Figure 23.4 When One Nucleotide Does or Doesn’t Make a Difference (A) Synonymous (silent) substitutions do not change the amino acid specified and do not affect protein function; such substitutions are unlikely to be subject to natural selection. (B) Nonsynonymous (missense and nonsense) substitutions do change the amino acid sequence and are likely to have an effect (often deleterious) on protein function; such substitutions are targets for natural selection.