422 MUTATION AND PLANT BREEDING 



proflavine mutants were reversible by treatment with base analogues. 

 Furthermore, mutants induced by 5-bromouracil are more readily 

 reverted by 2-aminopurine than by 5-bromouracil and, vice versa, 

 for those originally induced by 2-aminopurine. In summary, muta- 

 genic specificity has been demonstrated in rll alleles both for forward 

 mutations, i.e. different spectra of "hot spots", and reverse mutations. 

 The latter show different reversion rates both in general, according 

 to the origin of the mutant, as well as individually, according to the 

 specific site. 



Mechanisms for Mutagenic Specificity 



Most of the evidence for mutagenic specificity, as can be seen 

 from the preceding review, comes from experiments in which nucleic 

 acid base analogues or alkylating agents were used as the mutagenic 

 agents. It is unlikely that mutations are induced by a common 

 mechanism in all organisms or for all mutagens. However, the best 

 working hypothesis so far proposed is that hereditary information is 

 determined by the base pair sequence in DNA and that true intra- 

 genic mutations involve fundamentally an alteration in this sequence. 



Freese (23, 24, 25) postulated that certain base analogues through 

 "mistakes" in incorporation and replication of DNA would cause 

 errors in base pairing and an ultimate change in sequence of the 

 normal bases. Mutations are considered to result from these "transi- 

 tions", i.e., replacements of purine by purine or pyrimidine by pyrim- 

 idine. For example, diagrammatically: 



1. Substitution of a pyrimidine analogue, 5-bromouracil (5BU) 

 A-T (5BU) -> A-5BU -> G-5BU -> G-C 



G-C 5(BU) -> G-5BU -> A-5BU -* A-T 



2. Substitution of a purine analogue, 2-aminopurine (2AP) 

 T-A (2AP) -* T-2AP -> C-2AP -> C-G 



C-G (2AP) -> C-2AP -» T-2AP -> T-A 



A and G represent the natural DNA purine bases adenine and 

 guanine, respectively; T and C, the pyrimidine bases thymine and 

 cytosine. The new stable base pair, i.e., transition from one normal 

 purine-pyrimidine pair to another, at the mutant site would be 

 expected to be established after two replications of DNA, subsequent 

 to the initial incorporation of the analogue. Rudner (55) confirmed 

 that mutations induced by 5-bromodeoxyuridine and 2-aminopurine 



