Regulation of Gene Expression in Prokaryotes:- Some Genes Are Regulated by Genetic Recombination
Salmonella typhimurium, which inhabits the mammalian intestine, moves by rotating the flagella on its cell surface (Fig. 1). The many copies of the protein flagellin (Mr 53,000) that make up the flagella are prominent targets of mammalian immune systems. But Salmonella cells have a mechanism that evades the immune response: they switch between two distinct flagellin proteins (FljB and FliC) roughly once every 1,000 generations, using a process called phase variation. The switch is accomplished by periodic inversion of a segment of DNA containing the promoter for a flagellin gene. The inversion is a site-specific recombination reaction (see Fig. 25–39) mediated by the Hin recombinase at specific 14 bp sequences (hix sequences) at either end of the DNA segment. When the DNA seg ment is in one orientation, the gene for FljB flagellin and the gene encoding a repressor (FljA) are expressed (Fig. 2a); the repressor shuts down expression of the gene for FliC flagellin. When the DNA segment is inverted (Fig. 2b), the fljA and fljB genes are no longer transcribed, and the fliC gene is induced as the repressor becomes depleted. The Hin recombinase, en coded by the hin gene in the DNA segment that undergoes inversion, is expressed when the DNA segment is in either orientation, so the cell can always switch from one state to the other. This type of regulatory mechanism has the advantage of being absolute: gene expression is impossible when the gene is physically separated from its promoter (note the position of the fljB promoter in Fig. 2b). An absolute on/off switch may be important in this system (even though it affects only one of the two flagellin genes), because a flagellum with just one copy of the wrong flagellin might be vulnerable to host antibodies against that protein. The Salmonella system is by no means unique. Similar regulatory systems occur in a number of other bacteria and in some bacteriophages, and recombination systems with similar functions have been found in eukaryotes (Table 28–1). Gene regulation by DNA rearrangements that move genes and/or promoters is particularly common in pathogens that benefit by changing their host range or by changing their surface proteins, thereby staying ahead of host immune systems.
FIGURE 1 Salmonella typhimurium, with flagella evident.
FIGURE 2 Regulation of flagellin genes in Salmonella: phase variation. The products of genes fliC and fljB are different flagellins. The hin gene encodes the recombinase that catalyzes inversion of the DNA segment containing the fljB promoter and the hin gene. The recombination sites (inverted repeats) are called hix (yellow). (a) In one orientation, fljB is expressed along with a repressor protein (product of the fljA gene) that represses tran scription of the fliC gene. (b) In the opposite orientation only the fliC gene is expressed; the fljA and fljB genes cannot be transcribed. The interconversion between these two states, known as phase variation, also requires two other nonspecific DNA-binding proteins (not shown), HU (histonelike protein from U13, a strain of E. coli) and FIS (factor for inversion stimulation).
