identifier: METPO:1000432
label: GC high
definition: A GC-content phenotype with genome-wide GC composition at or below approximately
  42.65% (the METPO `GC_<=42.65` bin; note that the upstream label 'high' does not
  match this numeric threshold, but the synonym is preserved as the authoritative
  bin definition).
definition_source: DOI:10.1038/nrg2358
trait_category: GENOMICS
term_kind: CLASS
mapping_status: REVIEWED
parent_traits:
- METPO:1000127
synonyms:
- synonym_text: GC_<=42.65
  synonym_type: RELATED_SYNONYM
  source: metpo.owl
evidence:
- reference: DOI:10.1038/nrg2358
  snippet: GC content
  notes: Bacterial-genome review supports the lower end of GC content as a distinct
    genomic-composition phenotype.
causal_graphs:
- graph_id: gc_high_low_gc_bin
  title: GC-high (METPO ≤42.65%) low-GC bin
  description: DOI-backed graph linking AT-biased mutation pressure to a GC content
    at or below ~42.65% (the threshold encoded by the METPO synonym GC_<=42.65 on
    this record).
  nodes:
  - node_id: gc_high_trait
    label: GC high
    node_type: TRAIT
    grounding: METPO:1000432
    description: GC content at or below ~42.65% (per METPO synonym GC_<=42.65).
  - node_id: gc_content
    label: GC content
    node_type: TRAIT
    grounding: METPO:1000127
    description: Percentage of guanine and cytosine nucleotides in genomic DNA.
  - node_id: at_mutation_bias
    label: AT-biased mutation pressure
    node_type: BIOLOGICAL_PROCESS
    description: Mutational bias favoring AT base pairs that lowers genome-wide GC
      content.
  - node_id: cytosine_deamination
    label: Cytosine deamination
    node_type: BIOLOGICAL_PROCESS
    description: Spontaneous conversion of cytosine to uracil, read as thymine at
      replication, causing GC-eroding G->A transitions.
  - node_id: udg_loss
    label: Loss of uracil-DNA glycosylase (UDG family)
    node_type: BIOLOGICAL_PROCESS
    description: Loss of UDG-family base-excision repair activity, leaving deaminated
      cytosine (uracil) unrepaired.
  - node_id: ber_glycosylase_loss
    label: Loss of BER glycosylases (Tag/AlkA/MPG/Nei)
    node_type: BIOLOGICAL_PROCESS
    description: Concerted loss of base-excision-repair glycosylases removing defenses
      against GC-eroding small-base lesions.
  - node_id: mutt_loss
    label: Loss of MutT nucleotide-pool sanitization
    node_type: BIOLOGICAL_PROCESS
    description: Loss of MutT-family dNTP-pool sanitizing activity, contributing to
      mutational dysregulation.
  - node_id: hypermutator_state
    label: Hypermutator phenotype
    node_type: STATE
    description: Elevated genome-wide mutation rate with GC-eroding mutation spectra
      arising from repair-gene loss.
  - node_id: gc3_at_enrichment
    label: Third-codon-position AT enrichment
    node_type: BIOLOGICAL_PROCESS
    description: Preferential substitution of synonymous third codon positions toward
      AT-rich nucleotides.
  - node_id: purifying_selection_bgc
    label: Purifying selection and biased gene conversion
    node_type: BIOLOGICAL_PROCESS
    description: Selection and GC-biased gene conversion that counteract AT mutation
      bias and resist GC decline.
  edges:
  - subject: at_mutation_bias
    predicate: produces
    object: gc_high_trait
    description: AT-biased mutation pressure produces low genome-wide GC composition.
    evidence:
    - reference: DOI:10.1186/1471-2148-10-374
      snippet: mutation bias
      notes: Supports mutation bias as the primary driver of low-GC composition.
    predicate_id: METPO:2000202
  - subject: gc_high_trait
    predicate: is a
    object: gc_content
    description: GC high is a quantitative bin of the GC-content phenotype.
    evidence:
    - reference: DOI:10.1038/nrg2358
      snippet: GC content
      notes: Supports the ≤42.65% bin as a value within the GC-content distribution.
    predicate_id: rdfs:subClassOf
  - subject: cytosine_deamination
    predicate: contributes to
    object: gc_high_trait
    description: Cytosine deamination drives AT-enriching G->A transitions lowering
      genome-wide GC.
