Protein Sequences Recapitulate Genetic Code Evolution.

Area of Science:

• Biochemistry
• Molecular Biology
• Evolutionary Biology

Background:

• The genetic code assigns codons to amino acids, with hypotheses predicting specific assignment ranks.
• Understanding these assignments is crucial for deciphering protein evolution and function.

Purpose of the Study:

• To investigate the correlation between amino acid assignment ranks and their positions within protein sequences.
• To test if Juke's neutral mutation hypothesis explains observed amino acid distribution patterns.
• To explore the potential role of amino acid sequence gradients in protein folding and stability.

Main Methods:

• Analysis of average amino acid positions in various protein groups.
• Comparison of amino acid positions with predicted assignment ranks based on evolutionary hypotheses.
• Examination of pairwise residue contact energies to infer selection pressures.
• Investigation of protein sequence gradients from the 5' to 3' gene extremities.

Main Results:

• A significant correlation was found between amino acid assignment ranks and their average positions in proteins.
• 'Recent' amino acids appear closer to the 5' end of genes than 'ancient' ones across tested protein groups.
• Stereochemical selection of early amino acids by later ones stabilizes protein cores, creating sequence gradients.
• These gradients may mitigate protein misfolding, even after mutations.

Conclusions:

• The study supports Juke's neutral mutation hypothesis for codon assignments and demonstrates its extension to protein folding.
• Amino acid sequence gradients (5'-late-to-3'-early) likely play a role in protein structure stability and folding.
• The findings suggest an apparent teleonomy between the genetic code's evolution and protein structure development.