GENETIC CONTROL 9 



medium. Tryptophan is an indol derivative, and the production of indol 

 by a mutant which is unable to make tryptophan strongly suggests that 

 indol is an intermediate in tryptophan biosynthesis and that in the mutant 

 strain the further utilization of the indol nucleus is impaired. 



Biochemical studies on the wild type mycelium indeed showed that 

 tryptophan is formed by the condensation of indol with serine (Tatum and 

 Bonner, 1944). This last step of tryptophan synthesis can be observed in 

 vitro ; it is catalysed by an enzyme present in extracts of wild type mycelium, 

 which was called tryptophan synthetase (Umbreit, 1946). The hereditary 

 defect is thus located at the level of one well defined chemical reaction, 

 catalysed by a known enzyme. 



HOCHp CH COOH 



+ I 



^-. /CH2 — CH COOH 



UL, 



NHc 



N^ NH2 ^^ ^N 



H H 



Indol Serine Tryptophan 



Fig. 9. 



It may be assumed that in tryptophan-less mutants which do not further 

 use indol, the mutation has resulted in the inhibition or destruction of the 

 enzyme, or else that it has prevented the formation of the enzyme. Mitchell 

 and Lein (1948) showed that the extracts obtained from the mycelium of 

 such mutants do not catalyse the condensation of indol with serine; if 

 tryptophan synthetase from a normal strain is added to the extract of the 

 mutant, it works perfectly. This indicates that no inhibitor of the enzyme 

 is contained in the extracts of the mutant. It is clear therefore that no 

 enzyme activity can be detected, simply because the enzyme is not present 

 in the extracts of the mutant mycelium. 



It must be concluded that mutation of a mendelian gene has prevented 

 the synthesis of an enzyme which is normally formed in the wild strain. 

 The whole field of microbial genetics is an illustration of this strict control 

 of enzyme formation by mendelian determinants. A list of some 50 

 examples of well studied cases of genetic control of enzyme formation in 

 microorganisms will be found in a recent review by Fincham (1959). 



In higher organisms, as well as in bacteria, enzymes depend on mende- 

 Uan genes. Inborn errors of metabolism in man, pigment heredity in flies 

 and flowers are explained by the genetic control of enzyme synthesis. Thus 

 the metabolic error in alcaptonuria results from the lack of homogentisic 

 acid oxidase (La Du et al, 1958) ; all the other enzymes of tyrosine oxida- 

 tion are present, only one is lacking as the result of one gene mutation. 

 Congenital galactosemia is due to absence of galactowaldenase (Kalckar 



