Chapter V 



Molecular Mechanism of Mutations 



ERNST FREESE^ 



Department of Genetics, 

 University of Wisconsin, 

 Madison, Wisconsin 



I. Introduction 207 



A. Classification of Heritable Variations 207 



B. Development of Genetic Systems and Discovery of the First Mutagens 209 



C. The Genetic System of rlj Mutants of T2 or T4 Phages . . . .211 



D. Further Subdivision of Mutations 212 



II. Structure, Duphcation, and Alteration of the Hereditary Material . . 215 



A. Structure and Replication of DNA and RNA 215 



B. Structure and Duplication of Chromosomes 216 



C. Classification of Base Alterations in Nucleic Acids 216 



III. Biochemistry of Mutagens and Theory of Base Alterations .... 217 



A. Inhibition of Nucleic Acid Precursors 218 



B. Incorporation of Base Analogs 219 



C. Dyes 224 



D. Chemical Alteration of Resting Nucleic Acid 225 



E. Radiations 240 



F. Unclassified Mutagens 245 



G. Spontaneous Mutations 245 



IV. The Extent of Point Mutations 248 



A. Genetic Mapping of Mutations 248 



B. Spontaneous and Induced Reverse Mutations 249 



C. The Kinetics of Mutation Induction 250 



V. Mutagenic Specificity 252 



A. The Specificity of Forward Mutations 252 



B. The Specificity of Reverse Mutations 253 



References 264 



I. Introduction^ 



A. CLASSIFICATION OF HERIT.\BLE VARIATIONS 



The concept of mutation has played an important role ever since the 

 large variety of biological species had been attributed to evolution from 



^Present address: Laboratory of Molecular Biology, National Institutes of 

 Health— NINDB, Bethesda, Maryland. 



'Abbreviations used throughout this paper: A, adenine; C, cytosine; HMC, 

 5-hydrox\'methylcytosine ; MeC, 5-methylcytosine ; G, guanine; T, thymine; H, 

 hypoxanthine ; U, uracil; X, xanthine; G-C, guanine-cytosine pair with anj^ of the 



207 



