MUTATION AS A CHEMICAL PROCESS 



213 



reversible would seem to involve substances like adenine and adenosine 

 which are naturally occurring metabolites. In some competitive way, 

 too much adenine may prevent the normal metabolism of adenosine so 

 that mutation becomes likely. The achievement of a proper balance in 

 the concentration of substances like these may be one of the regulatory 

 mechanisms that determine the mutation rate. It is strange that pyrimi- 

 dines have been found not to be mutagenic and, furthermore, that 

 deoxy hhosides are not antimutagens. 



Nonetheless, some unnatural analogues of pyrimidines, when supplied 

 to the cell, are actually incorporated into DNA. For example, 5- 

 bromouracil quantitatively replaces thymine in DNA and is mutagenic. 

 But it must be emphasized that even when almost 100 per cent of the 

 thymine has been replaced by 5-bromouracil, most of the genes do not 

 mutate and appreciable numbers of cells or phage survive. This implies 

 that the incorporation itself does not constitute the mutation, for a gene 

 which has incorporated 5-bromouracil cannot duplicate gene replicas 

 containing that abnormal base when it is no longer supplied in the 

 medium. Therefore, the replica of the gene containing that analogue 

 (Figure 8.6) must usually incorporate adenine at the corresponding site; 

 at the next replication, thymine would be incorporated in the new strand 

 opposite the adenine to restore the original condition. But it is likely 



Number of 

 Replications 



5-BrU-A 



T-A 



5-BrU-G 



T-A 



Copy Error at 

 Incorporation 



2. Seldom 



C-G 



/ 

 Usually 



5-BrU-G 



5-BrU-A 



C-G 



— \ 

 Seldom 



5-BrU-G 



C-G 



5-BrU-A 



C-G 

 Mutant 



5-BrU-A 



T-A 

 Mutant 



FIGURE 8.6. A speculation on the effect of substituting 5-bromouracil for thymine in 

 replicating DNA. 



