338 



CHAPTER 36 



distinguish two kinds of mutagens, a purine 

 type and a radiation type, which produce two 

 different kinds of mutations. In considering 

 the basis of the spontaneous mutation rate, 

 it can be postulated that, under the experi- 

 mental conditions described, about two thirds 

 of it is produced by the action of some purine 

 type of substance produced spontaneously 

 during the normal metabolism of the cell. 

 It may seem surprising that only purines, 

 their analogs, and purine nucleosides were 

 found to affect the mutation rate. Perhaps 

 this is related to the particular mutations 

 studied, namely resistance to T5 and T6. 

 It may be that these mutations happen to 

 depend more upon changes in purines than 

 upon changes in pyrimidines, and that other 

 mutations may prove to be relatively pyrim- 

 idine-sensitive and purine-insensitive. 

 While it is not clear how the purines and 



their nucleosides accomplish these mutagenic 

 and antimutagenic effects, and how these 

 effects are related to the changes in mutation 

 rate with generation length, two general con- 

 clusions are warranted. First, these experi- 

 ments prove that a considerable portion of 

 the spontaneous mutation rate is the normal 

 consequence of the cell's biochemical activity 

 in producing mutagens and antimutagens. 

 Second, these experiments demonstrate a 

 connection between mutation rate and nucleic 

 acid metabolism. While the mutation rate 

 was directly connected only with purines and 

 their nucleosides, it is not unreasonable to 

 suppose that there is also an indirect connec- 

 tion with DNA and its precursors. This 

 supposition is supported by the fact that 

 thymine, which is a component of DNA and 

 not RNA, is mutagenic when withheld from 

 bacteria requiring it. 



SUMMARY AND CONCLUSIONS 



Bacterial clones provide excellent experimental material for the study of the mutation process 

 and its rate. Mutants occur spontaneously, independently of the factors to which they 

 may be adaptive. 



A considerable portion of the spontaneous mutation rate is based upon the intracellular 

 production of mutagens and antimutagens. For this reason, spontaneous mutation is in 

 many respects an incident of the normal metabolism of the cell, in which nucleic acids are 

 specifically implicated. 



REFERENCES 



Lederberg, J., and Lederberg, E. M., "Replica Plating and Indirect Selection of Bacterial 

 Mutants," J. Bact., 63:399-406, 1952; reprinted in Papers on Bacterial Genetics, Adel- 

 berg, E. A. (Ed.), Boston, Little, Brown, 1960, pp. 24-31. 



Novick, A., "Mutagens and Antimutagens," Brookhaven Symposia on Biology, 8:201-215, 

 1956; reprinted in Papers on Bacterial Genetics, Adelberg, E. A. (Ed.), Boston, Little, 

 Brown, 1960, pp. 74-90. 



Novick, A., and Szilard, L., "Experiments on Spontaneous and Chemically Induced Mutations 

 of Bacteria Growing in the Chemostat," Cold Spring Harbor Sympos. Quant. Biol., 

 16:337-343, 1951; reprinted in Papers on Bacterial Genetics, Adelberg, E. A. (Ed.), 

 Boston, Little, Brown, 1960, pp. 47-57. 



