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In genetics, complementation occurs when two strains of an organism with different homozygous recessive mutations that produce the same mutant phenotype have offspring that express the wild-type phenotype when mated or crossed. Complementation will ordinarily occur if the mutations are in different genes. Complementation may also occur if the two mutations are at different sites within the same gene , but this effect is usually weaker than that of intergenic complementation. In the case where the mutations are in different genes, each strain's genome supplies the wild-type allele to "complement" the mutated allele of the other strain's genome. Since the mutations are recessive, the offspring will display the wild-type phenotype. A complementation test can be used to test whether the mutations in two strains are in different genes. Complementation ordinarily will occur more weakly or not at all if the mutations are in the same gene. The convenience and essence of this test is that the mutations that produce a phenotype can be assigned to different genes without the exact knowledge of what the gene product is doing on a molecular level. The complementation test was developed by American geneticist Edward B. Lewis.
If the combination of two genomes containing different recessive mutations yields a mutant phenotype, then there are three possibilities: