272 BENZER 



successful as a way to determine the detailed structure of the gene. 

 When this information is co?nbined with the model of the DNA 

 molecule provided by Watson and Crick (p. 241), and the knowl- 

 edge provided by Frae?ikel-Conrat a?id Williams (p. 264) on the 

 reimion of particles to for?n a functional vims, it can be seeii that 

 the science of ge?ietics is o?i the verge of a jnajor break-through, if 

 it hasn't already completed it. Slightly more than 50 years of work 

 has brought the sciefice to this point. It will be fascinati?ig to review 

 the classics of the field in a similar fashion SO years hence to see 

 where it has gone, and who has led it there. 



This paper describes a function- 

 ally related region in the genetic ma- 

 terial of a bacteriophage that is finely 

 subdivided by mutation and genetic 

 recombination. Th'e group of mutants 

 resembles similar cases which have 

 been observed in many organisms, 

 usually designated as "pseudo-alleles." 

 (See reviews by Lewis ^ and Ponte- 

 corvo.-) Such cases are of special in- 

 terest for their bearing on the structure 

 and function of genetic determinants. 



The phenomenon of genetic recom- 

 bination provides a powerful tool for 

 separating mutations and discerning 

 their positions along a chromosome. 

 When it comes to very closely neigh- 

 boring mutations, a difficulty arises, 

 since the closer two mutations lie to 

 one another, the smaller is the proba- 

 bility that recombination between 

 them will occur. Therefore, failure to 

 observe recombinant types among a 

 finite number of progeny ordinarily 

 does not justify the conclusion that the 

 two mutations are inseparable but can 

 only place an upper limit on the link- 

 age distance between them. A high de- 

 gree of resolution requires the exami- 

 nation of very many progeny. This can 

 best be achieved if there is available a 

 selective feature for the detection of 

 small proportions of recombinants. 



1 Lewis, E. B., Cold Spring Harbor Syrn- 

 posia Quant. Biol. 16:159-174, 1951. 



2 Ponrecorvo, G., Advances in Enzyinol. 

 13:121-149, 152. 



Such a feature is offered by the case 

 of the rll mutants of T4 bacteriophage 

 described in this paper. The wild-type 

 phage produces plaques on either of 

 two bacterial hosts, B or K, while a 

 mutant of the rll group produces 

 plaques only on B. Therefore, if a 

 cross is made between two different rll 

 mutants, any wild-type recombinants 

 which arise, even in proportions as 

 low as 10"^, can be detected by plat- 

 ing on K. 



This great sensitivity prompts the 

 question of how closely the attainable 

 resolution approaches the molecular 

 limits of the genetic material. From 

 the experiments of Hershey and 

 Chase,-^ it appears practically certain 

 that the genetic information of phage 

 is carried in its DNA. The amount of 

 DNA in a particle of phage T2 has 

 been determined by Hershey, Dixon, 

 and Chase ■* to be 4 X 10''' nucleotides. 

 The amount for T4 is similar.^ If we 

 accept the model of DNA structure 

 proposed by Watson and Crick,^ con- 

 sisting of two paired nucleotide chains, 

 this corresponds to a total length of 

 DNA per T4 particle of 2 X 10^ nu- 



3 Hershey, A. D., and Chase, M., /. Gen. 

 Physiol. 36:39-56, 1952. 



4 Hershey, A. D., Dixon, J., and Chase, M., 

 /. Gen. Physiol. 36:777-789, 1953. 



•'> Volkin, E. K., personal communication. 



« Watson, J. D., and Crick, F. H. C. Cold 

 Spring Harbor Symposia Quant. Biol. 18: 

 123-131, 1953. 



