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<p>The known diversity of CRISPR–Cas systems continues to expand. To encompass new discoveries, here we present an updated evolutionary classification of CRISPR–Cas systems. The updated CRISPR–Cas classification includes 2 classes, 7 types and 46 subtypes, compared with the 6 types and 33 subtypes in our previous survey 5 years ago. In addition, a classification of the cyclic oligoadenylate-dependent signalling pathway in type III systems is presented. We also discuss recently characterized alternative CRISPR–Cas functionalities, notably, type IV variants that cleave the target DNA and type V variants that inhibit the target replication without cleavage. Analysis of the abundance of CRISPR–Cas variants in genomes and metagenomes shows that the previously defined systems are relatively common, whereas the more recently characterized variants are comparatively rare. These low abundance variants comprise the long tail of the CRISPR–Cas distribution in prokaryotes and their viruses, and remain to be characterized experimentally.</p>

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An updated evolutionary classification of CRISPR–Cas systems including rare variants

  • 期刊论文

  • 出版模式：

    开放获取

  • 发表日期：

    2025年11月6日

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  • Kira S. Makarova,
  • Sergey A. Shmakov,
  • Yuri I. Wolf,
  • Pascal Mutz,
  • Han Altae-Tran,
  • Chase L. Beisel,
  • Stan J. J. Brouns,
  • Emmanuelle Charpentier,
  • David Cheng,
  • Jennifer Doudna,
  • Daniel H. Haft,
  • Philippe Horvath,
  • Sylvain Moineau,
  • Francisco J. M. Mojica,
  • Patrick Pausch,
  • Rafael Pinilla-Redondo,
  • Shiraz A. Shah,
  • Virginijus Siksnys,
  • Michael P. Terns,
  • Jesse Tordoff,
  • Česlovas Venclovas,
  • Malcolm F. White,
  • Alexander F. Yakunin,
  • Feng Zhang,
  • Roger A. Garrett,
  • Rolf Backofen,
  • John van der Oost,
  • Rodolphe Barrangou,
  • Eugene V. Koonin

摘要

The known diversity of CRISPR–Cas systems continues to expand. To encompass new discoveries, here we present an updated evolutionary classification of CRISPR–Cas systems. The updated CRISPR–Cas classification includes 2 classes, 7 types and 46 subtypes, compared with the 6 types and 33 subtypes in our previous survey 5 years ago. In addition, a classification of the cyclic oligoadenylate-dependent signalling pathway in type III systems is presented. We also discuss recently characterized alternative CRISPR–Cas functionalities, notably, type IV variants that cleave the target DNA and type V variants that inhibit the target replication without cleavage. Analysis of the abundance of CRISPR–Cas variants in genomes and metagenomes shows that the previously defined systems are relatively common, whereas the more recently characterized variants are comparatively rare. These low abundance variants comprise the long tail of the CRISPR–Cas distribution in prokaryotes and their viruses, and remain to be characterized experimentally.