- Polymorphism (more fully genetic polymorphism) refers to the simultaneous occurrence in the population of genomes showing variations at a given position. The original definition applied to alleles producing different phenotypes. Now it is also used to describe changes in DNA affecting the restriction pattern or even the sequence. For practical purposes, to be considered as an example of a polymorphism, an allele should be found at a frequency > 1% in the population.
- A locus may have a polymorphic distribution of alleles, with no individual allele that can be considered to be the sole wild-type.
There is not necessarily a unique wild-type allele at any particular locus. Control of the human blood group system provides an example. Lack of function is represented by the null type, O group. But the functional alleles A and B provide activities that are codominant with one another and dominant over O group. The basis for this relationship is illustrated in Figure 1.30.
The O (or H) antigen is generated in all individuals, and consists of a particular carbohydrate group that is added to proteins. The ABO locus codes for a galactosyltransferase enzyme that adds a further sugar group to the O antigen. The specificity of this enzyme determines the blood group. The A allele produces an enzyme that uses the cofactor UDP-N-acetylgalactose, creating the A antigen. The B allele produces an enzyme that uses the cofactor UDP-galactose, creating the B antigen. The A and B versions of the transferase protein differ in 4 amino acids that presumably affect its recognition of the type of cofactor. The O allele has a mutation (a small deletion) that eliminates activity, so no modification of the O antigen occurs.
This explains why A and B alleles are dominant in the AO and BO heterozygotes: the corresponding transferase activity creates the A or B antigen. The A and B alleles are codominant in AB heterozygotes, because both transferase activities are expressed. The OO homozygote is a null that has neither activity, and therefore lacks both antigens.
Neither A nor B can be regarded as uniquely wild type, since they represent alternative activities rather than loss or gain of function. A situation such as this, in which there are multiple functional alleles in a population, is described as a polymorphism.