Replication-dependent and selection-induced mutations in respiration-competent and respiration-deficient strains of Saccharomyces cerevisiae

Adaptive or selection-induced mutations are defined as mutations that occur in non-dividing cells as a response to prolonged non-lethal selective pres sure such as starvation for an essential amino acid. In the absence of DNA replication, the processing of endogenous DNA lesions by repair enzymes pro bably acts as a source of mutations. We are studying selection-induced reve rsions of frameshift alleles in the eukaryote Saccharomyces cerevisiae. Her e we show that respiration-deficient strains, totally devoid of mitochondri al DNA, yield selection-induced mutants at slightly elevated frequencies co mpared to isonucleic respiration-competent strains. Therefore factors of mi tochondrial origin such as reactive oxygen species or hypothetical recombin ogenic DNA fragments are unlikely to be mediators of selection-induced nucl ear frameshift mutation in yeast. Furthermore we compared sequence spectra of reversions of the +1 hom3-10 frameshift allele and found a strong prefer ence for -1 deletions in mononucleotide repeats in selection-induced and re plication-dependent revertants, indicating slippage errors during DNA repai r synthesis as well as during DNA replication Remarkably, a higher degree o f variation in the site of the reverting frameshift and accompanying base s ubstitutions was found among selection-induced revertants.