Replacement of a nucleic acid with a different nucleic acid base, particularly though not exclusively as occurs in the course of mutation fixation.

See synonymous substitution, nonsynonymous substitution, and dN/dS.

Note the potential contrast of the concept of "substitution" with that of "base substitution", i.e., with the former in some contexts strictly representing mutation plus fixation while the latter instead is typically used to describe mutation alone. Substitution in some contexts therefore will mean point mutation but in others instead will explicitly be a description of the fixation of an equivalent mutation.