HOROWITZ AND LEUPOLD 



in Drosophila, where lethal mutations, 

 as well as visibles, result in irreplace- 

 able losses, frequently organ-specific in 

 character. In some measure this may 

 reflect fundamental biological difi^er- 

 ences between Drosophila and Neuro- 

 spora or E. coli, but also, and to an 

 indeterminate extent, it reflects the dif- 

 ferences in methodological approach 

 to these organisms. It would not be 

 surprising to find that non-difl^usible 

 products play a more important role 

 in the development of a highly differ- 

 entiated organism like Drosophila than 

 in relatively undifferentiated ones like 

 Neiirospora and E. coli. But on the 

 other hand, it must be recognized that 

 the methods of Drosophila culture are 

 such as virtually^ to exclude the pos- 

 sibility of detecting nutritional mu- 

 tants even if they occur. 



The results we have obtained from 

 the microorganisms suggest that in 

 the great majority of cases the meta- 

 bolic function of the gene is to pro- 

 duce an enzyme which catalyzes the 

 formation of a low molecular weight 

 product. If there exists a large class 

 of enzymes whose function is other 

 than this, we must conclude either that 

 they are not individually essential to 

 survival, or else that they are independ- 

 ent of the genes for their production. 

 There is a strong suggestion in this 

 result that the mechanism of biosyn- 

 thesis of large molecules, especially 

 proteins, is not an enzymatic mechan- 

 ism in the usual sense. That is to say, 

 the protein molecule may not be built, 

 cathedral-like, by a process of accre- 

 tion; but rather may be made directly 

 from the amino acids or their simple 

 derivatives by a single catalyst. 



It is interesting to note that such a 

 mechanism provides a simple explana- 

 tion of another essential feature of our 

 findings; namely, the mutual independ- 

 ence of the pathways of synthesis of 

 different enzymes. On the hypothesis 



219 



of growth by accretion of peptide 

 fragments it seems unlikely that a one 

 gene-one enzyme relationship could 

 be found, even if it existed, since loss 

 or modification of any peptide frag- 

 ment would be expected to result in 

 loss or modification of a particular 

 group of enzymes; namely, those 

 which contain this fragment in their 

 structures. Unless the fragment could 

 be introduced into the cells, the result 

 would be the frequent occurrence of 

 multiple unrelated biochemical defi- 

 ciencies among the mutants. This has 

 not been found. We find considerable 

 appeal in the notion that the proposed 

 mechanism of enzyme synthesis may 

 underlie the results we have obtained. 



SUMMARY 



The one gene-one enzyme hypo- 

 thesis is supported by the following 

 evidence: 



The great majority, at least 84 per 

 cent, of the known nutritional mutants 

 of Neurospora require single chemical 

 substances as essential growth factors. 

 Provision of the essential factor re- 

 sults in a normal phenotype in most 

 cases; where a fully normal phenotype 

 is not attained, the evidence indicates 

 that this is to be accounted for on the 

 basis of secondary effects unrelated to 

 the mode of gene action. 



Biochemical analysis of the mutants 

 has indicated in many instances that 

 the effect of the mutation is to block 

 sensibly a single step in the pathway 

 of synthesis of the growth factor. In a 

 few cases it has been possible to show 

 that the mutants are lacking in the 

 specific enzyme involved. 



The question of whether the known 

 biochemical mutants are a highly se- 

 lected sample from which multifunc- 

 tional mutants are excluded by virtue 

 of the screening procedure employed 

 has been attacked by the temperature 

 mutant method. Evidence has been 



