Carmen Sánchez

David Perrin

François Jacob

Jacques Monod

CR Biologies

3/C. R. Biologies 328 (2005) 514–520http://france.elsevier.com/direct/CRASSFac-similé de la note / Facsimile of the articleL’opéron : groupe de gènes à expression coordonnéepar un opérateur[C. R. Acad. Sci. Paris 250 (1960) 1727–1729]François Jacob, David Perrin, Carmen Sánchez, Jacques MonodAvailable online 26 May 2005s oftemntalral-tionsild-edeu-henceer-siblere-, innesionallencePréfaceLes origines de l’opéron lactoseÀ la fin des années 1940, Jacques Monod com-mença à étudier les systèmes qui, chezE. coli, per-mettent d’utiliser le maltose ou le lactose. Très vite,il apparut que le système lactose était plus facile àmanier et offrait plus de possibilités expérimentalesque le système maltose.Le système lactose se trouva concerner plusieursprotéines : laβ-galactosidase, laβ-galactoside-per-méase et une galactoside-acétylase. Une série de mu-tations fut obtenue. Toutes ces protéines, chezE. colisauvage, n’étaient synthétisées qu’en présence deβ-galactoside. Elles furent appelées « inductives ».Parmi les mutations obtenues, certaines produisaientles protéines, même en l’absence de galactoside. Ellesfurent appelées « constitutives ». L’étude comparée in-ductif/constitutif montra que c’était le gène « induc-tif » qui était actif et produisait ce qui fut appelé un« répresseur ».Par conséquent, à côté des gènes dits « de struc-ture » existaient des gènes dits « régulateurs », quimodulaient l’expression des gènes de structure. Dansle système lactose, tous ces gènes étaient groupés sousforme d’une séquence appelée « opéron ».François JacobPrefaceThe origins of the lactose operonIn the late 1940s, Jacques Monod began studiethe systems that permitE. coli to utilize maltose orglucose. It rapidly became clear that the lactose syswas easier to handle and offered more experimepossibilities than the maltose system.The lactose system was found to involve seveproteins: β-galactosidase, theβ-galactoside permease, and a galactoside acetylase. A series of mutain the genes for these proteins was obtained. In wtypeE. coli, all three of the proteins were synthesizonly in the presence ofβ-galactoside and they werdefined as ‘inducible’. A certain fraction of the mtations obtained (defined as ‘constitutive’) led to tproduction of the three proteins, even in the abseof galactoside. Comparative studies on inducible vsus constitutive demonstrated that the gene responfor induction produced a factor that was named ‘pressor’.The conclusion of these observations was thataddition to the genes called ‘structural’, other gecalled ‘regulatory’ exist that modulate the expressof the structural genes. For the lactose system,of these genes were grouped together in a sequnamed ‘operon’.François Jacob1631-0691/2005 Published by Elsevier SAS on behalf of Académie des sciences.doi:10.1016/j.crvi.2005.04.005F. Jacob et al. / C. R. Biologies 328 (2005) 514–520 515516 F. Jacob et al. / C. R. Biologies 328 (2005) 514–520F. Jacob et al. / C. R. Biologies 328 (2005) 514–520 517C. R. Biologies 328 (2005) 514–520http://france.elsevier.com/direct/CRASS3/English translationThe operon: a group of genes with expressioncoordinated by an operator✩François Jacob, David Perrin Carmen Sánchez, Jacques MonodServices de physiologie microbienne et de biochimie cellulaire, Institut Pasteur, Paris, FrancePresented by Jacques TrefouelThe analysis of various bacterial systems has led to the conclusion that the synthesis of certain proteins (en-zymatic or viral) involves a double genetic determinism, which calls into play two genes with distinct functions:one, the structural gene, is responsible for the structure of the molecule; the other, the regulatory gene, governsthe expression of the first gene through the intervention of a repressor[1]. The regulatory genes that have so farbeen identified manifest the remarkable property of exercising acoordinated pleiotropic effect, with each regula-tory gene governing the expression of several structural genes that are tightly linked and that correspond to proteinenzymes belonging to the same biochemical pathway. In order to explain this effect, it appears necessary to hypoth-esize a new genetic entity, called ‘operator’ that would be: (a) adjacent to a group of genes and in control of theiractivity; (b) sensitive to the repressor produced by a particular regulatory gene[1]. In the presence of the repressor,the expression of the group of genes would be inhibited through the intermediary of the operator. This hypothesisleads to very distinct predictions concerning the mutations that could affect the structure of the operator. In effect:– (1) certain mutations that alter an operator are manifested by loss of the capability to synthesize the proteinsspecified by the group of linked genes that are ‘coordinated’ by this operator. These simple mutations behave asphysiological deletions and could not be complemented by any mutant for which one of the structural genes of thesequence had been altered;– (2) other mutations, which lead for example to a loss of sensitivity (affinity) of the operator for the correspond-ing repressor, are manifested by the constitutive synthesis of the proteins specified by the coordinated genes. Theseconstitutive mutations, in contrast to those resulting from the inactivation of regulatory genes, would bedominantin a heterozygous diploid, but their effect is only observed on genes located incis position with respect to themutated operator.We have studied certain mutations that alter the metabolism of lactose inEscherichia coli K 12 and exert aneffect on the synthesis of