68 MUTATIONS 



in a cistron, then you might very well end up with differences of that 

 order. 



Auerbach: Oh, yes, certainly. 



Goldstein: I might add that we have evidence in the case of the 

 mutator strain of E. coli that we have been working with, in which 

 one is studying spontaneously high mutability in one and the same 

 organism, that there is a variation of several orders of magnitude in 

 the mutability of different sites for forward mutation. To give you a few 

 examples, the incidence of lac+ to lac" is of the order of 10"^. The 

 incidence of T4 resistance is about 4 X 10"^. The incidence of resistance 

 to a variety of other antibiotics, where w^e don't know the specific 

 genes involved, for example, penicillin, erythromycin, chloramphenicol, 

 is very low, about lO^'^. The incidence of total auxotrophs is about 

 3 X 10"^, of which the largest are histidine auxotrophs, and if one took 

 the forjvard rate on any particular one, such as uracil, for example, 

 this would be around 10"^ or 10"^. 



Auerbach: The first ones you mentioned, are they known to be due 

 to mutations at a particular locus, like reversions? Or could one of 

 them be due to mutations at several loci and the other one only to 

 mutations at one locus? 



Goldstein: None of these has been subjected to genetic test. The 

 lac~ changes include both galactosidase and permease. 



Neel: Perhaps I can try now to answer Dr. Benzer's question as to 

 whether today we have been discussing what it was intended we 

 should discuss under the heading of "mutation." It was hoped that 

 today would bring out precisely what it has brought out; namely, 

 that persons who work with different organisms think along somewhat 

 different lines when they speak of a mutation. I think that the 

 ultimate in how far your thinking can go has come out in the last 

 ten minutes, where, in discussing differences in locus rates, we have 

 wondered whether the number of nucleotides comprising the loci in 

 question are the same. 



There is one aspect of this problem of measuring mutation, and par- 

 ticularly in comparative mutation rates for man to mouse or Dro- 

 sophila to bacteria, that has not been touched on. This is the question 

 of whether, from one species to the next, we are detecting with our 

 usual laboratory techniques the same proportion of all the mutations 

 which are occurring. 



Let me state an extreme case. Possibly the structure of a bacterium 

 is such that any change in the genetic information results in a 

 phenotypic effect that can be picked up by a suitable technical method. 



