The study of these mutants was to lead to the notion that, in bacteria, genetic material is organized into units of activity known as operons, which are often more complex than the gene considered as a unit of function. In fact, the E.coli lactose system comprises three known proteins, and the three genes governing the structure of these proteins happen to be adjacent on a small segment of the chromosome, with the operon located at one end of this segment. Constitutive mutations, whether due to damage to the regulatory gene or to the operator, always have the remarkable property of being pleiotropic, i.e. they affect the production of all three proteins simultaneously and to the same degree. The regulatory circuit therefore had to be able to act on an integral structure containing the information that specifies the structure of all three proteins. This structure could only be the DNA itself, or a messenger common to all three genes. This view was further supported by the properties found in mutations affecting the structural genes of the lactose system. While some of these mutations obey Beadle and Tatum's "one gene-one enzyme" rule, in that they abolish just one of the three biochemical activities, other mutations, on the contrary, violate this rule, as they affect the expression not of just one gene, but of several at once.

The notion of operon, a grouping of adjacent structural genes whose regulation is controlled by a common operator, explained why genes governing enzymes of the same biochemical chain tend to remain grouped in bacteria, as Demerec and Hartman had observed. It also explained the coordinated production of enzymes already observed in certain biosynthetic chains. While the concept of an operon was originally based exclusively on genetic criteria, it is now complemented by biochemical criteria. There are many experimental arguments, both genetic and biochemical, to suggest that an operon produces an integral messenger which combines with ribosomes to form the series of peptide chains determined by the operon's various structural genes.

The activity of the E. coli genome can thus be represented as follows. The expression of genetic material requires a continuous flow of unstable messengers, which dictate the specificity of the proteins to be produced by the ribosome machines. The genetic material is made up of operons containing one or more genes, each operon forming an integral messenger. Messenger production by the operon is, in one way or another, inhibited by regulatory loops made up of three elements: regulatory gene - repressor - operator. It is at the level of these loops that specific metabolites act as signals: in inducible systems, to inactivate the repressor, thus enabling messenger and hence protein production; in repressible systems, to activate the repressor, thus inhibiting messenger and protein production. According to this scheme, only a fraction of the cell's genes can be expressed at any given time, the others remaining repressed. It's a network of specific, genetically determined circuits that selects at any given moment which segments of DNA are to be transcribed into messengers, and thus translated into proteins, according to chemical signals from the cytoplasm and the environment.

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Excerpts from the Nobel Lecture delivered on December 11, 1965
Copyright © The Nobel Foundation)

Source: article taken from La Lettre n° 35, Collège de France