MUTAGENESIS 123 



Therefore, how did it get established in evolution? It would be estab- 

 lished if it also has selective advantage as being a duplication at the 

 same time, which would overpower the disadvantage of its instability. 

 Is that correct reasoning? 



Auerbach: You wouldn't find mutations. Also, the silent mutants 

 in this region would be protected. That may outbalance this disad- 

 vantage. 



Lederberg: Could I raise this bugaboo — why there should be more 

 than four mutation rates and just what chemical basis there might 

 be for higher order differences in different parts of the DNA? Does 

 anybody have some ideas on this? 



Glass: I have a somewhat speculative question that I would like to 

 ask in regard to the peroxide (and perhaps it relates as well to the 

 other radiomimetic chemical mutagens) . 



We now know that in all organisms that carry on photosynthesis 

 with chlorophyll, where water is split, a big step is the formation of 

 hydroxyl radicals which results in the liberation of molecular oxygen. 

 The peroxide phase that results from the combination of the hydroxyl 

 radicals is very brief and the concentration of peroxide is never per- 

 mitted to rise in the cytoplasm, because of the deleterious effects that 

 it would produce in general. 



The questions which this brings to my mind relate on a comparative 

 basis to the possible differential action of such mutagens in micro- 

 organisms, in multicellular animals, and in green plants. The effects 

 with peroxide were originally discovered in microorganisms, and my 

 first question would be, does this mean that in the microorganisms there 

 is an abundance — even in the photosynthetic bacteria which do not 

 split water — an abundance of catalase or peroxidase or at least 

 peroxide-destroying enzymes, or is there a lack of these that would 

 permit the action of the mutagens much more strongly than in green 

 plants? 



The second question that arises from this consideration is whether 

 peroxide-destroying enzymes are limited to the cytoplasm, and whether, 

 therefore, the production of hydroxyl radicals or of peroxides in the 

 nucleus would be able to act on the genetic material, whereas if perox- 

 ide were produced in the cytoplasm it would normally be neutralized 

 before it could ever have a chance to act. I would ask whether anyone 

 knows whether there is good evidence of the existence in green plants 

 of a real peroxide effect when peroxide is applied externally? Can it 

 get through the cytoplasm to the genetic material in the nucleus and 



