MOLECULAR RESURRECTION OF AN EXTINCT ANCESTRAL PROMOTER FOR MOUSE L1

The F-type subfamily of LINE-1 or L1 retroposons [for long intersperse d (repetitive) element 1] was dispersed in the mouse genome several mi llion years ago. This subfamily appears to be both transcriptionally a nd transpositionally inactive today and therefore may be considered ev olutionarily extinct. We hypothesized that these F-type L1s are inacti ve because of the accumulation of mutations. To test this idea we used phylogenetic analysis to deduce the sequence of a transpositionally a ctive ancestral F-type promoter, resurrected it by chemical synthesis, and showed that it has promoter activity. In contrast, F-type sequenc es isolated from the modern genome are inactive. This approach, in whi ch the automated DNA synthesizer is used as a ''time machine,'' should have broad application in testing models derived from evolutionary st udies.