MDC Researchers Reconstruct Jumping Gene

They can be found in plants, animals and even in humans – inactive remains of jumping genes, transposons. Researchers are striving to develop active transposons from these remains, using them as tools to decode gene function.

At the Max Delbrück Center for Molecular Medicine (MDC) Berlin-Buch, Germany, researchers have now succeeded in reconstructing the first active transposon of the Harbinger transposon superfamily.

In the laboratory, the artificial transposon developed by Dr. Ludivine Sinzelle, Dr. Zsuzsanna Izsvák, and Dr. Zoltán Ivics also shows cut-and-paste transposition in human cells and promises to serve as a useful experimental system for investigating human gene function.

The findings of the MDC researchers have just been published online in the Proceedings of the National Academy of Sciences (PNAS)*.

Transposons comprise about half of the human genome. “They are molecular parasites, similar to fleas, only that they are in the genome of the host and not on its back,” Dr. Zoltán Ivics explained. They jump, move, and proliferate through the host, without whom they could not survive. In most cases, transposons do not fulfill any function in the human genome. “However, not all are superfluous,” Dr. Ivics went on to say. “More than 100 active genes, including some associated with the immune system, have been recognized as probably derived from transposons.”

To reconstruct an active transposon, Dr. Ivics' team compared the DNA of various inactive Harbinger transposons, one of the largest superfamilies of transposons. Based on these results, they developed an artificial jumping gene. “We were very lucky,” Dr. Ivics said. “The very first experiment was successful.”

New tool for basic research
In the cell lab, the MDC researchers inserted the transposon into the human cell by means of a gene shuttle. Via a cut-and-paste mechanism, the artificial transposon excises itself from its transport vehicle and inserts itself into the genome of the cell. If the transposon jumps into an important gene and deactivates it, it may impair important processes in the cell. As a result, researchers can draw conclusions about the function of the gene.

Moreover, in the course of evolution, transposons have been responsible for the emergence of new genes. Thus, through computerized gene analysis, Dr. Ivics' research team has discovered two new elements related to the Harbinger transposon. In a new project, Dr. Ivics aims to elucidate just what role these play in the human body.

Over the long term, scientists hope to use such transposons in gene therapy as well. With the aid of a transposon, an intact copy of a gene could be incorporated into the genome of a patient to repair a defective gene. “But until this can happen, there is still a lot to be done,” Dr. Ivics pointed out. “The new gene should not just jump in anywhere.”

*Transposition of a Reconstructed Harbinger Element in Human Cells and Functional Homology with Two Transposon-derived Cellular Genes

Ludivine Sinzelle1, Vladimir V. Kapitonov,2, Dawid P. Grzela1, Tobias Jursch1, Jerzy Jurka2, Zsuzsanna Izsvák1,3 and Zoltán Ivics1

1Max Delbrück Center for Molecular Medicine, Berlin, Germany;
2Genetic Information Research Institute, Mountain View, California, USA
3Institute of Biochemistry, Biological Research Center of the Hungarian Academy of Sciences, Szeged, Hungary
A photo of the research group of Dr. Zoltán Ivics can be downloaded from the Internet at:

http://www.mdc-berlin.de/en/news/2008/index.html

Barbara Bachtler
Press and Public Affairs
Max Delbrück Center for Molecular Medicine (MDC) Berlin-Buch
Robert-Rössle-Straße 10; 13125 Berlin; Germany
Phone: +49 (0) 30 94 06 – 38 96
Fax: +49 (0) 30 94 06 – 38 33
e-mail: presse@mdc-berlin.de