Synonymous and Nonsynonymous Nucleotide Substitutions

Abstract

Abstract In chapter 3, we have seen that the rate of nucleotide substitution is much higher at the third positions of codons than at the first and second positions. This is caused by the fact that many nucleotide substitutions at the third positions are silent and do not change amino acids. However, not all substitutions at the third positions are silent. Furthermore, some silent substitutions may also occur at the first positions. It is therefore interesting to know the rates of synonymous and nonsynonymous substitution separately. Since synonymous substitutions are apparently free from natural selection, the rate of synonymous substitution is often equated to the rate of neutral nucleotide substitution (Miyata et al. 1980). Indeed, the rate of synonymous substitution is similar for many genes, unless it is disturbed by codon usage bias and other factors. By contrast, the rate of nonsynonymous substitution is generally much lower than that of synonymous substitution and varies extensively from gene to gene. This is considered to be due to purifying selection, the extent of which varies from gene to gene (Kimura 1983).