What’s the cost of a slip in translation?
Programmed ribosomal frameshifting has translational costs that may influence codon usage bias.
The genetic code has some redundancy—the same amino acid is often encoded by several codons. However, these codons are not necessarily equal in their effect, as evidenced by the codon usage bias observed in many organisms. The translation efficiency hypothesis posits that some codons are more easily translated than others, and these are the ones more commonly used. Based on this hypothesis, the codon usage bias index of a given mRNA should correlate closely with its translation efficiency—but in a report in G3: Genes|Genomes|Genetics, Garcia et al. explain why this might not always be the case.
Programmed ribosomal frameshifting (PRF) occurs when a ribosome stalls at specific sequences—appropriately termed “slippery sites”—which shifts translation to a new reading frame. The authors were specifically interested in “-1 PRF” cases, where the ribosome moves a single nucleotide backward during translation. This phenomenon is ubiquitous across the tree of life, and it is generally used by eukaryotes as a way to regulate gene expression, but the authors wondered if it could also induce translational costs.
To test this, they used the database PRFdb to examine associations between -1 PRF signals and gene expression in yeast, determining that -1 PRF signals are less common in highly expressed genes. They also found that these signals tend to be present towards the start of open reading frames, which makes sense if the -1 PRF signals are causing translational costs—if the signals occur towards the start of the mRNA, translation is disrupted more quickly, so less energy is wasted. These lines of evidence support the idea that PRF signals do incur translational costs.
The authors then retested the association between codon usage bias and translational efficiency while accounting for the cost of -1 PRF signals. Using a set of mathematical models, they found that incorporating this data generally strengthened support of the translational efficiency hypothesis—that is, more costly transcripts were less often translated, whether the cost was incurred due to codon usage bias or -1 PRF signals. Better understanding these phenomena may help elucidate how translational efficiency is controlled.
Accounting for Programmed Ribosomal Frameshifting in the Computation of Codon Usage Bias Indices
Victor Garcia, Stefan Zoller, Maria Anisimova