GENETIC CONTROL OF CELL INTEGRATION 321 



protein seems to play a role in initiating each cycle of DNA synthesis in 

 E. coli, and one may speculate that the timing of DNA synthesis is also 

 under precise cellular control in other forms. 



A prevalent current hypothesis states that the genetic specifications 

 (information) carried in the DNA are transferred to RNA by DNA-RNA 

 pairing during RNA synthesis, and that this RNA, in turn, is built into 

 ribosomes which function in the cytoplasm as the sites of protein forma- 

 tion. One weakness of this hypothesis is its lack of discrimination among 

 the various classes of RNA and perhaps even of DNA, as well as of pro- 

 tein. As with the categories of "nuclear ' and "cytoplasmic," those of 

 DNA, RNA, and protein are too sweeping. 



A great refinement in methodology has been contributed by investiga- 

 tions of the formation of individual, identified proteins, coupled with 

 an analysis of the genetic determinants which control their specificity 

 and rate of formation. As we shall see, studies of the metabolic control 

 of enzyme formation have led to some of the most direct findings con- 

 cerning the intimate involvement of genes in this process. 



GENETIC CONTROL OF ENZYME FORMATION 



It is not a rare occurrence in research that a problem appearing 

 relevant within one frame of reference early in its study develops along 

 unpredicted lines and later becomes centrally important in quite a differ- 

 ent context. The study of enzyme adaptation in microorganisms has had 

 many unexpected turns in its history, and seems now to be reaching a 

 focal point of development, uniting many divergent lines of research and 

 providing the basis for a more penetrating analysis of cell integration. 



The phenomenon of enzyme adaptation, that is, the change in enzyme 

 content of cells occasioned by specific environmental changes, was first 

 described in microorganisms before 1900. It was shown, for example, 

 that yeast cells grown on glucose do not contain the galactose-fermenting 

 enzyme, galactozymase, but that after a delay (lag period), in the pres- 

 ence of galactose, such cells will begin to ferment that sugar, gradually 

 increasing their galactozymase activity. This kind of phenomenon was 

 observed widely among microorganisms, and aroused interest in terms of 

 the economy of the cell, which seemed to be manufacturing enzymes only 

 when needed, and in terms of possible mechanisms by which this en- 

 vironmental control might be elicited. After a long quiescent period, 

 interest in enzyme adaptation reappeared in the mid-I930's, and has 

 been accelerating ever since. At present, this field is providing some 

 of the best material for the integrated analysis of protein synthesis, 



