Muller's morphs
Encyclopedia
Neomorph redirects here. It is also one of the post-human types of persons in the novel Eon
Eon (novel)
Eon is a 1985 science fiction novel by Greg Bear. It is the first story written in The Way fictional universe.Events in Eon take place in 2005, when the U.S.A. and U.S.S.R. are on the verge of nuclear war. In that tense political climate, a 290 km asteroid appears within the solar system...

by Greg Bear.


1946 Nobel Prize winner Hermann J. Muller (1890-1967) coined the terms
amorph, hypomorph, hypermorph, antimorph and neomorph to classify mutations based on their behaviour in various genetic
Genetics
Genetics , a discipline of biology, is the science of genes, heredity, and variation in living organisms....

 situations. These classifications are still widely used in
Drosophila
Drosophila
Drosophila is a genus of small flies, belonging to the family Drosophilidae, whose members are often called "fruit flies" or more appropriately pomace flies, vinegar flies, or wine flies, a reference to the characteristic of many species to linger around overripe or rotting fruit...

genetics to describe mutations. For a more general description of mutations, see mutation
Mutation
In molecular biology and genetics, mutations are changes in a genomic sequence: the DNA sequence of a cell's genome or the DNA or RNA sequence of a virus. They can be defined as sudden and spontaneous changes in the cell. Mutations are caused by radiation, viruses, transposons and mutagenic...

, and for a discussion of allele interactions, see dominance relationship
Dominance relationship
Dominance in genetics is a relationship between two variant forms of a single gene, in which one allele masks the effect of the other in influencing some trait. In the simplest case, if a gene exists in two allelic forms , three combinations of alleles are possible: AA, AB, and BB...

.

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

Amorph

Amorphic describes a mutation that causes complete loss of gene
Gene
A gene is a molecular unit of heredity of a living organism. It is a name given to some stretches of DNA and RNA that code for a type of protein or for an RNA chain that has a function in the organism. Living beings depend on genes, as they specify all proteins and functional RNA chains...

 function. Amorph is sometimes used interchangeably with "genetic null
Null allele
A null allele is a mutant copy of a gene that completely lacks that gene's normal function. This can be the result of the complete absence of the gene product at the molecular level, or the expression of a non-functional gene product...

". 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
Zygosity refers to the similarity of alleles for a trait in an organism. If both alleles are the same, the organism is homozygous for the trait. If both alleles are different, the organism is heterozygous for that trait...

 and when heterozygous
Zygosity
Zygosity refers to the similarity of alleles for a trait in an organism. If both alleles are the same, the organism is homozygous for the trait. If both alleles are different, the organism is heterozygous for that trait...

 to a chromosomal deletion
Genetic deletion
In genetics, a deletion is a mutation in which a part of a chromosome or a sequence of DNA is missing. Deletion is the loss of genetic material. Any number of nucleotides can be deleted, from a single base to an entire piece of chromosome...

 or deficiency that disrupts the same gene. This relationship can be represented as follows:

m/m = m/Df

An amorphic allele is commonly recessive
Dominance relationship
Dominance in genetics is a relationship between two variant forms of a single gene, in which one allele masks the effect of the other in influencing some trait. In the simplest case, if a gene exists in two allelic forms , three combinations of alleles are possible: AA, AB, and BB...

 to its wildtype counterpart. It is possible for an amorph to be dominant
Dominance relationship
Dominance in genetics is a relationship between two variant forms of a single gene, in which one allele masks the effect of the other in influencing some trait. In the simplest case, if a gene exists in two allelic forms , three combinations of alleles are possible: AA, AB, and BB...

 if the gene in question is required in two copies to elicit a normal phenotype (i.e. haploinsufficient
Haploinsufficiency
Haploinsufficiency occurs when a diploid organism only has a single functional copy of a gene and the single functional copy of the gene does not produce enough of a gene product to bring about a wild-type condition, leading to an abnormal or diseased state...

).

Hypomorph

Hypomorphic describes a mutation that causes a partial loss of gene
Gene
A gene is a molecular unit of heredity of a living organism. It is a name given to some stretches of DNA and RNA that code for a type of protein or for an RNA chain that has a function in the organism. Living beings depend on genes, as they specify all proteins and functional RNA chains...

 function. A hypomorph is a reduction in gene (protein, RNA) expression, 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
Haploinsufficiency occurs when a diploid organism only has a single functional copy of a gene and the single functional copy of the gene does not produce enough of a gene product to bring about a wild-type condition, leading to an abnormal or diseased state...

.

Hypermorph

A hypermorphic mutation causes an increase in normal gene
Gene
A gene is a molecular unit of heredity of a living organism. It is a name given to some stretches of DNA and RNA that code for a type of protein or for an RNA chain that has a function in the organism. Living beings depend on genes, as they specify all proteins and functional RNA chains...

 function. Hypermorphic alleles are dominant gain of function alleles. A hypermorph can result from an increase in gene dose (a gene duplication), from increased mRNA
Messenger RNA
Messenger RNA is a molecule of RNA encoding a chemical "blueprint" for a protein product. mRNA is transcribed from a DNA template, and carries coding information to the sites of protein synthesis: the ribosomes. Here, the nucleic acid polymer is translated into a polymer of amino acids: a protein...

 or protein
Protein
Proteins are biochemical compounds consisting of one or more polypeptides typically folded into a globular or fibrous form, facilitating a biological function. A polypeptide is a single linear polymer chain of amino acids bonded together by peptide bonds between the carboxyl and amino groups of...

 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
Dominance relationship
Dominance in genetics is a relationship between two variant forms of a single gene, in which one allele masks the effect of the other in influencing some trait. In the simplest case, if a gene exists in two allelic forms , three combinations of alleles are possible: AA, AB, and BB...

 mutations that act in opposition to normal gene
Gene
A gene is a molecular unit of heredity of a living organism. It is a name given to some stretches of DNA and RNA that code for a type of protein or for an RNA chain that has a function in the organism. Living beings depend on genes, as they specify all proteins and functional RNA chains...

 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
Gene duplication is any duplication of a region of DNA that contains a gene; it may occur as an error in homologous recombination, a retrotransposition event, or duplication of an entire chromosome.The second copy of the gene is often free from selective pressure — that is, mutations of it have no...

.

m/+ > m/Dp

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 gene
Gene
A gene is a molecular unit of heredity of a living organism. It is a name given to some stretches of DNA and RNA that code for a type of protein or for an RNA chain that has a function in the organism. Living beings depend on genes, as they specify all proteins and functional RNA chains...

 function that is different from the normal function. A neomorphic mutation can cause ectopic mRNA
Messenger RNA
Messenger RNA is a molecule of RNA encoding a chemical "blueprint" for a protein product. mRNA is transcribed from a DNA template, and carries coding information to the sites of protein synthesis: the ribosomes. Here, the nucleic acid polymer is translated into a polymer of amino acids: a protein...

 or protein
Protein
Proteins are biochemical compounds consisting of one or more polypeptides typically folded into a globular or fibrous form, facilitating a biological function. A polypeptide is a single linear polymer chain of amino acids bonded together by peptide bonds between the carboxyl and amino groups of...

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

Sources

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.

Wilkie, A. O. 1994. The molecular basis of genetic dominance. Journal of Medical Genetics 31: 89-98.
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