The standard genetic code is designed to generate transmembrane domains and intrinsically disordered regions as projections of the thymine density on the gene

Abstract

We know that the codon-amino acid correspondence in the genetic code is not random. However, there was no established theory as to whether this correspondence was designed for any purpose or function. In a previous report, I showed that the proteins with high amounts of transmembrane domains and the proteins with high amounts of intrinsically disordered regions correspond to the high and low TA (thymine adenine) skew of their gene, respectively, and I speculated that these reflect the purpose behind the design of the genetic code. However, since most protein genes use their synonymous codon selection to balance their GC (guanine cytosine) content, i.e., their TA content, I hypothesized that the amount of only one of these two nucleic acids, thymine or adenine, might actually originate the characteristics of the amino acid composition of these two functional domains/regions.

In this study, I examined the correspondence between these two functional domains/regions and the estimated composition of each nucleic acid of various protein genes from different organism proteomes by back-calculating the possible nucleic acid compositions of the gene from the amino acid residue composition of the protein.

The results showed that the proteins with high amounts of transmembrane domains and the proteins with high amounts of intrinsically disordered regions were indeed correlated with the higher and lower estimated thymine composition on the genes, respectively. Upon detailed analysis, the transmembrane domains correlated more strongly with the maximum estimated thymine composition and the intrinsically disordered regions correlated more strongly with the minimum estimated thymine composition.

Since the amino acid compositions of membrane proteins with higher thymine composition genes correspond to the maximum estimated thymine compositions, and the amino acid compositions of intrinsically disordered proteins with lower thymine composition genes correspond to the minimum estimated thymine compositions, it is more reasonable to assume that the characteristic amino acid compositions of the two domains/regions are both formed by the thymine densities of the genes, rather than these thymine density structures being formed by selective pressure on amino acid compositions.  Thus, the functions of these two functional domains/regions are thought to arise as projections of the thymine densities of their properly preformed gene sequences.

The results shown in this study suggest that the standard genetic code has an optimized structure that allows for optimized translation and synthesis of the functional domains of proteins. I conclude that the current genetic code must have been selected for this functional advantage, and I propose this as the "optimized translation" theory that explains the origin of the genetic code.