title: Unique cost dynamics elucidate the role of frameshifting errors in promoting translational robustness.
abstract: There is now considerable evidence supporting the view that codon usage is frequently under selection for translational accuracy. There are, however, multiple forms of inaccuracy (missense, premature termination, and frameshifting errors) and pinpointing a particular error process behind apparently adaptive mRNA anatomy is rarely straightforward. Understanding differences in the fitness costs associated with different types of translational error can help us devise critical tests that can implicate one error process to the exclusion of others. To this end, we present a model that captures distinct features of frameshifting cost and apply this to 641 prokaryotic genomes. We demonstrate that, although it is commonly assumed that the ribosome encounters an off-frame stop codon soon after the frameshift and costs of mis-elongation are therefore limited, genomes with high GC content typically incur much larger per-error costs. We go on to derive the prediction, unique to frameshifting errors, that differences in translational robustness between the 5' and 3' ends of genes should be less pronounced in genomes with higher GC content. This prediction we show to be correct. Surprisingly, this does not mean that GC-rich organisms necessarily carry a greater fitness burden as a consequence of accidental frameshifting. Indeed, increased per-error costs are often more than counterbalanced by lower predicted error rates owing to more diverse anticodon repertoires in GC-rich genomes. We therefore propose that selection on tRNA repertoires may operate to reduce frameshifting errors.
authors.affiliation: Department of Biology and Biochemistry, University of Bath, Bath, United Kingdom.
authors.forename: Tobias
authors.initials: T
authors.lastname: Warnecke
authors.forename: Yang
authors.initials: Y
authors.lastname: Huang
authors.forename: Teresa M
authors.initials: TM
authors.lastname: Przytycka
authors.forename: Laurence D
authors.initials: LD
authors.lastname: Hurst
mesh_terms: D001482:Base Composition / Q000235:genetics; D016368:Frameshift Mutation / Q000235:genetics*; D008957:Models, Genetic; D014176:Protein Biosynthesis / Q000235:genetics*; D012343:RNA, Transfer / Q000235:genetics
chemical_list: D012343:RNA, Transfer