Evidence map›Paper›PMID 41198952›Full record

ArticleNature microbiology2025

An updated evolutionary classification of CRISPR-Cas systems including rare variants.

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 and 19 more

Abstract read
In one paragraph

Article in Nature microbiology, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 59 papers.

0numbers the graph read from it
0cells of the map it votes in
59citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

59 citing papers in PubMed.

  1. Article
  2. Article
  3. Article
  4. Article
  5. Article
  6. Review
  7. 3D Genome Engineering Using CRISPR/dCas Systems.International journal of molecular sciences · 2026
    Review
  8. Article
  9. Review
  10. Article
  11. Review
  12. Review
  13. Article
  14. Article
  15. Article
  16. Bacterial small regulatory RNAs.Nature reviews. Microbiology · 2026
    Review
  17. Article
  18. Review
  19. Review
  20. Review
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

29 authors.

Kira S Makarova *Division of Intramural Research, National Library of Medicine, National Institutes of Health, Bethesda, MD, USA.ORCID http://orcid.org/0000-0002-8174-2844
Sergey A Shmakov *Division of Intramural Research, National Library of Medicine, National Institutes of Health, Bethesda, MD, USA.
Yuri I WolfDivision of Intramural Research, National Library of Medicine, National Institutes of Health, Bethesda, MD, USA.ORCID http://orcid.org/0000-0002-0247-8708
Pascal MutzDivision of Intramural Research, National Library of Medicine, National Institutes of Health, Bethesda, MD, USA.ORCID http://orcid.org/0000-0002-0430-2095
Han Altae-TranInstitute for Protein Design, University of Washington, Seattle, WA, USA.
Chase L BeiselHelmholtz Institute for RNA-based Infection Research (HIRI), Helmholtz Centre for Infection Research (HZI), Würzburg, Germany.ORCID http://orcid.org/0000-0003-0650-9943
Stan J J BrounsKavli Institute of Nanoscience, Department of Bionanoscience, Delft University of Technology, Delft, The Netherlands.
Emmanuelle CharpentierMax Planck Unit for the Science of Pathogens, Humboldt University, Berlin, Germany.ORCID http://orcid.org/0000-0002-0254-0778
David ChengArbor Biotechnologies, Cambridge, MA, USA.
Jennifer DoudnaDepartment of Chemistry, University of California, Berkeley, CA, USA.
Daniel H HaftNational Center for Biotechnology Information, National Library of Medicine, National Institutes of Health, Bethesda, MD, USA.
Philippe HorvathIFF, Dangé-Saint-Romain, France.ORCID http://orcid.org/0000-0003-2015-8123
Sylvain MoineauDépartement de biochimie, de microbiologie et de bio-informatique, Faculté des sciences et de génie, Université Laval, Québec City, Quebec, Canada.ORCID http://orcid.org/0000-0002-2832-5101
Francisco J M MojicaDepartamento de Fisiología, Genética y Microbiología, Universidad de Alicante, Alicante, Spain.ORCID http://orcid.org/0000-0002-6660-4996
Patrick PauschLSC-EMBL Partnership Institute for Genome Editing Technologies, Life Sciences Center, Vilnius University, Vilnius, Lithuania.ORCID http://orcid.org/0000-0001-8947-9107
Rafael Pinilla-RedondoSection of Microbiology, Department of Biology, University of Copenhagen, Copenhagen, Denmark.ORCID http://orcid.org/0000-0003-3521-460X
Shiraz A ShahCopenhagen Prospective Studies on Asthma in Childhood (COPSAC), Herlev and Gentofte Hospital, University of Copenhagen, Gentofte, Denmark.ORCID http://orcid.org/0000-0002-4665-577X
Virginijus SiksnysInstitute of Biotechnology, Life Sciences Center, Vilnius University, Vilnius, Lithuania.ORCID http://orcid.org/0000-0003-1983-2096
Michael P TernsBiochemistry and Molecular Biology, Genetics and Microbiology, University of Georgia, Athens, GA, USA.ORCID http://orcid.org/0000-0001-8330-1789
Jesse TordoffArbor Biotechnologies, Cambridge, MA, USA.
Česlovas VenclovasInstitute of Biotechnology, Life Sciences Center, Vilnius University, Vilnius, Lithuania.ORCID http://orcid.org/0000-0002-4215-0213
Malcolm F WhiteBiomedical Sciences Research Complex, University of St. Andrews, St. Andrews, UK.ORCID http://orcid.org/0000-0003-1543-9342
Alexander F YakuninDepartment of Chemical Engineering and Applied Chemistry, University of Toronto, Toronto, Ontario, Canada.ORCID http://orcid.org/0000-0003-0813-6490
Feng ZhangBroad Institute of MIT and Harvard, Cambridge, MA, USA.ORCID http://orcid.org/0000-0003-0178-7995
Roger A GarrettArchaea Centre, Department of Biology, Copenhagen University, Copenhagen, Denmark.ORCID http://orcid.org/0000-0001-8452-9099
Rolf BackofenBIOSS Centre for Biological Signaling Studies, Cluster of Excellence, University of Freiburg, Freiburg, Germany.ORCID http://orcid.org/0000-0001-8231-3323
John van der OostLaboratory of Microbiology, Wageningen University, Wageningen, The Netherlands.ORCID http://orcid.org/0000-0001-5024-1871
Rodolphe BarrangouDepartment of Food, Bioprocessing, and Nutrition Sciences, North Carolina State University, Raleigh, NC, USA.ORCID http://orcid.org/0000-0002-0648-3504
Eugene V KooninDivision of Intramural Research, National Library of Medicine, National Institutes of Health, Bethesda, MD, USA. koonin@ncbi.nlm.nih.gov.ORCID http://orcid.org/0000-0003-3943-8299

Funding

CRISPR Capture, Destroy, and Counter-Attack MechanismsR35GM118160 · NIGMS · UNIVERSITY OF GEORGIA · PI TERNS, MICHAEL P · 2016 to 2025
$5.8M
NIGMS NIH HHS R35 GM118160U.S. Department of Health & Human Services | National Institutes of Health (NIH) Intramural funds
6 · The paper itself

Abstract

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.

Indexed as

BacteriaCRISPR-Cas SystemsEvolution, MolecularGenetic VariationClustered Regularly Interspaced Short Palindromic Repeats

Identifiers

PMID41198952
PMCPMC12669027

What OpenQuestion holds

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Registered trials

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.