Complementation (genetics)
Encyclopedia
In genetics
, complementation refers to a relationship between two different strains
of an organism which both have homozygous recessive mutation
s that produce the same phenotype
(for example, a change in wing structure in flies). These strains are true breeding for their mutation. If, when these strains are crossed with each other, some offspring show recovery of the wild-type phenotype, these strains show "genetic complementation". When this occurs, each strain's haploid supplies a wild-type allele to "complement" the mutated allele of the other strain's haploid, causing the offspring to have heterozygous mutations in all related genes. Since the mutations are recessive, the offspring display the wild-type phenotype. A complementation test (sometimes called a "cis-trans" test) refers to this experiment, developed by American
geneticist
Edward B. Lewis
. It answers the question: "Does a wild-type copy of gene X rescue the function of the mutant allele that is believed to define gene X?". If there is an allele with an observable phenotype whose function can be provided by a wild type genotype (i.e., the allele is recessive), one can ask whether the function that was lost because of the recessive allele can be provided by another mutant genotype. If not, the two alleles must be defective in the same gene. The beauty of this test is that the trait can serve as a read-out of gene function even without knowledge of what the gene is doing at a molecular level.
Complementation arises because loss of function in gene
s responsible for different steps in the same metabolic pathway
can give rise to the same phenotype. When strains are bred together, offspring inherit wildtype versions of each gene from either parent. Because the mutations are recessive, there is a recovery of function in that pathway, so offspring recover the wild-type phenotype
. Thus, the test is used to decide if two independently derived recessive mutant
phenotype
s are caused by mutations in the same gene
or in two different genes. If both parent strains have mutations in the same gene, no normal versions of the gene are inherited by offspring; they express the same mutant
phenotype and complementation has failed to occur.
In other words:
. In this species, wild type
flies have red eyes and eye color is known to be related to two genes, A and B. Each one of these genes has two alleles, a dominant one that codes for a working protein (A and B respectively) and a recessive one that codes for a malfunctioning protein (a and b respectively). Since both proteins are necessary for the synthesis of red pigmentation in the eyes, if a given fly is homozygous for either a or b, it will have white eyes.
Knowing this, the geneticist may perform a complementation test on two separately obtained strains of pure-breeding white-eyed flies. The test is performed by crossing two flies, one from each strain. If the resulting progeny have red eyes, the two strains are said to complement; if the progeny have white eyes, they do not.
If the strains complement, we imagine that one strain must have a genotype aa BB and the other AA bb, which when crossed yield the genotype AaBb. In other words, each strain is homozygous for a different deficiency that produces the same phenotype. If the strains do not complement, they both must have genotypes aa BB, AA bb, or aa bb. In other words, they are both homozygous for the same deficiency, which obviously will produce the same phenotype.
, 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.
Genetics
Genetics , a discipline of biology, is the science of genes, heredity, and variation in living organisms....
, complementation refers to a relationship between two different strains
Strain (biology)
In biology, a strain is a low-level taxonomic rank used in three related ways.-Microbiology and virology:A strain is a genetic variant or subtype of a micro-organism . For example, a "flu strain" is a certain biological form of the influenza or "flu" virus...
of an organism which both have homozygous recessive mutation
Mutation
In molecular biology and genetics, mutations are changes in a genomic sequence: the DNA sequence of a cell's genome or the DNA or RNA sequence of a virus. They can be defined as sudden and spontaneous changes in the cell. Mutations are caused by radiation, viruses, transposons and mutagenic...
s that produce the same phenotype
Phenotype
A phenotype is an organism's observable characteristics or traits: such as its morphology, development, biochemical or physiological properties, behavior, and products of behavior...
(for example, a change in wing structure in flies). These strains are true breeding for their mutation. If, when these strains are crossed with each other, some offspring show recovery of the wild-type phenotype, these strains show "genetic complementation". When this occurs, each strain's haploid supplies a wild-type allele to "complement" the mutated allele of the other strain's haploid, causing the offspring to have heterozygous mutations in all related genes. Since the mutations are recessive, the offspring display the wild-type phenotype. A complementation test (sometimes called a "cis-trans" test) refers to this experiment, developed by American
United States
The United States of America is a federal constitutional republic comprising fifty states and a federal district...
geneticist
Geneticist
A geneticist is a biologist who studies genetics, the science of genes, heredity, and variation of organisms. A geneticist can be employed as a researcher or lecturer. Some geneticists perform experiments and analyze data to interpret the inheritance of skills. A geneticist is also a Consultant or...
