noncomplementation

Noncomplementation is a concept in genetics that describes the phenomenon where two mutations affecting the same gene or pathway do not produce a wild-type phenotype when combined. If two mutations were in different genes and both genes were essential for a particular trait, then combining them would result in a mutant phenotype. However, if they are in the same gene, or in different genes that are part of the same functional unit or pathway, then having mutations in both might not necessarily restore the wild-type phenotype if the functional unit is already sufficiently disrupted by a single mutation.

In essence, noncomplementation implies that the two mutations are occurring in different functional domains or subunits of a protein complex or pathway, and that the deficiency in one is not compensated for by the wild-type function of the other. This is in contrast to complementation, where the combination of two mutations in different genes, or in different parts of the same gene that produce distinct mutant proteins, can restore the wild-type phenotype. For example, if gene A produces protein X and gene B produces protein Y, and both are needed for a trait, then a mutation in A and a mutation in B will result in a mutant trait. However, if gene C produces protein Z, and a mutation in C leads to a mutant trait, and another mutation in C also leads to a mutant trait, but combining these two mutations does not restore the wild-type trait, then these mutations are noncomplementing. This often indicates that the mutations are within the same gene or functionally linked genes.