{"doi":"10.1093/nar/gkae1171","title":"Exploring the diversity of anti-defense systems across prokaryotes, phages and mobile genetic elements","abstract":"The co-evolution of prokaryotes, phages and mobile genetic elements (MGEs) has driven the diversification of defense and anti-defense systems alike. Anti-defense proteins have diverse functional domains, sequences and are typically small, creating a challenge to detect anti-defense homologs across prokaryotic and phage genomes. To date, no tools comprehensively annotate anti-defense proteins within a desired sequence. Here, we developed 'AntiDefenseFinder'-a free open-source tool and web service that detects 156 anti-defense systems of one or more proteins in any genomic sequence. Using this dataset, we identified 47 981 anti-defense systems distributed across prokaryotes and their viruses. We found that some genes co-localize in 'anti-defense islands', including Escherichia coli T4 and Lambda phages, although many appear standalone. Eighty-nine per cent anti-defense systems localize only or preferentially in MGE. However, >80% of anti-Pycsar protein 1 (Apyc1) resides in nonmobile regions of bacterial genomes. Evolutionary analysis and biochemical experiments revealed that Apyc1 likely originated in bacteria to regulate cyclic nucleotide (cNMP) signaling, but phage co-opted Apyc1 to overcome cNMP-utilizing defenses. With the AntiDefenseFinder tool, we hope to facilitate the identification of the full repertoire of anti-defense systems in MGEs, the discovery of new protein functions and a deeper understanding of host-pathogen arms race.","journal":"Nucleic Acids Research","year":2024,"id":417874,"datarank":1.1445075725852052,"base_score":4.110873864173311,"endowment":4.110873864173311,"self_citation_contribution":0.6166310796259968,"citation_network_contribution":0.5278764929592084,"self_endowment_contribution":0.6166310796259968,"citer_contribution":0.5278764929592084,"corpus_percentile":null,"corpus_rank":null,"citation_count":60,"citer_count":54,"citers_with_citation_signal":29,"citers_with_endowment":29,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9113,"is_data_producer":true,"deposit_databanks":{"figshare":["26526487"]},"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2024-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":471706,"name":"Erin Huiting","orcid":"0000-0002-5454-2679","position":1,"is_corresponding":false},{"id":1041949,"name":"Linlin Wei","orcid":"0000-0002-2958-5925","position":2,"is_corresponding":false},{"id":109402,"name":"Jie Ren","orcid":"0000-0002-6450-3163","position":3,"is_corresponding":false},{"id":267004,"name":"Matthew C. Johnson","orcid":"0000-0002-1477-7801","position":4,"is_corresponding":false},{"id":1204487,"name":"Rémi Planel","orcid":"0000-0002-7826-3316","position":5,"is_corresponding":false},{"id":985453,"name":"Jean Cury","orcid":"0000-0002-6462-8783","position":6,"is_corresponding":false},{"id":397880,"name":"Yue Feng","orcid":"0000-0002-1576-1385","position":7,"is_corresponding":false},{"id":238123,"name":"Joseph Bondy‐Denomy","orcid":"0000-0002-4909-9481","position":8,"is_corresponding":false},{"id":854615,"name":"Aude Bernheim","orcid":"0000-0003-0212-777X","position":9,"is_corresponding":false},{"id":1204486,"name":"Florian Tesson","orcid":"0000-0003-4038-1154","position":0,"is_corresponding":true}],"reference_count":72,"raw_metadata":null,"created_at":"2026-07-19T01:56:56.807779Z","pmid":"39657785","pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}