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Nobel Prize in Physiology or Medicine: François Jacob with André Lwoff and Jacques Monod in 1965

p. 12

Notes de la rédaction

Excerpts from the Nobel Lecture delivered on 11 December 1965

Copyright © The Nobel Foundation

Source: La lettre, no. 35, December 2012

Texte intégral

Genetics of the Bacterial Cell

1Having thus constructed the requisite genetic tool for our analy­sis, we set out to isolate under different conditions a whole series of mutants constitutive for the lactose system, in order to subject them to functional analysis. These mutants proved to belong to two quite distinct groups, which possessed the predicted properties for the transmitter and the receiver, respectively. Many of these mutations were found to be “recessive” with respect to the wild-type allele. They allowed a definition of the transmitter, that is, of the regulatory gene.

2In the second group, the mutations turned out to be “dominant” over the wild-type allele, and only those genes which were located on the same chromosome, that is, in cis position, were expressed constitutively. With these mutations, it was possible to define the receptor of the repressor, termed the operator.

3The study of these mutants led, furthermore, to the notion that in bacteria the genetic material is organized into units of acti­vity called operons, which are often more complex than the gene considered as the unit of function. In fact, the lactose system of E. coli contains three known proteins, and the three genes governing their structure are adjacent to one another on a small segment of the chromosome with the operator at one end. Constitutive mutations, whether due to the alteration of the regulatory gene or of the operator, always display the remarkable property of being pleiotropic; that is, they affect simultaneously, and to the same extent, the production of the three proteins. The regulatory circuit therefore had to act on one integral structure containing the information which specifies the amino acid sequences of the three proteins. This structure could only be either the DNA itself or a messenger common to the three genes. This idea was further supported by the properties observed in mutations affecting the structural genes of the lactose system. Whereas some of these mutations obey Beadle and Tatum’s “one gene-one enzyme” rule in the sense that they abolish only one of the three biochemical activities, others violate this rule by affecting the expression of several genes at a time.

4The notion of the operon, a grouping of adjacent structural genes controlled by a common operator, explained why the genes controlling the enzymes of the same biochemical pathway tend to remain clustered in bacteria, as observed by Demerec and Hartman. Similarly, it accounted for the coordinate production of enzymes already found in certain biochemical pathways. Although at first the operon concept was based exclusively on genetic criteria, it now includes biochemical criteria as well. There are, in fact, a number of experimental arguments, both genetics and biochemical, in support of the inference that an operon produces a single messenger, which binds to ribosomes to form the series of peptide chains determined by the different structural genes of the operon.

5We can therefore envision the activity of the genome of E. coli as follows. The expression of the genetic material requires a continuous flow of unstable messengers which dictate to the ribosomal machinery the specificity of the proteins to be made. Thed to remain clusteosome -tO

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