Food for Health


Date of this Version


Document Type



AcaFinder: Genome Mining for Aca Genes. November/December 2022 Volume 7 Issue 6. 10.1128/msystems.00817-22


Open access.


Anti-CRISPR (Acr) proteins are encoded by (pro)viruses to inhibit their host’s CRISPR-Cas systems. Genes encoding Acr and Aca (Acr associated) proteins often colocalize to form acr-aca operons. Here, we present AcaFinder as the first Aca genome mining tool. AcaFinder can (i) predict Acas and their associated acr-aca operons using guilt-by-association (GBA); (ii) identify homologs of known Acas using an HMM (Hidden Markov model) database; (iii) take input genomes for potential prophages, CRISPR-Cas systems, and self-targeting spacers (STSs); and (iv) provide a standalone program ( and a web server (http://aca AcaFinder was applied to mining over 16,000 prokaryotic and 142,000 gut phage genomes. After a multistep filtering, 36 high-confident new Aca families were identified, which is three times that of the 12 known Aca families. Seven new Aca families were from major human gut bacteria (Bacteroidota, Actinobacteria, and Fusobacteria) and their phages, while most known Aca families were from Proteobacteria and Firmicutes. A complex association network between Acrs and Acas was revealed by analyzing their operonic colocalizations. It appears very common in evolution that the same aca genes can recombine with different acr genes and vice versa to form diverse acr-aca operon combinations.