Dictionary:

epistasis

  (ĭ-pĭs'tə-sĭs)

Also from Answers.com... Arthritis What is Arthritis? Learn about how to manage the aches and pains.

1. An interaction between nonallelic genes, especially an interaction in which one gene suppresses the expression of another.
2. A film that forms over the surface of a urine specimen.
3. The suppression of a bodily discharge or secretion.

[Greek, stoppage, from epistanai, to stop, check : ep-, epi-, epi- + histanai, to place.]

Epistasis, first defined by the English geneticist William Bateson in 1907, is the masking of the expression of a gene at one position in a chromosome, or locus, at one or more genes at other positions. Epistasis should not be confused with dominance, which refers to the interaction of genes at the same locus. The human genome contains from 30,000 to 70,000 gene loci. Some of them are involved in numerous interactions, making it difficult to identify their role in development and metabolism. As we learn more about the human and other genomes, it becomes clear that the borrowed phrase "no gene is an island" is an appropriate expression to describe the interplay among gene loci.

Puzzling Inheritance Patterns Explained

There are many examples of epistasis. One of the first to be described in humans is the Bombay phenotype, involving the ABO blood group system. Individuals with this phenotype lack a protein called the H antigen (geno-type hh), which is used to form A and B antigens. Even though such individuals may have A or B genes, they appear to be blood group O because they lack the H antigen.

Another well-known example is coat color in mice. Two coat-color loci are involved. At locus A, color is dominant over albino (lack of pigment). At locus B, the coat color agouti is dominant over black. A mouse that is homozygous for the albino gene will show no pigment regardless of its genotype at the other locus. Thus the A and B loci are epistatic.

It is likely that the phenomenon of lack of penetrance, in which a dominant gene fails to be expressed, is often due to epistasis. There are many cases where dominant disorders, such as polydactyly (in which individuals have extra fingers or toes), appear to "skip generations." The nonexpression of the dominant gene is likely due to the alleles the individual has at an independent locus that is epistatic to the polydactyly locus. Lack of penetrance may also be accompanied by variable expressivity, where a gene is only partially expressed. As the molecular basis of these disorders becomes known, the reason for nonpenetrance will be easier to determine.

Such interactions between loci probably occur in the genetic etiology of complex traits such as the psychiatric disorders schizophrenia and manic depression. David Lykken, a genetic psychologist at the University of Minnesota, coined the term "emergenesis" to describe multiple gene interactions involved in a specific complex trait. After comparing EEG (electroencephalogram, or "brain wave") data from identical and fraternal twins, Lykken concluded that multiple-level interactions of independent or partly independent genes must be involved.

Epistatic interactions make it difficult to identify loci conferring risk for complex disorders, and they may be a major reason that researchers have made only slow progress in mapping susceptibility genes for complex disorders. To locate interacting loci involved in the genetic origins of complex diseases requires collecting DNA samples from a large number of families where two or more individuals have the disorder. Such large-scale studies are usually difficult to conduct.

Interactions Among Proteins

As the Bombay phenotype demonstrates, it is actually proteins, not the genes, that interact. After identifying interacting loci, the next step is determining the proteins that the genes at those loci encode, and the properties of those proteins.

The emerging field that involves the study of proteins and protein interactions is called proteomics. New techniques are now available to locate proteins that interact with one another. In the yeast two-hybrid system, one such technique, one protein is used as bait, and a pool of unknown proteins, referred to as prey proteins, are tested to see if any of them bind to the bait. Binding, if it occurs, triggers a reaction that causes yeast cells to turn blue. In one experiment testing a protein's interactions with more than 1,000 other proteins, 950 interactions were found. Not all of these interactions are likely to occur or be important in the organism, but such results indicate how common, and complex, protein interactions are in living organisms.

Bibliography

Blum, Kenneth, and Ernest P. Noble, eds. Handbook of Psychiatric Genetics. New York:CRC Press, 1996.

Ezell, Carol. "Beyond the Human Genome." Scientific American 283 (2000): 64-69.

Mange, Arthur P., and Elaine J. Mange. Genetics: Human Aspects. Sunderland, MA:Sinauer Associates, 1990.

Race, Robert R., and Ruth Sanger. Blood Groups in Man, 6th ed. Oxford: BlackwellScientific Publications, 1975.

—P. Michael Conneally

Non-allelic masking of one gene by another, e.g. the masking of the black gene by the orange gene in tortoiseshell cats.

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 gene depends in a complicated way on many other genes; 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 statistical properties of the phenomenon.

Examples of tightly linked genes having epistatic effects on fitness are found in supergenes 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 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 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

Diagram illustrating different relationships between numbers of mutations and fitness. Synergistic epistasis is the red line - each mutation has a disproportionately large effect on the organism's fitness. Antagonistic epistasis is the blue line. See Evolution of Sex

Two-locus epistatic interactions can be either synergistic (positive) or antagonistic (negative). In the example of a haploid organism with genotypes (at two 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):

	AB	Ab	aB	ab
No epistasis (additive across loci)	2	1	1	0
Synergistic epistasis	3	1	1	0
Antagonistic epistasis	1	1	1	0

Hence, we can classify thus:

Trait values	Type of epistasis
AB = Ab + aB - ab	No epistasis, additive inheritance
AB > Ab + aB - ab	Synergistic epistasis
AB < Ab + aB - ab	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. Thus the idea is that sex selects for negative epistasis.^[1]

However, this view is not agreed by many others. For example, see Proc Natl Acad Sci U S A. 2007 Jul 31;104(31):12801-6. Coevolution of robustness, epistasis, and recombination favors asexual reproduction. MacCarthy T, Bergman A.

Publications from Otto and Feldman also disagree with Azaevedo et al.

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 complement and yet do not map to the same locus.
• Intragenic complementation, allelic complementation, or interallelic complementation - two mutations map to the same locus, yet the two alleles complement in the heteroallelic diploid. Causes of intragenic complementation include:
  • homology effects such as 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

1. ^ Azevedo R, Lohaus R, Srinivasan S, Dang K, Burch C (2006). "Sexual reproduction selects for robustness and negative epistasis in artificial gene networks". Nature 440 (7080): 87-90. PMID 16511495. 

External links

• GeneticInteractions.org
• Epistasis.org

The development of phenotype
Key concepts	Genotype-phenotype distinction · Norms of reaction · Gene-environment interaction · Heritability · Quantitative genetics
Genetic architecture	Dominance relationship · Epistasis · Polygenic inheritance · Pleiotropy · Plasticity · Canalisation · Fitness landscape
Non-genetic influences	Epigenetics · Maternal effect · Dual inheritance theory
Developmental architecture	Segmentation · Modularity
Evolution of genetic systems	Evolvability · Mutational robustness · Evolution of sex
Influential figures	C. H. Waddington · Richard Lewontin
Debates	Nature versus nurture
List of evolutionary biology topics

This entry is from Wikipedia, the leading user-contributed encyclopedia. It may not have been reviewed by professional editors (see full disclaimer)