Edward B. Lewis
Edward B. Lewis
- External links :* *...
. It answers the question: "Does a wild-type copy of gene X rescue the function of the mutant allele that is believed to define gene X?". If there is an allele with an observable phenotype whose function can be provided by a wild type genotype (i.e., the allele is recessive), one can ask whether the function that was lost because of the recessive allele can be provided by another mutant genotype. If not, the two alleles must be defective in the same gene. The beauty of this test is that the trait can serve as a read-out of gene function even without knowledge of what the gene is doing at a molecular level.
Complementation arises because loss of function in gene
Gene
A gene is a molecular unit of heredity of a living organism. It is a name given to some stretches of DNA and RNA that code for a type of protein or for an RNA chain that has a function in the organism. Living beings depend on genes, as they specify all proteins and functional RNA chains...
s responsible for different steps in the same metabolic pathway
Metabolic pathway
In biochemistry, metabolic pathways are series of chemical reactions occurring within a cell. In each pathway, a principal chemical is modified by a series of chemical reactions. Enzymes catalyze these reactions, and often require dietary minerals, vitamins, and other cofactors in order to function...
can give rise to the same phenotype. When strains are bred together, offspring inherit wildtype versions of each gene from either parent. Because the mutations are recessive, there is a recovery of function in that pathway, so offspring recover the wild-type phenotype
Phenotype
A phenotype is an organism's observable characteristics or traits: such as its morphology, development, biochemical or physiological properties, behavior, and products of behavior...
. Thus, the test is used to decide if two independently derived recessive mutant
Mutant
In biology and especially genetics, a mutant is an individual, organism, or new genetic character, arising or resulting from an instance of mutation, which is a base-pair sequence change within the DNA of a gene or chromosome of an organism resulting in the creation of a new character or trait not...
phenotype
Phenotype
A phenotype is an organism's observable characteristics or traits: such as its morphology, development, biochemical or physiological properties, behavior, and products of behavior...
s are caused by mutations in the same gene
Gene
A gene is a molecular unit of heredity of a living organism. It is a name given to some stretches of DNA and RNA that code for a type of protein or for an RNA chain that has a function in the organism. Living beings depend on genes, as they specify all proteins and functional RNA chains...
or in two different genes. If both parent strains have mutations in the same gene, no normal versions of the gene are inherited by offspring; they express the same mutant
Mutant
In biology and especially genetics, a mutant is an individual, organism, or new genetic character, arising or resulting from an instance of mutation, which is a base-pair sequence change within the DNA of a gene or chromosome of an organism resulting in the creation of a new character or trait not...
phenotype and complementation has failed to occur.
In other words:
- If the combination of two haploid 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.
- If the combination of two haploid genomes containing different recessive mutations yields the wild type phenotype, then the mutations must be in different genes.
Example of a Simple Complementation Test
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 melanogasterDrosophila melanogaster
Drosophila melanogaster is a species of Diptera, or the order of flies, in the family Drosophilidae. The species is known generally as the common fruit fly or vinegar fly. Starting from Charles W...
. In this species, wild type
Wild type
Wild type refers to the phenotype of the typical form of a species as it occurs in nature. Originally, the wild type was conceptualized as a product of the standard, "normal" allele at a locus, in contrast to that produced by a non-standard, "mutant" allele...
flies have red eyes and eye color is known to be related to two genes, A and B. Each one of these genes has two alleles, a dominant one that codes for a working protein (A and B respectively) and a recessive one that codes for a malfunctioning protein (a and b respectively). Since both proteins are necessary for the synthesis of red pigmentation in the eyes, if a given fly is homozygous for either a or b, it will have white eyes.
Knowing this, the geneticist may perform a complementation test on two separately obtained strains of pure-breeding white-eyed flies. The test is performed by crossing two flies, one from each strain. If the resulting progeny have red eyes, the two strains are said to complement; if the progeny have white eyes, they do not.
If the strains complement, we imagine that one strain must have a genotype aa BB and the other AA bb, which when crossed yield the genotype AaBb. In other words, each strain is homozygous for a different deficiency that produces the same phenotype. If the strains do not complement, they both must have genotypes aa BB, AA bb, or aa bb. In other words, they are both homozygous for the same deficiency, which obviously will produce the same phenotype.
Exceptions
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 transvectionTransvection (genetics)
Transvection is an epigenetic phenomenon that results from an interaction between an allele on one chromosome and the corresponding allele on the homologous chromosome. Transvection can lead to either gene activation or repression...
, 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.