158 



( IIAPTFR 36 



upon which those enzymes act), however, 

 the repressor substance made by i ' is in- 

 activated, so that the formation of enzymes 

 b\ v • and z ' becomes possible. Lactose 

 functions as an inducer. Therefore. E. coli 

 of genotype y z •' i + cannot produce per- 

 mease or galactosidase constitutively ( in the 

 absence of lactose) but can do so induc- 

 tively ( in the presence of lactose ) . This 

 example serves as a model to explain the 

 genetic basis for many cases of induced en- 

 zyme formation. In this instance, the feed- 

 back system controls the production but not 

 the activity of certain enzymes. 



The order of these genes in the linkage 

 map is: TL . . . Pro . . . (Lac) yzi . . . 

 Ad . . . Gal. Note that all three Lac 

 genes specify unique substances. Because 

 i + produces a repressor substance which, 

 in the absence of lactose, is capable of plei- 

 otropic effects — that is, of phenotypic sup- 

 pression of both >' + and z + — / + can be 

 called a regulator gene. 



Consider the consequences of certain mu- 

 tations in the Lac region. Mutants capable 

 of synthesizing permease and galactosidase 

 constitutively can have the genotype y + z + i 

 in which the specific repressor is not pro- 

 duced, and their y+ and z + genes can act 

 under all circumstances. E. coli hybrid for 

 the Lac region can be produced by intro- 

 ducing into F~ cells, F merogenotes carry- 

 ing the Lac region (p. 357). Thus, we can 

 obtain an E. coli individual whose chromo- 

 some is y + z i (which by itself would make 

 permease and Cz protein constitutively), 

 and whose F-Lac particle is y + z + i + 

 (which by itself would make permease and 

 galactosidase only inductively). In the hy- 

 brid, no products are formed in noninduced 

 bacteria (in the absence of lactose), al- 

 though all three (permease, galactosidase, 

 and Cz protein) are formed in induced bac- 

 teria (exposed to lactose). We can con- 

 clude, therefore, that a single r gene can 

 manufacture a repressor substance which 



prevents the products of both normal and 

 mutant y and z genes from being formed 

 constitutively but not inductively, whether 

 or not these genes are located in the same 

 chromosome segment. In other words, the 

 repressor substance is dillusible and can act 

 at a distance. Various lines of evidence in- 

 dicate that the repressor substance is pro- 

 tein. 1 An allele of /+, /* — called a super- 

 repressor — prevents the v and z loci from 

 functioning even in the presence of lactose. 

 Apparently the superrepressor substance is 

 insensitive to lactose, and the v and z loci 

 cannot be derepressed. 



Another mutant has been found which 

 permits both v f and z + products to form 

 constitutively, and may, therefore, be a mu- 

 tation of /+. Let us call this mutant allele 

 /'■''. When an F-Lac particle of the geno- 

 type y + z + /' is placed in a cell with a chro- 

 mosome y + z i (which by itself is found to 

 produce permease and Cz protein consti- 

 tutively), no Cz protein is formed consti- 

 tutively in noninduced bacteria. Contrary 

 to the assumption that /' is a mutant of i + , 

 /' must actually be i+ since it produces a 

 repressor capable of repressing Cz protein 

 formation constitutively. In what respect, 

 then, is the F-Lac particle mutant? Sup- 

 pose the F-Lac particle is mutant at an ad- 

 ditional locus, o + . The new allele, o r , 

 would permit only the y and z loci in the 

 same chromosome (or particle) to act con- 

 stitutively regardless of which allele of i is 

 present in the cell. Assuming this is so and 

 ignoring gene order for the present, then the 

 F-Lac particle is genotypically y + z + o'/ + , 

 while the genotype of the chromosome can 

 be written y + z o + i. According to this 

 new hypothesis, the hybrid ought to pro- 

 duce permease and galactosidase constitu- 

 tively and, in addition, to produce Cz pro- 

 tein inductivelv. This is found to be true; 



1 See A. Garen and N. Otsuji ( 1964). and M. E. 

 Balis. J. S. Salser, and A. Elder (1964). 



