FIG 1.

Illustration of how phase-variable switching of inverting Type I systems occurs. Type I R-M loci are made up of three genes encoding a restriction enzyme (hsdR; R), a methyltransferase (hsdM; M), and a target sequence specificity protein (hsdS; S). Inverting Type I systems contain an extra hsdS gene termed hsdS′ (S′). Each hsdS gene is made up of two target recognition domains (TRDs). In inverting systems there are multiple variable TRDs present in the two hsdS loci. In the illustrated example, there are two different 5′-TRDs (5′-TRD-1 in orange and 5′-TRD-2 in white) and two different 3′TRDs (3′-TRD-1 in purple and 3′-TRD-2 in green). Inverted repeats are located before 5′-TRD (gray) and between the 5′-TRD and 3′-TRD (yellow). Recombination between these inverted repeats means that four possible hsdS coding sequences are present in the expressed hsdS locus: allele A = 5′-TRD-1 + 3′-TRD-1; allele B = 5′-TRD-1 + 3′-TRD-2; allele C = 5′-TRD-2 + 3′-TRD-2; allele D = 5′-TRD-2 + 3′-TRD-1. These four different hsdS variants mean four different HsdS proteins are produced. Following oligomerization with an HsdM dimer to form an active methyltransferase, the four different HsdS protein subunits result in four different methyltransferase specificities. This would be described as a “four-way” or “four-phase” switch, since four different HsdS proteins are produced from the four different hsdS genes possible in the expressed hsdS locus.