Mutation as an error in base pairing

Summary The model of mutation by transitional change (Freese 1959) predicts that a heritable change in genotype is established when two replications of DNA succeed the initial incorporation of an analogue. The model was tested in populations ofSalmonella typhimurium strainstryD-10 andtryD-79 whose division had been synchronized by fractional filtration. Mutation from auxotrophy to prototrophy (try^–try⁺) induced by 5-bromodeoxyuridine (BUDR) and 2-aminopurine (AP) occurred in accordance with DNA replication. Two subsequent DNA replications were necessary to obtain BUDR-induced prototrophs inD-79, one subsequent DNA replication was required for AP-induced prototrophs inD-79, while no subsequent DNA replication was necessary for AP-induced prototrophs inD-10. This was observed whether the mutagens were present continuously or during only the first replication and also when the cells were allowed to replicate their DNA without cell division in the presence of inhibitory concentrations of the base analogue or when protein synthesis was blocked in the presence of chloramphenicol. A statistical analysis of the patterns of mutant increase observed for six mutant strains was used to distinguish between errors in replication and errors in incorporation induced by the base analogues and thereby the base pair at the mutant site was identified.With 10 Figures in the TextSupported in part by grants from the American Cancer Society the U.S. Public Health Service and the National Science Foundation administered by ProfessorF. J. Ryan.