A Computational Investigation on Properties of the Standard Genetic Code with Implications for its Origin

Abstract

The amino acid blueprints for many essential biomolecules, including proteins like immunoglobulins, insulin, metabolic enzymes, electron transporters, and structural molecules, are encoded within the standard genetic code (SGC). These blueprints are stored in nucleic acids such as DNA or RNA and translated into amino acids by tRNA and ribosomes. Investigations into the origins of and principles guiding SGC structure have been performed since the 1960s, with a majority revealing that amino acids with similar physicochemical properties are to assigned triplet codons with similar nucleotides. A significant amount of degeneracy is seen particularly at the third position of most codons, leading to hypotheses that buffering against transcriptional and translational error was the driving force behind SGC structure. In this study, we review some prominent theories on the origins of the triplet codon system and possible mechanisms for how those codons became assigned to amino acids and examine briefly non-bonding forces and their effects on amino acid interactions. A computational program was developed to run simulations comparing the SGC to other, hypothetical genetic codes (HGCs), generated by shuffling amino acid identities among codon blocks and performing error measure calculations. The SGC was ranked against the HGCs for 54 properties. Shuffling of stop codon positions was implemented for only the second time with such analyses. When stop codons were included in error measure calculations, minimum, zero, and maximum penalties were assigned to nonsense mutations. Long-range non-bonded energy was found to be the most conserved property when accounting for stop codon effects.