GC content

METPO:1000127 · CLASS · REVIEWED

A quality that is describing the percentage of guanine and cytosine nucleotides in genomic DNA, calculated as the ratio of GC base pairs to total base pairs.

GC content composition drivers

DOI-backed graph linking mutation bias, GC-biased gene conversion, and selection on codon usage to the genome-wide GC content phenotype, with `is a` edges to the four METPO GC-content bins.

GC content composition drivers Interactive directed graph showing evidence-backed causal relationships for GC content.

Edge evidence

  • genomic DNA carries GC content

    Genomic DNA is the substrate on which the GC content phenotype is measured.

    • DOI:10.1038/nrg2358 GC content Supports GC content as a property of the genomic DNA sequence.
  • GC/AT mutation bias causes GC content biolink:causes

    Asymmetric GC/AT mutation bias shapes the equilibrium genome-wide GC content.

    • DOI:10.1186/1471-2148-10-374 mutation bias Supports mutation bias as a primary driver of bacterial GC content.
  • GC-biased gene conversion causes GC content biolink:causes

    GC-biased gene conversion elevates GC content at recombination hotspots and across the genome.

    • DOI:10.1186/1471-2148-10-374 GC-biased gene conversion Supports GC-biased gene conversion as a recombination-driven contributor to GC content.
  • selection on codon usage contributes to GC content RO:0002326

    Selection on synonymous codon usage contributes to genome-wide GC content patterns.

    • DOI:10.1038/nrg2358 codon usage Supports translational selection on codon usage as a contributor to GC composition.
  • GC high is a GC content rdfs:subClassOf

    GC high is a quantitative bin of the GC-content phenotype.

    • DOI:10.1038/nrg2358 GC content Supports the binned phenotype as a value within the GC-content distribution.
  • GC low is a GC content rdfs:subClassOf

    GC low is a quantitative bin of the GC-content phenotype.

    • DOI:10.1038/nrg2358 GC content Supports the binned phenotype as a value within the GC-content distribution.
  • GC mid1 is a GC content rdfs:subClassOf

    GC mid1 is a quantitative bin of the GC-content phenotype.

    • DOI:10.1038/nrg2358 GC content Supports the binned phenotype as a value within the GC-content distribution.
  • GC mid2 is a GC content rdfs:subClassOf

    GC mid2 is a quantitative bin of the GC-content phenotype.

    • DOI:10.1038/nrg2358 GC content Supports the binned phenotype as a value within the GC-content distribution.
  • cytosine deamination decreases GC content RO:0002212

    Cytosine deamination introduces GC-to-AT changes, reducing genome-wide GC content.

    • DOI:10.1128/spectrum.02145-22 cytosine deamination reduces the GC content Strong mechanistic statement from bacterial comparative study; general mutation-bias edge.
  • guanine oxidation (8-oxoG) decreases GC content RO:0002212

    Guanine oxidation (8-oxoG) promotes G:C to A:T mispairing, biasing composition toward lower GC.

    • DOI:10.1128/spectrum.02145-22 guanine oxidation (8OG) causes A mis-pairing Source-backed oxidative-damage mechanism shifting the mutational spectrum toward AT.
  • DNA replication and repair (DRR) system change causes GC content biolink:causes

    Changes in the DNA replication and repair system drive mutational biases that shape GC-content evolution.

    • DOI:10.1128/spectrum.02145-22 ancient adaptations transformed the DRR system, producing mutational biases that shaped GC-content evolution Core, directly stated high-level mechanistic edge for the mutation-bias module.
  • error-prone translesion synthesis increases GC content RO:0002213

    Error-prone translesion synthesis polymerases are causally linked to increases in genomic GC content.

    • DOI:10.1128/spectrum.02145-22 Error-prone polymerases are causally linked to increases in genomic GC Direction explicit in comparative study; complements existing mutation-bias drivers.

Provenance

Source
METPO (2025-11-25)
Author
Luke Wang
Definition source
DOI:10.1038/nrg2358

Parent traits (1)

kg-microbe context

Matched 1 kg-microbe node via direct_metpo.

  • METPO:1000127 [-0.539, -1.149, -2.445, +1.588, …]

512-dim DeepWalkSkipGramEnsmallen embedding from kg-microbe (2026-04-25).

Nearest neighbors in embedding space

Top-8 cosine-similar METPO traits from the 2026-04-25 deepwalk (512-D).

