CHAPTER I 



The Genetic Control of Protein Synthesis 



A. THE ONE GENE-ONE ENZYME HYPOTHESIS 



1. Basic Observations 



At the beginning of this century, Garrod called attention to several 

 hereditary abnormalities of man. These abnormal conditions are character- 

 ized by obvious biochemical defects, for instance the excretion of unusual 

 substances in the urine, or changes in pigmentation. These traits are 

 transmitted from parent to progeny as if they were controlled by single 

 recessive alleles. A classical case of 'inborn error of metabolism' is alcap- 

 tonuria. Patients excrete in the urine homogentisic acid which gives rise 

 to a black pigment. When the acid is fed to an alcaptonuric, it can be re- 

 covered in the urine, whereas it disappears in a normal individual. It was 

 established as early as 1914 by Gross that normal human serum destroys 

 homogentisic acid whereas this substance is not changed in alcaptonuric 

 serum. Clearly, alcaptonurics suffer from a metabolic lesion, from the 

 failure of some enzymic processes. Since the disease is controlled by a 

 single gene, it looks as if genes could control enzymic processes in some 

 specific way. 



Indications in the same direction were provided by studies on the in- 

 heritance of flower pigments, which were initiated by Onslow and Bassett 

 (1913, 1914) and brilHantly developed by Scott-Moncrieff (1930, 1939) 

 and Lawrence (1935, 1950). These researches are well illustrated by the 

 work on the Cape primrose Streptocarpus. 



The chemical structure and the genetic control of the petal pigments 

 were analysed in a series of hybrids. Each strain was found to contain 

 essentially one single pigment. All the pigments are closely related sub- 

 stances belonging to the class of anthocyanidins ; they differ from each other 

 by the presence of a few glycosyl or methoxy groups on the hydroxyls of 

 the basic anthocyanin structure. The pigments are inherited as if they were 

 controlled by three pairs of alleles, with one dominant and one recessive in 

 each pair. Go, Rr, Dd. In the triple recessive genotype ord, the pigment is 

 mainly pelargonin-3-pentose-hexoside. Replacement of the recessive 

 allele r by the dominant R results in the substitution of a methoxy group 

 at position 3'. When the dominant allele O replaces the recessive o, two 



