Translationally optimal codons associate with aggregation-prone sites in proteins

We analyze the relationship between codon usage bias and residue aggregation propensity in the genomes of four model organisms Escherichia colt yeast fly and mouse as well as the archaeon Halobacterium species NRC 1 Using the Mantel-Haenszel procedure we find that translationally optimal codons associate with aggregation prone residues Our results are qualitatively and quantitatively similar to those of an earlier study where we found an association between translationally optimal codons and buried residues We also combine the aggregation propensity data with solvent accessibility data Although the resulting data set is small and hence statistical power low results indicate that the association between optimal codons and aggregation prone residues exists both at buried and at exposed sites By comparing codon usage at different combinations of sites (exposed aggregation prone sites versus buried, non aggregation prone sites buried, aggregation prone sites versus exposed non aggregation prone sites) we find that aggregation propensity and solvent accessibility seem to have independent effects of (on average) comparable magnitude on codon usage Finally m fly we assess whether optimal codons associate with sites at which amino acid substitutions lead to an increase m aggregation propensity and find only a very weak effect These results suggest that optimal codons may be required to reduce the frequency of translation errors at aggregation prone sites that coincide with certain functional sites such as protein protein interfaces Alternatively optimal codons may be required for rapid translation of aggregation prone regions