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Dr. Locke’s “Muller’s Morphs” Cheat-Sheet.
Oct 15’04
Every allele can be classified into one of Muller’s Morph (MM). The types of mutations at a locus provide information on how the
gene and its product are acting, and how it is functioning.
The first attribute is to determine whether the mutation is dominant or recessive to the wild type allele.
If m/+ shows a wild type phenotype then the mutation is recessive to wild type and is either amorphic or hypomorphic.
If m/+ shows a mutant phenotype then the mutation is dominant to wild type and is most likely to be neomorphic, antimorphic, or
hypermorphic, although it could be either amorphic or hypomorphic as well.
Type of
morph
A
morphic
Dominant
or
recessive.
recessive
Dominant
HYPO
morphic
recessive
Gain/loss Freq.
of function
Descrip. of m/+
mutant
function
None
wild type
Loss
Most
-complete common
Loss
uncommon None:
mutant
-complete
Haploinsufficient
Loss
common
Reduced
wild type
-partial
Dominant
Loss
-partia
Rare
HYPER
morphic
Dominant
Gain in
normal
Rare
NEO
morph
ANTI
morph
Dominant
Reduced: mutant
Haploinsufficient
Increased mutant
m/m
m/del
m/dup
Key
mutant
= m/del
Mutant
(more
severe)
less
mutant
than
m/del
more
mutant
than m/+
more
mutant
than m/+
mutant
= m/m
mutant
(more
severe)
more
mutant
than m/m
wild type
Recessive &
m/del = m/m
Dominant &
m/del = m/m
wild type
m/del is more
mutant than m/m
more
mutant
than m/m
less
mutant
than m/+
wild type
m/del is more
mutant than m/m
More
mutant
than m/+
- m/del is less
mutant than m/+
- m/dup is more
mutant than m/+
- dup/+ may mimic
mutant
m/+ = m/m
= m/del
m/+ is more mutant
than m/dup
wild
type?
Gain in
Uncommon New and
mutant
mutant
mutant
mutant
new
different
Dominant Gain of
Very rare
Works
mutant
less
against
against
mutant
wild type
wild type
Haplo-insufficent: a locus where two normal copies of gene product are needed for a normal phenotype. Loss of one (or part of
one) copy results in a mutant phenotype.
READ: Pages 535-537 Griffiths 8th Edition.
10/16/07
BIOLOGY 207 - Dr.Locke
Muller's Morphs
See pages 535-537 in Griffiths 8th Edition.
Muller, H. J. (1932). Further studies on the nature and causes of gene mutations. Proc. 6th Inter. Congr. Genet. 1, 213-255.
Note:
(1) Each of these different "morphs" are mutant forms (mutant alleles) derived from wild type
alleles by changes in the DNA sequence.
(2) Any gene can be changed (mutated) into one (or more) of these different morphs,
although not every gene can be mutated into every morph type.
If you have any questions about this supplementary page please see Dr. Locke.
Amorph – most common type of mutation
• - mutation that causes the absence of any gene product function.
• - also known as a "null" mutation
• - also known as a complete loss-of-function mutation
Molecular level explanation for a protein-coding gene.
Genetic/phenotypic level of expression
Changes in the DNA base pair sequence of the amorphic allele RECESSIVE:
may cause one or more of the following:
- amorphic mutations of most genes act as recessive to wild
- no gene - change in the DNA sequence removed the gene type.
from the chromosome.
- They are haplo-sufficient – only one functional copy is
Gene is present but:
needed for a wild type phenotype.
- no transcription (e.g. changed DNA sequence in the
e.g. white gene in Drosophila
promoter or enhancer/regulatory elements.)
- a white null = wnull
- normal transcription but aberrant processing of the
w+/w+ is wild type and red eyed
transcript (e.g. base pair changes that cause the mature
w+/wnull is wild type and red eyed
mRNA to not (or incorrectly) splice introns, therefore the
wnull/wnull is mutant and white eyed
translated amino acid sequence would be altered and not
function.)
DOMINANT:
- no translation (e.g. changes in the base pair sequences
- With some genes the amorphic mutations are dominant to
would preclude the mRNA from binding to the ribosome for
wild type
proper translation.)
-They are haplo-insufficient – having only one functional copy
- non-functional protein product (normal translation,
results in a mutant phenotype.
processing, translation but base pair changes a key amino acid e.g. Minute locus in Drosophila Min the polypeptide sequence so it is not functional - no activity ) M+/M+ is wild type and long bristled
M+/M- is mutant and short bristled
M-/M- is dead, a recessive lethal
We conclude that for this gene the organism needs both copies
to have a wild type phenotype. Loss of one copy (an amorphic
mutation) produces a mutant phenotype.
The classic amorphic mutation is a deletion (absence of the
gene) :
Identification of an amorphic mutation:
Recessive and Dominant:
Phenotype of m-/m- is the same as phenotype of m-/del if the wallele is an amophic mutation.
Wild type m-/m- = m-/del
mutant.
Deletions do not revert.
Hypomorph – common type of mutation
• - mutation that causes a reduction in normal gene product function.
• - also known as a "leaky" mutation
• - also known as a partial loss-of-function mutation
Molecular level explanation for a protein-coding gene.
