title: Effects of codon sequence on the dynamics of genetic networks.
abstract: In prokaryotes, the rate at which codons are translated varies from one codon to the next. Using a stochastic model of transcription and translation at the nucleotide and codon levels, we investigate the effects of the codon sequence on the dynamics of protein numbers. For sequences generated according to the codon frequencies in Escherichia coli, we find that mean protein numbers at near equilibrium differ with the codon sequence, due to the mean codon translation efficiencies, in particular of the codons at the ribosome binding site region. We find close agreement between these predictions and measurements of protein expression levels as a function of the codon sequence. Next, we investigate the effects of short codon sequences at the start/end of the RNA sequence with linearly increasing/decreasing translation efficiencies, known as slow ramps. The ramps affect the mean, but not the fluctuations, in proteins numbers by affecting the rate of translation initiation. Finally, we show that slow ramps affect the dynamics of small genetic circuits, namely, switches and clocks. In switches, ramps affect the frequency of switching and bias the robustness of the noisy attractors. In repressilators, ramps alter the robustness of periodicity. We conclude that codon sequences affect the dynamics of gene expression and genetic circuits and, thus, are likely to be under selection regarding both mean codon frequency as well as spatial arrangement along the sequence.
authors.affiliation: Computational Systems Biology Research Group, Department of Signal Processing, Tampere University of Technology, P.O. Box 527, FIN-33101, Finland. ilya.potapov@tut.fi
authors.forename: Ilya
authors.initials: I
authors.lastname: Potapov
authors.forename: Jarno
authors.initials: J
authors.lastname: Mäkelä
authors.forename: Olli
authors.initials: O
authors.lastname: Yli-Harja
authors.forename: Andre S
authors.initials: AS
authors.lastname: Ribeiro
mesh_terms: D001483:Base Sequence; D003062:Codon / Q000235:genetics*; D004926:Escherichia coli / Q000235:genetics*; D029968:Escherichia coli Proteins / Q000235:genetics / Q000378:metabolism; D005583:Fourier Analysis; D015964:Gene Expression Regulation, Bacterial; D053263:Gene Regulatory Networks / Q000235:genetics*; D007700:Kinetics; D008957:Models, Genetic; D014176:Protein Biosynthesis / Q000235:genetics; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D014158:Transcription, Genetic
chemical_list: D003062:Codon; D029968:Escherichia coli Proteins; D012333:RNA, Messenger