216 CELL HEREDITY 



H H H 



N \l— H---0^ C^ 



C Q Q Q p H 



\ // "^ / v\ Thymine 



N— C N---H— N C — H 



/ \ / \ / 



C N=C C— N 



/ \ // \ 



HOC 



Adenine 



\ 



H H 



\ / 



N N- — H— N H 



c^ c— c \ c— c 



\ // \ ^ // \ 



N— C N— H---N C— H 



/ \ / \ / 



C N=C C— N Cytosme 



/ \ // \ 



HOC 



\ 



FIGURE 8.8. The pairing possibilities of adenine in its two tautomeric states. 



change A:T to C:G in Figure 8.7 could not. In the latter case, the 

 mutagen could convert C:G only into T:A. Yet all these changes should 

 be spontaneously reversible. 



Some evidence relating to these speculations has been provided by 

 Freese. Both 5-bromouracil and 2-amino-purine (which might substitute 

 for adenine in DNA) induce mutations in bacteriophage T4. When 

 mutants so produced are treated with either chemical they are induced 

 to back-mutate at a low rate. But these mutagens cannot reverse muta- 

 tions induced by proflavin and are able to reverse only about 10 per cent 

 of spontaneous mutations. Nevertheless, all of these mutations revert 

 spontaneously. We may presume, therefore, that 5-bromouracil and 

 2-amino-purine cause mutations of the first kind (transitions), whereas 

 most spontaneous and proflavin-induced mutations are transversions. 

 It is not known whether these two mechanisms bear any relation to the 

 spontaneous bacterial mutations allowed and prevented by adenosine in 

 the chemostat. Nor is it understood how suprastructural factors deter- 

 mine the likelihood of copy-errors at replication. We may be sure that 

 they do, for, as was observed in Figure 6.7, the incorporation of base 

 analogues resulted in a large number of different instabilities peculiar 

 to the sites affected. No doubt the neighboring nucleotides in some way 

 determine the chance of incorporation or the chance that an unusual 

 choice of a base partner will be made at replication, or both. It is even 

 possible that an analogue may choose a partner in error with a lower fre- 



