Complementation is the phenomenon where two strains of organisms, each homozygous-recessive for mutations in different genes contributing to the same phenotype, are crossed to give an offspring with the wild-type phenotype. This is due to the fact that the offspring can inherit the mutant alleles from each parent, so long as it also inherits the complementary wild-type alleles from the other parent.

Simply put: for two genes, A and B, that contribute to a phenotype, if individual 1 has the genotype aaBB and a mutant phenotype, and individual 2 has the genotype AAbb and has a mutant phenotype, then a cross between individual 1 and individual 2 can potentially give rise to an offspring, AaBb, who has the wild-type phenotype.

Complementation testing (also cis-trans testing), then, allows us to ascertain whether mutant phenotypes in two (or more) individuals are caused by mutations in the same genes or in different genes for that phenotype, by doing crosses and seeing whether the wild-type phenotype can be restored in the offspring.

If a pairwise crossing between two individuals with the same mutant phenotype only bears offspring with that mutant phenotype, then there are three possibilities:
  • ´╗┐The mutations in the parent individuals are in the same gene (i.e. the parents are in the same complementation group)
  • There is an epistatic interaction going on (i.e. the mutant allele of one gene is epistatic to the wild-type allele of another)
  • The mutant allele of one gene encodes an inhibitory product that prevents expression of the wild-type allele of another