Often, the effects of harmful muta lions can be reversed by a second genetic change. Some of these subsequent mutations are easy to understand, being simple reverse (back) mutations, which change an altered nucleotide sequence back to its original arrangement. Morn difficult to understand are the mutations occurring at different locations on the chromosome that suppress the change due to a mutation at site A by producing an additional genetic change at site B. Such suppressor mutations fall into two main categories: those ttccurring within the same gene as the original mutation, but at a different site in this gene (intragenic suppression) and those occurring in another gene (intergenic suppression). Genes that cause suppression of mutations in other genes are called suppressor genes. Both of the types of suppression that we are considering here work by causing the production of good (or partially good) copies of the protein made inactive by the original harmful mutation. For example, if the first mutation caused the production of inactive copies of one of the enzymes involved in making arginine, then the suppressor mutation allows arginine to be made by restoring the synthesis of some good copies of this same enzyme. However, the mechanisms by which intergenic and intragenic suppressor mutations cause the resumption of the synthesis of good proteins are completely different.
As an example of intragenic supression, consider the case of a missense mutation. Its effect can sometimes be reversed through an additional missense mutation in tht? same gene. In such cases, the original loss of enzymatic activity is due to an altered three-dimensional configuration resulting from the presence of an incorrect amino acid in the encoded protein sequence. A second missense mutation Sn the same gene can bring back biological activity if it somehow restores the original configuration around the functional part of the molecule. Figure 15-6 shows another example of intragenic suppression, this time for the case of a frameshift mutation.
Suppressor genes do not act by changing the nucleotide sequence of a mutant gene. Instead, they change the way the mRNA template is read. One of the best known examples of suppressor mutations are mutant tRNA genes that suppress the effects of nonsense mutations in protein-coding genes (but mutant tRNAs that suppress missense mutations and
FIGURE 15-6 Suppression of frameshift mutations, (a) A deletion tn the nucleotide coding sequence can result in an incomplete, inactive polypeptide chain (b) The effect of the deletion, shown in pane! <j, can be overcome by a second mutation, an insertion in the coding sequence This insertion results in Elie production of a compete polypeptide chain having two amino acid replacements. Depending ofi the change in sequence, the protein may have partial or full activity.
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