VARIATION AND MUTATION IN ENZYME SYSTEMS 295 



increased production of enzyme. Catalase, urease and formic dehydrogenase were 

 included in these enzymes, one of whose essential functions appeared to be removal 

 of inhibitory products of metabolism ; these were maintained at an efficient level 

 over a large pH range. The enzymes of the second group displayed only a small 

 degree of compensatory formation when the growth pH shifted from the pH of 

 their optimal activity. They behaved like adaptive enzymes, but adaptive in 

 respect of pH rather than of substrates. Nevertheless, they contributed to the 

 stability of cellular equilibrium. Thus, in an acid medium, amino-acid decarboxy- 

 lases, and consequently amines, were produced ; on the other hand, amino-acid 

 deaminases, and consequently hydroxy acids, were produced in an alkaline medium. 



Adaptation occurs much more readily in physiologically young than in 

 older cells (see, for example, Hegarty 1939), and we have already seen that 

 adaptation takes place in resting bacteria. The independence of reproduction and 

 some forms of adaj)tation is confirmed by the interesting study of Doudoroff 

 (1940) on the adaptation of Bact. coli to sodium chloride. 



When the cultural conditions, such as air supply, concentration of nutrient, and pH, 

 were standardized, a fairly constant fraction of a fresh-water culture of Bact. coli was 

 able to reproduce when inoculated into a medium of definite NaCl concentration. The 

 accUmatization to salt was independent of reproduction, since bacteria in the stationary 

 phase were far more readily acclimatized than those in the phase of logarithmic growth 

 or the phase of decUne. Only acclimatized c'ells were capable of reproduction in saline 

 media, but if after accUmatization the non-dividing cells were returned to salt-free media, 

 they rapidly lost the capacity to grow in saline media. Once acclimatized, the cells could 

 be propagated in saline media without further acclimatization, though the division rate 

 was considerably lower than that in salt-free cultures. 



Optimal acclimatization to growth, even in high salt concentration, was achieved 

 by preliminary exposure to a single intermediate salt concentration. In other words, 

 the adaptive response of the bacteria consisted firstly of a reversible acclimatization, 

 independent of reproduction, and secondly of a selection of the cells with the widest 

 range of potentiaUties for growth in various concentrations of saline. 



The distinction between adaptive and constitutive enzymes is perhaps more 

 a quantitative than a qualitative one. The production of constitutive enzymes 

 varies according to the conditions of culture, and sometimes according to the 

 presence or absence of the substrate. Moreover, adaptive enzymes are con- 

 stitutive in the sense that they are a constant feature of the bacterial cell. As 

 far as we are aware, there is no recorded instance of a bacterial strain losing the 

 capacity to make a given adaptive enzyme response by continuous subculture 

 in media which preserve the general characters of the strain. In other words, 

 though by definition the adaptation is not heritable, the specific adaptability 

 certainly is. We do not know whether the potentiality for adaptation is main- 

 tained as a precursor or as the enzyme itself, but in some cases it is possible that 

 the enzyme is present as such when no substrate is present, though in undetectable 

 amounts. 



Variation and Mutation in Enzyme Systems.^At the other end of the scale 

 of variation, we have those changes which are presumably due to the selection, 

 over a large number of bacterial generations, of relatively rare mutations. Changes 

 in environment of the kind that induce an adaptive response in bacteria may also 

 serve to make mutations manifest. In a case of this kind, the distinction between 

 the two eifects would lie mainly in the persistence of the mutation effect when 



