132 MUTATIONS 



locus. In one experiment on the delayed action of diepoxybiitane, 

 which Dr. K0lmark and I carried out together (42), we got the fol- 

 lowing results. When we plated at once, survival was about 80 per 

 cent, mutation frequency per 10" survivors, and mutation frequency 

 was 110 for the adenine locus and 5 for the inositol locus. When the 

 suspension was kept for 4 hours at 30° between treatment and plating, 

 survival remained sensibly the same, but mutation frequency at the 

 adenine locus had increased to 830 per lO'', while there had been no 

 increase at the inositol locus. Thus, the simple expedient of keeping the 

 treated suspensions for a few hours had intensified the difference be- 

 tween the two loci very much. 



A more important source of mutagen specificity is one found re- 

 cently by Witkin (81) in her work on UV induced mutations in E. coli. 

 All her reverse mutations to prototrophy required stabilization of the 

 premutated state, and this in turn required protein synthesis. She 

 found now that this is not so for mutations from streptomycin sen- 

 sitivity to streptomycin resistance, or from streptomycin dependence 

 to independence. If, therefore, one would score reversions from 

 auxotrophy to prototrophy and mutations from streptomycin sensi- 

 tivity to resistance in the same strain, prevention of protein synthesis, 

 for instance by chloramphenicol, would prevent mutations to proto- 

 trophy but not to streptomycin resistance. Operationally under these 

 circumstances, there would be specificity of UV for mutations at the 

 streptomycin locus. 



Goodgal: 1 don't agree with that, because it may very well be that 

 it is the postmutational step which is involved rather than the pre- 

 mutational step. 



Auerbach: This is what I meant to say. I don't want to reinterpret 

 or reassess Witkin's explanation. All I wanted to point out here was 

 that you would get a marked specificity, which is not due to a specific 

 reaction of the UV on the streptomycin locus. 



Goldstein: Another difference here is not the difference between the 

 tryptophan locus and the streptomycin locus, but the fact that the 

 tryptophan locus is mutating in a backward direction from depend- 

 ence to independence, and the streptomycin locus, from sensitivity to 

 resistance, is mutating in a forward direction. And if the change from 

 dependence to independence is a suppressor change, that is also moving 

 in a forward direction. So you are comparing a backward mutation 

 with a forward mutation, and this says nothing necessarily about the 

 two loci involved. If one wants to ask a question about specificity 

 differences between genes, then one cannot use a back mutation system, 



