INDUCTION OF SPECIFIC MUTATIONS WITH 5-BROMOURACIL* 



By Seymour BENZERf and Ernst FreeseJ 



BIOPHYSICAL LABORATORY, PURDUE UNIVERSITY, LAFAYETTE, INDIANA 



Communicated by M. Delbruck, December 6, 1957 



Introduction 



The hereditary characteristics of an organism occasionally undergo abrupt 

 changes (mutations), and genetic techniques have traced these to alterations at 

 definite locations in the genetic structure. Recently, the fineness of this genetic 

 mapping has been extended to the level where the finite molecular units (nucleotides) 

 of the hereditary material limit further subdivision. At this level, local details of 

 the hereditary material should exert their influence; the frequency of mutation at a 

 particular point should depend upon the local molecular configuration. It is there- 

 fore feasible to try to correlate genetic observations with precise molecular models, 

 such as the one proposed by Watson and Crick' for the structure of DNA. 



In a fine-structure study of spontaneous mutations in phage T4, the mutability 

 at different points in the genetic structure was, in fact, found to be strikingly 

 varied.^ To relate mutability to actual chemical structure, it would seem promising 

 to employ mutagenic agents of specific types, to act selectively on particular con- 

 figurations. Since the initial discovery by Muller* and Stadler^ on induct on of 

 mutations with X-rays and the discovery of chemical mutagenesis by Auerbach 

 and Robson^ and by Oehlkers,^ many physical agents and chemical substances have 

 been found to be mutagenic in many organisms. Some mutagens act selectively; 

 in particular the induced reversion from biochemically dependent to independent 

 strains has been shown to depend upon the mutant and the mutagen used. (For 

 chemical mutagens in bacteria see Demerec.^) A recent comprehensive review of 

 this subject has been published by Westergaard.* Mutagens in some cases pro- 

 duce gross chromosomal aberrations; in others the alterations are so small as to 



Reprinted by permission of the authors and the National Academy 



of Sciences from the Proceedings of the National Academy of 



Sciences, 44 (2), 112-119, February, 1958. 



220 



