Complementation refers to a genetic process when two strains of an

organism An organism is any life, living thing that functions as an individual. Such a definition raises more problems than it solves, not least because the concept of an individual is also difficult. Many criteria, few of them widely accepted, have be ...

with different homozygous recessive

mutation In biology, a mutation is an alteration in the nucleic acid sequence of the genome of an organism, virus, or extrachromosomal DNA. Viral genomes contain either DNA or RNA. Mutations result from errors during DNA or viral replication, ...

s that produce the same mutant

phenotype In genetics, the phenotype () is the set of observable characteristics or traits of an organism. The term covers the organism's morphology (physical form and structure), its developmental processes, its biochemical and physiological propert ...

(for example, a change in wing structure in flies) have offspring that express the

wild-type The wild type (WT) is 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, " ...

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. When the mutations are in different genes, each strain's genome supplies the wild-type

allele An allele is a variant of the sequence of nucleotides at a particular location, or Locus (genetics), locus, on a DNA molecule. Alleles can differ at a single position through Single-nucleotide polymorphism, single nucleotide polymorphisms (SNP), ...

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 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. American geneticist Edward B. Lewis developed the complementation test.

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 melanogaster ''Drosophila melanogaster'' is a species of fly (an insect of the Order (biology), order Diptera) in the family Drosophilidae. The species is often referred to as the fruit fly or lesser fruit fly, or less commonly the "vinegar fly", "pomace fly" ...
, more commonly known as the common fruit fly. In this species,

flies have red eyes, and eye color is known to be related to two genes, A and B. Each of these genes has two alleles, a dominant one that codes for a working protein (''A'' and ''B'' respectively) and a

recessive In genetics, dominance is the phenomenon of one variant (allele) of a gene on a chromosome masking or overriding the effect of a different variant of the same gene on the other copy of the chromosome. The first variant is termed dominant and ...

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 Zygosity (the noun, zygote, is from the Greek "yoked," from "yoke") () is the degree to which both copies of a chromosome or gene have the same genetic sequence. In other words, it is the degree of similarity of the alleles in an organism. Mos ...

for either ''a'' or ''b'', it will have white eyes. In genetics, a complementation test can be conducted to understand the interaction between different genetic strains. This test often involves crossing two pure-breeding strains, such as white-eyed flies, from separate origins. The process entails mating two flies, each from a different strain. The eye color of the resulting progeny determines the outcome of the test. If the progeny exhibit red eyes, it indicates that the two strains complement each other. Conversely, if the progeny have white eyes, it suggests non-complementation. Complementation occurs when each strain possesses a different homozygous mutation (for example, one strain having the genotype 'aa BB' and the other 'AA bb'), resulting in a heterozygous genotype ('AaBb') in the progeny that produces a different phenotype from the parents. Non-complementation is observed when both strains share the same homozygous mutation, such as 'aaBB', 'AAbb', or 'aabb', leading to progeny with a phenotype identical to the parent strains.

Complementation tests in fungi and bacteriophage

Complementation tests can also be carried out with

haploid Ploidy () is the number of complete sets of chromosomes in a cell (biology), cell, and hence the number of possible alleles for Autosome, autosomal and Pseudoautosomal region, pseudoautosomal genes. Here ''sets of chromosomes'' refers to the num ...

eukaryotes The eukaryotes ( ) constitute the domain of Eukaryota or Eukarya, organisms whose cells have a membrane-bound nucleus. All animals, plants, fungi, seaweeds, and many unicellular organisms are eukaryotes. They constitute a major group of ...

such as

fungi A fungus (: fungi , , , or ; or funguses) is any member of the group of eukaryotic organisms that includes microorganisms such as yeasts and mold (fungus), molds, as well as the more familiar mushrooms. These organisms are classified as one ...

, with bacteria, and with viruses such as

bacteriophage A bacteriophage (), also known informally as a phage (), is a virus that infects and replicates within bacteria. The term is derived . Bacteriophages are composed of proteins that Capsid, encapsulate a DNA or RNA genome, and may have structu ...

. Research on the fungus

Neurospora crassa ''Neurospora crassa'' is a type of red bread mold of the phylum Ascomycota. The genus name, meaning 'nerve spore' in Greek, refers to the characteristic striations on the spores. The first published account of this fungus was from an infestatio ...

led to the development of the one-gene-one-enzyme concept that provided the foundation for the subsequent development of molecular genetics. The complementation test was one of the main tools used in the early Neurospora work, because it was easy to do, and allowed the investigator to determine whether any two nutritional mutants were defective in the same or different genes. The complementation test was also used in the early development of molecular genetics when bacteriophage T4 was one of the main objects of study. In this case the test depends on mixed infections of host bacterial cells with two different bacteriophage mutant types. Its use was key to defining most of the genes of the virus, and provided the foundation for the study of such fundamental processes as DNA replication and repair, and how

molecular machine Molecular machines are a class of molecules typically described as an assembly of a discrete number of molecular components intended to produce mechanical movements in response to specific stimuli, mimicking macromolecular devices such as switch ...

s are constructed.

