V. MOLECULAR MECHANISM OF MUTATIONS 223 



most frequently in the place of A which in itself would not yet be 

 mutagenic. But whenever AP pairs with C, either in its normal tauto- 

 meric state or by two hydrogen bonds after it has undergone a tautomeric 

 shift, a base pair cliange results. The frecjuency of the pairing "mis- 

 takes" between AP and C, per base incorporated, should be much larger 



N-C N H-N C-H 



/ \ / \ / 



/ N— C C— N 



N-H O ^ 



/ 

 H 



2-Aminopurine Thymine 



(A) 



H 



H\ N H H— N H 



C \ / \ / 



N— C N N C— H 



/ \ / \ / 



N— C C— N 



N— H O ^ 



/ 

 H 



2-Aminopurine Cytosine 



(B) 

 Fig. 7. Normal (A) and rare (B) base pairing of 2-aminopurine. 



than between BU and G ; this may explain why, in spite of its very small 

 incorporation, AP is highly mutagenic. Analogous to the mechanism 

 explained for BU in Fig. 6, AP is expected to induce base pair transitions 

 in both directions. It does induce point mutations (Freese, 1959b; 

 Demerec, 1960). 



In bacteria, kinetic studies on the induction of reverse mutations by 

 BD and AP, have been used in the attempt to distinguish the direction 

 of the base pair transitions, by the time and pattern of mutant increase 

 after a pulse of the mutagen (Rudner, 1960, 1961; Strelzoff, 1962). The 

 authors observed that for some biochemical mutants the frequency of 

 revertants increases at some time after the pulse, within one generation, 

 and then remains constant in later generations: this indicates that the 

 reverse mutation was induced by a mistake in incorporation. In contrast, 



