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Defining the Origins and Evolution of the Chemokine/Chemokine Receptor System¹

Mark E. DeVries^*, Alyson A. Kelvin^*, Luoling Xu^*, Longsi Ran^*, John Robinson and David J. Kelvin^2,*

^* Division of Experimental Therapeutics and Department of Immunology, University of Toronto, Toronto General Research Institute, Toronto General Hospital, University Health Network, Toronto, Ontario, Canada; and Robarts Research Institute, London, Ontario, Canada

The chemokine system has a critical role in mammalian immunity, but the evolutionary history of chemokines and chemokine receptors are ill-defined. We used comparative whole genome analysis of fruit fly, sea urchin, sea squirt, pufferfish, zebrafish, frog, and chicken to identify chemokines and chemokine receptors in each species. We report 127 chemokine and 70 chemokine receptor genes in the 7 species, with zebrafish having the most chemokines, 63, and chemokine receptors, 24. Fruit fly, sea urchin, and sea squirt have no identifiable chemokines or chemokine receptors. This study represents the most comprehensive analysis of the chemokine system to date and the only complete characterization of chemokine systems outside of mouse and human. We establish a clear evolutionary model of the chemokine system and trace the origin of the chemokine system to 650 million years ago, identifying critical steps in their evolution and demonstrating a more extensive chemokine system in fish than previously thought.

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