Complementation (genetics)
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genetics Genetics is the study of genes, genetic variation, and heredity in organisms.Hartl D, Jones E (2005) It is an important branch in biology because heredity is vital to organisms' evolution. Gregor Mendel, a Moravian Augustinian friar wor ...
, complementation occurs when two strains of an organism 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, mi ...
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 or physical form and structure, its developmental processes, its biochemical and physiological proper ...
(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, "m ...
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 An allele (, ; ; modern formation from Greek ἄλλος ''állos'', "other") is a variation of the same sequence of nucleotides at the same place on a long DNA molecule, as described in leading textbooks on genetics and evolution. ::"The chro ...
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 American(s) may refer to: * American, something of, from, or related to the United States of America, commonly known as the "United States" or "America" ** Americans, citizens and nationals of the United States of America ** American ancestry, pe ...
geneticist A geneticist is a biologist or physician who studies genetics, the science of genes, heredity, and variation of organisms. A geneticist can be employed as a scientist or a lecturer. Geneticists may perform general research on genetic processe ...
Edward B. Lewis Edward Butts Lewis (May 20, 1918 – July 21, 2004) was an American geneticist, a corecipient of the 1995 Nobel Prize in Physiology or Medicine. He helped to found the field of evolutionary developmental biology. Early life Lewis was born in Wi ...
. 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.


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 (the taxonomic 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" or "pomace fly". Starting with Ch ...
, more commonly known as the common fruit fly. In this species,
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, "m ...
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 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. Mo ...
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.


Complementation tests in fungi and bacteriophage

Complementation tests can also be carried out with haploid eukaryotes such as fungi, with bacteria and with viruses such as bacteriophage. Research on the fungus Neurospora crassa 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 A molecular machine, nanite, or nanomachine is a molecular component that produces quasi-mechanical movements (output) in response to specific stimuli (input). In cellular biology, macromolecular machines frequently perform tasks essential for l ...
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 of ...
is the tendency for hybrid individuals to exceed their pure bred 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 (; , since it is a reductional division) is a special type of cell division of germ cells in sexually-reproducing organisms that produces the gametes, such as sperm or egg cells. It involves two rounds of division that ultimately resu ...
, 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 can be a useful ...
. 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 of ...
). 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 Kin recognition, also called kin detection, is an organism's ability to distinguish between close genetic kin and non-kin. In evolutionary biology and psychology, such an ability is presumed to have evolved for inbreeding avoidance, though animals d ...
,
Inbreeding depression Inbreeding depression is the reduced biological fitness which has the potential to result from inbreeding (the breeding of related individuals). Biological fitness refers to an organism's ability to survive and perpetuate its genetic material. In ...
and
Incest taboo An incest taboo is any cultural rule or norm that prohibits sexual relations between certain members of the same family, mainly between individuals related by blood. All human cultures have norms that exclude certain close relatives from tho ...
).


Quantitative Complementation Test

Used by Quantitative Genetics to uncover recessive mutants. Here one takes deficiencies and crosses them to a haplotype that is believed to contain the recessive mutant.


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 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 t ...
. 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.


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 ''
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 infestation ...
'', ''
Saccharomyces cerevisiae ''Saccharomyces cerevisiae'' () (brewer's yeast or baker's yeast) is a species of yeast (single-celled fungus microorganisms). The species has been instrumental in winemaking, baking, and brewing since ancient times. It is believed to have been o ...
'' 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 rod-shaped (bacillus) Gram-negative bacteria of the family Enterobacteriaceae. The two species of ''Salmonella'' are ''Salmonella enterica'' and ''Salmonella bongori''. ''S. enterica'' is the type species and is fur ...
typhimurium''; and the virus
bacteriophage T4 Escherichia virus T4 is a species of bacteriophages that infect ''Escherichia coli'' bacteria. It is a double-stranded DNA virus in the subfamily '' Tevenvirinae'' from the family Myoviridae. T4 is capable of undergoing only a lytic lifecycle ...
. In several such studies, numerous
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, mi ...
s defective in the same gene were isolated and mapped in a linear order on the basis of recombination frequencies to form a genetic map 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. doi:10.1073/pnas.50.3.516


See also

* Blue-white screen


References


External links

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