56 Perspecfives in Microbiology 



the most direct evidence so far is furnished by the findings 

 of Maas (20) and of Horowitz (16), who have shown that 

 some mutants produce a qualitatively altered enzyme — one 

 that performs the same reaction as the normal enzyme, but 

 is much more sensitive to heat denaturation. With respect 

 to the amount of the corresponding enzyme (or rather of 

 its activity), we have shown with Mitsuhashi that in a group 

 of aromatic auxotrophs the incompleteness of the block, as 

 inferred from growth requirements (5), is directly related 

 to the amount of enzyme (5-dehydroquinase) extractable 

 from the cell (24). 



I have not touched on the deeper problems raised by the 

 one-gene-one-enzyme hypothesis: for example, how in some 

 cases mutations at different loci block the same reaction; 

 how mutations of modifier genes can restore a blocked re- 

 action; whether all genes have the same kind of relation to 

 protein synthesis as the genes that are altered in auxo- 

 trophic mutants; how directly or indirectly, and by what 

 mechanisms, the structural specificity of a gene is trans- 

 lated into terms of structure and amount of an enzyme; 

 how these mechanisms interact with inductive ("adaptive") 

 environmental effects on enzyme formation; whether the 

 loss of activity of an enzyme in a mutant might be a special 

 case of formation of an altered protein — one so drastically 

 altered as to be no longer recognizable as an enzyme. In a 

 sense, it is no longer profitable to argue about the validity 

 of the one-gene-one-enzyme theory; we have all come to 

 accept, consciously or unconsciously, the idea of a close con- 

 nection between individual genes and individual enzymes. 

 The problem now is that of analyzing the detailed mechan- 

 isms underlying this connection; and this genetic problem 

 merges into other disciplines. These include physiology 

 (for example, study of the environmental factors that induce 

 or inhibit enzyme formation) and biochemistry (for ex- 

 ample, study of protein synthesis and nucleic acid function). 



