identifier: traitmech:000502 label: Metis system definition: A phage defense system in which an organism possesses a Metis locus that senses phage-mediated host-genome degradation through N6-methyl-deoxyadenosine monophosphate and activates a type-specific toxic effector. definition_source: DOI:10.1126/science.aed6782 trait_category: GENOMICS term_kind: CLASS mapping_status: PROPOSED parent_traits: - traitmech:000209 synonyms: - synonym_text: Metis synonym_type: EXACT_SYNONYM source: https://raw.githubusercontent.com/mdmparis/defense-finder-models/afb0e5a8b466be53586b13266f5d38d98c3ac268/List_system_article.md evidence: - reference: DOI:10.1126/science.aed6782 snippet: In this work, we describe Metis, a bacterial defense system that directly senses phage-mediated host genome degradation. notes: Osterman et al. directly name Metis as a bacterial system sensing host-genome degradation during phage infection. - reference: DOI:10.1126/science.aed6782 snippet: Metis aborts phage infection once it detects the modified mononucleotide N6-methyl-deoxyadenosine monophosphate (m6dAMP). notes: Osterman et al. identify m6dAMP as the modified mononucleotide cue detected by Metis. - reference: DOI:10.1126/science.aed6782 snippet: As methylation of deoxyadenosines usually occurs on the DNA polymer, accumulation of m6dAMP signals that the host genome has been degraded. notes: Osterman et al. explain why free m6dAMP reports host-genome degradation. - reference: DOI:10.1126/science.aed6782 snippet: In type I Metis, sensing of m6dAMP activates a nicotinamide adenine dinucleotide (NAD+) diphosphatase, leading to NAD+ depletion and cessation of the infection process, whereas the effector in type II Metis is a membrane-spanning protein whose toxicity is triggered in response to the modified mononucleotide. notes: Osterman et al. distinguish type I and type II Metis effectors without resolving a DefenseFinder rule-level model in the pinned registry. - reference: DOI:10.1126/science.aed6782 snippet: We further show that Metis defense depends on endogenous DNA methylases and that phages can escape Metis through mutations that inactivate host genome degradation. notes: Osterman et al. link Metis immunity to endogenous DNA methylases and to phage genome-degradation activity. - reference: https://raw.githubusercontent.com/mdmparis/defense-finder-models/afb0e5a8b466be53586b13266f5d38d98c3ac268/List_system_article.md snippet: '| Metis | 10\.1101/2025\.11\.05\.686725 | Bacteria sense virus-induced genome degradation via methylated mononucleotides | ' notes: The pinned DefenseFinder article registry maps the named Metis system to the Osterman et al. preprint. causal_graphs: - graph_id: metis_m6damp_toxic_effector_defense title: Metis systems detect methylated mononucleotides description: Conservative system-level sketch linking a Metis locus to phage-mediated host-genome degradation, modified mononucleotide sensing, toxic effector activation, and Metis system possession. scope_status: NONMECHANISTIC scope_notes: The graph captures Metis as a named m6dAMP-sensing phage-defense system while leaving exact type I and type II locus composition, native host breadth, subtype distribution, effector biochemistry, and DefenseFinder HMM/rules detection criteria unresolved. nodes: - node_id: metis_locus label: Metis locus node_type: GENETIC_ELEMENT description: A Metis anti-phage locus encoding m6dAMP sensing and type-specific toxic effector functions. - node_id: phage_mediated_host_genome_degradation label: phage-mediated host genome degradation node_type: BIOLOGICAL_PROCESS description: Degradation of bacterial host genomic DNA to individual nucleotides during phage infection. - node_id: modified_mononucleotide_sensing label: modified mononucleotide sensing node_type: BIOLOGICAL_PROCESS description: Detection of the modified mononucleotide m6dAMP as a signal of phage-mediated host-genome degradation. - node_id: type_specific_toxic_effector_activation label: type-specific toxic effector activation node_type: BIOLOGICAL_PROCESS description: Activation