smith: directed mutation 419 



nutritional deficiencies in Escherichia coli involving 11 amino acids 

 were tested for frequency of spontaneous reversions and those induced 

 by MnCU, ultraviolet, and beta— propiolactone. The material included 

 a number of alleles governing deficiencies for tryptophane, methio- 

 nine, histidine, and leucine. These studies were extended by Glover 

 (26) to additional alleles and mutagens. He showed that in E. coli the 

 frequency of induced mutations at one locus can be influenced by the 

 type of allele present at another locus. 



Extensive evidence of inter-allelic specificity of induced muta- 

 tion has now been demonstrated in Salmonella typhimurium. About 

 60 per cent of auxotrophic and fermentation alleles in this species are 

 "mutagen stable", i.e., although they mutate spontaneously, their 

 mutation rates are not increased by treatment with any of a large 

 number of mutagens which are effective on other alleles (14). Back- 

 mutation tests have revealed that different "mutagen-labile" alleles 

 at a locus may differ widely in rates of induced mutability. The most 

 extensive analysis reported to date is that of Kirchner (37) with a 

 series of alleles at the histidine locus in two strains of S. typhimurium. 

 The histidine mutants were either of spontaneous origin or induced 

 by either ultraviolet irradiation or 2-aminopurine. The mutagenic 

 agents used to revert the mutant alleles to prototrophy were 2-amino- 

 purine (2AP), 5-bromodeoxyuridine (BDU), sodium nitrite (N0 2 ), 

 t-butyl hydroperoxide (TBP), and beta-propionactone (BPL). Of 54 

 mutants tested in one strain 23 were mutagen-stable. Data on the 31 

 mutaoen-labile mutants are summarized in condensed form from 

 Kirchner's results in Table 1. 



In the table + signifies an increased back-mutation frequency, — 

 means that there was no increase. The highly reactive polymerizing 

 agents, BPL and TBP, are grouped, as are the base analogues, BDU 

 and 2AP. The mutant alleles show considerable specificity of response 

 to the mutagens, and this is further emphasized if the relative amount 

 of increased mutation is also taken into consideration. Seventeen of 

 the alleles responded to the mutagenic action only of the highly 

 reactive compounds, nine to both groups, four only to the analogue 

 2AP, and only one to all three categories of mutagenic agents. Eleven 

 of the 12 auxotrophs that were obtained originally after treatment 

 with 2AP showed an increased reversion frequency with BDU, 

 whereas the ultraviolet-induced auxotrophs showed no particular 



