The expected frequencies of amino-acid to amino-acid mutations versus observed frequencies of the genetic disease mutations, nonsynonymous benign SNPs, and interspecies mutations. Comparison with (a) genetic disease mutations from the Mendelian Inheritance in Man (MIM) database , (b) nonsynonymous benign SNPs, based on the study by Stephens et al. , and (c) interspecies mutations based on the PAM1 matrix . Each point in the figure represents a certain type of amino-acid to amino-acid mutation. Only amino-acid transitions resulting from single-nucleotide mutations in amino-acid codons were considered. The mutation frequencies in each class (benign, disease and interspecies) were normalized to 100.