Intervening Sequences of Regularly Spaced Prokaryotic Repeats Derive from Foreign Genetic Elements Francisco J.M. Mojica Email author Chc)sar Díez-Villaseñor Jesús García-Martínez Elena Soria Article Received: 06 February 2004 Accepted: 01 October 2004 DOI :
10.1007/s00239-004-0046-3
Cite this article as: Mojica, F.J., Díez-Villaseñor, C., García-Martínez, J. et al. J Mol Evol (2005) 60: 174. doi:10.1007/s00239-004-0046-3 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.
Keywords CRISPR DNA repeats Conjugative plasmids Bacteriophages Lateral gene transfer Prokaryotic evolution Pathogenicity Reviewing Editor: Dr. John Huelsenbeck
References Altschul, SF, Madden, TL, Schaffer, AA, Zhang, J, Zhang, Z, Miller, W, Lipman, DJ 1997 Gapped BLAST and PSI-BLAST: A new generation of protein database search programs Nucleic Acids Res 25 3389 3402 PubMed Google Scholar Banks, DJ, Beres, SB, Musser, JM 2002 The fundamental contribution of phages to GAS evolution, genome diversification and strain emergence Trends Microbiol 10 515 521 Google Scholar Beres, SB, Sylva, GL, Barbian, KD, Lei, BF, Hoff, JS, Mammarella, ND, Liu, MY, Smoot, JC, Porcella, SF, Parkins, LD, Campbell, DS, Smith, TM, McCormick, JK, Leung, DYM, Schlievert, PM, Musser, JM 2002 Genome 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 Birkenbihl, RP, Neef, K, Prangishvili, D, Kemper, B 2001 Holliday junction resolving enzymes of archaeal viruses SIRV1 and SIRV2 J Mol Biol 309 1067 1076 Google Scholar Boucher, Y, Douady, CJ, Papke, RT, Walsh, DA, Boudreau, ME, Nesbo, CL, Case, RJ, Doolittle, WF 2003 Lateral gene transfer and the origins of prokaryotic groups Annu Rev Genet 37 283 328 Google Scholar Boyd, EF, Brussow, H 2002 Common themes among bacteriophage-encoded virulence factors and diversity among the bacteriophages involved Trends Microbiol 10 521 529 Google Scholar Cabezón, E, Sastre, JI, la Cruz, F 1997 Genetic evidence of a coupling role for the TraG protein family in bacterial conjugation Mol Gen Genet 254 400 406 Google Scholar Canchaya, C, Proux, C, Fournous, G, Bruttin, A, Brq/4ssow, H 2003 Prophage genomics Microbiol Mol Biol Rev 67 38 276 Google Scholar Cunningham, MW 2000 Pathogenesis of group A streptococcal infections Clin Microbiol Rev 13 470 511 Google Scholar Easter, CL, Sobecky, PA, Helinski, DR 1997 Contribution of different segments of the par region to stable maintenance of the broad-host-range plasmid RK2 J Bacteriol 179 6472 6479 PubMed Google Scholar Ferretti, JJ, McShan, WM, Ajdic, D, et al. 2001 Complete genome sequence of an M1 strain of Streptococcus pyogenes Proc Natl Acad Sci USA 98 4658 4663 Google Scholar Firth, N, Skurray, R 1992 Characterization of the F plasmid bifunctional conjugation gene traG Mol Gen Genet 232 145 153 Google Scholar Glaser, P, Frangeul, L, Buchrieser, C, et al. 2001 Comparative genomics of Listeria species Science 294 849 852 CrossRef PubMed Google Scholar Iida, S, Streiff, MB, Bickle, TA, Arber, W 1987 Two DNA antirestriction systems of bacteriophage P1, darA, and darB: Characterization of darA↓ phages Virology 157 156 166 Google Scholar Jansen, R, Embden, JD, Gaastra, W, Schouls, LM 2002 Identification of genes that are associated with DNA repeats in prokaryotes Mol Microbiol 43 1565 1575 Google Scholar Kawarabayasi, Y, Hino, Y, Horikawa, H, et al. 2001 Complete genome sequence of an aerobic thermoacidophilic crenarchaeon, Sulfolobus tokodaii strain7 DNA Res 8 123 140 PubMed Google Scholar Lane, D, Feyter, R, Kennedy, M, Phua, SH, Semon, D 1986 D protein of miniF plasmid acts as a repressor of transcription and as a site-specific resolvase Nucleic Acids Res 14 9713 9728 Google Scholar Luo, YN, Pfister, P, Leisinger, T, Wasserfallen, A 2001 The genome of archaeal prophage Ψ M100 encodes the lytic enzyme responsible for autolysis of Methanothermobacter wolfeii J Bacteriol 183 5788 5792 Google Scholar Martin, KA, Davis, MA, Austin, S 1991 Fine-structure analysis of the P1 plasmid partition site J Bacteriol 173 3630 3634 Google Scholar