Energy efficiency trade-offs drive nucleotide usage in transcribed regions

Nat Commun. 2016 Apr 21;7:11334. doi: 10.1038/ncomms11334.


Efficient nutrient usage is a trait under universal selection. A substantial part of cellular resources is spent on making nucleotides. We thus expect preferential use of cheaper nucleotides especially in transcribed sequences, which are often amplified thousand-fold compared with genomic sequences. To test this hypothesis, we derive a mutation-selection-drift equilibrium model for nucleotide skews (strand-specific usage of 'A' versus 'T' and 'G' versus 'C'), which explains nucleotide skews across 1,550 prokaryotic genomes as a consequence of selection on efficient resource usage. Transcription-related selection generally favours the cheaper nucleotides 'U' and 'C' at synonymous sites. However, the information encoded in mRNA is further amplified through translation. Due to unexpected trade-offs in the codon table, cheaper nucleotides encode on average energetically more expensive amino acids. These trade-offs apply to both strand-specific nucleotide usage and GC content, causing a universal bias towards the more expensive nucleotides 'A' and 'G' at non-synonymous coding sites.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acids / genetics*
  • Bacteria / genetics*
  • Base Composition
  • Base Pairing
  • Biological Evolution
  • Codon
  • Genome, Bacterial*
  • Models, Genetic
  • Mutation
  • Nucleotides / genetics*
  • Operon
  • Protein Biosynthesis*
  • Selection, Genetic
  • Thermodynamics
  • Transcription, Genetic*


  • Amino Acids
  • Codon
  • Nucleotides