Evidence map›Paper›PMID 26712934›Full record

ArticleJournal of bacteriology2015

ISC, a Novel Group of Bacterial and Archaeal DNA Transposons That Encode Cas9 Homologs.

Vladimir V Kapitonov, Kira S Makarova, Eugene V Koonin

Open access · hybridAbstract read
In one paragraph

Article in Journal of bacteriology, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 73 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
73citing papers in PubMed, 1 pooled it
2.3field-weighted citation impact, top 12% of its field
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

73 citing papers in PubMed, 1 synthesis or guideline pooled it, 113 citations in OpenAlex.

  1. Engineering CRISPR guide RNAs for programmable RNA sensors.Biochemical Society transactions · 2023
    Pooled it
  2. Article
  3. Article
  4. Review
  5. Article
  6. Article
  7. Review
  8. Article
  9. Structural visualization of the molecular evolution of CRISPR-Cas9.Nature structural & molecular biology · 2026
    Article
  10. Article
  11. Review
  12. Review
  13. Review
  14. Article
  15. Article
  16. Review
  17. Efforts to Downsize Base Editors for Clinical Applications.International journal of molecular sciences · 2025
    Review
  18. Article
  19. Article
  20. Article

13 more citing papers are in PubMed but not listed here.

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

3 authors at 2 institutions in 1 country.

Vladimir V KapitonovNational Center for Biotechnology Information, National Library of Medicine, National Institutes of Health, Bethesda, Maryland, USA.
Kira S MakarovaNational Center for Biotechnology Information, National Library of Medicine, National Institutes of Health, Bethesda, Maryland, USA.
Eugene V KooninNational Center for Biotechnology Information, National Library of Medicine, National Institutes of Health, Bethesda, Maryland, USA koonin@ncbi.nlm.nih.gov.
National Institutes of Health · USNational Center for Biotechnology Information · US

Funding

Comparative Analysis Of Completely Sequenced GenomesZIALM000073 · NLM · NATIONAL LIBRARY OF MEDICINE · PI KOONIN, EUGENE V · 2009 to 2025
$43.1M
Finding Protein Sequence Motifs--Methods And ApplicationsZIALM000061 · NLM · NATIONAL LIBRARY OF MEDICINE · PI KOONIN, EUGENE V · 2009 to 2025
$10.6M
Intramural NIH HHS
6 · The paper itself

Abstract

unlabelledBacterial genomes encode numerous homologs of Cas9, the effector protein of the type II CRISPR-Cas systems. The homology region includes the arginine-rich helix and the HNH nuclease domain that is inserted into the RuvC-like nuclease domain. These genes, however, are not linked to cas genes or CRISPR. Here, we show that Cas9 homologs represent a distinct group of nonautonomous transposons, which we denote ISC (insertion sequences Cas9-like). We identify many diverse families of full-length ISC transposons and demonstrate that their terminal sequences (particularly 3' termini) are similar to those of IS605 superfamily transposons that are mobilized by the Y1 tyrosine transposase encoded by the TnpA gene and often also encode the TnpB protein containing the RuvC-like endonuclease domain. The terminal regions of the ISC and IS605 transposons contain palindromic structures that are likely recognized by the Y1 transposase. The transposons from these two groups are inserted either exactly in the middle or upstream of specific 4-bp target sites, without target site duplication. We also identify autonomous ISC transposons that encode TnpA-like Y1 transposases. Thus, the nonautonomous ISC transposons could be mobilized in trans either by Y1 transposases of other, autonomous ISC transposons or by Y1 transposases of the more abundant IS605 transposons. These findings imply an evolutionary scenario in which the ISC transposons evolved from IS605 family transposons, possibly via insertion of a mobile group II intron encoding the HNH domain, and Cas9 subsequently evolved via immobilization of an ISC transposon. IMPORTANCE: Cas9 endonucleases, the effectors of type II CRISPR-Cas systems, represent the new generation of genome-engineering tools. Here, we describe in detail a novel family of transposable elements that encode the likely ancestors of Cas9 and outline the evolutionary scenario connecting different varieties of these transposons and Cas9.

Indexed as

Amino Acid MotifsAmino Acid SequenceArchaeal ProteinsBacterial ProteinsBase SequenceCRISPR-Cas SystemsDNA Transposable ElementsEndonucleasesGene Expression Regulation, ArchaealGene Expression Regulation, BacterialMolecular Sequence DataMutagenesis, InsertionalPhylogenyArchaeal ProteinsBacterial ProteinsDNA Transposable ElementsEndonucleases

Identifiers

PMID26712934
PMCPMC4810608
OpenAlexW2197109003

What OpenQuestion holds

Textmetadata
LicenceCC BY-NC-SA
Read underepoch 390

Registered trials

None linked

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.