of a Metis effector that depletes NAD in type I systems or triggers membrane-linked toxicity in type II systems. - node_id: metis_system_trait label: Metis system node_type: TRAIT grounding: traitmech:000502 description: Possession of a genome-encoded Metis phage-defense system. - node_id: phage_defense_system label: phage defense system node_type: TRAIT grounding: traitmech:000209 description: Possession of one or more genome-encoded immune systems that inhibit bacteriophage infection. edges: - subject: metis_locus predicate: contributes to predicate_id: RO:0002326 object: modified_mononucleotide_sensing description: Metis loci directly sense m6dAMP after phage-mediated host-genome degradation. evidence: - reference: DOI:10.1126/science.aed6782 snippet: In this work, we describe Metis, a bacterial defense system that directly senses phage-mediated host genome degradation. notes: Osterman et al. directly name Metis as a bacterial system sensing host-genome degradation during phage infection. - reference: https://raw.githubusercontent.com/mdmparis/defense-finder-models/afb0e5a8b466be53586b13266f5d38d98c3ac268/List_system_article.md snippet: '| Metis | 10\.1101/2025\.11\.05\.686725 | Bacteria sense virus-induced genome degradation via methylated mononucleotides | ' notes: The pinned DefenseFinder article registry maps the named Metis system to the Osterman et al. preprint. - subject: phage_mediated_host_genome_degradation predicate: contributes to predicate_id: RO:0002326 object: modified_mononucleotide_sensing description: Accumulation of free m6dAMP after host-genome degradation provides the modified mononucleotide signal detected by Metis. evidence: - reference: DOI:10.1126/science.aed6782 snippet: Metis aborts phage infection once it detects the modified mononucleotide N6-methyl-deoxyadenosine monophosphate (m6dAMP). As methylation of deoxyadenosines usually occurs on the DNA polymer, accumulation of m6dAMP signals that the host genome has been degraded. notes: Osterman et al. connect Metis detection of m6dAMP to the accumulation of that nucleotide after host-genome degradation. - reference: DOI:10.1126/science.aed6782 snippet: We further show that Metis defense depends on endogenous DNA methylases and that phages can escape Metis through mutations that inactivate host genome degradation. notes: Osterman et al. link Metis immunity to endogenous DNA methylases and to phage genome-degradation activity. - subject: modified_mononucleotide_sensing predicate: activates predicate_id: RO:0002213 object: type_specific_toxic_effector_activation description: m6dAMP sensing activates a Metis type-specific toxic effector. evidence: - reference: DOI:10.1126/science.aed6782 snippet: In type I Metis, sensing of m6dAMP activates a nicotinamide adenine dinucleotide (NAD+) diphosphatase, leading to NAD+ depletion and cessation of the infection process, whereas the effector in type II Metis is a membrane-spanning protein whose toxicity is triggered in response to the modified mononucleotide. notes: Osterman et al. distinguish type I and type II Metis effectors without resolving a DefenseFinder rule-level model in the pinned registry. - subject: type_specific_toxic_effector_activation predicate: confers predicate_id: METPO:2007700 object: metis_system_trait description: Triggered Metis effector toxicity realizes the Metis system trait by aborting phage infection. evidence: - reference: DOI:10.1126/science.aed6782 snippet: Metis aborts phage infection once it detects the modified mononucleotide N6-methyl-deoxyadenosine monophosphate (m6dAMP). notes: Osterman et al. connect m6dAMP sensing to type-specific effector toxicity and abortion of the phage infection process. - subject: metis_system_trait predicate: is a predicate_id: rdfs:subClassOf object: phage_defense_system description: Metis system possession is a phage-defense-system trait. evidence: - reference: DOI:10.1126/science.aed6782 snippet: In this work, we describe Metis, a bacterial defense system that directly senses phage-mediated host genome degradation. Metis