Epistasis 370724 220602710 2008-06-20T17:32:47Z DOI bot 6652755 Citation maintenance. You can [[WP:DOI|use this bot]] yourself! Please [[User:DOI_bot/bugs|report any bugs]]. '''Epistasis''' is the [[interaction]] between genes. Epistasis takes place when the action of one [[gene]] is modified by one or several other genes, which are sometimes called '''modifier genes'''. The gene whose [[phenotype]] is expressed is said to be '''epistatic''', while the phenotype altered or suppressed is said to be '''hypostatic'''. In general, the fitness increment of any one allele depends in a complicated way on many other alleles; but, because of the way that the science of [[population genetics]] was developed, evolutionary scientists tend to think of epistasis as the exception to the rule. In the first models of [[natural selection]] devised in the early 20th century, each gene was considered to make its own characteristic contribution to fitness, against an average background of other genes. In introductory college courses, [[population genetics]] is still taught this way. Epistasis and '''genetic interaction''' refer to the same phenomenon; however, epistasis is widely used in [[population genetics]] and refers especially to the [[statistics|statistical]] properties of the phenomenon. Examples of tightly linked genes having epistatic effects on fitness are found in [[supergene]]s and the human [[major histocompatibility complex]] genes. The effect can occur directly at the genomic level, where one gene could code for a [[protein]] preventing [[Transcription (genetics)|transcription]] of the other gene. Alternatively, the effect can occur at the phenotypic level. For example, the gene causing [[albinism]] would hide the gene controlling color of a person's hair. In another example, a gene coding for a [[widow's peak]] would be hidden by a gene causing baldness. [[Fitness (biology)|Fitness]] epistasis (where the affected trait is fitness) is one cause of [[linkage disequilibrium]]. Studying genetic interactions can reveal gene function, the nature of the mutations, functional redundancy, and protein interactions. Because protein complexes are responsible for most biological functions, genetic interactions are a powerful tool. ==Classification by fitness or trait value== [[Image:Evolsex-dia3a.png|thumb|250px|Diagram illustrating different relationships between numbers of mutations and fitness. ''Synergistic'' epistasis is the blue line - each mutation has a disproportionately large effect on the organism's fitness. ''Antagonistic'' epistasis is the red line. See [[Evolution_of_sex#Sex_acts_to_encourage_removal_of_deleterious_genes|Evolution of Sex]]]] Two-locus epistatic interactions can be either synergistic (negative) or antagonistic (positive).<ref name=azevedo>{{cite journal |author=Azevedo R, Lohaus R, Srinivasan S, Dang K, Burch C |title=Sexual reproduction selects for robustness and negative epistasis in artificial gene networks |journal=Nature |volume=440 |issue=7080 |pages=87–90 |year=2006 |pmid=16511495 |doi=10.1038/nature04488}}</ref><ref name=bonhoeffer>{{cite journal |author=Bonhoeffer S, Chappey C, Parkin NT, Whitcomb JM, Petropoulos CJ |title=Evidence for positive epistasis in HIV-1 |journal=Science |volume=306 |issue=5701 |pages=1547–50 |year=2004 |pmid=15567861 |doi=10.1126/science.1101786}}</ref> In the example of a [[haploid]] organism with genotypes (at two [[locus (genetics)|loci]]) ''AB'', ''Ab'', ''aB'' and ''ab'', we can think of the following trait values where higher values suggest greater expression of the characteristic (the exact values are simply given as examples): {| cellpadding="2" | | ''AB'' | ''Ab'' | ''aB'' | ''ab'' |- | No epistasis (additive across loci)&nbsp; | 2 | 1 | 1 | 0 |- | Synergistic epistasis | 3 | 1 | 1 | 0 |- | Antagonistic epistasis | 1 | 1 | 1 | 0 |} Hence, we can classify thus: {| cellpadding="2" | '''Trait values''' | '''Type of epistasis''' |- | ''AB'' = ''Ab'' + ''aB'' - ''ab''&nbsp; | No epistasis, additive inheritance |- | ''AB'' > ''Ab'' + ''aB'' - ''ab''&nbsp; | Synergistic epistasis |- | ''AB'' < ''Ab'' + ''aB'' - ''ab''&nbsp; | Antagonistic epistasis |} Understanding whether the majority of genetic interactions are synergistic or antagonistic will help solve such problems as the [[evolution of sex]]. ==Epistasis and sex== Negative epistasis and sex are thought to be intimately correlated. Experimentally, this idea has been tested in using digital simulations of asexual and sexual populations. Over time, sexual populations move towards more negative epistasis, or the lowering of fitness by two interacting alleles. It is thought that negative epistasis allows individuals carrying the interacting deleterious mutations to be removed from the populations efficiently. This removes those alleles from the population, resulting in an overall more fit population. This hypothesis was proposed by [[Alexey Kondrashov]], and is sometimes known as the ''deterministic mutation hypothesis''<ref name="kondrashov">{{Cite journal | author = A. S. Kondrashov | title = Deleterious mutations and the evolution of sexual reproduction | year = 1988 | journal = [[Nature (journal)|Nature]] | volume = 336 | pages = 435–440 | doi = 10.1038/336435a0 }}</ref> and has also been tested using artificial gene networks.<ref name=azevedo/> However, the evidence for this hypothesis has not always been straightforward and the model proposed by Kondrashov has often been criticized for assuming mutation parameters far from real world observations. For example, see <ref>{{Cite journal | journal = [[Proc Natl Acad Sci U S A]] | year = 2007 | month = July | volume = 104 | issue = 31 | pages = 12801–6 | title = Coevolution of robustness, epistasis, and recombination favors asexual reproduction | author = MacCarthy T, Bergman A. | doi = 10.1073/pnas.0705455104 | pmid = 17646644 }}</ref> ==Functional or mechanistic classification== *'''Genetic suppression''' - the double mutant has a less severe phenotype than either single mutant. *'''Genetic enhancement''' - the double mutant has a more severe phenotype than one predicted by the additive effects of the single mutants. *'''Synthetic lethality''' or '''unlinked non-complementation''' - two mutations fail to [[complementation (genetics)|complement]] and yet do not map to the same [[Locus (genetics)|locus]]. *'''Intragenic complementation''', '''allelic complementation''', or '''interallelic complementation''' - two mutations [[genetic map|map]] to the same [[locus]], yet the two alleles complement in the heteroallelic diploid. Causes of intragenic complementation include: **homology effects such as [[transvection (genetics)|transvection]], where, for example, an enhancer from one allele acts in ''trans'' to activate transcription from the promoter of the second allele. **trans-splicing of two mutant RNA molecules to produce a functional RNA. **At the protein level, another possibility involves proteins that normally function as dimers. In a heteroallelic diploid, two different abnormal proteins could form a functional dimer if each can compensate for the lack of function in the other. ==See also== *[[Co-adaptation]] *[[Mutation]] ==References== <references/> ==External links== *[http://www.geneticinteractions.org GeneticInteractions.org] *[http://www.epistasis.org Epistasis.org] {{genarch}} [[Category:Classical genetics]] [[ca:Epístasi]] [[de:Epistase]] [[es:Epistasia]] [[fr:Épistasie]] [[he:אפיסטזה]] [[it:Epistasi]] [[lv:Epistāze]] [[nl:Epistasie]] [[pl:Epistaza]] [[pt:Epistasia]] [[sr:Интеракције гена]]