Frydman Lab | Stanford University

Supplementary Information for

Pechmann S & Frydman J Evolutionary conservation of codon optimality reveals hidden signatures of co-translational folding. Nat Struct Mol Biol (2012) | doi:10.1038/nsmb.2466

The choice of codons can influence local translation kinetics during protein synthesis. Whether codon preference is linked to co-translational regulation of polypeptide folding remains unclear. Here, we derive a revised translational efficiency scale that takes into account the competition between tRNA supply and demand, which allows us to uncover the evolutionary conservation of codon optimality across ten yeasts. This analysis reveals distinct and universal patterns of conserved optimal and nonoptimal codons, which associate with the secondary structure of the translated polypeptides independent of the levels of expression. Our analysis thus suggests an evolved function for codon optimality in regulating the rhythm of elongation to facilitate co-translational nascent chain folding, beyond its previously proposed role of adapting to the cost of expression. These findings establish how mRNA sequences are generally under selection to optimize the co-translational folding of corresponding polypeptides.

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Supplementary data

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Translational efficiency scales for 10 closely related yeasts

cTE - Classical translational efficiency scales (tRNA adaptation index)
nTE - Normalized translational efficiency scales

Tables of optimal and nonoptimal codons for 10 closely related yeasts

Evolutionary conservation profiles of codon optimality

Q:	Where do I find a detailed description of the methods and datasets?
A:	Detailed materials and methods are included in the original publication. Please contact us for any further questions or requests for reprints at codonoptimality[at]gmail.com.

Q:	Why does the current dataset not cover the full genome?
A:	We included in this original study only yeast species for which genomic sequences and expression levels were available to compute the codon usage. We required a minimum of 7 orthologous sequences per alignment to compute meaningful conservation scores, and discarded alignments with too many gaps.

Q:	Can you add other organisms?
A:	Please contact us if you find this webserver useful and would like to see additional organisms added to compute translational efficiency profiles.

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