366 General Discussion 



the course of evolution? If we were to take a series of reactions going 

 from substrate A to product M, through n stages, I suspect that, 

 during the course of evolution, at each reaction stage there might 

 have been about ten different reaction possibilities taken from the 

 organic chemistry textbook. We would end up ten reactions away 

 with a compound, cytidylic acid, which can inhibit the first reaction. 

 I have been mulling over the probability of this occurring during 

 the course of selection. If there are ten different reaction possi- 

 bilities at each of ten different reactions in sequence, this involves a 

 lot of selection. Can Dr. Pardee and Dr. Magasanik say if there is a 

 known genetical link between the cytidylic acid enzyme and the 

 first one in the series? If there were a linkage this would be easier 

 for me to understand. It w^ould put two characters together, each 

 of which is an end of a metabolic sequence. 



Pardee: I don't think anyone has mapped the genes in pyrimidine 

 synthesis. 



Magasanik: In Salmonella typhimuriuin the genes responsible for 

 histidine biosynthesis are closely linked and are arranged on the 

 chromosome in the same order as the biosynthetic steps leading 

 from AMP (or ATP) and ribose phosphate, the first specific step and 

 the one inhibited by histidine, all the way to histidine (Hartman, 

 P. E. (1957). In The Chemical Basis of Heredity, p. 408. Baltimore: 

 Johns Hopkins Press; Moyed, H. S., and Magasanik, B. (1957). 

 J. Amer. chem. Soc, 79, 4812; Moyed, H. S. (1958). Fed. Proc, 17, 

 279). The gene responsible for the reaction immediately preceding 

 the first specific step in histidine biosynthesis, namely the gene con- 

 trolling the enzyme which produces AMP from adenylosuccinate, 

 is not linked to the "histidine genes". This finding would support 

 your suggestion. Prof. Lehninger. However, as far as I know, the 

 genes responsible for the synthesis of purines in the same organism 

 are not closely linked; yet, there is good evidence that a derivative 

 of guanine exerts a feedback effect by inhibiting an early step on the 

 common pathway to guanine and adenine. 



Lehninger: Speaking of sequential induction of a long series of 

 enzymes in a chain, such as Stanier has done (Stanier, R. Y. (1947). 

 J. Bact., 54, 339), are these all genetically linked? 



Magasanik: No. 



Lehninger: Would you say that the probability is fairly good? 



Pardee: I do not think so. There is much argument among 

 bacteriogeneticists as to whether sequences are genetically linked or 

 not. 



Lehninger: I can see the possibility of there having been some 

 sense to the evolution of a system like this if all the enzymes in that 

 sequence were adaptive. I am wondering about the constitutive 



