194 Discussion 



Lederberg: You had a similar evidence for the specificity of interaction 

 with chloramphenicol, Cavalli-Sforza. 



Cavalli-Sforza: Specificity of interaction is of some interest. As a conse- 

 quence of it, every process of selection, leading to multistep resistance, is 

 in itself more or less unique, because much depends, for the later stages, 

 on which is the first resistant gene that came in. The later ones are 

 bound to interact with that one ; they have to increase the resistance of 

 that one. Therefore, you may even find situations where the second gene 

 that gives second-step resistance does not give resistance by itself; if you 

 isolate it by recombination, you may find that that second gene is only a 

 modifier of the first. It may have an effect on resistance only in combina- 

 tion with the first. 



Lederberg: It should then be possible to cross two strains obtained 

 separately, but of equal resistance, and get progeny which are more 

 sensitive than either parent. 



Cavalli-Sforza: Exactly, that is what is happening. 



Dernerec: In the work you have completed so far. Dr. Hotchkiss, have 

 you obtained any evidence that throws light on the mechanism by which 

 transformation is accomplished? In this particular case dealing with 

 transfer of high resistance to sulphurs, you assume that you have three 

 genes which are linked together and which would be carried in one 

 transforming unit of DNA. You assume the order of these genes to be 

 adb. Have you any evidence of a combination of ab ? Can you tell if that 

 may be transferred when you start with a donor which carries all three ? 



Hotchkiss: As far as we can see we don't get the ab's from the donor 

 which has adb. We get either the whole piece or fragments. If we create 

 ab by using the a and the b separately, then the ab transfers approxi- 

 mately as often as the adb. So the frequencies fit, in this case, and it is 

 the rareness of this type that is the basic argument for the sequence, the 

 db's and the ad's are much more frequent than the ab's. 



Davis : Is the linking of these close enough for you to have any idea as 

 to whether these different units are likely to be concerned with a single 

 genetic unit in terms of physiological function ? Do you know any other 

 cases in which a single mutation can give you divisible changes? 



Hotchkiss: Mutations can be inversions of whole regions and trans- 

 positions and so on. It would require many markers to find them in 

 bacteria, but it would not be out of the question. We tend to think of 

 mutations in the purest case as more or less point mutation. 



Demerec: There are large numbers of mutations known which affect a 

 region involving several gene loci, but this is the first case, as far as I am 

 aware, where such mutation is divisible. In most other cases, probably 

 we are dealing with deficiencies involving a part of a gene or adjacent 

 genes. 



Davis: Prof. Cavalli-Sforza published evidence some years ago that 

 in multiple-step resistance several different loci can be concerned, each 

 making its contribution. That result may perhaps have lent support to 

 the impression, which seems widespread, that it is hard to picture muta- 

 tions as giving rise to the enormous numbers of degrees of resistance you 

 can get, because you would have to have so many different loci involved. 



