GENETICS OF SELECTION-INDUCED MUTATIONS .1. UVRA, UVRB, UVRC, AND UVRD ARE SELECTION-INDUCED SPECIFIC MUTATOR LOCI

Selection-induced mutations, sometimes called ''directed,'' ''adaptive ,'' or ''Cairnsian'' mutations, are spontaneous mutations that occur a s specific responses to environmental challenges, usually during perio ds of prolonged stress, and that occur more often when they are select ively advantageous than when they are selectively neutral. In this stu dy I show that lesions in uvrA, uvrB, uvrC, or uvrD increase the mutat ion rate from trpA46 to trpA(+) by 10(2)- to 10(4)-fold during tryptop han starvation, but those same lesions do not affect random mutation r ates in growing cells when tryptophan is present. The increased select ion-induced mutation rates remain specific to the gene that is under s election in that no increase in the mutation rate from trpA46 to trpA( +) is detected during proline starvation. Evidence is presented showin g that proline starvation produces a state of cellular stress which re sults in a burst of mutations from trpA46 to trpA(+) when proline-star ved cells are plated onto medium lacking tryptophan but containing pro line. These results are consistent with the hypermutable state model f or selection-induced mutagenesis.