GC skew

Edge evidence

• DNA replication causes GC skew biolink:causes

  Asymmetric mutation between leading and lagging strands during replication produces strand-specific G/C bias.

  • DOI:10.1093/oxfordjournals.molbev.a025626 Lobry first described replication-linked asymmetric substitution patterns between the two DNA strands.
• GC skew associated with replication origin / terminus biolink:associated_with

  GC skew inversions mark the replication origin and terminus.

  • DOI:10.1016/S0378-1119(99)00297-8 Frank & Lobry review strand-asymmetry signatures used to locate replication boundaries.
• lagging-strand single-stranded DNA exposure increases cytosine deamination at replication forks RO:0002213

  Single-stranded exposure of the lagging strand increases cytosine deamination.

  • DOI:10.1101/2023.11.15.567178 Lagging strand exposed as ssDNA, increasing cytosine-to-thymine mutations and thus contributing to GC skew.
• cytosine deamination at replication forks contributes to GC skew RO:0002326

  Cytosine deamination at the replication fork generates strand-specific G/C bias.

  • DOI:10.3389/fmicb.2026.1727296 Cytosine deamination at the replication fork is explicitly implicated in generating GC skew.
• leading-strand gene density / gene strand bias contributes to GC skew RO:0002326

  Biased gene density on leading versus lagging strands contributes to skew.

  • DOI:10.1101/2023.11.15.567178 Biased gene density on leading vs lagging strands is highlighted as a major contributor to skew.
• translational selection and genetic code constraints contributes to GC skew RO:0002326

  Translational selection and genetic-code constraints shape asymmetric G/C distributions.

  • DOI:10.3389/fmicb.2026.1727296 Translational selection and the nature of the genetic code are universal determinants of asymmetric G/C distributions.
• third-codon-position mutational bias contributes to GC skew RO:0002326

  Mutational bias at the degenerate third codon position contributes to strand compositional asymmetry.

  • DOI:10.1007/pl00006428 Third-position skews probably reflect mutational biases, separating mutational from protein-coding constraints.
• strand-specific DNA repair contributes to GC skew RO:0002326

  Strand-specific MMR and transcription-coupled NER contribute to strand compositional asymmetry.

  • DOI:10.3389/fmicb.2026.1727296 Strand-specific DNA repair pathways (MutSL-dependent MMR, transcription-coupled NER) contribute to asymmetry.