Slippery runs, shifty stops, backward steps and forward hops: -2, -1, +1, +2, +5 and +6 Ribosomal frameshifting

Frameshift mutations frequently express residual levels of gene activity; that is, they are often leaky. This leakiness can be used as a tool to define the functional components that affect the reading frame during gene expression. Recent technological advances in the capability to efficiently build synthetic DNA sequences have facilitated the construction of small, defined "frameshift windows." These windows are regions where frameshift events can be detected and measured. The cloned synthetic window is fused onto th 5' coding region of an active B-galactosidase gene that provides a sensitive monitor for the frameshift events. Fusions onto the lac Z gene have the advantages of simple colorimetric assays for B-galactosidase activity and little or no effect of the fused sequence on the specific activity or stability of the enzyme. A frameshift event also leaves a clue to its character in the protein sequence translated from the window's m-RNA sequence. Recovery of the frameshift containing B-galactosidase in sufficient yield and purity for determining its amino-terminal sequence provides hard evidence for the occurrence of a frameshift, and this sequence may be used to infer the kind of event generating the loss of reading frame.