10 THE BIOSYNTHESIS OF PROTEINS 



et al., 1956). Various forms of glycogen deposition diseases are due to lack 

 of glucose-6-phosphatase, amylo-l-6-glucosidase or muscle phosphorylase 

 (Hers and Malbrain, 1959; Hauk et al, 1959; Mommaerts et al, 1959; 

 Yi Yung Hsia and Kot, 1959; Larner and Villar Palasi, 1959; Gilles et al, 

 1960). Pentosuria may be due to hereditary deficiency in xylulose dehydro- 

 genase (Bozian and Touster, 1959). The eyes of vermilion mutants (v) of 

 Drosophila are devoid of tryptophan peroxidase, the enzyme which makes 

 kynurenine (Glass, 1957; Baglioni, 1959). 



Mutation of a mendelian gene thus suppresses the formation of an enzyme, 

 i.e. of a protein endowed with well specified catalytic properties. One may 

 wonder whether the enzyme protein does not form at all in the mutant, or 

 whether another protein lacking enzymic activity is made instead of the 

 normal enzyme. 



Yanofsky studied 25 independent mutants of Neiirospora crassa all lack- 

 ing tryptophan synthetase activity. He found for many of them, that each 

 contains a protein which is closely related to the enzyme for it gives strong 

 cross reactions with an antiserum prepared against normal tryptophan 

 synthetase. Moreover, this cross reacting material behaves exactly like the 

 normal enzyme in biochemical fractionation procedures. A few mutants, 

 however, do not contain any such 'cross reacting material' (Suskind et al., 

 1955; Yanofsky, 1956; Suskind, 1957). 



In many cases, mutation thus results in the replacement of a normal 

 enzyme by some closely related protein devoid of normal catalytic proper- 

 ties. Cases are also known in which the abnormal protein formed still 

 possesses some enzymic activity, but it is more heat labile, or it is more 

 sensitive to an inhibitor, or it has an altered coenzyme requirement, or it 

 has an abnormal optimum of pH or temperature. 



In the last case, the mutant may behave like an auxotroph at the usual 

 temperature and be able to grow like the wild strain at a higher tempera- 

 ture (Horowitz and Fling, 1953; Fincham, 1957; Yura, 1959; Lerner and 

 Yanofsky, 1957; Yanofsky and Stadler, 1958; Yanofsky, 1957; De Moss 

 and Bonner, 1959). 



A shght change in the properties of the protein produced may thus be 

 brought about by gene mutation. The nature of the chemical change pro- 

 duced is not revealed by these studies : one may think of slight modifica- 

 tions in the folding of the polypeptide chains, or of breakages in the chains 

 or of changes in the amino acid sequence. 



Extremely interesting and illuminating data were obtained in this respect 

 in studies on hereditary blood diseases of man. Genetic analysis, no doubt, 

 is at a great disadvantage here, but the ready availability of the proteins 

 involved and the ease of purification proved favourable to detailed chemical 

 investigation. 



Sickle cell anaemia, a blood disease found rather frequently in popula- 



