Protein Sequences Recapitulate Genetic Code Evolution

Several hypotheses predict ranks of amino acid assignments to genetic code's codons. Analyses here show that average positions of amino acid species in proteins correspond to assignment ranks, in particular as predicted by Juke's neutral mutation hypothesis for codon assignments. In all tested protein groups, including co- and post-translationally folding proteins, ‘recent’ amino acids are on average closer to gene 5′ extremities than ‘ancient’ ones. Analyses of pairwise residue contact energies matrices suggest that early amino acids stereochemically selected late ones that stablilize residue interactions within protein cores, presumably producing 5′-late-to-3′-early amino acid protein sequence gradients. The gradient might reduce protein misfolding, also after mutations, extending principles of neutral mutations to protein folding. Presumably, in self-perpetuating and self-correcting systems like the genetic code, initial conditions produce similarities between evolution of the process (the genetic code) and ‘ontogeny’ of resulting structures (here proteins), producing apparent teleonomy between process and product.