Deep research

Generated by just research-trait; source: research/traits/genomics/gc_content-deep-research-falcon.md

Unreviewed literature output — not curated TraitMech content Ontology identifiers suggested below have not been resolved against their ontologies, and some are known to be wrong. Check any CURIE against the source before using it.
# Curation report: microbial GC content

## Executive summary

**Target trait:** **GC content**  
**Trait CURIE:** **“METPO:1000127”**  
**Category/kind/status:** GENOMICS / CLASS / REVIEWED  
**Parent:** METPO:1000188

GC content is a quantitative genome-composition property: the fraction of genomic DNA nucleotides that are guanine or cytosine, normally reported as `100 × (G+C)/(A+T+G+C)`. It is an assay-derived genomic descriptor rather than a physiological activity. Published prokaryotic ranges vary with dataset and inclusion criteria: approximately 16–77% in a 2023 large-scale analysis and 8–75% in a 2022 survey. The latter extreme likely reflects highly reduced genomes and emphasizes the need to record assembly type, completeness, and taxonomic scope. (hu2022apositivecorrelation pages 1-2, aliperti2023rkselectionof pages 1-3)

The most defensible TraitMech core is:

1. biased mutation supplies unequal AT↔GC changes, with a broad bacterial excess of GC→AT mutation pressure;
2. homologous recombination can produce **GC-biased gene conversion** (gBGC), a fixation bias favoring G/C alleles;
3. mutation bias and gBGC jointly move long-term genomic GC content in opposing directions;
4. replication and repair machinery modifies mutation/fixation spectra, but individual-gene claims such as `dnaE2 → high GC` or `polC → low GC` remain comparative and lineage-dependent;
5. horizontal acquisition introduces local compositional deviations, which may subsequently ameliorate toward host composition.

Temperature, genome size, lifestyle, endosymbiosis, and ecological r/K strategy are important associations, but most should not yet be represented as direct, universal causes.

| priority | subject (with safe CURIE if available) | predicate | object | evidence strength | key qualifier |
|---|---|---|---|---|---|
| 1 | AT-biased mutation spectrum | decreases | METPO:1000127 genomic GC content | strong (hershberg2015mutation—theengineof pages 6-7, lassalle2015gccontentevolutionin pages 4-6) | Broad bacterial pattern; mutation pressure alone predicts lower GC than observed |
| 1 | GO:0006310 DNA recombination | enables | GC-biased gene conversion | strong (lassalle2015gccontentevolutionin pages 4-6, lassalle2015gccontentevolutionin pages 6-9) | Supported by higher GC in recombinant genes/regions; mechanism inferred from recombination-associated fixation bias |
| 1 | GC-biased gene conversion | increases fixation of | G/C alleles | strong (lassalle2015gccontentevolutionin pages 9-11, lassalle2015gccontentevolutionin pages 11-14) | Acts during homologous recombination repair; can mimic natural selection |
| 1 | GC-biased gene conversion | increases | METPO:1000127 genomic GC content | strong (lassalle2015gccontentevolutionin pages 4-6, lassalle2015gccontentevolutionin pages 9-11) | Best-supported counterforce to universal AT-biased mutation; not necessarily universal in every lineage |
| 2 | dnaE2 (label only) | associated with increased | METPO:1000127 genomic GC content | moderate (wu2012onthemolecular pages 2-4) | Taxon-dependent comparative association, not a universally validated direct mechanism |
| 2 | polC (label only) / replication-repair machinery | associated with decreased | METPO:1000127 genomic GC content | moderate (wu2012onthemolecular pages 2-4) | Comparative genomic signal; mechanism remains unresolved and lineage-specific |
| 2 | Horizontal gene transfer | creates local deviation in | genomic GC composition | moderate (lassalle2015gccontentevolutionin pages 14-16, hayek2013lateraltransferand pages 2-3) | Best curated as local/regional GC heterogeneity or foreign-DNA signal, not direct whole-genome GC change |
| 3 | ENVO:09200013 optimal growth temperature | associated with increased | METPO:1000127 genomic GC content | moderate/uncertain (hu2022apositivecorrelation pages 1-2, wu2012onthemolecular pages 2-4) | Correlation reported, but debated and confounded by phylogeny, sample size, and indirect repair effects |
| 4 | genome size | correlated with | METPO:1000127 genomic GC content | moderate/noncausal (wu2012onthemolecular pages 2-4, aliperti2023rkselectionof pages 3-6) | Association should not be curated as direct causation without mechanism |
| 4 | ecological r/K selection regime (label only) | correlated with | METPO:1000127 genomic GC content | moderate/noncausal (aliperti2023rkselectionof pages 6-9, aliperti2023rkselectionof pages 9-11) | Recent broad comparative hypothesis; useful for context, not yet safe as TraitMech causal edge |


