Hermann J. Muller Hermann Joseph Muller (December 21, 1890 – April 5, 1967) was an American geneticist, educator, and Nobel laureate best known for his work on the physiological and genetic effects of radiation (mutagenesis), as well as his outspoken politica ...

(1890–1967), who was a 1946 Nobel Prize winner, coined the terms amorph, hypomorph, hypermorph, antimorph and neomorph to classify mutations based on their behaviour in various genetic situations, as well as

gene interaction Epistasis is a phenomenon in genetics in which the effect of a gene mutation is dependent on the presence or absence of mutations in one or more other genes, respectively termed modifier genes. In other words, the effect of the mutation is dep ...

between themselves.Muller, H. J. 1932. Further studies on the nature and causes of gene mutations. ''Proceedings of the 6th International Congress of Genetics'', pp. 213–255. These classifications are still widely used in ''

Drosophila ''Drosophila'' () is a genus of flies, belonging to the family Drosophilidae, whose members are often called "small fruit flies" or (less frequently) pomace flies, vinegar flies, or wine flies, a reference to the characteristic of many species ...

'' genetics to describe mutations. For a more general description of mutations, see

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 ...

, and for a discussion of

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 ...

interactions, see

dominance relationship 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 ...

. ''Key: In the following sections, alleles are referred to as +=wildtype, m=mutant, Df=gene deletion, Dp=gene duplication. Phenotypes are compared with '>', meaning 'phenotype is more severe than

Loss of function

Amorph

Amorphic describes a mutation that causes complete loss of

gene In biology, the word gene (from , ; "...Wilhelm Johannsen coined the word gene to describe the Mendelian units of heredity..." meaning ''generation'' or ''birth'' or ''gender'') can have several different meanings. The Mendelian gene is a ba ...

function. Amorph is sometimes used interchangeably with "genetic null". An amorphic mutation might cause complete loss of protein function by disrupting translation ("protein null") and/or preventing transcription ("RNA null"). An amorphic allele elicits the same phenotype when

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 ...

and when

heterozygous 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 ...

to a

chromosomal deletion In genetics, a deletion (also called gene deletion, deficiency, or deletion mutation) (sign: Δ) is a mutation (a genetic aberration) in which a part of a chromosome or a sequence of DNA is left out during DNA replication. Any number of nucleoti ...

or deficiency that disrupts the same gene.Wilkie, A. O. 1994. The molecular basis of genetic dominance. ''Journal of Medical Genetics'' 31: 89-98

/ref> This relationship can be represented as follows: m/m = m/Df An amorphic allele is commonly dominance relationship, recessive to its wildtype counterpart. It is possible for an amorph to be dominant if the gene in question is required in two copies to elicit a normal phenotype (i.e. haploinsufficient).

Hypomorph

Hypomorphic describes a mutation that causes a partial loss of

function. A hypomorph is a reduction in gene function through reduced (protein, RNA) expression or reduced functional performance, but not a complete loss. The phenotype of a hypomorph is more severe in ''trans'' to a deletion allele than when homozygous. m/DF > m/m Hypomorphs are usually recessive, but occasional alleles are dominant due to

haploinsufficiency Haploinsufficiency in genetics describes a model of dominant gene action in diploid organisms, in which a single copy of the wild-type allele at a locus in heterozygous combination with a variant allele is insufficient to produce the wild-type ...

