Structural Gene Clusters Are Coordinately Controlled

KEY CONCEPT
- Genes coding for proteins that function in the same pathway may be located adjacent to one another and controlled as a single unit that is transcribed into a polycistronic mRNA.
Bacterial genes are often organized into operons that include genes coding for proteins whose functions are related. The genes coding for the enzymes of a metabolic pathway are commonly organized into such a cluster. In addition to the enzymes actually involved in the pathway, other related activities may be included in the unit of coordinated control, such as the protein responsible for transporting the small molecule substrate into the cell.
The cluster of the lac operon containing the three lac structural genes—lacZ, lacY, and lacA—is typical. FIGURE 1 summarizes the organization of the structural genes, their associated cis-acting regulatory elements, and the trans-acting regulatory gene. The key feature is that the structural gene cluster is transcribed into a single polycistronic mRNA from a promoter where initiation of transcription is regulated.

FIGURE 1. The lac operon occupies ~6,000 bp of DNA. At the left the lacI gene has its own promoter and terminator. The end of the lacI region is adjacent to the lacZYA promoter, P. Its operator, O, occupies the first 26 bp of the transcription unit. The long lacZ gene starts at base 39 and is followed by the lacY and lacA genes and a terminator.
The protein products enable cells to take up and metabolize β-galactoside sugars, such as lactose. The roles of the three structural genes are as follows:
- lacZ codes for the enzyme β-galactosidase, whose active form is a tetramer of approximately 500 kD. The enzyme breaks the complex β-galactoside into its component sugars. For example, lactose is cleaved into glucose and galactose (which are then further metabolized). This enzyme also produces an important by-product, β-1,6-allolactose, which, as will be discussed later, has a role in regulation.
- nlacY codes for the β-galactoside permease, a 30-kD membrane-bound protein constituent of the transport system.This transports β-galactosides into the cell.
- lacA codes for β-galactoside transacetylase, an enzyme that transfers an acetyl group from acetyl-CoA to β-galactosides.
Mutations in either lacZ or lacY can create the lac genotype, in which cells cannot utilize lactose. (The genotypic description “lac” without a qualifier indicates loss of function.) The lacZ mutations abolish enzyme activity, directly preventing metabolism of lactose. The lacY mutants cannot take up lactose efficiently from the medium. (No defect is identifiable in lacA cells, which is puzzling. The acetylation reaction might give an advantage when the bacteria grow in the presence of certain analogs of β-galactosides that cannot be metabolized, because the modification results in detoxification and excretion.)
The entire system, including structural genes and the elements that control their expression, forms a common unit of regulation called an operon. The activity of the operon is controlled by regulator gene(s) whose protein products interact with the cis-acting control elements.