Modified from figure 1 of Kornberg, T. Another arrow in the Drosophila quiver. Proc Natl Acad. Sci USA 99, 9607–9608 (2002).

The P transposable element holds a venerable position in Drosophila genetics. Ever since the discovery of its mutagenic properties about 30 years ago, it has been been a component of countless fly genetic techniques, from ectopic expression to mutagenesis. The completion of the Drosophila melanogaster genome sequence brings a new urgency to the fly field — that of understanding the biological role of every transcription unit. A group of fly geneticists, headed by Bill Gelbart, has now risen to this challenge: by combining the intrinsic properties of the P element and that of another transposon, hobo, they have produced a hybrid construct that can generate molecularly defined deletions in vivo, in an unbiased and systematic way. Given the high density and efficiency at which deletions are generated — based on two successful cases — this method could become the most user-friendly way to annotate the fly genome.

The construct developed by Huet et al. — called P(wHy) — consists of a single hobo element contained between two P element ends (see diagram). In the presence of P transposase, the P(wHy) jumps around and so stable strains of flies can be generated in which P(wHy) elements are inserted in single copies anywhere in the genome. If the P element is in charge of 'carrying' the P(wHy), then the hobo element is in charge of deleting the surrounding sequence. Unlike the P transposase, the hobo transposase has two functions: first, it causes hobo to hop, by conservative transposition, to a nearby location. Then, it catalyses homologous recombination between the old and the new hobo copies. This last step leads to the deletion of the genomic sequence between the newly transposed hobo element and its parent sequence within the P(wHy), with the length of the sequence depending on how far out the new hobo element has hopped. The direction and the occurrence of the deletion event is reliably monitored by the loss of one of the two visible markers in P(wHy) that are on either side of hobo. A broad set of genomic deletions — which can be up to 400 kb but with the highest density ∼60 kb — can be generated in this way, all of which, importantly, start at one end of the hybrid element.

This deletion technique is not the first gene disruption method known in flies: RNA interference and targeted gene knockouts have been used by many labs over the past few years. What makes the P(wHy) deletion system so appealing, however, is that it can be applied globally to the genome. Moreover, as the components of P(wHy) have their equivalents outside Drosophila, it might not be long before this phenotypic analysis tool takes a leap into other eukaryotes.