A Locus Can Have More Than One Wild-Type Allele

KEY CONCEPT
-A locus can have a polymorphic distribution of alleles with no individual allele that can be considered to be the sole wild type.
In some instances, such as the gene that controls the human ABO blood group system, there is not necessarily a unique wild-type allele for a particular locus. Lack of function is represented by the null, or O, allele. However, the functional alleles A and B are codominant with one another and dominant to the O allele. The basis for this relationship is illustrated in FIGURE 1.

FIGURE 1. The ABO human blood group locus encodes a galactosyltransferase whose specificity determines the blood group.
The H antigen is generated in all individuals and consists of a particular carbohydrate group that is added to proteins and lipids. The ABO locus encodes a galactosyltransferase enzyme that puts an additional sugar group on the H antigen. The specificity of this enzyme determines the blood group. The A allele produces an enzyme that uses the modified sugar UDP-N-acetylgalactose to form the A antigen. The B allele produces an enzyme that uses the modified sugar UDP-galactose to form the B antigen. The A and B versions of the transferase enzyme differ in four amino acids that presumably affect its ability to catalyze the addition of specific sugars. The O allele has a small deletion that eliminates the activity of the transferase, so no modification of the H antigen occurs.
This explains why A and B alleles are dominant in the AO and BO heterozygotes: The corresponding transferase activity forms 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 A and B antigens.
Neither A nor B alleles can be regarded as uniquely wild type because they represent alternative activities rather than loss or gain of function. A situation such as this—that is, there are multiple functional alleles in a population—is described as a polymorphism .