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 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.
''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
Null may refer to:
Science, technology, and mathematics Computing
* Null (SQL) (or NULL), a special marker and keyword in SQL indicating that something has no value
* Null character, the zero-valued ASCII character, also designated by , often use ...
". 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
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 ...
).
Hypomorph
Hypomorphic describes a mutation that causes a partial 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. 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 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. 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 ...
or 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 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 ...
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.
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 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 that is different from the normal function. A neomorphic mutation can cause ectopic 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 ...
or 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 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 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 ...
.
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
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, -
, 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 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 ...
, 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 interac ...
, 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 interac ...
, 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 interac ...
, 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 interac ...
, 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 de ...
, Identical expression with original (parent) allele, mostly resulting from silent point mutations
A point mutation is a genetic mutation where a single nucleotide base is changed, inserted or deleted from a DNA or RNA sequence of an organism's genome. Point mutations have a variety of effects on the downstream protein product—consequence ...
, -
References
Classical genetics
*