Complementation refers to a genetic process when two strains of an organism with different homozygous recessive mutations that produce the same mutant phenotype (for example, a change in wing structure in flies) have offspring that express the wild-type phenotype when mated or crossed. Complementation will ordinarily occur if the mutations are in different genes (intergenic complementation). Complementation may also occur if the two mutations are at different sites within the same gene (intragenic complementation), 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 (sometimes called a "cis-trans" test) can be used to test whether the mutations in two strains are in different genes. Complementation is usually weaker or absent 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: Mutations occur in the same gene. One mutation affects the expression of the other. One mutation may result in an inhibitory product. For a simple example of a complementation test, suppose a geneticist is interested in studying two strains of white-eyed flies of the species Drosophila melanogaster, more commonly known as the common fruit fly. In this species, wild-type flies have red eyes and eye color is known to be related to two genes, A and B.

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