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Distribution and molecular evolution of the anti-CRISPR family AcrIF7
Open accessPreprint — published as 10.1371/journal.pbio.3002072 · Paper page
Abstract
Anti-CRISPRs are proteins capable of blocking CRISPR-Cas systems and typically encoded in mobile genetic elements. Since their discovery, numerous anti-CRISPR families have been identified. However, little is known about the distribution and sequence diversity of members within a family, nor how these traits influence the anti-CRISPR’s function and evolution. Here we use AcrIF7 to explore the dissemination and molecular evolution of an anti-CRISPR family. We uncovered five sub-clusters and prevalent anti-CRISPR variants within the group. Remarkably, AcrIF7 homologs display high similarity despite their broad geographical, ecological and temporal distribution. Although mainly associated with Pseudomonas aeruginosa , AcrIF7 was identified in distinct genetic backgrounds indicating horizontal dissemination, primarily by phages. Using mutagenesis, we recreated variation observed in databases but also extended the sequence diversity of the group. Characterisation of the variants identified residues key for the anti-CRISPR function and other contributing to its mutational tolerance. Moreover, molecular docking revealed that variants with affected function lose key interactions with its CRISPR-Cas target. Analysis of publicly available data and the generated variants suggests that the dominant AcrIF7 variant corresponds to the minimal and optimal anti-CRISPR selected in the family. Our study provides a blueprint to investigate the molecular evolution of anti-CRISPR families.
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Metadata
- Authors
- Figueroa, W., Cazares, A., Cazares, D., Wu, Y., de la Cruz, A., Welch, M., Kameyama, L., Nobrega, F. L., & Guarneros, G.
- Affiliations
- University of Cambridge (GB)
- European Bioinformatics Institute (GB)
- Universidad Nacional Autónoma de México (MX)
- University of Southampton (GB)
- Instituto Politécnico Nacional (MX)
- Corresponding author
- Figueroa, Wendy
- Cazares, Adrián
- Guarneros, Gabriel
- ORCID
- Venue
- PLoS Biology
- Publisher
- openRxiv
- Published
- 2021-06-27
- Volume
- 21
- Issue
- 4
- Pages
- e3002072-e3002072
- ISSN
- 1544-9173 (ISSN-L)
- PMC
- PMC10155984
- OpenAlex
- W4366602903
- Cited by
- 2
- References
- 70
- Citations by year
- 2025: 1 · 2024: 1
- FWCI
- 0.18
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- cc-by
- Locations
- PLoS Biology (publishedVersion, cc-by)
- bioRxiv (Cold Spring Harbor Laboratory) (acceptedVersion, cc-by-nc-nd)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- ePrints Soton (University of Southampton) (acceptedVersion)
- Apollo (University of Cambridge) (submittedVersion, cc-by)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Apollo (cc-by)
- Funders
- Wellcome Trust
- European Bioinformatics Institute
- European Molecular Biology Laboratory
- Consejo Nacional de Ciencia y Tecnología (586079, 591274 and 706017, 255255, 706017)
- Cambridge Trust (10469474)
- Centro de Investigación y de Estudios Avanzados del Instituto Politécnico Nacional
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › CRISPR and Genetic Engineering
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Bacterial Genetics and Biotechnology
- Life Sciences › Immunology and Microbiology › Virology › Bacteriophages and microbial interactions
- Keywords
- anti-CRISPR proteins, CRISPR-Cas, molecular evolution, horizontal gene transfer, phage-bacteria interactions, Pseudomonas aeruginosa, sequence diversity, mutational tolerance, protein structure-function relationship, molecular docking
- MeSH terms
- Bacteriophages, Humans, Mutation, Evolution, Molecular, Molecular Docking Simulation, CRISPR-Cas Systems
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