The Molecular Basis of Mutation 401 



SUMMARY AND CONCLUSIONS 



A considerable portion of the spontaneous mutation rate is based upon the intracellular 

 production of mutagens and antimutagens. For this reason, spontaneous mutation is 

 in many respects an incident of the normal metabolism of the cell in which nucleic 

 acids are specifically implicated. 



Mutational "hot spots" found at the nucleotide level are different for mutants oc- 

 curring spontaneously and those induced by various chemical mutagens. 



Mutation is defined operationally as any detectable, unnatural change affecting the 

 chemical or physical constitution, mutability, replication, phenotypic function, or re- 

 combination of one or more nucleotides. One or more whole nucleotides can be added, 

 deleted, substituted for, inverted, or transposed to a new position with or without 

 inversion. Chemical and physical mutagens capable of such mutations are discussed. 



The components of a nucleotide serve as sites for mutation. Mutations involving 

 the phosphate portion are described, and those affecting the sugar portion are hy- 

 pothesized. Base changes in the old gene may be produced in a number of ways, 

 including tautomeric shifts, deamination, depurination, rotational substitution, and 

 dimerization. Base changes in new genes can result — for example, after treatment 

 with chemical analogs — from mistakes in incorporation and replication. Eventually, 

 base changes can result in deletion, transition, or transversion. 



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