REGULATION 135 



four enzymes involved in the conversion of imidazolglycerolphosphate into 

 histidine (Ames and Garry, 1959). The use of a choice of mutants makes it 

 clear that the effect cannot be explained by the prevention of sequential 

 inductions. The four genes corresponding to the four enzymes are con- 

 tiguous (Hartman, 1956). It looks as if a group of closely linked genes could 

 be put into operation or blocked simultaneously. The existence of a lock or 

 'operator' is supported by direct genetical studies in the case of /3-galactosi- 

 dase (Jacob et al, 1960) where mutants have been isolated which have 

 the properties one would predict if the mutation had occurred within the 

 operator. It was also shown that in heterozygotes the operator controls the 

 expression of the genes when they are in cis position with the operator, and 

 does not act on the genes which are in a piece of genetic material separated 

 from the homologous one which contains the operator. These facts can be 

 tentatively interpreted in the following way (Jacob et al., 1960) : besides the 

 locus which contains the structural information for the synthesis of an 

 enzyme, one should distinguish a new genetical unit, the operon, made of 

 an operator and a group of closely linked loci, the expression of which is 

 controlled by the operator. The operator is acted upon by a repressor pro- 

 duced under the action of the controlling gene (for instance, in the case 

 of galactosidase). The repressor blocks the operon; the locked operon can 

 be released by an inducer. 



This fascinating scheme contains implications which are amenable to 

 experimental test; future research will tell whether it is a good picture of 

 reality. It provides an interesting interpretation for the clustering of genes 

 controlling the enzymes of a single metabolic pathway (Hartman, 1956). 

 At first sight, the operator hypothesis might be taken to mean that the 

 repressor acts at the level of the genome. Actually, the available data are 

 just as compatible with an action of the repressor on cytoplasmic replicas of 

 the operator. This would, however, imply that the operon is copied as a unit 

 and that the cytoplasmic templates corresponding to the several genetic 

 loci of an operon work in a co-ordinate manner. It will be interesting to 

 compare the size of the operon with those of the DNA molecule and of 

 ribosomal RNA. The DNA molecule is large enough to accommodate 

 several loci, and the RNA molecule of the ribosome large enough to serve 

 as a template for several proteins. One may wonder whether the new 

 physiological unit of expression, the operon, will be superposable to the 

 chemical unit of structure, the molecule, and to the RNA quantum of the 

 ribosomes. 



How can one visualize at the molecular level the process of repression 

 and induction in this perspective? The keys which lock or release the system 

 must be of such a nature that they can interact with the lock. The operator 

 may be assumed to be a region of a DNA molecule or of its cytoplasmic 

 RNA replica. The key should be able to interact in a specific way with a 



K 



