THE MUTABLE UNIT OF HEREDITY 37 



Hypoxanthine and xanthine are expected to have, in replicating DNA, 

 pairing properties Hke those of guanine; uracil should be like thymine. 

 As a result, following deamination and two subsequent replications, a 

 mutation might occur in the following way: 



When the RNA of tobacco mosaic virus is isolated from its protein, 

 treated with nitrous acid, and allowed to infect a tobacco leaf, mutant 

 TMV are produced. When a treatment was used which inactivated 

 about half of the virus population, the number of mutants increased 

 some twentyfold over the number present in the untreated control. This 

 absolute increase in the number of mutants cannot be attributed to a 

 selective survival of pre-existing mutants in nitrous acid, for their number 

 could not, in that case, have increased above that initially present. The 

 new mutants must have been induced by the nitrous acid. 



The same effect is found with DNA which may be extracted from 

 drug-sensitive pneumococci, treated with nitrous acid, and then tested 

 for its ability to transform sensitive cells to a resistant condition. The 

 nitrous acid treatment caused mutations to a streptomycin-resistant con- 

 dition in DNA from streptomycin-sensitive bacteria. Once again, an 

 absolute increase in the number of mutant molecules was observed. 



The dose of mutagen may be increased by exposing the RNA or DNA 

 to the same concentration of nitrous acid for increasing periods of time. 

 With this procedure, the rate of production of mutants may be constant 

 with time (e.g.. Figure 2.2). Such kinetics, in which each successive 

 and equal unit of dose induces the same number of mutants, indicate 

 that a one-event process is at work. Were two chemical events required 

 for mutation, the first small exposure would mostly bring about only one 

 reaction per cell; in very few cells would both events occur. Further 

 treatment would induce the second event in cells that had already 

 undergone the first reaction. As a consequence, the rate of production 



