170 Bernard D. Davis 



was shown by the results of another experiment in which wild- 

 type extract, mutant extract, and a mixture of the two were 

 incubated at an intermediate temperature, i.e. one that caused 

 destruction of essentially all of the enzyme in the mutant 

 extract and none in the wild-type extract. The mixture lost a 

 fraction of its activity corresponding to the mutant component 

 of the total. 



It is evident that mutations can result in subtle alterations 

 in the nature of the enzyme performing a given reaction. 

 Those resulting in increased thermal sensitivity appear to be 

 frequent, probably because they are easy to select. Mutants 

 with temperature-sensitive blocks in a number of biosynthetic 

 reactions have been detected in our laboratory by starting 

 with an auxotroph which lacks a given reaction at all tempera- 

 tures, selecting reversions at 15°, and then finding which of 

 these fail to grow at 37° (^laas, unpublished). 



Another kind of qualitative alteration, which completely 

 destroys the activity of an enzyme, has been observed by 

 Suskind and co-workers (Suskind, Yanofsky and Bonner, 

 1955; Yanofsky, 1956). They found that certain mutants 

 which had lost the power to form tryptophan synthase con- 

 tinued to form a protein that reacted serologically with anti- 

 body to tryptophan synthase. Other mutants blocked in the 

 same biosynthetic reaction failed to form the serologically 

 crossreacting protein. It therefore appears that the former 

 mutants form an "inactive enzyme" corresponding to the 

 altered gene, while the latter mutants are even more drastic- 

 ally altered. 



It seems reasonable to expect that mutations can lead to all 

 sorts of qualitative changes in enzymes, temperature sensitiv- 

 ity and loss of catalytic activity being recognized first because 

 of the ease of their selection. These findings encourage the 

 search for other qualitative changes that would lead to drug 

 resistance. 



Indirect evidence for such a phenomenon has been provided 

 by a study (Davis and INIaas, 1952) of analogues of two struc- 

 turally related but metabolically distinct bacterial vitamins. 



