Evidence map›Paper›PMID 36593295›Full record

ArticleNature microbiology2023

Evolution of CRISPR-associated endonucleases as inferred from resurrected proteins.

Borja Alonso-Lerma, Ylenia Jabalera, Sara Samperio, Matias Morin, Almudena Fernandez, Logan T Hille, Rachel A Silverstein, Ane Quesada-Ganuza, Antonio Reifs, Sergio Fernández-Peñalver and 12 more

Open access · greenAbstract read
In one paragraph

Article in Nature microbiology, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers.

0numbers the graph read from it
0cells of the map it votes in
12citing papers in PubMed
4.6field-weighted citation impact, top 5% 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

12 citing papers in PubMed, 30 citations in OpenAlex.

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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

22 authors at 9 institutions in 3 countries.

Borja Alonso-Lerma *CIC nanoGUNE BRTA, San Sebastian, Spain.
Ylenia Jabalera *CIC nanoGUNE BRTA, San Sebastian, Spain.ORCID 0000-0003-1786-959X
Sara SamperioCIC nanoGUNE BRTA, San Sebastian, Spain.
Matias MorinServicio de Genética, Hospital Universitario Ramón y Cajal, IRYCIS and Centro de Investigaciones Biomédicas en Red de Enfermedades Raras, Madrid, Spain.ORCID 0000-0002-7985-592X
Almudena FernandezDepartment of Molecular and Cellular Biology, National Centre for Biotechnology and Centre for Biomedical Network Research on Rare Diseases, Madrid, Spain.ORCID 0000-0002-4983-5362
Logan T HilleCenter for Genomic Medicine and Department of Pathology, Massachusetts General Hospital, Boston, MA, USA.ORCID 0000-0001-7515-124X
Rachel A SilversteinCenter for Genomic Medicine and Department of Pathology, Massachusetts General Hospital, Boston, MA, USA.
Ane Quesada-GanuzaCIC nanoGUNE BRTA, San Sebastian, Spain.
Antonio ReifsCIC nanoGUNE BRTA, San Sebastian, Spain.
Sergio Fernández-PeñalverServicio de Genética, Hospital Universitario Ramón y Cajal, IRYCIS and Centro de Investigaciones Biomédicas en Red de Enfermedades Raras, Madrid, Spain.
Yolanda BenitezDepartment of Molecular and Cellular Biology, National Centre for Biotechnology and Centre for Biomedical Network Research on Rare Diseases, Madrid, Spain.
Lucia SolettoServicio de Genética, Hospital Universitario Ramón y Cajal, IRYCIS and Centro de Investigaciones Biomédicas en Red de Enfermedades Raras, Madrid, Spain.ORCID 0000-0002-5768-5317
Jose A GaviraLaboratorio de Estudios Cristalográficos, IACT, Armilla, Spain.
Adrian DiazInteruniversity Institute of Bioinformatics in Brussels, ULB-VUB, Brussels, Belgium.
Wim VrankenInteruniversity Institute of Bioinformatics in Brussels, ULB-VUB, Brussels, Belgium.ORCID 0000-0001-7470-4324
Avencia Sanchez-MejiasIntegra Therapeutics S.L., Barcelona, Spain.
Marc GüellIntegra Therapeutics S.L., Barcelona, Spain.
Francisco J M MojicaDpto. Fisiología, Genética y Microbiología and Instituto Multidisciplinar para el Estudio del Medio 'Ramón Margalef', Universidad de Alicante, Alicante, Spain.ORCID 0000-0002-6660-4996
Benjamin P KleinstiverCenter for Genomic Medicine and Department of Pathology, Massachusetts General Hospital, Boston, MA, USA.ORCID 0000-0002-5469-0655
Miguel A Moreno-PelayoServicio de Genética, Hospital Universitario Ramón y Cajal, IRYCIS and Centro de Investigaciones Biomédicas en Red de Enfermedades Raras, Madrid, Spain.ORCID 0000-0003-3839-5098
Lluis MontoliuDepartment of Molecular and Cellular Biology, National Centre for Biotechnology and Centre for Biomedical Network Research on Rare Diseases, Madrid, Spain.ORCID 0000-0003-3941-1176
Raul Perez-JimenezCIC nanoGUNE BRTA, San Sebastian, Spain. r.perezjimenez@nanogune.eu.ORCID 0000-0001-7094-6799
CIC nanoGUNE · ESCentro de Investigación Biomédica en Red · ESHarvard University · USCentre for Biomedical Network Research on Rare Diseases · ESVrije Universiteit Brussel · BEHospital Universitario La Paz · ESIkerbasque · ESUniversitat Pompeu Fabra · ESUniversity of Alicante · ES

Funding

PROJECT 4: Somatic evolution of the hematopoietic system in cardiovascular diseaseP01HL142494 · NHLBI · MASSACHUSETTS GENERAL HOSPITAL · PI Matthias Nahrendorf · 2019 to 2026
$19.5M
NHLBI NIH HHS P01 HL142494NIMHD NIH HHS L60 MD003721
6 · The paper itself

Abstract

Clustered regularly interspaced short palindromic repeats (CRISPR)-associated Cas9 is an effector protein that targets invading DNA and plays a major role in the prokaryotic adaptive immune system. Although Streptococcus pyogenes CRISPR-Cas9 has been widely studied and repurposed for applications including genome editing, its origin and evolution are poorly understood. Here, we investigate the evolution of Cas9 from resurrected ancient nucleases (anCas) in extinct firmicutes species that last lived 2.6 billion years before the present. We demonstrate that these ancient forms were much more flexible in their guide RNA and protospacer-adjacent motif requirements compared with modern-day Cas9 enzymes. Furthermore, anCas portrays a gradual palaeoenzymatic adaptation from nickase to double-strand break activity, exhibits high levels of activity with both single-stranded DNA and single-stranded RNA targets and is capable of editing activity in human cells. Prediction and characterization of anCas with a resurrected protein approach uncovers an evolutionary trajectory leading to functionally flexible ancient enzymes.

Indexed as

BacillotaCRISPR-Cas SystemsEndonucleasesCRISPR-Associated Protein 9Gene EditingRNA, Guide, CRISPR-Cas SystemsCRISPR-Associated Protein 9EndonucleasesRNA, Guide, CRISPR-Cas Systems

Identifiers

PMID36593295
PMCPMC10324499
OpenAlexW4313409002

What OpenQuestion holds

Textmetadata
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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.