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 interaction 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'' (), from Ancient Greek δρόσος (''drósos''), meaning "dew", and φίλος (''phílos''), meaning "loving", is a genus of fly, belonging to the family Drosophilidae, whose members are often called "small fruit flies" or p ...

'' 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, ...

, and for a discussion of

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), ...

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 ...

. ''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 has two meanings. The Mendelian gene is a basic unit of heredity. The molecular gene is a sequence of nucleotides in DNA that is transcribed to produce a functional RNA. There are two types of molecular genes: protei ...

function. Amorph is sometimes used interchangeably with "genetic

null Null may refer to: Science, technology, and mathematics Astronomy *Nuller, an optical tool using interferometry to block certain sources of light Computing *Null (SQL) (or NULL), a special marker and keyword in SQL indicating that a data value do ...

". 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. Mos ...

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. Mos ...

to a chromosomal deletion 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 residue (biochemistry), residues. Proteins perform a vast array of functions within organisms, including Enzyme catalysis, catalysing metab ...

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 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, mitosis ...

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

gene expression Gene expression is the process (including its Regulation of gene expression, regulation) by which information from a gene is used in the synthesis of a functional gene product that enables it to produce end products, proteins or non-coding RNA, ...

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.

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, " ...

, Referent

, full ("normal"), expression of parent allele , - , Amorph , Dysfunctional, with null expression , - , Hypomorph , Reduced, or partial reduced gene activity , - , Hypermorph , Increased or partial increased parent gene activity , - , Neomorph , Novel function, comparing with the initial, new property , - , Antimorph , Opposing, antagonizing, or interfering gene activity , - ,

Isomorph An isomorph is an organism that does not change in shape during growth. The implication is that its volume is proportional to its cubed length, and its surface area to its squared length. This holds for any shape it might have; the actual shape d ...

, Identical expression with original (parent) allele, mostly resulting from silent point mutations , -

References

Classical genetics *