Biology & Life Sciences

Synonymous codon choice is non-random and has been linked to translation speed, but whether local codon usage is organised to assist cotranslational folding remains contested. We state a precise, falsifiable hypothesis: rare-codon clusters should be enriched immediately downstream of domain boundaries, where a translational pause would let a completed domain fold before the next is synthesised. We test this prediction purely by re-analysing publicly available ribosome-profiling and structural-domain datasets, with all processing steps and statistics specified for reproduction. We report the analysis design and the controls that would distinguish the folding hypothesis from confounders such as mRNA structure and amino-acid composition. No new experiments were performed; the contribution is a sharpened hypothesis and a transparent reanalysis protocol.