Gain of function

Hypermorph

A hypermorphic mutation causes an increase in normal

function. Hypermorphic alleles are gain of function alleles. A hypermorph can result from an increase in gene dose (a gene duplication), from increased

mRNA In molecular biology, messenger ribonucleic acid (mRNA) is a single-stranded molecule of RNA that corresponds to the genetic sequence of a gene, and is read by a ribosome in the process of Protein biosynthesis, synthesizing a protein. mRNA is ...

protein Proteins are large biomolecules and macromolecules that comprise one or more long chains of amino acid residues. Proteins perform a vast array of functions within organisms, including catalysing metabolic reactions, DNA replication, respo ...

expression, or constitutive protein activity. The phenotype of a hypermorph is worsened by increasing the wildtype gene dose, and is reduced by lowering wildtype gene dose. m/Dp > m/+ > m/Df

Antimorph

Antimorphs are dominant mutations that act in opposition to normal

activity. Antimorphs are also called dominant negative mutations. Increasing wildtype gene function reduces the phenotypic severity of an antimorph, so the phenotype of an antimorph is worse when heterozygous than when in ''trans'' to a

gene duplication Gene duplication (or chromosomal duplication or gene amplification) is a major mechanism through which new genetic material is generated during molecular evolution. It can be defined as any duplication of a region of DNA that contains a gene. ...

. m/m > m/Df > m/+ >>> +/Df > +/+ An antimorphic mutation might affect the function of a protein that acts as a

dimer Dimer may refer to: * Dimer (chemistry), a chemical structure formed from two similar sub-units ** Protein dimer, a protein quaternary structure ** d-dimer * Dimer model, an item in statistical mechanics, based on ''domino tiling'' * Julius Dimer ( ...

so that a dimer consisting of one normal and one mutated protein is no longer functional.

Neomorph

A neomorphic mutation causes a dominant gain of

function that is different from the normal function. A neomorphic mutation can cause ectopic

expression, or new protein functions from altered protein structure. Changing wildtype gene dose has no effect on the phenotype of a neomorph. m/Df = m/+ = m/Dp

Isomorph

After Muller's classification of

gene 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, mitos ...

, an isomorph was described as a silent point mutant with identical

gene expression Gene expression is the process by which information from a gene is used in the synthesis of a functional gene product that enables it to produce end products, protein or non-coding RNA, and ultimately affect a phenotype, as the final effect. The ...

as the original

. m/Df = m/Dp Therefore, with respect to the relationship between the original and mutated genes, one cannot talk about the effects of dominance and/or

recessiveness 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 ...

Overview

;Muller’s classification of mutant alleles {, border=1 cellpadding=4 cellspacing=0 class="toccolours" style="align: left; margin: 0.5em 0 0 0; border-style: solid; border: 1px solid #999; border-right-width: 2px; border-bottom-width: 2px; border-collapse: collapse; font-size: 100%;" , - , style="background:#ddffdd;" align="center" , Category , colspan=1 style="background:#ddffdd;" align="center" , Alternative function , - ,

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 ...

, Referent

, full ("normal"), expression of parent allele , - , Amorph , Dysfunctional, with null expression , - ,

Hypomorph Hermann J. Muller (1890–1967), who was a 1946 Nobel Prize winner, coined the terms amorph, hypomorph, hypermorph, antimorph and neomorph to classify mutations based on their behaviour in various genetic situations, as well as gene interact ...

, Reduced, or partial reduced gene activity , - ,

Hypermorph Hermann J. Muller (1890–1967), who was a 1946 Nobel Prize winner, coined the terms amorph, hypomorph, hypermorph, antimorph and neomorph to classify mutations based on their behaviour in various genetic situations, as well as gene interact ...

, Increased or partial increased parent gene activity , - ,

Neomorph Hermann J. Muller (1890–1967), who was a 1946 Nobel Prize winner, coined the terms amorph, hypomorph, hypermorph, antimorph and neomorph to classify mutations based on their behaviour in various genetic situations, as well as gene interact ...

, Novel function, comparing with the initial, new property , - ,

Antimorph Hermann J. Muller (1890–1967), who was a 1946 Nobel Prize winner, coined the terms amorph, hypomorph, hypermorph, antimorph and neomorph to classify mutations based on their behaviour in various genetic situations, as well as gene interact ...

, Opposing, antagonizing, or interfering gene activity , - , Isomorph , Identical expression with original (parent) allele, mostly resulting from silent point mutations , -

References

Classical genetics *