The principle of complementation is a fundamental concept in genetics that refers to the ability of two different mutations in the same pathway or biological process to restore a wild-type phenotype when they are present together in the same organism.

The Principle of Complementation:
If two recessive mutations are alleles of the same gene, then a cross between homozygous strains yields F1 progeny that is mutant (noncomplementation); if they are alleles of different genes, then the F1 progeny are wildtype (complementation).

Hartl, D., & Jones, E. (2001). Introduction to molecular genetics and genomics.

Complementation occurs because the two different mutations affect different genes or different regions of the same gene. Therefore, they produce different non-functional proteins. When the mutations are present in different genes, the functional protein produced by one gene can compensate for the non-functional protein produced by the other gene allowing for the restoration of the wild-type phenotype.

First Discovered in 20th Century

The idea of complementation was established in the early 20th century by geneticists examining the inheritance of features in fruit flies and has since been documented in a wide range of organisms. It is an important tool in genetic analysis because it allows researchers to evaluate whether two separate mutants with the same phenotype are caused by mutations in the same or different genes.

The complementation principle has substantial practical uses, such as plant breeding and medicine development. Complementation can be used in plant breeding to develop hybrid plants with desirable features by crossing two distinct kinds with different mutations affecting the same pathway. Complementation can be utilized in drug research to uncover new therapeutic targets by identifying genes that complement each other in disease models.

Complementation Test

Based on the principle of complementation, this test is a genetic experiment used to determine whether two different mutations that produce the same phenotype are in the same or different genes.

To perform a complementation test, researchers cross two different mutant strains that have the same phenotype of interest.

  • If the resulting progeny have the wild-type phenotype, then the two mutations are likely in different genes and have complemented each other.
  • If the progeny have the mutant phenotype, then the two mutations are likely in the same gene and have failed to complement each other.

The complementation test is often used in genetic research to identify the genes involved in a particular pathway or process.

For example, if researchers observe two different mutations in a gene that both result in a non-functional protein, they can use a complementation test to determine whether the mutations are in the same or different regions of the gene.

If the mutations complement each other and restore the wild-type phenotype, then they are likely in different regions of the gene. If the mutations fail to complement each other and produce the mutant phenotype, then they are likely in the same region of the gene.

complementation and noncomplementation
Image: Complementation Test | Hartl, D., & Jones, E. (2001). Introduction to molecular genetics and genomics.

What is non complementation?

Non-complementation refers to a phenomenon in genetics where two mutations that affect the same gene fail to complement each other. This results in a non-functional protein or phenotype.

Noncomplementation occurs when both alleles of a gene are mutated at the same site or region, resulting in a protein with a non-functional or altered structure. If the two mutations are in different parts of the gene, the resulting proteins may still interact and form a functional complex, and complementation may occur.

It is frequently used in genetic research to investigate a gene’s functional domains and interactions between different protein subunits. It is also seen in genetic disorders, where two different mutations in the same gene can result in a loss of function and disease. Other factors, such as the presence of a dominant negative mutant protein that interferes with the function of the wild-type protein, can also cause non complementation in some cases.

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