THE CHEMICAL BASIS OF HEREDITY 31 



synthesis, " and that by so doing, "genes directly determine enzyme 

 specificities and thereby control in a primary way enzymatic syntheses 

 and other chemical reactions in the organism;" and (2) "that a given 

 enzyme will usually have its final specificity set by one and only one 

 gene. " 



This hypothesis involves a number of important assumptions. In the 

 first place, there is a conceptual jump from the mutant phenotype 

 to the function of the unmutated allele, in the assumption that the 

 activity of the unmutated form of the gene is to carry out the reaction 

 which is blocked in the mutant. Secondly, it is assumed that the gene- 

 determined effect is upon the enzyme which catalyzes the reaction 

 blocked in the mutant; and thirdly, that the gene influences the enzyme 

 solely by determining its specificity. Finally, it is proposed that a one- 

 to-one correlation exists between each gene and a particular enzyme. 



This hypothesis can be considered more concretely with the aid of an 

 example based upon studies by Horowitz and co-workers. In Neuro- 

 spora, some strains produce the black pigment, melanin, only when 

 grown at temperatures of 25° C or lower, while other strains produce the 

 pigment at all temperatures. This difference is correlated with a single 

 gene diff^erence; the allele T^ is carried in temperature-sensitive strains, 

 and T^ in the others. T^" strains contain a thermolabile form of the 

 enzyme tyrosinase, which catalyzes one step in melanin formation, and 

 T^ strains contain a thermostable form of the enzyme. Thus, the pheno- 

 typic difference between strains results from alterations in a physical 

 property of an enzyme. Two other genes, ty-l and ty-2, are known 

 which also aff^ect tyrosinase activity. When the mutant form of either 

 ty-\ or ty-2 is present, no tyrosinase is formed, unless the strain is 

 grown on a special medium, in which case large amounts of the enzyme 

 are produced. Neither ty-\ nor ty-2 appears to alter the properties of 

 tyrosinase; when formed, its thermostability is determined by whichever 

 T allele is present. 



This example supports the one-gene-one-enzyme hypothesis insofar as 

 the blocked reaction can be attributed to absence or alteration of the 

 enzyme, tyrosinase. However, not one but three genes have been found 

 which influence the appearance of this enzyme, and apparently they act 

 in different ways. T influences enzyme structure, whereas ty-\ and 

 ty-2 appear to exert their influence upon enzyme formation. Other 

 mutant systems provide evidence consistent with this picture: that the 

 controls of enzyme formation, of enzyme activation, and of specificity are 

 all devices in the armentarium of gene action. However, the precise 

 mechanisms by which the genes bring about these effects are hardly 

 known at all. 



In the absence of more direct information, certain formal considera- 



