Not Only Residue Amino Acid Composition but Also Gene Thymine–Adenine Balance Reflect Protein Hydropathy

抄録

Kyte and Doolittle’s landmark study established the concept that a protein’s hydropathy governs its conformation and membrane-spanning regions, and they also demonstrated that this hydropathy can be estimated by applying coefficients to the amino acid residue composition of the protein sequence. In contrast, the possibility of estimating protein hydropathy from the nucleotide composition of its gene sequence has rarely been explored. In my previous study, I showed that the balance of thymine and adenine in protein genes, termed “TA skew,” correlates positively with the proportion of hydrophobic transmembrane domains (TMD) and negatively with that of hydrophilic intrinsically disordered regions (IDR). Therefore, I hypothesized that a gene’s TA skew correlates with the hydropathy of its encoded protein sequence.

To test this hypothesis, I revisited the six example proteins examined in Kyte and Doolittle’s original study to determine whether the TA skew of their gene sequences corresponds to their hydropathic indices and the documented structural features of their corresponding residue sequences. Furthermore, using sufficiently large protein datasets, I analyzed whether each gene’s TA skew correlates with the GRAVY score (the average hydropathy of each entire protein) and with the proportions of two distinct protein domains (TMDs and IDRs).

Analysis of the proteins from that landmark study revealed strong correlations between TA skew, hydropathic indices, and their structural features. Moreover, in larger protein datasets, evident correlations between TA skew, the GRAVY score, and these representative protein domains were also observed. These findings reveal a previously unrecognized dimension of the correspondence between nucleotide composition and protein structures, suggesting the existence of an intricate function within the genetic code’s codon–amino acid correspondence.