54 MUTATIONS 



Auerbach: But they were in opposite chromosome? 



Magni: Yes. 



Atwood: Among the explanations that were suggested for Szybalski 

 and Bryson's case was the possibility that only a small proportion of 

 the cells accounts for a majority of the mutation, and this leads im- 

 mediately to an apparent lack of independence. Is it clear why it 

 should, or should I give a numerical example? 



Novick: Yes, do. 



Atwood: Let's say that the apparent rates of the two are 10"'^, so 

 then you expect the double mutation to be 10"^'*. But let's say that, as 

 an extreme case, 1 per cent of the cells are mutable and 99 per cent are 

 not, so that the actual rate accounting for just the mutable cells is 

 10"^, you see. 



Now, among this 1 per cent of cells, the double mutants will be 10"^°, 

 and since they are occurring only in 1 per cent of the cells, the ob- 

 served double mutant frequency relative to the total population would 

 be 10"^^, so in this case you expect 10"^^, and you obtain a hundred 

 times more than that. That kind of explanation is a suitable hypothesis 

 for further investigation. 



ZamenhoJ: We have found one case of a double mutant (11) which 

 was peculiar. The mutants were obtained stepwise; that is, it is not 

 the case where only one gene is involved; the parent strain was 

 tryptophan-dependent which was also induced to be histidine-depend- 

 ent by heat. This double histidine-dependent tryptophan-dependent 

 mutates back to histidine-independent tryptophan-independent every 

 time by a single mutational step. Moreover, by transformation we 

 always obtained histidine-independent tryptophan-independent by a 

 single transformation. Thus, one "back mutation" affects two functions, 

 tryptophan function and histidine function. To repeat, the mutants 

 were obtained by two separate mutational steps, but they mutate back 

 in a single event, and transformation always occurs with what we call 

 100 per cent linkage, that is, the cell is always transformed to both 

 prototrophic markers together. 



Freese: What is your evidence for two different cistrons? 



Zamenhof: The tryptophan locus is known to influence one enzyme, 

 and histidine locus, another one. 



Freese: This you assume. 



Zamenhof: In this particular case, we know it. 



Freese: I mean, it could be that one genetic region would be involved 

 in both enzymes. 



Zamenhof: One region which is necessary for both enzymes? 



