Recombination, meiotic expression and human codon usage

Elife. 2017 Aug 15;6:e27344. doi: 10.7554/eLife.27344.


Synonymous codon usage (SCU) varies widely among human genes. In particular, genes involved in different functional categories display a distinct codon usage, which was interpreted as evidence that SCU is adaptively constrained to optimize translation efficiency in distinct cellular states. We demonstrate here that SCU is not driven by constraints on tRNA abundance, but by large-scale variation in GC-content, caused by meiotic recombination, via the non-adaptive process of GC-biased gene conversion (gBGC). Expression in meiotic cells is associated with a strong decrease in recombination within genes. Differences in SCU among functional categories reflect differences in levels of meiotic transcription, which is linked to variation in recombination and therefore in gBGC. Overall, the gBGC model explains 70% of the variance in SCU among genes. We argue that the strong heterogeneity of SCU induced by gBGC in mammalian genomes precludes any optimization of the tRNA pool to the demand in codon usage.

Keywords: biased gene conversion; codon Usage; evolutionary biology; genomics; human; meiosis; recombination; translational selection.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Base Composition
  • Codon*
  • Gene Conversion*
  • Genetic Code*
  • Genetic Variation
  • Genome, Human
  • Humans
  • Meiosis*
  • Models, Genetic*
  • RNA, Transfer / genetics
  • RNA, Transfer / metabolism


  • Codon
  • RNA, Transfer

Grant support

The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.