658 The Journal of Clinical Investigation| March 2001| Volume 107| Number 6 of translation or changes in the level of promoter activity. Two features of these loci distinguish them from other mechanisms of phenotypic variation. First, the hypermutation of these loci is independent of classic recombination genes, in contrast to other mechanisms of phase variation such as gene conversion, transposition, and “flip-flop.” Second, the reversibility and hypermutability of simple sequences result from expansion or contraction of the repeat tracts by one or more repeat units, such that there are multiple possible “ON” and “OFF” states. For example, the gain or loss of one or two repeat units could switch an ON tetranucleotide repeat tract in a reading frame to OFF. Because these mutations can occur in a small number of generations, these loci can appear highly polymorphic even between cells of a single clone.