pierceessentials3e

Suppressor Mutations

A suppressor mutation is a genetic change that hides or suppresses the effect of another mutation. This type of mutation is different from a reverse mutation, in which the mutated site changes back into the original wild-type sequence (Figure 13.7). A suppressor mutation occurs at a site that is distinct from the site of the original mutation; thus, an individual with a suppressor mutation is a double mutant, possessing both the original mutation and the suppressor mutation but exhibiting the phenotype of a nonmutated wild type. Geneticists distinguish between two classes of suppressor mutations: intragenic and intergenic.

Figure 13.7: Relation of forward, reverse, and suppressor mutations.

INTRAGENIC SUPPRESSOR MUTATIONS An intragenic suppressor mutation takes place in the same gene that contains the mutation being suppressed. It may work in any of several ways. The suppressor may change a second nucleotide in the same codon altered by the original mutation, producing a codon that specifies the same amino acid that was specified by the original, nonmutated codon (Figure 13.8).

Figure 13.8: An intragenic suppressor mutation occurs in the gene containing the mutation being suppressed.

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Intragenic suppressors may also work by suppressing a frameshift mutation. If the original mutation, for example, is a one-base deletion, then the addition of a single base elsewhere in the gene will restore the former reading frame. Consider the following nucleotide sequence in DNA and the amino acids that it encodes:

Suppose that a one-base deletion occurs in the first nucleotide of the second codon. This deletion shifts the reading frame by one nucleotide and alters all the amino acids that follow the mutation.

If a single nucleotide is added to the third codon (the suppressor mutation), the reading frame is restored, although two of the amino acids differ from those specified by the original sequence.

Similarly, a mutation due to an insertion may be suppressed by a subsequent deletion in the same gene.

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A third way in which an intragenic suppressor may work is by making compensatory changes in the protein. A first missense mutation can alter the folding of a polypeptide chain by changing the way in which amino acids in the protein interact with one another. A second missense mutation at a different site (the suppressor) can recreate the original folding pattern by restoring interactions between the amino acids.

INTERGENIC SUPPRESSOR MUTATIONS An intergenic suppressor mutation occurs in a gene other than the one bearing the original mutation. These suppressors sometimes work by changing the way that the mRNA is translated. In the example illustrated in Figure 13.9a, the original DNA sequence is AAC (UUG in the mRNA) and specifies leucine. This sequence mutates to ATC (UAG in mRNA), a stop codon (Figure 13.9b). The ATC nonsense mutation could be suppressed by a second mutation in a different gene that encodes a tRNA; this second mutation would result in a codon capable of pairing with the UAG stop codon (Figure 13.9c). For example, the gene that encodes the tRNA for tyrosine (tRNA^Tyr), which has the anticodon AUA, might be mutated to have the anticodon AUC, which would then pair with the UAG stop codon. Instead of translation terminating at the UAG codon, tyrosine would be inserted into the protein, and a full-length protein would be produced, although tyrosine would now substitute for leucine. The effect of this change would depend on the role of this amino acid in the overall structure of the protein, but the effect of the suppressor mutation would probably be less detrimental than the effect of the nonsense mutation, which would halt translation prematurely.

Figure 13.9: An intergenic suppressor mutation occurs in a gene other than the one bearing the original mutation. (a) The wild-type sequence produces a full-length, functional protein. (b) A base substitution at a site in the same gene produces a premature stop codon, resulting in a truncated, nonfunctional protein. (c) A base substitution at a site in another gene, which in this case encodes tRNA, alters the anticodon of tRNA^Tyr so that tRNA^Tyr can pair with the stop codon produced by the original mutation, allowing tyrosine to be incorporated into the protein and translation to continue.

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Because cells in many organisms have multiple copies of tRNA genes, other nonmutated copies of tRNA^Tyr would remain available to recognize tyrosine codons in the transcripts of the mutant gene in question and in other genes being expressed concurrently. We might expect that the tRNAs that have undergone the suppressor mutation just described would also suppress the normal stop codons at the ends of other coding sequences, resulting in the production of longer-than-normal proteins, but this event does not usually take place.

Characteristics of some of the different types of mutations are summarized in Table 13.2.

TABLE 13.2 Characteristics of different types of mutations

Type of mutation	Definition
Base substitution	Changes a single DNA nucleotide
Transition	Base substitution in which a purine replaces a purine or a pyrimidine replaces a pyrimidine
Transversion	Base substitution in which a purine replaces a pyrimidine or a pyrimidine replaces a purine
Insertion	Addition of one or more nucleotides
Deletion	Deletion of one or more nucleotides
Frameshift mutation	Insertion or deletion that alters the reading frame of a gene
In-frame deletion or insertion	Deletion or insertion of a multiple of three nucleotides that does not alter the reading frame
Expanding nucleotide repeats	Increases the number of copies of a set of nucleotides
Forward mutation	Changes the wild-type phenotype to a mutant phenotype
Reverse mutation	Changes a mutant phenotype back to the wild-type phenotype
Missense mutation	Changes a sense codon into a different sense codon, resulting in the incorporation of a different amino acid in the protein
Nonsense mutation	Changes a sense codon into a nonsense (stop) codon, causing premature termination of translation
Silent mutation	Changes a sense codon into a synonymous codon, leaving the amino acid sequence of the protein unchanged
Neutral mutation	Changes the amino acid sequence of a protein without altering its ability to function
Loss-of-function mutation	Causes a complete or partial loss of function
Gain-of-function mutation	Causes the appearance of a new trait or function or causes the appearance of a trait in inappropriate tissue or at an inappropriate time
Lethal mutation	Causes premature death
Suppressor mutation	Suppresses the effect of an earlier mutation at a different site
Intragenic suppressor mutation	Suppresses the effect of an earlier mutation within the same gene
Intergenic suppressor mutation	Suppresses the effect of an earlier mutation in another gene

CONCEPTS

A suppressor mutation overrides the effect of an earlier mutation at a different site. An intragenic suppressor mutation occurs within the same gene as that containing the original mutation; an intergenic suppressor mutation occurs in a different gene.

CONCEPT CHECK 2

How does a suppressor mutation differ from a reverse mutation?

A reverse mutation restores the original phenotype by changing the DNA sequence back to the wild type. A suppressor mutation restores the phenotype by causing an additional change in the DNA at a site that is different from that of the original mutation.