The Synonymous Codon Usage of a Protein Gene Is Primarily Determined by the Guanine + Cytosine Content of the Individual Gene Rather Than the Species to Which It Belongs To Synthesize Proteins With a Balanced Amino Acid Composition

Abstract

In the genetic code, most amino acids have multiple corresponding codons, and codons corresponding to the same amino acid are called synonymous codons. The use of synonymous codons in protein genes is known to be biased rather than random, and such bias is often explained by species differences in the guanine + cytosine (GC) content of their genomes, or in the abundance of tRNAs that intervene between codons and amino acids in the translation process.

In this study, I statistically analyzed the synonymous codon usage in protein genes of the proteomes of 79 species from 3 domains, published as Reference Proteome, and found that the GC content of the individual gene, rather than the species to which it belongs, primarily determines its synonymous codon usage.

Why then does the GC content of the individual gene determine its codon usage selection? Some papers have already mentioned that the GC content of the third letters of codons is even higher in genes with high total GC content and even lower in genes with low total GC content, and these were usually explained by evolutionary pressure on their genomic GC content and its subsequent shift. However, while this explanation explained the behavior of the third letter of the codon, it did not explain the behavior of the first and second letters. To provide a new explanation for the overall behavior of synonymous codon usage, I added an analysis. Since in previous work the amino acid composition distributions of organisms appeared to be in a state of narrow convergence, and since we know that most organisms share some highly conserved proteins across species boundaries, an additional analysis, based on the assumption that the organism maintains a proteome close to the amino acid composition of a particular conserved protein, suggests that this codon selection counteracts the effect of the GC content of the gene on the amino acid composition of the protein and behaves in the direction of counterbalancing and maintaining a constant and balanced amino acid composition.

From the results of this study, I concluded that synonymous codon selection in a protein gene primarily counterbalances its GC content to maintain a balanced amino acid composition for the proteome. The ability to generate proteins with balanced amino acid composition from genes with different ranges of GC content is considered to be one of the basic functions achieved by the genetic code itself.