Relation of forward reverse and suppressor mutations

^^^ One-nucleotide deletion

AAA XCAC TTG GCG TAC AA Phe Val Asn Arg Stop

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.

p, One-nucleotide duplication

AAA CAC TTT GGC GTA CAA Phe Val Lys Pro His Val

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

A third way in which an intragenic suppressor may work is by making compensatory changes in the protein. A first missense mutation may alter the folding of a poly-peptide 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) may recreate the original folding pattern by restoring interactions between the amino acids.

Intergenic suppressors, in contrast, occur in a gene that is different from 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 17.10), the original DNA sequence is AAC (UUG in the mRNA) and specifies leucine. This sequence mutates to ATC (UAG in mRNA), a termination codon. The ATC nonsense mutation could be suppressed by a mutation in a gene that encodes a tRNA molecule by changing the anticodon on the tRNA so that it is capable of pairing with the UAG termination codon. For example, the gene that encodes the tRNA for tyrosine (tRNATyr), which has the anticodon AUA, might be mutated to have the anticodon AUC, which will then pair with the UAG stop codon. Instead of translation terminating at the UAG codon, tyro-sine 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 is likely to be less detrimental than the effect of the nonsense mutation, which would halt translation prematurely.

Because cells in many organisms have multiple copies of tRNA genes, other unmutated copies of tRNATyr would a

A missense mutation alters a single codon.

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