Operon theory

While molecular biologists were investigating the structure of the molecules that store and serve to transfer specificity from DNA to protein, microbiologists investigated the spontaneous and induced mutations that occur in bacteria. Jacob and Monod used all the modern discoveries in molecular biology and bacterial genetics in a theory on the organization 

Much of the experimental evidence on which the operon theory is based was obtained by studying the induction and repression of bacterial enzymes. Induction is indicated by an increase in enzyme activity, and repression by a decrease in that activity. The inducer is usually a substrate of the enzyme the repressor is usually a product of the enzyme reaction. The changes in enzyme activities result from alterations in the rate of protein synthesis. 

Studies on bacterial mutation have shown that the induction of a specific enzyme is usually accompanied by an increase in activity of several other enzymes involved in the same catabolic or anabolic pathways. When E. coli are grown in the presence of galactosides, the formation of j8-galactosidase is induced, and it has been established that the new enzyme formed (1000 times the activity present in the wild type of E. coli) is not derived from the activation of preexisting proenzyme, but from the net synthesis of new enzyme. In 1953, Monod [213] discovered that the activity of tryptophan synthetase is inhibited by tryptophan and certain of its analogs. It was established that the inhibition or repression resulted from a block of the enzyme biosynthesis. 

Studies on bacterial mutations have shown that the induction or repression of a specific enzyme is usually accompanied by change in activity of several other enzymes, which catalyze reactions of the same catabolic or anabolic pathway. 

Studies on the biosynthesis of histidine in Salmonella by Ames and Hartman [214] established the simultaneous repression of several enzymes. In the series of reactions (at least 10 different steps) involved in the biosynthesis of the histidine molecule, the 5-carbon chain of phosphoribosyl pyrophosphate is converted to the 5-carbon chain of histidine. In Sal- 

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The biosynthesis of a particular enzyme is itself an elaborate and complex process Involving several cellular components. The genetic information for any particular enzyme is carried in a stretch of DNA which is the structural gene for that protein. The pattern is transcribed in a strip of the messenger RNA that dictates the proper sequence of amino acids in the synthesis of the enzyme. Van Dedem and Moo-Young have made an interesting beginning into incorporation of the operon theory of Jacob and Monod into a kinetic model for enzyme syntheses [3]. Indeed even a relatively simple model leads to many unidentifiable kinetic constants. 

The molecular structures of only a few repressors are known. On the basis of the operon theory, appar-... 

Represslble Biosynthetic Systems. In enteric bacteria the represslble systems for histidine and tryptophan biosynthesis provide examples of systems controlled by positive and negative elements, respectively (see Table IV). Since the level of histidine In the colon Is among the lowest of all amino acids, expression of the histidine biosynthetic operon In the bacterium will be In hl demand (Table III). Thus, demand theory predicts that the histidine biosynthetic operon will be positively regulated (Table II). In fact, there Is good evidence to show that this operon Is controlled primarily by an antiterminator mechanism (, ). On the other hand, the level of tryptophan In the colon Is among the hipest of the amino acids and, therefore, expressl( i of the tryptophan biosynthetic operon In the bacterium... 

The gene order in the histidine operon does not correspond to the order of the reactions in the pathway. It is possible that the order is simply one of chance, but one theory [47] suggests that ordering in... 

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. 

Aspects of the One Operon—One Molecule of Messenger RNA Theory, Modulators of the Velocity of Synthesis... 

I mentioned above that there are two views regarding the character of transcription of information frompolycistroniclociof DNA. According to one view, every gene (cistron) synthesizes its own molecule of RNA (the one gene—one mRNA molecule theory) according to the other, an individual messenger RNA is synthesized by a complete operon and carries information for several proteins (the one operon-one mRNA molecule theory Fig. 27). 

According to their theory, as the polycistronic messenger RNA moves in relation to the polysome system, the velocity of protein synthesis in its various parts is slowed. They postulated that the sequence of the genes in the histidine operon (which does not correspond to the biochemical sequence of reactions) is connected with the number of molecules of each enzyme synthesized. By analyzing the frequency of mutations of polarity, they concluded that many triplets (of the 64 possible) can retard the transcription and translation of information. The essence of the matter is that if any nucleotide triplet (codon) XYZ requires an anticodon in the molecules of acceptor sRNA for itstranslationinto a protein "text," a lowered content of this fraction of sRNA with the corresponding anticodon may act as modulator of the velocity of translation, which is reduced at this locus in connection with a decrease in the number of codon-anticodon interactions. 

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