Genetic complementation, heterosis, and the evolution of sexual reproduction

Heterosis Heterosis, hybrid vigor, or outbreeding enhancement is the improved or increased function of any biological quality in a hybrid offspring. An offspring is heterotic if its traits are enhanced as a result of mixing the genetic contributions o ...

is the tendency for hybrid individuals to exceed their purebred parents in size and vigor. The phenomenon has long been known in animals and plants. Heterosis appears to be largely due to genetic complementation, that is the masking of deleterious recessive alleles in hybrid individuals. In general, the two fundamental aspects of sexual reproduction in eukaryotes are

meiosis Meiosis () is a special type of cell division of germ cells in sexually-reproducing organisms that produces the gametes, the sperm or egg cells. It involves two rounds of division that ultimately result in four cells, each with only one c ...

and

outcrossing Out-crossing or out-breeding is the technique of crossing between different breeds. This is the practice of introducing distantly related genetic material into a breeding line, thereby increasing genetic diversity. Outcrossing in animals Out ...

. These two aspects have been proposed to have two natural selective advantages, respectively. Meiosis is proposed to be adaptive because it facilitates recombinational repair of DNA damages that are otherwise difficult to repair. Outcrossing is proposed to be adaptive because it facilitates complementation, that is the masking of deleterious recessive alleles (also see

heterosis Heterosis, hybrid vigor, or outbreeding enhancement is the improved or increased function of any biological quality in a hybrid offspring. An offspring is heterotic if its traits are enhanced as a result of mixing the genetic contributions o ...

). The benefit of masking deleterious alleles has been proposed to be a major factor in the maintenance of sexual reproduction among eukaryotes. Further, the selective advantage of complementation that arises from outcrossing may largely account for the general avoidance of inbreeding in nature (e.g. see articles kin recognition,

inbreeding depression Inbreeding depression is the reduced biological fitness caused by loss of genetic diversity as a consequence of inbreeding, the breeding of individuals closely related genetically. This loss of genetic diversity results from small population siz ...

, and

incest taboo Incest ( ) is sex between close relatives, for example a brother, sister, or parent. This typically includes sexual activity between people in consanguinity (blood relations), and sometimes those related by lineage. It is condemned and con ...

Quantitative Complementation Test

Used by

quantitative genetics Quantitative genetics is the study of quantitative traits, which are phenotypes that vary continuously—such as height or mass—as opposed to phenotypes and gene-products that are Categorical variable, discretely identifiable—such as eye-col ...

to uncover recessive mutants. Here one takes deficiencies and crosses them to a

haplotype A haplotype (haploid genotype) is a group of alleles in an organism that are inherited together from a single parent. Many organisms contain genetic material (DNA) which is inherited from two parents. Normally these organisms have their DNA orga ...

that is believed to contain the recessive mutant.

Exceptions

These rules (patterns) are not without exceptions. Non-allelic mutants may occasionally fail to complement (this is known as "non-allelic non-complementation" or "unlinked non-complementation"). This is an uncommon occurrence that depends on the type of mutants being investigated. Two mutations, for example, could be synthetically dominant negative. Transvection is another instance, in which a heterozygous combination of two alleles with mutations in distinct sections of the gene complement one other to restore a wild-type phenotype.

Intragenic complementation

When complementation between two mutants defective in the same gene is measured, it is generally found that there is either no complementation or the complementation phenotype is intermediate between the mutant and wild-type phenotypes. Intragenic complementation (also called inter-allelic complementation) has been demonstrated in many different genes in a variety of organisms including the fungi ''

'', ''

Saccharomyces cerevisiae ''Saccharomyces cerevisiae'' () (brewer's yeast or baker's yeast) is a species of yeast (single-celled fungal microorganisms). The species has been instrumental in winemaking, baking, and brewing since ancient times. It is believed to have be ...

,'' and ''

Schizosaccharomyces pombe ''Schizosaccharomyces pombe'', also called "fission yeast", is a species of yeast used in traditional brewing and as a model organism in molecular and cell biology. It is a unicellular eukaryote, whose cells are rod-shaped. Cells typically meas ...

''; the bacterium ''

Salmonella ''Salmonella'' is a genus of bacillus (shape), rod-shaped, (bacillus) Gram-negative bacteria of the family Enterobacteriaceae. The two known species of ''Salmonella'' are ''Salmonella enterica'' and ''Salmonella bongori''. ''S. enterica'' ...

typhimurium''; and the virus bacteriophage T4. In several such studies, numerous

s defective in the same gene were isolated and mapped in a linear order based on recombination frequencies to form a

genetic map Genetic linkage is the tendency of DNA sequences that are close together on a chromosome to be inherited together during the meiosis phase of sexual reproduction. Two genetic markers that are physically near to each other are unlikely to be separ ...

of the gene. Separately, the mutants were tested in pairwise combinations to measure complementation. An analysis of the results from such studies led to the conclusion that intragenic complementation, in general, arises from the interaction of differently defective polypeptide monomers to form an aggregate called a “multimer.” Genes that encode multimer-forming polypeptides appear to be common. One interpretation of the data is that polypeptide monomers are often aligned in the multimer in such a way that mutant polypeptides defective at nearby sites in the genetic map tend to form a mixed multimer that functions poorly, whereas mutant polypeptides defective at distant sites tend to form a mixed multimer that functions more effectively. The intermolecular forces likely responsible for self-recognition and multimer formation were discussed by Jehle.Jehle H. Intermolecular forces and biological specificity. Proc Natl Acad Sci U S A. 1963;50(3):516-524.

References

External links

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