Changes in the DNA base pair sequence of the hypomorphic
allele may cause one or more of the following:
Gene present but:
Biol207 Dr. Locke section
Muller!s Morphs
Genetic/phenotypic level of expression
- hypomorphic mutations of most (all?) genes usually act as
recessive to wild type.
e.g. white-apricot (wa ) allele of the white gene in Drosophila
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- reduced transcription (e.g. changed DNA sequence in the w+/w+ is wild type and red eyed
promoter or enhancer/regulatory elements that reduces the
w+/wa is wild type and red eyed (w+ is dominant to wa)
level of transcription.)
wa/wa is mutant and apricot eye colour (not a white eye)
- normal transcription but aberrant processing of the
wa/wnull is mutant and has a less coloured eye (more mutant)
transcript (e.g. base pair changes that cause the mature
wnull/ wnull has a white eye
mRNA to incorrectly splice introns, therefore the translated
- hypomorphic mutations theoretically could be dominant to
protein sequence would be altered and function at a reduced wild type - no example is provided – would be haplo-insufficient.
level.)
The classic hypomorphic mutation is usually either an altered
- reduced translation (e.g. changes in the base pair
amino acid that makes the polypeptide less active or a reduction
sequences would reduce the efficiency of the mRNA binding to in transcription that results in less normal transcript.
the ribosome for translation.)
Identification of a hypomorphic mutation:
- reduced-function protein product (normal translation,
Phenotype of wa/wa is more wild type (redder in colour) than the
processing, translation but base pair changes certain amino
phenotype of wa/del heterozygote.
acid in the polypeptide sequence so it's function (activity) is
Wild type wa/wa > wa/del mutant
reduced.)
(where > means more wild type than or more normal than)
Hypermorph – rare type of mutation
• - gain of function
• - mutation that causes a an increase in expression of normal gene product function.
Molecular level explanation for a protein-coding gene.
Genetic/phenotypic level of expression
Changes in the DNA base pair sequence of the hypermorphic - hyper-morphic mutations of most (all?) genes usually act as
allele may cause one or more of the following:
a dominant to wild type since they are a gain-of-function .
Gene duplication - extra copy(ies) of the gene
- no example is provided but if an extra dosage give a
One gene present but:
phenotype (dominant) implies that the product is dose sensitive.
- Increased transcription (e.g. changed DNA sequence in the The classic hyper-morphic mutation is usually a gene
promoter or enhancer/regulatory elements that increases the duplication that results in more normal transcript being
level of transcription.)
produced.
- increased translation (e.g. changes in the base pair
Identification of a hyper-morphic mutation:
sequences would increase the efficiency of the mRNA binding Phenotype of mutation/+ is more mutant than the phenotype of
to the ribosome for translation.)
mutation/del if mutant allele is a hypermophic mutation.
- increased-function protein product (normal translation,
Mutation homozygote is more mutant than mutation/+.
processing, translation but base pair changes certain amino
Duplication may mimic the mutation and will make the mutation
acid in the polypeptide sequence so it's function (activity) is
more severe.
normal but increased in amount.)
Wild type
m/del > m/+ > m/m > m/Dp mutant
(where > means “more wild type than” or “more normal than”)
Dose of wild type affects phenotype.
Duplications revert at a high frequency.
Neomorph – uncommon type of mutation
• - gain of function
• - mutation that causes a new function from the mutant gene.
Molecular level explanation for a protein-coding gene.
Changes in the DNA base pair sequence of the neomorphic
allele may cause one or more of the following:
Gene present but:
- new transcription (e.g. changed DNA sequence in the
promoter or enhancer/regulatory elements that makes new
transcription - either temporally or tissue specific.)
- new-function protein product (normal translation,
processing, translation but base pair changes certain amino
acid in the polypeptide sequence so it acquires a new function
(activity) that is different from the normal function.)
Biol207 Dr. Locke section
Muller!s Morphs
Genetic/phenotypic level of expression
- neo-morphic mutations of most (all?) genes act as a
dominant to wild type since they are a gain-of-function .
- Example: Antennapedia mutation in Drosophila (see class
notes)
The classic neo-morphic mutation is usually a translocation
that moves a new regulatory element next to a gene so it is
expressed in a new tissue or at a new time during development.
Identification of a neo-morphic mutation:
Phenotype of mutation/+ is equally mutant to the phenotype of
mutation/del if mutant allele is a neo-morphic mutation.
Wild type
m/del = m/+ = m/m = m/Dp mutant
Dose of wild type allele has no effect on phenotype.
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Antimorph – very rare type of mutation - also known as “Dominant-negative” mutation
• - gain of function
• - mutation that causes the function from the mutant gene to work against the normal
gene.
Molecular level explanation for a protein-coding gene.
Changes in the DNA base pair sequence of the anti-morphic
allele may cause one or more of the following:
Gene present but:
- new-function protein product that works against the
normal product (normal translation, processing, translation
but base pair changes certain amino acid in the polypeptide
sequence so it acquires the ability to work against the normal
function.)
Biol207 Dr. Locke section
Muller!s Morphs
Genetic/phenotypic level of expression
- anti-morphic mutations of most (all?) genes usually act as a
dominant to wild type since they are a gain-of-function.
-Example: Stubble-bristle mutation in Drosophila
The classic anti-morphic mutation is usually an amino acid
change that prevents a polypeptide from functioning in a multimeric protein complex.
Identification of an anti-morphic mutation:
Phenotype of mutation/+ is more mutant than the phenotype of
mutation/Dp if mutant allele is an anti-mophic mutation.
mutation/+ > mutation/+/+
Wild type m/Dp > m/+ > m/del (lethal?) mutant
The more normal product (or gene dosage) the more wild type
the phenotype.
Help pages
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