Scientists wake up ancient Sleeping Beauty jumping gene
transposon - a piece of DNA which randomly "jump" around the
genome, cutting and pasting itself throughout the strands of DNA.
The researchers hope the artificial transposon, dubbed "Sleeping Beauty", could be used to probe the activity of different parts of the genome, and with a bit of tweaking it could provide an efficient way of transferring genes between organisms. While transposons form about half of all the human genome, only a tiny fraction of these still actively jump around the genome proliferating, and the vast majority are passive remnants that stay in one place. Even the active transposons rarely cause a noticeable affect. "In the human situation transposition very rarely causes diseases," said Dr. Zoltán Ivics from the Max Delbrück Center for Molecular Medicine (MDC) Berlin-Buch, who led the study. The mechanism for replication is similar to the way pathogens spread, except the proliferation only occurs within the nucleus and the transposon cannot naturally move outside the cell. "They replicate just like a virus, but in an intracellular way. A protein product - the transposase, cuts the transposon from its location and moves it to another location. The transposon can not leave the cell on its own, but otherwise there's a lot of similarity. Many believe that integrating viruses evolved from transposable elements," says Ivics. To create an active transposon, the team studied the fish genome to find an ancient passive transposon that had been active a long time ago. They then studied this passive transposon to try to predict what its DNA sequence might have looked like when it had been active many years before, and tried to recreate this sequence in the lab. The team eventually created the transposon they dub "Sleeping Beauty", which they then inserted into a human cell using a gene shuttle. The results showed that Sleeping Beauty did indeed replicate itself within the genome. "We were very lucky," Dr. Ivics said. "The very first experiment was successful." Currently, the team hope that the transposon could be used to study the function of different parts of the genome. By studying which genes the transposon has replaced, and the effect this has on the cell's activity, researchers may be able to deduce the function of replaced gene. "There is also an increasing interest to use the transposon for gene therapy. It's like classical gene transfer into the genome, except now we are equipped with the power of the transposition process which does this very efficiently," he says. However, to do this the scientists will need to find a way of controlling the transposition process, so that the new gene does not proliferate indefinitely.
