34 CONTROL MECHANISMS IN CELLULAR PROCESSES 



Relations Between Structural and Regulatory Genes. Genetic 

 evidence shows that the synthesis of yS-galactosidase in E. coli is con- 

 trolled by a portion of the genome which has been called the Lac 

 region (cf. Lederberg et al., 1951). For recent discussions of this 

 subject, see Wollman and Jacob ( 1959 ) , Pardee et al. ( 1959 ) , Jacob 

 (1960), and Jacob et al (1960b). This (relatively small but com- 

 plex ) region contains at least four loci ( y, z, o, and i ) concerned with 

 the metabolism of yS-galactosides. The ij locus governs the formation 

 of a permease for ^-galactosides ( Rickenberg et al., 1956; Cohen and 

 Monod, 1957) and is not of immediate relevance to the synthesis of 

 /3-galactosidase. The z locus, on the other hand, is intimately con- 

 nected with the synthesis of this enzyme, and has for some time 

 been thought to contain the code for the latter's amino acid sequence. 

 The o and i loci are considered to have regulatory functions in the 

 above-defined sense. Mutations at the z locus, as expected for a 

 structural gene, can result in the loss of the capacity to synthesize 

 ^-galactosidase; mutations at the i locus can bring about conversion 

 from inducibility (i.e., ability to respond with enzyme formation to 

 an inducer that can antagonize an endogenous repressor) to con- 

 stitutivity (i.e., ability to form the enzyme in the absence of an 

 added inducer ) ; and mutations at the o locus can lead either to con- 

 stitutivity or to simultaneous loss of the ability to synthesize the 

 enzyme and the permease (Jacob et al., 1960a). An elegant analysis 

 of the properties of the o and i loci has been performed by Jacob 

 et al. ( 1960a ) who studied the dominance and position behavior of 

 suitable heterozygotes ( see below) . The role of the z locus has been 

 exhibited graphically by recent experiments of Perrin et al. ( 1959 ) : 

 mutations at the ;:: locus can bring about the synthesis of proteins 

 that are antigenically related to ;S-galactosidase but enzymatically 

 inactive; nevertheless, these structurally altered proteins can exhibit 

 the properties of repressibility and inducibility characteristic of 

 yS-galactosidase. The interrelations among structural and regulatory 

 genes as established by studies with bacteria have a counterpart in 

 results with Neurospora that have suggested gene functions in ad- 

 dition to those performed by structural-type genes (Bonner et al., 

 1960). 



Functioning of Regulatory Genes. The finding of two regulatory 

 loci governing ^-galactosidase synthesis in E. coli (see Jacob et al., 

 1960a) has uncovered the existence of a complex genetic control 



