BASIC SCIENCE: Single Cell Signals to Multiple Cells

Applied Genetics News, Jan, 2002

In analyzing single-celled choanoflagellates, Sean Carroll and Nicole King, from the University of Wisconsin, Madison, discovered that the organisms have a receptor tyrosine kinase, the first that has been found in a single-celled organism. Their findings are reported in the December 18, 2001,edition of the Proceedings of the National Academy of Sciences. The presence of the tyrosine kinase in these organisms supports the idea that these are similar to the immediate ancestors of multi-cellular organisms.

Choanoflagellates are a group of about 150 species of single- celled protists, which use a whip-like flagellum to swim and draw in food. Surrounding this flagellum is a circle of closely packed, finger-like microvilli that filter food from the water. Scientists have long suspected that choanoflagellates might represent modern examples of what the ancestors of multicellular animals, or metazoans, looked like. And the circumstantial evidence supporting that notion was compelling-choanoflagellates are nearly identical to cells called choanocytes in sponges that also carry out food- gathering, and some species of choanoflagellates tend to form colonies.

"The existing scientific literature, however, has been conflicting or ambiguous about whether these protists are the closest living relatives of animals without actually being animals," says Carroll, who is a Howard Hughes medical investigator. "So, Nicole King proposed that we explore protein sequences that hadn't been examined before, and which might provide unambiguous support for the relationship between choanoflagellates and animals."

Carroll and King compared genes in one species of choanoflagellate, Monosiga brevicollis, to four animal genes- elongation factor 2, alpha-tubulin, beta-tubulin and actin-that are widely used as molecular markers to explore relationships among species.

"When we compared the sequences of the choanoflagellate and animal genes, we got a much clearer statistical signal than we expected that they were related," says Carroll. The researchers next surveyed the choanoflagellate genome for animal-related genes. The search concentrated on molecules involved in cell adhesion and cell signaling, which single-cell organisms would not be expected to have.

"Among several hundred common gene sequences we obtained, out popped this receptor tyrosine kinase, a molecule that has never before been found outside of metazoans," Carroll says. "We'd like to know if this protein might be a founding member of this class of molecules-a common ancestor that may have appeared on the eve of animal evolution."

"In general, these discoveries have made us confident that we've picked the right organism to understand what happened on the eve of animal evolution," says Carroll. "Thus, we believe we can discover in this organism more elements of the genetic toolkit that was first used to build animals."