title: The evolution of the four subunits of voltage-gated calcium channels: ancient roots, increasing complexity, and multiple losses.
abstract: The alpha subunits of voltage-gated calcium channels (Ca(v)s) are large transmembrane proteins responsible for crucial physiological processes in excitable cells. They are assisted by three auxiliary subunits that can modulate their electrical behavior. Little is known about the evolution and roles of the various subunits of Ca(v)s in nonbilaterian animals and in nonanimal lineages. For this reason, we mapped the phyletic distribution of the four channel subunits and reconstructed their phylogeny. Although alpha subunits have deep evolutionary roots as ancient as the split between plants and opistokonths, beta subunits appeared in the last common ancestor of animals and their close-relatives choanoflagellates, gamma subunits are a bilaterian novelty and alpha2/delta subunits appeared in the lineage of Placozoa, Cnidaria, and Bilateria. We note that gene losses were extremely common in the evolution of Ca(v)s, with noticeable losses in multiple clades of subfamilies and also of whole Ca(v) families. As in vertebrates, but not protostomes, Ca(v) channel genes duplicated in Cnidaria. We characterized by in situ hybridization the tissue distribution of alpha subunits in the sea anemone Nematostella vectensis, a nonbilaterian animal possessing all three Ca(v) subfamilies common to Bilateria. We find that some of the alpha subunit subtypes exhibit distinct spatiotemporal expression patterns. Further, all six sea anemone alpha subunit subtypes are conserved in stony corals, which separated from anemones 500 MA. This unexpected conservation together with the expression patterns strongly supports the notion that these subtypes carry unique functional roles.
authors.affiliation: Department of Ecology, Evolution and Behavior, Alexander Silberman Institute of Life Sciences, Faculty of Science, Hebrew University of Jerusalem, Israel yehu.moran@mail.huji.ac.il h.zakon@austin.utexas.edu.
authors.forename: Yehu
authors.initials: Y
authors.lastname: Moran
authors.affiliation: Department of Integrative Biology and Center for Computational Biology and Bioinformatics, University of Texas, Austin Department of Neuroscience, University of Texas at Austin Josephine Bay Paul Center for Molecular Biology and Evolution, Marine Biological Laboratory, Woods Hole, Massachusetts yehu.moran@mail.huji.ac.il h.zakon@austin.utexas.edu.
authors.forename: Harold H
authors.initials: HH
authors.lastname: Zakon
mesh_terms: D000818:Animals; D019143:Evolution, Molecular; D008969:Molecular Sequence Data; D010802:Phylogeny; D024642:Potassium Channels, Voltage-Gated / Q000235:genetics*; D021122:Protein Subunits / Q000235:genetics*; D012615:Sea Anemones / Q000145:classification / Q000235:genetics*
chemical_list: D024642:Potassium Channels, Voltage-Gated; D021122:Protein Subunits
keywords: Cnidaria; Nematostella vectensis; evolution of nervous system; ion channel; voltage-gated calcium channel