MCAT Biochemistry Review
Chapter 7: RNA and the Genetic Code
7.4 Control of Gene Expression in Prokaryotes
An organism's DNA encodes all of the RNA and protein molecules required to construct its cells. Yet organisms are able to differentially express their genes to make cell-specific products necessary for cellular development at specific times. In the next section, we'll look at these processes in eukaryotic cells; for now, we'll focus on the regulatory processes governing gene expression in prokaryotes—rules that are necessary in determining which subset of genes are selectively expressed or silenced in the prokaryotic cell.
The simplest example of an on–off switch that regulates gene expression levels in prokaryotes was discovered in E. coli. E. coli regulates the expression of many genes according to food sources that are available in the environment. For example, five genes in E. coli encode for enzymes that manufacture the amino acid tryptophan, and these are arranged in a cluster on the chromosome. By sharing a single common promoter region on the DNA sequence, these genes are transcribed as a group. This type of structure is called an operon—a cluster of genes transcribed as a single mRNA; this particular cluster in E. coli is known as the trp operon. Operons are incredibly common in the prokaryotic cell.
The Jacob–Monod Model is used to describe the structure and function of operons. In this model, operons contain structural genes, an operator site, a promoter site, and a regulator gene, as shown in Figure 7.14. The structural gene codes for the protein of interest. Upstream of the structural gene is the operator site, a nontranscribable region of DNA that is capable of binding a repressor protein. Further upstream is the promoter site, which is similar in function to promoters in eukaryotes: it provides a place for RNA polymerase to bind. Furthest upstream is theregulator gene, which codes for a protein known as the repressor. There are two types of operons: inducible systems and repressible systems.
Figure 7.14. Inducible Systems Allow for gene transcription only when an inducer is present to bind the otherwise present repressor protein.
Operons include both inducible and repressible systems, and offer a simple on–off switch for gene control in prokaryotes.
In inducible systems, the repressor is bound tightly to the operator system and thereby acts as a roadblock. RNA polymerase is unable to get from the promoter to the structural gene because the repressor is in the way. To remove that block, an inducer must bind the repressor protein so that RNA polymerase can move down the gene, as shown in Figure 7.14. Inducible systems operate on a principle analogous to competitive inhibition for enzyme activity: as the concentration of the inducer increases, it will pull more copies of the repressor off of the operator region, freeing up those genes for transcription. This system is useful because it allows gene products to be produced only when they are needed. Inducible systems are sometimes referred to as positive control mechanisms.
A classic example of an inducible system is the lac operon, which contains the gene for lactase, as demonstrated in Figure 7.15. Bacteria can digest lactose, but it is more energetically expensive than digesting glucose. Therefore, bacteria only want to use this option if lactose is high and glucose is low. The lac operon is induced by the presence of lactose; thus, these genes are only transcribed when it is useful to the cell.
The lac operon is assisted by binding of the catabolite activator protein (CAP). CAP is a transcriptional activator used by E. coli when glucose levels are low to signal that alternative carbon sources should be used. Falling levels of glucose cause an increase in the signaling molecule cyclic AMP (cAMP), which binds to CAP. This induces a conformational change in CAP that allows it to bind the promoter region of the operon, further increasing transcription of the lactase gene.
Figure 7.15. The lac Operon An example of an inducible system.
Repressible systems allow constant production of a protein product. In contrast to the inducible system, the repressor made by the regulator gene is inactive until it binds to a corepressor. This complex then binds the operator site to prevent further transcription, as shown in Figure 7.16. Repressible systems tend to serve as negative feedback; often, the final structural product can serve as a corepressor. Thus, as its levels increase, it can bind the repressor, and the complex will attach to the operator region to prevent further transcription of the same gene. Repressible systems are sometimes referred to as negative control mechanisms.
Positive control is accomplished by inducible systems, in which a repressor is removed from the operon by the inducer to promote transcription of a gene. Negative control is accomplished by repressible systems, in which a repressor–corepressor complex binds to the operon to prevent transcription.
The trp operon, described above, operates in this way. When tryptophan is high in the local environment, it acts as a corepressor. The binding of two molecules of tryptophan to the repressor causes the repressor to bind the operator site. Thus, the cell turns off its machinery to synthesize its own tryptophan, which is an energetically expensive process because of its easy availability in the environment.
Figure 7.16. Repressible Systems Continually allow gene transcription unless a corepressor binds to the repressor to stop transcription.
MCAT Concept Check 7.4:
Before you move on, assess your understanding of the material with these questions.
1. What type of operon is the trp operon? The lac operon?
2. From 5′ to 3′, what are the components of the operon, and what are their roles?
3. What is required to turn on a positive control system? What is required to turn off a negative control system?
· Positive control system:
· Negative control system: