the total specificity of a particular enzyme might somehow be derived from 

 a single gene. The finding in Neurospora that many nutritionally deficient 

 mutant strains can be repaired by supplying single chemical compounds was 

 a verification of our prediction and as such reinforced our belief in the hypoth- 

 esis, at least in its more general form. 



As I hope Professor Tatum will point out in detail, there are now known 

 a number of instances in which mutations of independent origin, all abolishing 

 or reducing the activity of a specific enzyme, have been shown to involve 

 one small segment of genetic material (8, 12, 24). To me these lend strong 

 support to the more restricted form of the hypothesis. 



Regardless of when it was first written down on paper, or in what form, I 

 myself am convinced that the one gene-one enzyme concept was the product 

 of gradual evolution beginning with Garrod and contributed to by many, 

 including Moore, Goldschmidt, Troland, Haldane, Wright, Gruneberg 

 and many others (2, 13, 19, 22, 23). Horowitz and his co-workers (15, 16) 

 have given it, in both forms referred to above, its clearest and most explicit 

 formulation. They have summarized and critically evaluated the evidence for 

 and against it, with the result that they remain convinced of its continued value. 



In additition Horowitz has himself made an important application of the 

 concept in arriving at a plausible hypothesis as to how sequences of biosyn- 

 thetic reactions might originally have evolved (14). He points out that many 

 biologically important compounds are known to be synthesized in a stepwise 

 manner in which the intermediate compounds as such seem not to serve useful 

 purposes. How could such a synthetic pathway have evolved if it serves no 

 purpose unless complete? Simultaneous appearance of several independent 

 enzymes would of course be exceedingly improbable. 



Horowitz proposes that the end product of such a series of reactions was 

 at first obtained directly from the environment, it having been produced 

 there in the first place by non-biological reactions such as have been postu- 

 lated by a number of persons, including Darwin, Haldane, Oparin and Urey 

 and demonstrated by Miller, Fox and others (10). It is then possible reasonably 

 to assume that the ability to synthesize such a compound biologically could 

 arise by a series of separate single mutations, each adding successive enzy- 

 matically catalyzed steps in the synthetic sequence, starting with the one im- 

 mediately responsible for the end product. In this was each mutational step 

 could confer a selective advantage by making the organism dependent on 

 one less exogenous precursor of a needed end product. Without some such 

 mechanism, by which no more than a single gene mutation is required for the 



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