33. NUCLEIC ACIDS OF THE BACTERIAL VIRUSES 



225 



Cistron A 



Segment© © ® ® \\ © © 



Mutations Induced by 5- Bromouracil 



Segment© © ® © H© © 



Mutations Induced by Proflavine 



Spontaneous Mutations 



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Cistron B 



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and 



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Fig. 5. Genetic map showing the location of mutations in the rll region of phage 

 T4. Each mutation is represented by a box placed in the proper segment of the map. 

 (The over-all mutation rate is different in each case. The occurrence at a given loca- 

 tion of one mutation in the bromouracil set corresponds to roughly 10 3 times higher 

 mutability at that spot than one occurring in the spontaneous set. In the case of 

 proflavine this factor is of the order of 10 2 ). [From S. Brenner, S. Benzer, and L. 

 Barnett, Nature 182, 983 (1958).] 



matographic differences between heat-degraded DNAs from phage grown 

 in the presence or absence of proflavine. 



If the hypotheses presented concerning the action of 5-bromouracil, 2- 

 aminopurine, nitrous acid, and pH 5 are correct — and they form a self- 

 consistent pattern — then it seems evident that changes of a single nucleo- 

 tide pair can result in demonstrable mutation. This view is supported by 

 the relative homogeneity of spontaneous reversion rates of 5-bromouracil- 

 induced mutants, and by the great rarity of nonreversible mutants of 

 this type. 155 



Fine structure genetic maps have been made of the location in the rll 

 region of mutants induced by these agents. The striking result has been 

 obtained that particular sites in the genetic map appear to be unusually 

 susceptible to the action of particular mutagens, e.g., 5-bromouracil will 

 induce mutants at a particular site many times more frequently than at 

 another nearby locus. 155 By genetic analysis all the mutants induced at 

 the particularly sensitive locus failed to recombine with each other. 



Such sites of frequent occurrence of mutation are observed upon analy- 

 sis of spontaneous mutants and of the mutants induced by 5-bromoura- 

 cil, 155 2-aminopurine, 156 and proflavine. 161 The sensitive sites are, however, 

 different for each mutagen (Fig. 5). Treatment with nitrous acid, or by 

 pH 5 at 45°, produced a much more uniform distribution of mutants. 



The existence of such distinct mutagenically susceptible sites suggests 



