identifier: traitmech:000097
label: GC skew
definition: A genome-sequence property describing strand asymmetry in guanine versus
  cytosine content between the leading and lagging replication strands, commonly used
  to locate the replication origin and terminus.
definition_source: DOI:10.1093/oxfordjournals.molbev.a025626
trait_category: GENOMICS
term_kind: CLASS
mapping_status: REVIEWED
parent_traits:
- METPO:1000188
synonyms:
- synonym_text: strand compositional asymmetry
  synonym_type: RELATED_SYNONYM
  source: DOI:10.1016/S0378-1119(99)00297-8
evidence:
- reference: DOI:10.1093/oxfordjournals.molbev.a025626
  notes: Lobry first described asymmetric substitution patterns between the two DNA
    strands of bacteria, the basis of GC skew that marks replication boundaries.
- reference: DOI:10.1016/S0378-1119(99)00297-8
  notes: Frank & Lobry review the mutational and selective mechanisms underlying strand
    compositional asymmetry.
causal_graphs:
- graph_id: gc_skew_replication_strand_asymmetry
  title: GC skew arises from replication-strand mutational asymmetry
  description: Evidence-backed causal sketch linking DNA replication to leading-versus-lagging
    strand compositional asymmetry that marks the replication origin and terminus.
  nodes:
  - node_id: gc_skew_trait
    label: GC skew
    node_type: TRAIT
    grounding: traitmech:000097
    description: Strand asymmetry in guanine versus cytosine content along the replichores.
  - node_id: dna_replication
    label: DNA replication
    node_type: BIOLOGICAL_PROCESS
    grounding: GO:0006260
    description: Semiconservative duplication of the chromosome.
  - node_id: replication_boundary
    label: replication origin / terminus
    node_type: QUALITY
    description: Genomic position where leading/lagging strand identity switches.
  - node_id: lagging_strand_ssdna
    label: lagging-strand single-stranded DNA exposure
    node_type: STATE
    description: Transient ssDNA exposure of the lagging strand during replication.
  - node_id: cytosine_deamination
    label: cytosine deamination at replication forks
    node_type: BIOLOGICAL_PROCESS
    description: Cytosine-to-thymine conversion favored on transiently single-stranded
      DNA at forks.
  - node_id: gene_strand_bias
    label: leading-strand gene density / gene strand bias
    node_type: QUALITY
    description: Biased distribution of genes toward the leading strand of replichores.
  - node_id: translational_selection
    label: translational selection and genetic code constraints
    node_type: BIOLOGICAL_PROCESS
    description: Codon usage and genetic-code constraints shaping asymmetric base
      composition.
  - node_id: third_codon_mutational_bias
    label: third-codon-position mutational bias
    node_type: QUALITY
    description: Mutational bias detectable at the degenerate third codon position.
  - node_id: strand_specific_repair
    label: strand-specific DNA repair
    node_type: BIOLOGICAL_PROCESS
    description: MutSL-dependent mismatch repair and transcription-coupled NER acting
      asymmetrically on strands.
  edges:
  - subject: dna_replication
    predicate: causes
    object: gc_skew_trait
    description: Asymmetric mutation between leading and lagging strands during replication
      produces strand-specific G/C bias.
    evidence:
    - reference: DOI:10.1093/oxfordjournals.molbev.a025626
      notes: Lobry first described replication-linked asymmetric substitution patterns
        between the two DNA strands.
    predicate_id: biolink:causes
  - subject: gc_skew_trait
    predicate: associated with
    object: replication_boundary
    description: GC skew inversions mark the replication origin and terminus.
    evidence:
    - reference: DOI:10.1016/S0378-1119(99)00297-8
      notes: Frank & Lobry review strand-asymmetry signatures used to locate replication
        boundaries.
    predicate_id: biolink:associated_with
  - subject: lagging_strand_ssdna
    predicate: increases
    object: cytosine_deamination
    description: Single-stranded exposure of the lagging strand increases cytosine
      deamination.
    evidence:
    - reference: DOI:10.1101/2023.11.15.567178
      notes: Lagging strand exposed as ssDNA, increasing cytosine-to-thymine mutations
        and thus contributing to GC skew.
    predicate_id: RO:0002213
  - subject: cytosine_deamination
    predicate: contributes to
    object: gc_skew_trait
    description: Cytosine deamination at the replication fork generates strand-specific
      G/C bias.
    evidence:
    - reference: DOI:10.3389/fmicb.2026.1727296
      notes: Cytosine deamination at the replication fork is explicitly implicated
        in generating GC skew.
    predicate_id: RO:0002326
  - subject: gene_strand_bias
    predicate: contributes to
    object: gc_skew_trait
    description: Biased gene density on leading versus lagging strands contributes
      to skew.
    evidence:
    - reference: DOI:10.1101/2023.11.15.567178
      notes: Biased gene density on leading vs lagging strands is highlighted as a
        major contributor to skew.
    predicate_id: RO:0002326
  - subject: translational_selection
    predicate: contributes to
    object: gc_skew_trait
    description: Translational selection and genetic-code constraints shape asymmetric
      G/C distributions.
    evidence:
    - reference: DOI:10.3389/fmicb.2026.1727296
      notes: Translational selection and the nature of the genetic code are universal
        determinants of asymmetric G/C distributions.
    predicate_id: RO:0002326
  - subject: third_codon_mutational_bias
    predicate: contributes to
    object: gc_skew_trait
    description: Mutational bias at the degenerate third codon position contributes
      to strand compositional asymmetry.
    evidence:
    - reference: DOI:10.1007/pl00006428
      notes: Third-position skews probably reflect mutational biases, separating mutational
        from protein-coding constraints.
    predicate_id: RO:0002326
  - subject: strand_specific_repair
    predicate: contributes to
    object: gc_skew_trait
    description: Strand-specific MMR and transcription-coupled NER contribute to strand
      compositional asymmetry.
    evidence:
    - reference: DOI:10.3389/fmicb.2026.1727296
      notes: Strand-specific DNA repair pathways (MutSL-dependent MMR, transcription-coupled
        NER) contribute to asymmetry.
    predicate_id: RO:0002326
curation_history:
- timestamp: '2026-06-05T00:00:00Z'
  curator: claude
  action: PROPOSED_FROM_RESEARCH
  changes: Proposed candidate GENOMICS trait (GC skew) from literature research; distinct
    from the existing GC-content composition bins.
  llm_assisted: true
- timestamp: '2026-06-08T14:00:00Z'
  curator: claude
  action: CURATED_CAUSAL_GRAPH
  changes: Added evidence-backed causal graph (GC skew / replication strand asymmetry)
    with GO node grounding and biolink predicate groundings; promoted PROPOSED to
    REVIEWED.
  llm_assisted: true
- timestamp: '2026-06-23T00:00:00Z'
  curator: claude
  action: ENRICH_CAUSAL_GRAPH
  changes: Added 6 evidence-backed generic edges (6 new nodes) from the deep-research
    report.
  llm_assisted: true
- timestamp: '2026-06-24T17:21:11Z'
  curator: claude
  action: GROUND_CAUSAL_PREDICATES
  changes: Grounded 6 causal-edge predicate_id field(s) via mappings/predicate_grounding.tsv
    (RO:0002326×5, RO:0002213×1).
  llm_assisted: true