Molecular resurrection of an extinct ancestral promoter for mouse L1

The F-type subfamily of LINE-1 or L1 retroposons [for long interspersed (repetitive) element 1] was dispersed in the mouse genome several million years ago. This subfamily appears to be both transcriptionally and transpositionally inactive today and therefore may be considered evolutionarily extinct. We hypothesized that these F-type L1s are inactive because of the accumulation of mutations. To test this idea we used phylogenetic analysis to deduce the sequence of a transpositionally active ancestral F-type promoter, resurrected it by chemical synthesis, and showed that it has promoter activity. In contrast, F-type sequences isolated from the modern genome are inactive. This approach, in which the automated DNA synthesizer is used as a "time machine," should have broad application in testing models derived from evolutionary studies.