title: Species-specific codon context rules unveil non-neutrality effects of synonymous mutations.
abstract: BACKGROUND
  Codon pair usage (codon context) is a species specific gene primary structure feature whose evolutionary and functional roles are poorly understood. The data available show that codon-context has direct impact on both translation accuracy and efficiency, but one does not yet understand how it affects these two translation variables or whether context biases shape gene evolution.
  
  
  RESULTS
  Here we study codon-context biases using a set of 72 orthologous highly conserved genes from bacteria, archaea, fungi and high eukaryotes to identify 7 distinct groups of codon context rules. We show that synonymous mutations, i.e., neutral mutations that occur in synonymous codons of codon-pairs, are selected to maintain context biases and that non-synonymous mutations, i.e., non-neutral mutations that alter protein amino acid sequences, are also under selective pressure to preserve codon-context biases.
  
  
  CONCLUSIONS
  Since in vivo studies provide evidence for a role of codon context on decoding fidelity in E. coli and for decoding efficiency in mammalian cells, our data support the hypothesis that, like codon usage, codon context modulates the evolution of gene primary structure and fine tunes the structure of open reading frames for high genome translational fidelity and efficiency in the 3 domains of life.
authors: RNA Biology Laboratory, Department of Biology and CESAM, University of Aveiro, Aveiro, Portugal. gmoura@ua.pt
authors: Gabriela R
authors: GR
authors: Moura
authors: Miguel
authors: M
authors: Pinheiro
authors: Adelaide
authors: A
authors: Freitas
authors: José L
authors: JL
authors: Oliveira
authors: Jörg C
authors: JC
authors: Frommlet
authors: Laura
authors: L
authors: Carreto
authors: Ana R
authors: AR
authors: Soares
authors: Ana R
authors: AR
authors: Bezerra
authors: Manuel A S
authors: MA
authors: Santos
mesh_terms: D005075:Biological Evolution; D003062:Codon / Q000235:genetics*; D008957:Models, Genetic; D009154:Mutation; D014176:Protein Biosynthesis; D013045:Species Specificity
chemical_list: D003062:Codon