Evidence suggesting a non-random character to nucleotide replacements in naturally occurring mutations

Abstract

One may examine amino acid substitutions resulting from naturally occurring single-step mutations to determine the frequency with which varying nucleotide replacements must have occurred in the gene to account for the phenotypic changes. These may be compared to the frequency of nucleotide replacements one would expect to occur by chance. This has been done for 50 human hemoglobin mutations and for 229 mutations occurring in the phylogenetic descent of cytochrome c. In both cases there is a very significant departure from randomness, which is primarily a reflection of a high incidence of mutations in which a guanine is replaced by an adenine in the codon for the amino acid which is changed.