Slow Translation of the 5’ ends of genes may be a non-adaptive consequence of their rapid evolutionary turn-over and slow loss of rare codons

Previously, Tuller et al. found that the first 30 to 100 codons of the genes of yeast and other eukaryotes are slightly enriched for rare codons, and are presumably translated somewhat slowly. They argued, based on informatics, that this initial slow translation “ramp” was adaptive; and that it increased the efficiency of translation by provided a queuing mechanism to prevent ribosome collisions and traffic jams. Today, the translational speeds of the various codons are known, and there is a strong correlation between rare codon usage and slow translation speed. We have re-examined the slow translation ramp. We confirm the finding of Tuller et al. that a region of slow translation exists. However, we also find that the 5’ ends of yeast genes are poorly conserved, suggesting that they are unstable in evolution and turn over relatively rapidly. When a new 5’ end forms de novo , it is likely to include codons that would otherwise be rare. Because evolution has had a relatively short time to select against these codons, 5’ ends are typically slightly enriched for rare, slow codons. Opposite to the expectation of Tuller et al., we show by direct experiment that genes with slowly translated 5’ ends are translated poorly compared to genes with rapidly translated 5’ ends. Thus we conclude that slow 5’ translation may be a “spandrel”; it is a non-adaptive consequence of something else, in this case the turnover of 5’ ends in evolution. ### Competing Interest Statement The authors have declared no competing interest.