An Evolutionarily Conserved Mechanism for Controlling the Efficiency of Protein Translation

Recent years have seen intensive progress in measuring protein translation. However, the contributions of coding sequences to the efficiency of the process remain unclear. Here, we identify a universally conserved profile of translation efficiency along mRNAs computed based on adaptation between coding sequences and the tRNA pool. In this profile, the first ∼30–50 codons are, on average, translated with a low efficiency. Additionally, in eukaryotes, the last ∼50 codons show the highest efficiency over the full coding sequence. The profile accurately predicts position-dependent ribosomal density along yeast genes. These data suggest that translation speed and, as a consequence, ribosomal density are encoded by coding sequences and the tRNA pool. We suggest that the slow “ramp” at the beginning of mRNAs serves as a late stage of translation initiation, forming an optimal and robust means to reduce ribosomal traffic jams, thus minimizing the cost of protein expression. [Display omitted] [Display omitted] ► The efficiency of translation is universally lower across the first ∼50 codons ► Evolutionary forces act to maintain this profile of translation elongation speed ► The profile is predictive of ribosome density for translation of yeast genes ► The ramp in efficiency may contribute to fitness and managing the cost of translation