Differential codon usage for conserved amino acids: evidence that the serine codons TCN were primordial.

The availability of specialized sequence databanks for Escherichia coli, Saccharomyces cerevisiae and Bacillus subtilis made it possible to build a set of 105 protein-coding genes that are homologous in these three species. An analysis of the triplets at both the nucleotide and amino acid level revealed that the codon bias of some amino acids are significantly higher at conserved rather than at non-conserved positions. Comparisons of homologous genes in E. coli and Salmonella typhimurium, and in S. cerevisiae and Drosophila melanogaster, led to the same conclusion. A special case was made for serine in E. coli, whose major codon is AGC for non-conserved and TCC for conserved residues. We interpret this observation as evidence that the primordial codons for serine were TCN, while codons AGY appeared later. This conclusion is substantiated by an analysis of the codon usage of catalytic serine residues in ancient, ubiquitous and essential proteins (ATP synthases and topoisomerases). It is shown that in these proteins the proportion of the catalytic serine residues coded by TCN is significantly higher than the one expected from the overall codon usage of serine residues.