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Adaptive mutations occur in nongrowing populations of cells to overcome strong, nonlethal selection conditions. Several models have been proposed for the molecular mechanism(s) for this phenomenon inEscherichia coli, but the mechanisms involved in adaptive mutagenesis in the yeastSaccharomyces cerevisiaeare largely unknown. We present here a comparison of the mutational spectra of spontaneous and adaptive frameshift reversion events in yeast. In contrast to results fromE. coli, we find that the mutational spectrum of adaptive mutations inS. cerevisiaeis not similar to that seen in mismatch repair defective cells, but rather resembles the spontaneous mutational events that occur during normal growth.

A change in the number of base pairs within a coding sequence can result in a frameshift mutation, which almost invariably eliminates the function of the encoded protein. A frameshift reversion assay with Saccharomyces cerevisiaethat can be used to examine the types of insertions and deletions that are generated during DNA replication, as well as the editing functions that remove such replication errors, has been developed. Reversion spectra have been obtained in a wild-type strain and in strains defective for defined components of the postreplicative mismatch repair system (msh2, msh3, msh6, msh3 msh6, pms1, and mih1mutants). Comparison of the spectra reveals that yeast mismatch repair proteins preferentially remove frameshift intermediates that arise in homopolymer tracts and indicates that some of the proteins have distinct substrate or context specificities.