The TA Skew of a Gene Primarily Determines the Type of Protein, Such as Membrane Protein or Intrinsically Disordered Protein

Abstract

Proteins differ in function and cellular localization according to their amino acid composition; however, there are few reports on how these characteristic compositions are organized.

Principal component analysis of the amino acid composition of all proteins in the human proteome and plotting of all proteins by their first and second principal components revealed that proteins with high fractions of α-helical transmembrane domains and those with high fractions of intrinsically disordered regions were located at each extreme of the plot. At the same time, each functional domain fraction corresponded primarily to the high and low TA skew of the gene nucleotide composition.

The codon corresponding to each amino acid in the genetic code consists of four nucleic acids, but the nucleic acid composition in the codons for each amino acid is initially skewed. Therefore, the amino acid composition of a protein is inevitably affected by the nucleic acid composition of its genes. However, there are few reports on the consequences of this effect. In contrast, the present study showed that the largest source of diversity in the amino acid composition of proteins is the diversity in the nucleic acid composition of their genes, such as TA skew and GC content. Furthermore, this study showed that TA skew plays an important role in determining protein properties. Finally, I conclude that both the TA skew of the gene and the skewed assignment of the genetic code work together to maintain the correct properties of proteins in the proteome.