The Effects of Transgene Codon Bias on the Pool of Free Ribosomes
(A and B) As in Figure 2, we simulated translation of a transgene added to a wild-type yeast cell. Transgene mRNA levels were set at 1%, 10%, or 50% of all cellular mRNA. We measured the equilibrium fraction of ribosomes that are free (unbound). Increasing codon bias of the transgene reduces the number of ribosomes bound to its transcripts and thereby increases the pool of free ribosomes (A), especially when the transgene accounts for a large proportion of all cellular mRNA. For example, when transgene mRNAs comprise 50% of the total transcriptome, then optimizing codon bias of the transgene from CAI ≈ 0 to CAI ≈ 1 causes a 3.2-fold increase in the number of free ribosomes (triangles in [B]), which explains a large proportion of the corresponding gain in transprotein production. See also Table S4.