    evidence:
    - reference: DOI:10.1038/s41467-026-71228-y
      notes: Spontaneous cytosine deamination produces unrepaired uracil read as thymine,
        causing G->A transitions (pages 6-7).
    predicate_id: RO:0002326
  - subject: udg_loss
    predicate: causally promotes
    object: gc_high_trait
    description: Loss of UDG repair leaves deaminated cytosine unrepaired, promoting
      GC erosion.
    evidence:
    - reference: DOI:10.1038/s41467-026-71228-y
      notes: Absence of DNA glycosylases compromises repair of deaminated cytosine
        (uracil), causing G->A transitions (pages 6-7).
  - subject: ber_glycosylase_loss
    predicate: causally promotes
    object: gc_high_trait
    description: Concerted loss of BER glycosylases biases mutation spectra toward
      GC-eroding changes.
    evidence:
    - reference: DOI:10.1038/s41467-026-71228-y
      notes: Concerted loss of Tag/AlkA/MPG, UDG, Nei, MutT removed defenses against
        small-base lesions; mutation spectra biased toward GC-eroding changes (pages
        8-9).
  - subject: mutt_loss
    predicate: causally promotes
    object: gc_high_trait
    description: Loss of MutT nucleotide-pool sanitization contributes to GC-eroding
      mutational dysregulation.
    evidence:
    - reference: DOI:10.1038/s41467-026-71228-y
      notes: Concerted loss of sanitizing enzymes including MutT removed defenses;
        analogues showed mutation spectra biased toward GC-eroding changes (pages
        8-9).
  - subject: hypermutator_state
    predicate: causally promotes
    object: gc_high_trait
    description: Hypermutator state provides a mechanistic path to genome-wide AT
      enrichment.
    evidence:
    - reference: DOI:10.1038/s41467-026-71228-y
      notes: Mutator phenotypes (10- to 1e4-fold) with GC-eroding mutation spectra
        provide a mechanistic path to AT-enrichment (pages 8-9).
  - subject: gc3_at_enrichment
    predicate: contributes to
    object: gc_high_trait
    description: AT-rich substitution at third codon positions is a principal driver
      of decreased GC.
    evidence:
    - reference: DOI:10.1038/s41467-026-71228-y
      notes: Substitution of third codon positions with AT-rich nucleotides identified
        as a principal driver of decreased GC (pages 9-10).
    predicate_id: RO:0002326
  - subject: purifying_selection_bgc
    predicate: opposes
    object: gc_high_trait
    description: Purifying selection and biased gene conversion counteract AT bias,
      resisting GC decline.
    evidence:
    - reference: DOI:10.63635/mrj.v1i4.188
      notes: Purifying selection and biased gene conversion can counteract AT bias
        (pages 3-5).
curation_history:
- timestamp: '2026-05-05T01:35:46.818260+00:00'
  curator: seed_from_metpo
  action: SEEDED_FROM_METPO
  changes: imported from data/raw/metpo.owl (CLASS)
  llm_assisted: false
- timestamp: '2026-05-13T13:00:00-07:00'
  curator: claude
  action: CURATED_CAUSAL_GRAPH
  changes: Added DOI-backed definition (derived from METPO synonym GC_<=42.65) and
    causal graph linking AT-biased mutation pressure to this GC bin. Documented the
    upstream label-vs-threshold inconsistency.
  llm_assisted: true
- timestamp: '2026-05-20T03:35:30Z'
  curator: claude
  action: GROUND_CAUSAL_PREDICATES
  changes: Grounded 2 causal-edge predicate_id field(s) via mappings/predicate_grounding.tsv
    (METPO:2000202×1, rdfs:subClassOf×1).
  llm_assisted: true
- timestamp: '2026-06-23T00:00:00Z'
  curator: claude
  action: ENRICH_CAUSAL_GRAPH
  changes: Added 7 evidence-backed generic edges (7 new nodes) from the deep-research
    report.
  llm_assisted: true
- timestamp: '2026-06-24T17:21:11Z'
  curator: claude
  action: GROUND_CAUSAL_PREDICATES
  changes: Grounded 2 causal-edge predicate_id field(s) via mappings/predicate_grounding.tsv
    (RO:0002326×2).
  llm_assisted: true