Distribution and molecular evolution of the anti-CRISPR family AcrIF7.
Autor: | Figueroa W; Department of Biochemistry, University of Cambridge, Cambridge, United Kingdom., Cazares A; EMBL's European Bioinformatics Institute (EMBL-EBI), Wellcome Genome Campus, Hinxton, United Kingdom.; Wellcome Sanger Institute, Wellcome Genome Campus, Hinxton, United Kingdom., Cazares D; Centro de Ciencias Genómicas, Universidad Nacional Autónoma de México, Cuernavaca, Mexico., Wu Y; School of Biological Sciences, Faculty of Environmental and Life Sciences, University of Southampton, Southampton, United Kingdom., de la Cruz A; Department of Genetics and Molecular Biology, Center for Research and Advanced Studies of the National Polytechnic Institute, Mexico City, Mexico., Welch M; Department of Biochemistry, University of Cambridge, Cambridge, United Kingdom., Kameyama L; Department of Genetics and Molecular Biology, Center for Research and Advanced Studies of the National Polytechnic Institute, Mexico City, Mexico., Nobrega FL; School of Biological Sciences, Faculty of Environmental and Life Sciences, University of Southampton, Southampton, United Kingdom., Guarneros G; Department of Genetics and Molecular Biology, Center for Research and Advanced Studies of the National Polytechnic Institute, Mexico City, Mexico. |
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Jazyk: | angličtina |
Zdroj: | PLoS biology [PLoS Biol] 2023 Apr 21; Vol. 21 (4), pp. e3002072. Date of Electronic Publication: 2023 Apr 21 (Print Publication: 2023). |
DOI: | 10.1371/journal.pbio.3002072 |
Abstrakt: | Anti-clustered regularly interspaced short palindromic repeats (CRISPRs) are proteins capable of blocking CRISPR-Cas systems and typically their genes are located on 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 5 subclusters 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. Competing Interests: The authors have declared that no competing interests exist. (Copyright: © 2023 Figueroa et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.) |
Databáze: | MEDLINE |
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