticleTitleInteractions among strategies associated with bacterial infection: Pathogenicity, epidemicity, and antibiotic resistance Clin Microbiol Rev 15 647–679

    Google Scholar 

  • FJM Mojica C Ferrer G Juez F Rodríguez-Valera (1995) ArticleTitleLong stretches of short tandem repeats are present in the largest replicons of the Archaea Haloferax mediterranei and Haloferax volcanii and could be involved in replicon partitioning Mol Microbiol 17 85–93

    Google Scholar 

  • FJM Mojica C Díez-Villaseñor E Soria G Juez (2000) ArticleTitleBiological significance of a family of regularly spaced repeats in the genomes of Archaea, Bacteria and mitochondria Mol Microbiol 36 244–246

    Google Scholar 

  • I Nakagawa K Kurokawa A Yamashita M Nakata Y Tomiyasu N Okahashi S Kawabata K Yamazaki T Shiba T Yasunaga H Hayashi M Hattori S Hamada (2003) ArticleTitleGenome sequence of an M3 strain of Streptococcus pyogenes reveals a large-scale genomic rearrangement in invasive strains and new insights into phage evolution Genome Res 13 1042–1055

    Google Scholar 

  • H Ochman RK Selander (1984) ArticleTitleStandard reference strains of Escherichia coli from natural populations J Bacteriol 157 690–693

    Google Scholar 

  • P Pfister A Wesserfallen R Stettler T Leisinger (1998) ArticleTitleMolecular analysis of Methanobacterium phage ΨM2 Mol Microbiol 30 233–244

    Google Scholar 

  • D Prangishvili HP Arnold D Gotz U Ziese I Holz JK Kristjansson W Zillig (1999) ArticleTitleA novel virus family, the Rudiviridae: Structure, virus-host interactions and genome variability of the Sulfolobus viruses SIRV1 and SIRV2 Genetics 152 1387– 1396

    Google Scholar 

  • T Profit S Sriskandan L Yang JD Fraser (2003) ArticleTitleSuperantigens and streptococcal toxic shock syndrome Emerg Infect Dis 9 1211–1218

    Google Scholar 

  • C Schleper I Holz D Janekovic J Murphy W Zillig (1995) ArticleTitleA multicopy plasmid of the extremely thermophilic archaeon Sulfolobus effects its transfer to recipients by mating J Bacteriol 177 4417–4426

    Google Scholar 

  • Q She H Phan RA Garrett SV Albers KM Stedman W Zillig (1998) ArticleTitleGenetic profile of pNOB8 from Sulfolobus: The first conjugative plasmid from an archaeon Extremophiles 2 417–425

    Google Scholar 

  • Q She RK Singh F Confalonieri et al. (2001) ArticleTitleThe complete genome of the crenarchaeon Sulfolobus solfataricus P2 Proc Natl Acad Sci USA 98 7835–7840 Occurrence Handle10.1073/pnas.141222098 Occurrence Handle1:CAS:528:DC%2BD3MXlt1Kntr0%3D Occurrence Handle11427726

    Article  CAS  PubMed  Google Scholar 

  • Q She K Brugger L Chen (2002) ArticleTitleArchaeal integrative genetic elements and their impact on genome evolution Res Microbiol 153 325–332

    Google Scholar 

  • DR Smith LA DoucetteStamm C Deloughery et al. (1997) ArticleTitleComplete genome sequence of Methanobacterium thermoautotrophicum H: Functional analysis and comparative genomics J Bacteriol 179 7135–7155 Occurrence Handle1:CAS:528:DyaK2sXntlKkurs%3D Occurrence Handle9371463

    CAS  PubMed  Google Scholar 

  • JC Smoot KD Barbian JJ, Compel ParticleVan et al. (2002) ArticleTitleGenome sequence and comparative microarray analysis of serotype M18 group A Streptococcus strains associated with acute rheumatic fever outbreaks Proc Natl Acad Sci USA 99 4668–4673

    Google Scholar 

  • LM Smoot JK McCormick JC Smoot NP Hoe I Strickland RL Cole KD Barbian CA Earhart DH Ohlendorf LG Veasy HR Hill DYM Leung PM Schlievert JM Musser (2002) ArticleTitleCharacterization of two novel pyrogenic toxin superantigens made by an acute rheumatic fever clone of Streptococcus pyogenes associated with multiple disease outbreaks Infect Immun 70 7095–7104

    Google Scholar 

  • KM Stedman Q She H Phan I Holz H Singh D Prangishvili R Garrett W Zillig (2000) ArticleTitlepING family of conjugative plasmids from the extremely thermophilic archaeon Sulfolobus islandicus: Insights into recombination and conjugation in Crenarchaeota J Bacteriol 182 7014–7020

    Google Scholar 

  • KM Stedman Q She H Phan HP Arnold I Holz RA Garrett W Zillig (2003) ArticleTitleRelationships between fuselloviruses infecting the extremely thermophilic archaeon Sulfolobus: SSV1 and SSV2 Res Microbiol 154 295–302 Occurrence Handle10.1016/S0923-2508(03)00074-3 Occurrence Handle1:CAS:528:DC%2BD3sXkt1ymurk%3D Occurrence Handle12798235

    Article  CAS  PubMed  Google Scholar 

  • TH Tang JP Bachellerie T Rozhdestvensky ML Bortolin H Huber M Drungowski T Elge J Brosius A Huttenhofer (2002) ArticleTitleIdentification of 86 candidates for small non-messenger RNAs from the archaeon Archaeoglobus fulgidus Proc Natl Acad Sci USA 99 7536–7541

    Google Scholar 

  • BA Traxler EG Minkley SuffixJr (1988) ArticleTitleEvidence that DNA helicase I and oriT site-specific nicking are both functions of the F Tral protein J Mol Biol 5 205–209

    Google Scholar 

  • R Young (1992) ArticleTitleBacteriophage lysis: Mechanism and regulation Microbiol Rev 56 430–481

    Google Scholar 

  • W Zillig HP Arnold I Holz D Prangishvili A Schweier K Stedman Q She H Phan R Garrett JK Kristjansson (1998) ArticleTitleGenetic elements in the extremely thermophilic archaeon Sulfolobus Extremophiles 2 131–140

    Google Scholar 

Download references

Acknowledgments

This work was financed by research grants from the Conselleria de Cultura, Educació i Ciència, Generalitat Valenciana (CTIDIB/2002/155 and gv04B-457). C.D. is supported by a graduate fellowship from the Ministerio de Educación, Cultura y Deporte. We are indebted to Kathy Hernández for assistance and to J. Antón for critical reading of the manuscript.

Author information

Authors and Affiliations

  1. División de Microbiología, Departamento de Fisiología, Genhc)tica y Microbiología, Universidad de Alicante, Campus de San Vicente, E-03080, Spain

    Francisco J.M. Mojica, Chc)sar Díez-Villaseñor, Jesús García-Martínez & Elena Soria

Authors
  1. Francisco J.M. Mojica
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Chc)sar Díez-Villaseñor
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Jesús García-Martínez
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Elena Soria
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Francisco J.M. Mojica.

Additional information

Reviewing Editor: Dr. John Huelsenbeck

Rights and permissions

Reprints and permissions

About this article

Cite this article

Mojica, F.J., Díez-Villaseñor, C., García-Martínez, J. et al. Intervening Sequences of Regularly Spaced Prokaryotic Repeats Derive from Foreign Genetic Elements. J Mol Evol 60, 174–182 (2005). https://doi.org/10.1007/s00239-004-0046-3

Download citation

  • Received:

  • Accepted:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00239-004-0046-3

Keywords

Search

Navigation