title: Synonymous codon bias and functional constraint on GC3-related DNA backbone dynamics in the prokaryotic nucleoid.
abstract: While mRNA stability has been demonstrated to control rates of translation, generating both global and local synonymous codon biases in many unicellular organisms, this explanation cannot adequately explain why codon bias strongly tracks neighboring intergene GC content; suggesting that structural dynamics of DNA might also influence codon choice. Because minor groove width is highly governed by 3-base periodicity in GC, the existence of triplet-based codons might imply a functional role for the optimization of local DNA molecular dynamics via GC content at synonymous sites (≈GC3). We confirm a strong association between GC3-related intrinsic DNA flexibility and codon bias across 24 different prokaryotic multiple whole-genome alignments. We develop a novel test of natural selection targeting synonymous sites and demonstrate that GC3-related DNA backbone dynamics have been subject to moderate selective pressure, perhaps contributing to our observation that many genes possess extreme DNA backbone dynamics for their given protein space. This dual function of codons may impose universal functional constraints affecting the evolution of synonymous and non-synonymous sites. We propose that synonymous sites may have evolved as an 'accessory' during an early expansion of a primordial genetic code, allowing for multiplexed protein coding and structural dynamic information within the same molecular context.
authors.affiliation: Thomas H. Gosnell School of Life Sciences, Rochester Institute of Technology, Rochester NY, USA 14623 gabsbi@rit.edu.
authors.forename: Gregory A
authors.initials: GA
authors.lastname: Babbitt
authors.affiliation: B. Thomas Golisano College of Computing and Information Sciences, Rochester Institute of Technology, Rochester NY, USA 14623.
authors.forename: Mohammed A
authors.initials: MA
authors.lastname: Alawad
authors.affiliation: Department of Molecular and Human Genetics, Baylor College of Medicine, Houston TX, USA 77030.
authors.forename: Katharina V
authors.initials: KV
authors.lastname: Schulze
authors.affiliation: Thomas H. Gosnell School of Life Sciences, Rochester Institute of Technology, Rochester NY, USA 14623.
authors.forename: André O
authors.initials: AO
authors.lastname: Hudson
mesh_terms: D001426:Bacterial Proteins / Q000235:genetics; D001482:Base Composition; D003062:Codon; D004247:DNA / Q000737:chemistry*; D048028:DNA, Algal / Q000737:chemistry; D019641:DNA, Archaeal / Q000737:chemistry; D004269:DNA, Bacterial / Q000737:chemistry; D016678:Genome; D009154:Mutation; D012641:Selection, Genetic; D000637:Transaminases / Q000235:genetics
chemical_list: D001426:Bacterial Proteins; D003062:Codon; D048028:DNA, Algal; D019641:DNA, Archaeal; D004269:DNA, Bacterial; D004247:DNA; D000637:Transaminases