Martínez, JL, Baquero, F 2002 Interactions among strategies associated with bacterial infection: Pathogenicity, epidemicity, and antibiotic resistance Clin Microbiol Rev 15 647 679 Google Scholar Mojica, FJM, Ferrer, C, Juez, G, Rodríguez-Valera, F 1995 Long 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 Mojica, FJM, Díez-Villaseñor, C, Soria, E, Juez, G 2000 Biological significance of a family of regularly spaced repeats in the genomes of Archaea, Bacteria and mitochondria Mol Microbiol 36 244 246 Google Scholar Nakagawa, I, Kurokawa, K, Yamashita, A, Nakata, M, Tomiyasu, Y, Okahashi, N, Kawabata, S, Yamazaki, K, Shiba, T, Yasunaga, T, Hayashi, H, Hattori, M, Hamada, S 2003 Genome 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 Ochman, H, Selander, RK 1984 Standard reference strains of Escherichia coli from natural populations J Bacteriol 157 690 693 Google Scholar Pfister, P, Wesserfallen, A, Stettler, R, Leisinger, T 1998 Molecular analysis of Methanobacterium phage ΨM2 Mol Microbiol 30 233 244 Google Scholar Prangishvili, D, Arnold, HP, Gotz, D, Ziese, U, Holz, I, Kristjansson, JK, Zillig, W 1999 A 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 Profit, T, Sriskandan, S, Yang, L, Fraser, JD 2003 Superantigens and streptococcal toxic shock syndrome Emerg Infect Dis 9 1211 1218 Google Scholar Schleper, C, Holz, I, Janekovic, D, Murphy, J, Zillig, W 1995 A multicopy plasmid of the extremely thermophilic archaeon Sulfolobus effects its transfer to recipients by mating J Bacteriol 177 4417 4426 Google Scholar She, Q, Phan, H, Garrett, RA, Albers, SV, Stedman, KM, Zillig, W 1998 Genetic profile of pNOB8 from Sulfolobus : The first conjugative plasmid from an archaeon Extremophiles 2 417 425 Google Scholar She, Q, Singh, RK, Confalonieri, F, et al. 2001 The complete genome of the crenarchaeon Sulfolobus solfataricus P2 Proc Natl Acad Sci USA 98 7835 7840 CrossRef PubMed Google Scholar She, Q, Brugger, K, Chen, L 2002 Archaeal integrative genetic elements and their impact on genome evolution Res Microbiol 153 325 332 Google Scholar Smith, DR, DoucetteStamm, LA, Deloughery, C, et al. 1997 Complete genome sequence of Methanobacterium thermoautotrophicum H: Functional analysis and comparative genomics J Bacteriol 179 7135 7155 PubMed Google Scholar Smoot, JC, Barbian, KD, Compel, JJ,, et al. 2002 Genome 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 Smoot, LM, McCormick, JK, Smoot, JC, Hoe, NP, Strickland, I, Cole, RL, Barbian, KD, Earhart, CA, Ohlendorf, DH, Veasy, LG, Hill, HR, Leung, DYM, Schlievert, PM, Musser, JM 2002 Characterization 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 Stedman, KM, She, Q, Phan, H, Holz, I, Singh, H, Prangishvili, D, Garrett, R, Zillig, W 2000 pING 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 Stedman, KM, She, Q, Phan, H, Arnold, HP, Holz, I, Garrett, RA, Zillig, W 2003 Relationships between fuselloviruses infecting the extremely thermophilic archaeon Sulfolobus : SSV1 and SSV2 Res Microbiol 154 295 302 CrossRef PubMed Google Scholar Tang, TH, Bachellerie, JP, Rozhdestvensky, T, Bortolin, ML, Huber, H, Drungowski, M, Elge, T, Brosius, J, Huttenhofer, A 2002 Identification of 86 candidates for small non-messenger RNAs from the archaeon Archaeoglobus fulgidus Proc Natl Acad Sci USA 99 7536 7541 Google Scholar Traxler, BA, Minkley, EG,Jr 1988 Evidence 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 Young, R 1992 Bacteriophage lysis: Mechanism and regulation Microbiol Rev 56 430 481 Google Scholar Zillig, W, Arnold, HP, Holz, I, Prangishvili, D, Schweier, A, Stedman, K, She, Q, Phan, H, Garrett, R, Kristjansson, JK 1998 Genetic elements in the extremely thermophilic archaeon Sulfolobus Extremophiles 2 131 140 Google Scholar © Springer Science+Business Media, Inc. 2005
Authors and Affiliations Francisco J.M. Mojica Email author Chc)sar Díez-Villaseñor Jesús García-Martínez Elena Soria 1. División de Microbiología, Departamento de Fisiología, Genhc)tica y Microbiología Universidad de Alicante Spain