Whole cell biophysical modeling of codon-tRNA competition reveals novel insights related to translation dynamics
Fig 4
The model promotes understanding and provides analysis framework for heterologous expression problems.
(A) Total E. coli and GFP genes termination rates for various GFP variants as heterologous genes. Two method were used for variant generation, as described in the sub section Heterologous expression in the Methods. The original variant is shown in orange. Smaller blue dots are related to variants in which one codon was chosen as substituted all synonymous codons (61 such variants in total). Other dots represent variants in which a single representing codon was chosen for each amino acid, according to some optimality score (either TDR, ESDR or inverse occupancy). (B) Two variants (marked with arrows in (A)) are compared in terms of ESDR. Codons for which the ESDR is different represent changes in supply and demand of associated tRNAs and allow to understand the results in (A). (C) Comparison of three optimization variants in terms of their ESDR, per codon, relative to the unoptimized variant (red represents a higher ESDR value). Some codons (such as CCC) exhibit an increase in ESDR in all variants, indicating that increasing the supply/demand for these codons can improve overall translational efficiency.