Histidine operon regulatory mutants

The Jacob-Monod theory therefore predicts two types of constitutive mutants, one unlinked to the operon and recessive, and the other adjacent to the operon and cis-dominant. It generated some surprise, then, when regulatory mutants of the histidine operon were found to fall into a total of six different chromosomal positions. 

Responses of the regulatory mutants to the composition of the growth medium are also of interest. Like the wild type, nearly all the mutants do not reduce their enzyme levels when histidine is added to minimal medium. The only exceptions are hisS mutants having a histidyl-tRNA synthetase with a poorer K for histidine (see Section IV,E). Addition of all the amino acids, or growth on nutrient broth, however, does result in a lowering of the enzyme levels. In the case of hisO, hisR, and hisT, the reduction in enzyme levels might not reflect a specific repression of the histidine operon, but instead be due to the... 

Study of the repression control of the histidine operon has suggested that it may be more complicated than the model proposed by Jacob and Monod. This possibility is predicated on failure to find a pure repressor gene. This failure has left open the possibility that control may be exerted by aminoacylated tRNA alone, possibly at the level of protein synthesis rather than mRNA synthesis. Alternatively, the repressor could be encoded by one of the regulatory genes discussed, but could also serve an additional function vital to the cell. The necessity of maintaining this second function would prevent the isolation of mutants which had totally lost repressor activity. In line with this latter possibility, the complex of histidyl-tRNA synthetase with aminoacylated tRNA may serve as the repressor. The mutual affinity of these two macromolecules and their concentrations within the cell are such that a large portion of the aminoacylated tRNA may be complexed to the synthetase [20,118a]. 

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