402 



CHAPTER 44 



FIGURE 44-1. One postulated sequence of events leading to transition or transversion. 



NORMAL 

 MUTATED 



T:A 



A:T 



T:A 



/ \, 



CHAIN SEPARATION T A' 



etc. 

 REPLICATION 1 a' : C 



/ \ 



CHAIN SEPARATION A' C 



etc. 

 REPLICATION 2 C : G 



TRANSITION TRANSVERSION 



(A|G) (T^G) 



A:T 



/ \, 

 A T' 



etc. 



t':C 



T' C 



etc. 



C • G 



this is a transition. Or, given the original 

 pair G ; C, a mutagen may produce C which 

 specifies A (instead of G), which in turn speci- 

 fies T. So the net change from C to T also 

 is a transition. If A : T becomes A : T', 

 after which T' specifies C, and C specifies G, 

 the net result is that T has been replaced by G, 

 which is a transversion. Such transitions and 

 transversions would be expected to be fre- 

 quent following treatment with certain chemi- 

 cal mutagens. Penetrating radiations, es- 

 pecially ionizing ones, would be expected to 

 be less selective than chemical mutagens in 

 the nucleotides attacked this way. Note, in 

 the examples mentioned, that the transitions 

 and transversions were initiated by a change 

 in the old gene. A second mechanism can be 

 hypothesized in which the initial change lead- 

 ing to transition or transversion occurs in a 

 base which is subsequently used in construct- 

 ing a complementary DNA chain. 



A third possible mechanism for intra- 

 nucleotide change has been suggested ^ in 

 which the members of a base pair undergo 

 rotational substitution by breaking their bonds 

 to sugar, rotating 180°, and rejoining. Thus, 

 following rotational substitution, which may 



5 By H. J. MuUer, E. Carlson, and A. Schalet (1961). 



be a frequent consequence of ion action, 

 C : G would become G \ C, the resultant 

 double transversion being mutant. 



A fourth possible mechanism for intra- 

 nucleotide change involves the fact that the 

 bases in DNA may change their configura- 

 tions without changing their chemical con- 

 tent, that is, they can exist in several tauto- 

 meric forms. In the double helix configura- 

 tion of DNA, the most likely tautomers of 

 each base were assumed to obtain, Tauto- 

 mers of the bases can differ in the exact 

 positions where the hydrogen atoms are 

 attached, so that the pairing characteristics 

 are changed. Thus, for example, while the 

 usual tautomer of adenine pairs with thymine, 

 one of its less common tautomers could pair 

 with cytosine (Figure 44-2). In this way an 

 incorrect complement may be specified, lead- 

 ing to a transition or transversion.*' Such 

 tautomeric shifts, causing changes in the new 

 gene code, may play an important role in 

 spontaneous mutation. 



You will agree that there would be no 

 difficulty in identifying as mutant the com- 

 pleted transition or transversion or whole 



6 See reference on p. 318 (J. D. Watson and F. H. C. 

 Crick, 1953c). 



