REGULATION 129 



exogeneous inducer, it could be visualized that the inducer brings a comple- 

 ment of structural information, and that it is involved for instance in 

 organizing the active centre of the enzyme. Should the inducer cause the 

 polypeptide chain of the nascent enzyme to fold in a specific way, the 

 remarkable coaptation of enzyme with substrate would receive a rational 

 interpretation ; sequential induction would even partly explain the establish- 

 ment of metabolic chains of successive reactions (Pollock, 1953). 



The unitarj'^ hypothesis of general induction in enzyme synthesis looked 

 indeed very promising. It was difficult to test experimentally, however, for 

 the failure to isolate from a constitutive mutant a substance which can 

 induce an inducible strain does not prove much ; success has actually been 

 claimed (Kramer and Straub, 1956) in penicillinase induction, but the 

 results proved difficult to reproduce and the nature of the active agent could 

 not be quite clearly established. The problem has recently been approached 

 by the methods of genetics in the exceptionally favourable case of j3- 

 galactosidase of E. coli K 12. As mentioned in Chapter I, the genome of a 

 Hfr bacterium, or part of it, can be transferred during conjugation to an 

 F~ recipient bacterium. Crosses of this type were made between bacteria 

 which differed by the presence of normal or mutated genes either in the z 

 locus controlling the structure of ^-galactosidase, or in the i region which 

 controls the inducible or constitutive character of the synthesis of the 

 enzyme (Pardee et al., 1959). Let us call z+ the normal form of the z locus 

 and z" any mutated form of this locus which prevents the formation of 

 active enzyme protein. In the same way, i+ will refer to inducibility, i~ to 

 constitutivity. Let us consider the two genetic formulae z+i+ and z~i~; none 

 of these strains will produce /S-galactosidase in the absence of added 

 inducer: the former because it must be induced to do so, the second because 

 it does not possess the correct structural information for making the 

 enzyme. Zygotes resulting from the conjugation of a donor z^i" and of a 

 recipient z+i+ do not produce the enzyme in the absence of exogeneous 

 inducer, although they possess both the structural information z+ and the 

 constitutivity character i~. On the other hand, if a z~i~ strain which is 

 potentially constitutive but does not possess the structural information 

 receives the information z+ together with i+, i.e. inducibility, from a donor 

 strain, it immediately starts making the enzyme, but the synthesis stops 

 after some time; it will then be obtained again if an inducer is added. The 

 zygote at first behaved like a constitutive, but it became adaptive after some 

 time. When both forms of the i gene are present in the same bacterium, the 

 phenotype corresponding to inducibility prevails ; the 'inducible' character 

 is dominant, 'constitutive' is recessive. The constitutive bacterium, how- 

 ever, contains all that is necessary for making the enzyme, this is an obvious 

 certainty. Therefore, it must be concluded that the i+ gene which causes 

 inducibility prevents the spontaneous production of the enzyme by 



