The Molecular Basis of Mutation 



395 



or by removing the 2' O of ribose in an 

 RNA sequence. 



The phosphate part of a nucleotide can 

 be changed by substituting P 32 for P. When 

 single-stranded DNA viruses such as $X174 

 and 4>S13 incorporate P'' 1 ', a single radioac- 

 tive decay of P ; - to S is sufficient to inacti- 

 vate them. On the other hand, about ten 

 decays are required to inactivate </>T2 and 

 similar phages containing double-stranded 

 DNA. One simple explanation of such 

 suicide experiments is that each decay breaks 

 the backbone of the polynucleotide in which 

 it occurs, a single decay in one backbone 

 sometimes leading to a nearby break in the 

 backbone of a complementary strand if one 

 is present. According to this explanation, 

 scission of single- or double-stranded DNA 

 (or RNA, presumably) is sufficient for in- 

 activation. 



Base changes in old genes. Consider, 

 next, changes involving the base portion of 

 a nucleotide. We have already seen that 

 base changes can result from the substitu- 

 tion of one whole nucleotide for another. 

 We are now interested in the possible ways 

 the base portion of a nucleotide already in 

 a genetic sequence may be changed chemi- 

 cally. 



Certain atoms in each of the bases in DNA 

 and RNA can assume several different ar- 

 rangements; that is, each base can exist in 

 several tautomeric forms. In previous dis- 

 cussions and diagrams, the most likely tau- 

 tomer of each base — that is, its (=0) keto 

 or amino (NHo) form — was assumed to 

 occur. In the tautomers of uracil and ade- 

 nine shown in Figure 31-2, the alternatives 

 differ in the positions at which a hydrogen 

 atom is attached. The less likely tautomers 

 exist in the ( — OH) enol or imino (NH) 

 form. Although the usual amino tautomer 

 of adenine pairs with thymine, one of its 

 less common imino tautomers can pair with 

 cytosine (Figure 31-3). Reciprocally, a 

 rare imino tautomer of C can pair with A, 



forming two H bonds. A rare enol tautomer 

 of T can pair with G, forming three H bonds, 

 and the same T' : G pair can be formed when 

 the purine is in an uncommon tautomeric 

 state. In each of these cases, then, a tauto- 

 meric shift has made a new purine-pyrimi- 

 diiie base pair possible. 9 Tautomeric shifts 

 may play an important role in spontaneous 

 mutation. The relative frequencies of the 

 different tautomeric alternatives depends 

 upon several factors, including pH. The un- 

 usual base pairs, A:C and T|G, can also 

 occur after ionization of any one of the 

 bases. 



Chemical changes in the old bases can 

 also occur after treatment with chemical 



'•' See reference on p. 277 to J. D. Watson and 

 F. H. C. Crick (1953c). 



Adenine 



^ Oh 



Adenine Cytosine 



FIGURE 31-3. Tautomeric shift of adenine 

 which could change its complementary base 

 from thymine to cytosine. Upper diagram 

 shows adenine before, and lower diagram after, 

 undergoing a tautomeric shift of one of its 

 hydrogen atoms. (After J. D. Watson and 

 F. H. C. Crick.) 



