Research

The Dictyostelium genome encodes numerous RasGEFs with multiple biological roles

Andrew Wilkins^{* 1} , Karol Szafranski^{* 2} , Derek J Fraser³ , Deenadayalan Bakthavatsalam⁴ , Rolf Müller⁴ , Paul R Fisher³ , Gernot Glöckner² , Ludwig Eichinger⁴ , Angelika A Noegel⁴ and Robert H Insall¹

¹School of Biosciences, University of Birmingham, Birmingham B15 2TT, UK

²Genome Analysis, Institute for Molecular Biotechnology, Beutenbergstrasse 11, D-07745 Jena, Germany

³Department of Microbiology, La Trobe University, VIC 3086, Australia

⁴Centre for Biochemistry and Centre for Molecular Medicine Cologne, Medical Faculty, University of Cologne, Joseph-Stelzmann-Strasse 52, 50931 Cologne, Germany

author email corresponding author email* Contributed equally

Genome Biology 2005, 6:R68doi:10.1186/gb-2005-6-8-r68

Published:	28 July 2005

Subject areas: Cell biology, Evolution, Genome studies, Model organisms

Abstract

Background

Dictyostelium discoideum is a eukaryote with a simple lifestyle and a relatively small genome whose sequence has been fully determined. It is widely used for studies on cell signaling, movement and multicellular development. Ras guanine-nucleotide exchange factors (RasGEFs) are the proteins that activate Ras and thus lie near the top of many signaling pathways. They are particularly important for signaling in development and chemotaxis in many organisms, including Dictyostelium.

Results

We have searched the genome for sequences encoding RasGEFs. Despite its relative simplicity, we find that the Dictyostelium genome encodes at least 25 RasGEFs, with a few other genes encoding only parts of the RasGEF consensus domains. All appear to be expressed at some point in development. The 25 genes include a wide variety of domain structures, most of which have not been seen in other organisms. The LisH domain, which is associated with microtubule binding, is seen particularly frequently; other domains that confer interactions with the cytoskeleton are also common. Disruption of a sample of the novel genes reveals that many have clear phenotypes, including altered morphology and defects in chemotaxis, slug phototaxis and thermotaxis.

Conclusion

These results suggest that the unexpectedly large number of RasGEF genes reflects an evolutionary expansion of the range of Ras signaling rather than functional redundancy or the presence of multiple pseudogenes.