aborts phage infection once it detects the modified mononucleotide N6-methyl-deoxyadenosine monophosphate (m6dAMP). notes: Osterman et al. identify Metis as a bacterial defense system that aborts phage infection after sensing m6dAMP. discussions: - discussion_id: metis-subtype-and-model-coverage-gap prompt: Resolve Metis type I and type II locus composition, native host breadth, profile-to-component mapping, subtype-specific effector biochemistry, and DefenseFinder HMM/rule coverage before minting narrower Metis mechanism or component traits. kind: KNOWLEDGE_GAP status: OPEN rationale: Osterman et al. support Metis as a bacterial defense system that senses m6dAMP from phage-mediated host-genome degradation and activates type-specific toxic effectors. The pinned DefenseFinder article registry maps the Metis source key to the Osterman et al. preprint, but the pinned HMM inventory and rules table have no exact Metis rows. This first-pass record therefore does not resolve the complete locus model, subtype component boundaries, direct HMM/profile mapping, or native host breadth. evidence: - reference: DOI:10.1126/science.aed6782 snippet: In this work, we describe Metis, a bacterial defense system that directly senses phage-mediated host genome degradation. notes: Osterman et al. directly name Metis as a bacterial system sensing host-genome degradation during phage infection. - reference: DOI:10.1126/science.aed6782 snippet: In type I Metis, sensing of m6dAMP activates a nicotinamide adenine dinucleotide (NAD+) diphosphatase, leading to NAD+ depletion and cessation of the infection process, whereas the effector in type II Metis is a membrane-spanning protein whose toxicity is triggered in response to the modified mononucleotide. notes: Osterman et al. distinguish type I and type II Metis effectors without resolving a DefenseFinder rule-level model in the pinned registry. - reference: DOI:10.1126/science.aed6782 snippet: We further show that Metis defense depends on endogenous DNA methylases and that phages can escape Metis through mutations that inactivate host genome degradation. notes: Osterman et al. link Metis immunity to endogenous DNA methylases and to phage genome-degradation activity. - reference: https://raw.githubusercontent.com/mdmparis/defense-finder-models/afb0e5a8b466be53586b13266f5d38d98c3ac268/List_system_article.md snippet: '| Metis | 10\.1101/2025\.11\.05\.686725 | Bacteria sense virus-induced genome degradation via methylated mononucleotides | ' notes: The pinned DefenseFinder article registry maps the named Metis system to the Osterman et al. preprint. - reference: https://raw.githubusercontent.com/mdmparis/defense-finder-models/afb0e5a8b466be53586b13266f5d38d98c3ac268/Liste_hmm_system.md notes: A structured first-pass search of the pinned DefenseFinder HMM inventory found no exact Metis row. - reference: https://raw.githubusercontent.com/mdmparis/defense-finder-models/afb0e5a8b466be53586b13266f5d38d98c3ac268/DefenseFinder_rules.tsv notes: A structured first-pass search of the pinned DefenseFinder rules table found no exact Metis system row. attaches_to: - causal_graphs#metis_m6damp_toxic_effector_defense posed_by: codex posed_date: '2026-09-30' curation_history: - timestamp: '2026-09-30T22:51:08Z' curator: codex action: MINTED_TRAITMECH_ID changes: Minted Metis system as a Science-, PubMed-, and DefenseFinder-backed GENOMICS TraitRecord under phage defense system after an ignored-and-hidden duplicate review found no exact live TraitMech, METPO, history, research, or prior proposal record; the replacement placeholder is reserved in proposals/metpo_traitmech_v379. llm_assisted: true - timestamp: '2026-09-30T22:51:09Z' curator: codex action: REVIEW_CANONICAL_EXAMPLE_EVIDENCE_GAP changes: Reviewed Metis system canonical_examples and left them empty because public PubMed and DefenseFinder evidence supports the named phage-defense system but not a direct named native microbial isolate exemplar with experimentally verified endogenous Metis activity. No paid research was used. llm_assisted: true