RNA folding is unaffected by the nonrandom degenerate codon choice.

The frequent suggestion that the nonrandom codon usage is explained by its forming more stable mRNAs is tested in 22 genes. Only the histones, globins, and the rat preproinsulin gene show a correlation between the preferred degenerate codons and the stability of the secondary structure of the their mRNAs. However, the examined members from the histone and globin gene families, both among the oldest, in evolutionary sense, eukaryotic genes, have a high GC content (approx. 56% compared to an average of 42% in all eukaryotes) which is reflected in their degenerate codon choice and thus in their more stable folding.