Figure 15.17: When One Nucleotide Changes (A) Synonymous substitutions do not change the amino acid specified and do not affect protein function. Such substitutions are less likely to be subject to natural selection, although they contribute greatly to the buildup of neutral genetic variation in a population. (B) Nonsynonymous substitutions do change the amino acid sequence and are likely to have an effect (often deleterious, but sometimes beneficial) on protein function. Such nucleotide substitutions are targets for natural selection.