*Table: This table prioritizes the most curation-ready causal and associative edges for microbial genomic GC content. It separates strong mechanistic edges from broader comparative correlations that should be treated cautiously in TraitMech.*

## 1. Trait scope and boundary cases

### 1.1 Included phenotype

For `“METPO:1000127”`, the preferred observable is **whole-genome DNA GC percentage**, calculated over an assembled chromosome or an explicitly defined genome aggregate. For multipartite genomes, curation should state whether the value covers the chromosome only, all chromosomes, or chromosomes plus plasmids. GC content is relatively stable within a lineage and therefore acts as a genomic signature, while varying widely among prokaryotic species. A 2023 review distinguishes simple nucleotide concentration from higher-order di- and tetranucleotide signatures, the latter providing stronger taxonomic discrimination. (fuente2023genomicsignaturein pages 13-15)

Recommended value model:

```text
GC_percent = 100 × (count(G) + count(C)) / count(A + C + G + T)
```

Ambiguous bases should be excluded from the denominator or handled under a declared assay convention.

### 1.2 Excluded or separately modeled nearby traits

- **GC3:** GC fraction at third codon positions. It is especially responsive to synonymous substitutions and was the principal response variable in several recombination/gBGC analyses; it is not identical to whole-genome GC content. (lassalle2015gccontentevolutionin pages 9-11, lassalle2015gccontentevolutionin pages 6-9)
- **GC1 and GC2:** first- and second-codon-position composition, more constrained by protein sequence.
- **Gene, window, contig, plasmid, or genomic-island GC:** local measurements that can identify compositional heterogeneity but should not automatically be treated as organism-level GC content.
- **RNA or structural-RNA GC content:** mechanistically relevant to RNA stability, but distinct from genomic DNA GC%. Temperature associations can differ between structural RNA and whole genomes. (hu2022apositivecorrelation pages 1-2)
- **GC skew:** `(G−C)/(G+C)`, a strand-asymmetry measure used to investigate replication; it is not GC percentage.
- **Codon-usage bias:** influenced by genomic composition, mutation, selection, and gBGC, but it is a separate trait. Recombinant GC enrichment can occur independently of optimal-codon selection. (lassalle2015gccontentevolutionin pages 4-6, lassalle2015gccontentevolutionin pages 6-9)
- **Melting temperature or DNA thermostability:** molecular properties affected by sequence, length, salt, and context; they should not be equated with genomic GC content.

Showing the first 60 of 261 lines of findings; the linked file also carries the run's front matter and the prompt it was given — read the full report.

Curation history

  1. · SEEDED_FROM_METPO · seed_from_metpo

    imported from data/raw/metpo.owl (CLASS)

  2. · CURATED_CAUSAL_GRAPH · claude

    Added DOI-backed causal graph linking mutation bias, GC-biased gene conversion, and codon-usage selection to the GC-content phenotype, with is-a edges to the four METPO GC-content bins.

  3. · GROUND_CAUSAL_PREDICATES · claude

    Grounded 5 causal-edge predicate_id field(s) via mappings/predicate_grounding.tsv (rdfs:subClassOf×4, RO:0002326×1).

  4. · RENAME_PREDICATE_LABELS · claude

    Renamed 2 causal-edge predicate label(s) to align with existing groundings: shapes → causes ×2.

  5. · GROUND_CAUSAL_PREDICATES · claude

    Grounded 2 causal-edge predicate_id field(s) via mappings/predicate_grounding.tsv (biolink:causes×2).

  6. · ENRICH_CAUSAL_GRAPH · claude

    Added 4 evidence-backed generic edges (4 new nodes) from the deep-research report.

  7. · GROUND_CAUSAL_PREDICATES · claude

    Grounded 4 causal-edge predicate_id field(s) via mappings/predicate_grounding.tsv (RO:0002212×2, biolink:causes×1, RO:0002213×1).

  8. · GROUND_CAUSAL_NODES · claude

    Grounded 1 causal-node grounding field(s) via mappings/node_grounding.tsv (GO:0042276×1).