**9. Codon evolution**

The 20 amino acids are encoded by genes using nucleotide triplets; therefore, these sequences are determined according to triplet sequences. Additionally, amino acid sequences differ not only inter-gene but also intraspecies. These facts indicate that a comparison of codon evolution based on the complete genome, which comprises large numbers of different genes, would not be significant. Indeed, no clear evaluation has been obtained, despite the attempted explanations of many scientists [27–29]. However, as described in the previous section, it has been clarified that a whole genome is constructed from putative small units that encode proteins of similar amino acid composition. This suggests that the total codon usage deduced from the complete genome is stable and represents the whole genome characteristic. According to this concept, correlationships of nucleotide contents in a complete genome can be expressed by the linear formula, y = ax + b; where "y" and "x" are nucleotide contents, and "a" and "b" are constant values. In addition, as each codon usage is expressed by a linear formula among various organisms, the determination of any one nucleotide content in certain organism can essentially estimate other three nucleotide contents and, therefore, the 64 codon usages (**Figure 6**). The estimated codon usage patterns and amino acid compositions are almost the same between the original experimental results and estimated results. The codon usage patterns clearly indicate that codon usages changed synchronously among the 64 codons during biological evolution.

#### **Figure 6.**

*Codon usage patterns and amino acid compositions of* Homo sapience*. Codon usage (bar) and amino acid composition (radar chart) are expressed as a percent of total codons and amino acids, respectively. Upper and lower panels represent genomic and estimated data, respectively. This figure was reproduced from Sorimachi and Okayasu [38].*
