Complementation (genetics)

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A complementation test (sometimes called a "cis-trans" test) is used in genetics to decide if two independently derived recessive mutant phenotypes are caused by mutations in the same gene or in two different genes. American geneticist Edward B. Lewis is credited with developing the test.

Two different true breeding mutants are crossed with each other, bringing together the mutant genotypes of each parent in a single F1 individual (or transheterozygote). If that individual shows the mutant phenotype, then the complementation has failed, and the mutations were caused by two alleles of the same gene. If no mutant phenotype is observed in the F1 individual, then the mutant alleles have complemented each other, and must be different genes.

In other words:

  • If the combination of two haploid genomes containing different recessive mutations yields a mutant phenotype, then the mutations must be in the same gene (alleles).
  • If the combination of two haploid genomes containing different recessive mutations yields the wild type phenotype, then the mutations must be in different genes.

There are exceptions to these rules. Two non-allelic mutants may occasionally fail to complement (called "non-allelic non-complementation" or "unlinked non-complementation"). This situation is rare and is dependent on the particular nature of the mutants being tested. For example, two mutations may be synthetically dominant negative. Another exception is transvection, in which the heterozygous combination of two alleles with mutations in different parts of the gene complement each other to rescue a wild type phenotype.


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