MICROBIAL MOLECULAR BIOLOGY AND GENETICS
The expression of a mutation will only be readily noticed if it produces
a detectable, altered phenotype. A mutation from the most
prevalent gene form, the wild type, to a mutant form is called a
forward mutation. Later, a second mutation may make the mutant
appear to be a wild-type organism again. Such a mutation is
called a reversion mutation because the organism seems to have
reverted back to its original phenotype. A true back mutation
converts the mutant nucleotide sequence back to the wild-type
sequence. The wild-type phenotype also can be regained by a second
mutation in a different gene, a suppressor mutation, which
overcomes the effect of the first mutation. If the second
mutation is within the same gene, the change may be called
a second site reversion or intragenic suppression. Thus, although
revertant phenotypes appear to be wild types, the original DNA
sequence may not be restored. In practice, a mutation is visibly
expressed when a protein that is in some way responsible for the
phenotype is altered sufficiently to produce a new phenotype.
However, mutations may occur and not alter the phenotype for a
variety of reasons.
Although very large deletion and insertion mutations exist,
most mutations affect only one base pair in a given location and
therefore are called point mutations. There are several types of
point mutations .
One kind of point mutation that could not be detected until the
advent of nucleic acid sequencing techniques is the silent mutation.
If a mutation is an alteration of the nucleotide sequence of
DNA, mutations can occur and have no visible effect because of
code degeneracy. When there is more than one codon for a given
amino acid, a single base substitution could result in the formation
of a new codon for the same amino acid. For example, if the codon
CGU were changed to CGC, it usually would still code for arginine
even though a mutation had occurred. The expression of this mutation
often would not be detected except at the level of the DNA or
mRNA. When there is no change in the protein or its concentration,
there will be no change in the phenotype of the organism.
A second type of point mutation is the missense mutation. This
mutation involves a single base substitution in the DNA that changes
a codon for one amino acid into a codon for another. For example,
the codon GAG, which specifies glutamic acid, could be changed to
GUG, which codes for valine. The expression of missense mutations
can vary. Certainly the mutation is expressed at the level of protein
structure. However, at the level of protein function, the effect may
range from complete loss of activity to no change at all.
Mutations also occur in the regulatory sequences responsible
for the control of gene expression and in other noncoding portions
of structural genes. Constitutive lactose operon mutants in
E. coli are excellent examples. These mutations map in the operator
site and produce altered operator sequences that are not recognized
by the repressor protein, and therefore the operon is continuously
active in transcription. If a mutation renders the
promoter sequence nonfunctional, the coding region of the structural gene will be completely normal, but a mutant phenotype will
result due to the absence of a product. RNA polymerase rarely
transcribes a gene correctly without a fully functional promoter.
Mutations also occur in rRNA and tRNA genes and can alter
the phenotype through disruption of protein synthesis. In fact,
these mutants often are initially identified because of their slow
growth. One type of suppressor mutation is a base substitution in
the anticodon region of a tRNA that allows the insertion of the
correct amino acid at a mutant codon.
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