bothβ-galactosidase and galactoside permease and therefore would appear to correspondto modifications of the hypothetical operator. Note that three distinct genes have been identified in this system:(1) the y structural gene for galactoside-permease; (2) the z structural gene forβ-galactosidase, for which certainalleles lead to the synthesis of a modified protein, Cz, that is enzymatically inactive; and (3) the i regulator gene✩ Translated from French by Stuart Edelstein.1631-0691/2005 Published by Elsevier SAS on behalf of Académie des sciences.doi:10.1016/j.crvi.2005.04.005F. Jacob et al. / C. R. Biologies 328 (2005) 514–520 519Table 1Units of galactosidase and of protein Cz (see[3]) expressed as a percentage of the results obtained for the allele located onthe chromosome of induced bacteria. The units of permease (see[5]) are presented as a percentage of the results obtainedwith induced bacteria. nd, non-detectable. The excess of the product of the allele z located on the F-Lac factor appears toindicate the presence of several F-Lac factors per chromosome[2,3]that specifies the synthesis of a repressor. These three genes are tightly linked. Note as well that bacteria that arediploid for the genes of this group can be obtained by transfer of the sex factors (F), which have incorporated thecorresponding fragment of the bacterial genome (F-Lac)[2].Starting with a diploid i+z−/F-i+z+, constitutive mutants (oc) were isolated. Using appropriate re-combinationsand transfers, the different diploid genotypes presented inTable 1were obtained. It should be noted that the allelesz1 and z4 utilized permit the synthesis of inactive proteins (Cz1, Cz4) whose concentrations can be measured in thepresence ofβ-galactosidase by an immunochemical method[3]. It may be noted from the data inTable 1that forbacteria that are heterozygous for o and z, the permease, as well as the galactosidase or the protein Cz are partiallyconstitutive, but only the z or y alleles located inc s with respect to oc are expressed constitutively, with the allelein trans remaining strictly inducible, as in the genotype o+/ +. The mutation oc is therefore pleiotropic, dominant,and its effect is manifested only in positioncis.Starting with wild-type haploid bacteria, several other mutants were isolated, for which an apparently simplemutational event leads to the loss of the capacity to synthesize both the permease andβ-g lactosidase. Thesemutants revert to wild-type with a frequency of 10−7 to 10−8. They are recessive and are not complemented byeither z or y mutants. Genetic analysis reveals that these mutations (oo) are tightly linked to mutations oc and thatthey are located between the loci z and 1 (which are themselves tightly linked). The order of the loci in the segmentLac is:TL...Pro...y− z− o− i︸ ︷︷ ︸Lac...Ad...GalOn the basis of their characteristics, the mutations oo and oc appear to affect a genetic element that is not expressedby anindependent cytoplasmic product. The remarkable properties of these mutations are unexplainable accordingto the ‘classical’ conception of structural genes and are also distinct from mutations that affect the regulatory gene i.These mutations are, in contrast, in accord with the predictions based on the operator hypothesis. Several simpledefective mutations with coordinated pleiotropic effects (but not subject to complementation) have been describedfor other bacterial systems, in particular for galactose metabolism[4]. We suggest that these mutants might affectan operator.The operator hypothesis implies that between the classical gene (an independent unit of a biochemical function)and the chromosome, there exists an intermediate genetic organization. It is made up ofcoordinated units ofexpression (operons) composed of an operator and the group of structural genes that it coordinates. Each operonwould be, through the intermediary of the operator, susceptible to the action of a repressor whose synthesis isregulated by a regulatory gene (not necessarily linked to the group). The repression will be exerted either directlyat the level of the genetic material, or at the level of a ‘cytoplasmic version’ of the operon. This hypothesis would520 F. Jacob et al. / C. R. Biologies 328 (2005) 514–520explain the correlation observed very generally in bacteria between functional association and genetic linkage forsystems of sequential enzymes. It would also lead to other testable consequences, notably that the enzymes of asequence governed by the same operator cannot be inducedseparately [6].References1[1] F. Jacob, J. Monod, C. R. Acad. Sci. Paris 249 (1959) 1282.[2] F. Jacob, E.A. Adelberg, C. R. Acad. Sci. Paris 249 (1959) 189.[3] D. Perrin, A. Bussard, J. Monod, C. R. Acad. Sci. Paris 249 (1959) 778.[4] H.M. Kalckar, K. Kurahashi, E. Jordan, Proc. Natl Acad. Sci. USA 45 (1959) 1776.[5] H.W. Rickenberg, G.N. Cohen, G. Buttin, J. Monod, Ann. Inst. Pasteur 91 (1956) 829.[6] This research was supported by the Jane Coffin Childs Memorial Fund and the National Science Foundation..1 References have been re-formulated as they are currently in theComptes rendus. See the facsimile of the original text for their originalform.

L'opéron : groupe de gènes à expression coordonnée par un opérateur [C. R. Acad. Sci. Paris 250 (1960) 1727–1729]

Comptes Rendus Biologies (CRBIOL)

https://comptes-rendus.academie-sciences.fr/biologies/item/10.1016/j.crvi.2005.04.005.pdf

L'opéron : groupe de gènes à expression coordonnée par un opérateur [C. R. Acad. Sci. Paris 250 (1960) 1727–1729]

Abstract

Similar works

Full text

Available Versions

CR Biologies

Comptes Rendus Biologies (CRBIOL)