THE STRUCTURE OF DNA 



and guanine with one of the cytosines. This specificity results from our assump- 

 tion that each of the bases possesses one tautomeric form which is very much 

 more stable than any of the other possibilities. The fact that a compound is 

 tautomeric, however, means that the hydrogen atoms can occasionally change 

 their locations. It seems plausible to us that a spontaneous mutation, which as 

 implied earlier we imagine to be a change in the sequence of bases, is due to a 

 base occurring very occasionally in one of the less likely tautomeric forms, at 

 the moment when the complementary chain is being formed. For example, 

 while adenine will normally pair with thymine, if there is a tautomeric shift of 

 one of its hydrogen atoms it can pair with cytosine (Figure 7). The next time 

 pairing occurs, the adenine (having resumed its more usual tautomeric form) 

 will pair with thymine, but the cytosine will pair with guanine, and so a change 

 in the sequence of bases will have occurred. It would be of interest to know the 

 precise difference in free energy between the various tautomeric forms under 

 physiological conditions. 



General Conclusion 



The proof or disproof of our structure will have to come from further crystal- 

 lographic analysis, a task we hope will be accomplished soon. It would be 

 surprising to us, however, if the idea of complementary chains turns out to be 

 wrong. This feature was initially postulated by us to account for the crystal- 

 lographic regularity and it seems to us unlikely that its obvious connection with 

 self replication is a matter of chance. On the other hand the plectonemic coiling 

 is, superficially at least, biologically unattractive and so demands precise 

 crystallographic proof. In any case the evidence for both the model and the 

 suggested replication scheme will be strengthened if it can be shown unambig- 

 uously that the genetic specificity is carried by DNA alone, and, on the molecular 

 side, how the structure could exert a specific influence on the cell. 



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207 



