Q.Gene expresses itself in a cell system as a protein/enzyme. How does an expression of gene occur in a cell system and when does it need to occur, and how the gene expression is regulated in a prokaryote cell system was studied by the combined efforts of Jacque Monod, the biochemist and Francois Jacob, the geneticist. For their work on lactose metabolism in E. coli and introducing the concept of "lac operon" they were awarded the Nobel Prize in 1965.

The lac operon (Jacob and Monod) is the classic model of gene regulation in prokaryotes.

Part (a)

(a) It is called a transcriptionally regulated system because control acts at the initiation of transcription. In the absence of an inducer the repressor (product of the i gene) binds the operator and physically blocks RNA polymerase, so mRNA of the structural genes is never made. When an inducer (allolactose) is present it inactivates the repressor, freeing the operator so transcription can begin. Whether mRNA is made or not is the control point — hence transcriptional regulation.

(b) One structural gene, y, codes for permease, which carries lactose into the cell. If the operon were switched off completely, no permease would exist, no lactose could enter, no allolactose could form, and the operon could never be induced. So a very low basal level of expression must run continuously to keep a little permease available for the initial entry of lactose.

(c) The regulator gene is marked i because it codes for the repressor, which acts as an inhibitor of transcription of the structural genes.

(d) Schematic — absence of inducer (repressed state): the i gene continuously produces active repressor, which binds the operator (o) located between the promoter (p) and the structural genes (z, y, a). This physically blocks RNA polymerase from moving past the operator, so the structural genes are not transcribed and no lactose-metabolising enzymes are made. …

Gene expression yields proteins/enzymes, and its regulation in prokaryotes was worked out by François Jacob and Jacques Monod on lactose metabolism in E. coli, for which they shared the 1965 Nobel Prize. The lac operon has a promoter (p), an operator (o), three structural genes — z (β-galactosidase), y (permease), a (transacetylase) — and an upstream regulator gene i that constitutively makes the repressor.

Part (a)

1. Why "transcriptionally regulated". Regulation acts at transcription initiation. In the absence of lactose the repressor binds the operator and physically prevents RNA polymerase from transcribing z, y, a, so no mRNA is formed. When lactose is available it is converted to allolactose (the inducer), which binds and inactivates the repressor; the operator is freed and transcription proceeds. Because the cell decides whether the mRNA is made at all, the primary control is at the transcriptional level.
2. Why a low basal level is needed. Lactose must enter the cell to act as inducer, and its entry needs the enzyme permease, the product of the y gene of the operon itself. If the operon were fully off, no permease would be made, lactose could not enter, allolactose could not form, and the operon could never switch on. A small, constitutive (basal) level of transcription therefore keeps a trace of permease present, letting the first lactose molecules in to trigger full induction. (c) Why the regulator is the i gene. It codes for the repressor protein, whose role is to inhibit transcription of the structural genes by binding the operator — hence i for inhibitor.

(d) Schematic — absence of inducer. The i gene continuously produces active repressor, which binds the operator located between the promoter and the structural genes. This blocks RNA polymerase; the structural genes are not transcribed and no lactose enzymes are made (the repressed/OFF state). Gene order along the DNA: i — p — o — z — y — a, with the repressor bound at o and RNA polymerase halted just before it. …