Fig 1.
Phase variation can result in singular versus global regulation of cellular factors.
Phase variation via site-specific DNA recombination involves the inversion of a regulatory sequence by a serine or tyrosine recombinase. The recombinase binds flanking inverted repeats (LIRs and RIRs) and catalyzes the inversion of the intervening sequence. The orientation of the invertible element determines whether the downstream gene(s) are expressed (ON) or not (OFF). Top: In a simple system, recombination inverts a single element, controlling the expression of a single factor. Fimbrial phase variation in Escherichia coli is controlled in this manner. Middle: In a more complex scenario, a single recombinase inverts multiple elements. Inversion of the elements occurs stochastically and independently, yielding multiple discrete genetic combinations and phenotypic variants, thus allowing one recombinase to influence bacterial phenotypes on a broader scale. As an example, in C. difficile, the recombinase RecV inverts sequences upstream of multiple genes including those encoding CwpV, flagella, and intracellular factors [19, 22, 31]. Bottom: Phase variation of a single regulator, such as a transcription factor, results in a coordinated switch in multiple phenotypes regulated by that factor. LIR, left inverted repeat; RIR, right inverted repeat.