Research Article 9: Superrepressors of the lac Operon

Abstract

INTRODUCTION
Two superrepressed (i^s) mutants of the lac operon have been described so far (Willson, Perrin, Cohn, Jacob and Monod, 1964). They behave as noninducible mutants whose lac negative phenotype is dominant over the wild-type inducible one. Their dominance characteristics as well as their reversion pattern to the lac positive constitutive phenotype were interpreted as the result of a mutation in the regulatory gene i inactivating the inducer recognition site of the repressor (R) but leaving the operator (O) binding site intact. The discovery of i^s mutations has been the crucial genetic argument that the i gene product, R, recognizes the inducers directly and specifically, making it very likely, therefore, that R is a regulatory protein.

We have isolated a family of lac negative mutants which behave like i^s in all dominance tests and in their reversion pattern. However, we found that most of these new mutants, although noninducible by lactose, still respond to other lac inducers but at concentrations higher than those required by the wild type: they range in their induction capacity from nondetectably inducible, to different levels of partial inducibility, to almost normal inducibility by IPTG. They seemed to represent, therefore, inducer affinity mutants of R.

The i^s mutations could also, however, have increased the affinity of R for O and/or have altered the allosteric properties of R in such a way that, although having retained inducer binding capacity, the inducers could no longer catalyze the release of R from O. In vivo studies could not distinguish...