The Standard Genetic Code Predominantly Assigns Uracil-Containing Codons to Amino Acids Enriched in Transmembrane Domains and Uracil-Free Codons to Amino Acids Enriched in Intrinsically Disordered Regions

Abstract

All organisms on Earth share a nearly identical genetic code, and the most typical one is called the standard genetic code. In previous research, based on the results of studies of possible inverse translation of the genetic code applied to various protein amino acid sequences, I proposed the idea that the genetic code uses local thymine density in the gene sequence to determine the presence of transmembrane domains (TMDs) or intrinsically disordered regions (IDRs) on proteins. However, I had not performed an analysis to determine how each specific codon-amino acid correspondence supported this hypothesis.

In this study, I examined the specific difference in the amino acid composition of TMDs and IDRs of different organisms by comparing the ratios between the average amino acid residue compositions of TMDs, IDRs, and the total sequence of each protein by organism. The results showed that the difference ratios between TMDs to total, IDRs to total for all 20 amino acids were almost inversely different between two regions and were well consistent across organisms. This consistency suggests that, regardless of species, TMDs and IDRs each have distinct characteristics in their amino acid composition. Furthermore, a comparison of these results with the codons corresponding to each amino acid in the genetic code revealed that the standard genetic code predominantly assigns uracil-containing codons to amino acids enriched in transmembrane domains and uracil-free codons to amino acids enriched in intrinsically disordered regions.

In my other recent study, I showed that TMD-rich and IDR-rich proteins are consistently two of the most statistically distinct domains/regions of amino acid composition of the proteome in any organism, and combined with the previous research finding that the genetic code has a structure in which TMDs and IDRs are encoded by gene sequences of each specific nucleotide composition, I concluded that this may explain why the standard genetic code is universal. The results of the current study show that the differentiation function of the genetic code is based on an elaborate simultaneous coordination of codon-amino acid correspondence. This finding supports the idea that the structure of the standard genetic code, which is influenced by the commonality of TMDs/IDRs, is unlikely to be a product of mere chance and at least has a purpose in differentiating these regions. This finding should provide a crucial insight into the undiscovered origins of the standard genetic code as the statistically largest piece of its puzzle. But at the same time, the piece must be quite small in the over-complexity of its overall mystery.