title: Molecular evolution of voltage-sensitive ion channel genes: on the origins of electrical excitability.
abstract: We have analyzed nucleic acid and amino acid sequence alignments of a variety of voltage-sensitive ion channels, using several methods for phylogenetic tree reconstruction. Ancient duplications within this family gave rise to three distantly related groups, one consisting of the Na+ and Ca++ channels, another the K+ channels, and a third including the cyclic nucleotide-binding channels. A series of gene duplications produced at least seven mammalian homologues of the Drosophila Shaker K+ channel; clones of only three of these genes are available from all three mammalian species examined (mouse, rat, and human), pointing to specific genes that have yet to be recovered in one or another of these species. The Shaw-related K+ channels and the Na+ channel family have also undergone considerable expansion in mammals, relative to flies. These expansions presumably reflect the needs of the high degree of physiological and neuronal complexity of mammals. Analysis of the separate domains of the four-domain channels (Ca++ and Na+) supports their having evolved by two sequential gene duplications and implies the historical existence of a functional two-domain channel.
authors.affiliation: Department of Physiology and Biophysics, University of California, Irvine 92717.
authors.forename: M
authors.initials: M
authors.lastname: Strong
authors.forename: K G
authors.initials: KG
authors.lastname: Chandy
authors.forename: G A
authors.initials: GA
authors.lastname: Gutman
mesh_terms: D000818:Animals; D005075:Biological Evolution; D015220:Calcium Channels / Q000235:genetics; D004330:Drosophila / Q000235:genetics; D006801:Humans; D007473:Ion Channels / Q000235:genetics* / Q000502:physiology; D008564:Membrane Potentials / Q000235:genetics; D008958:Models, Molecular; D005810:Multigene Family; D010802:Phylogeny; D015221:Potassium Channels / Q000235:genetics; D016415:Sequence Alignment; D015222:Sodium Channels / Q000235:genetics
chemical_list: D015220:Calcium Channels; D007473:Ion Channels; D015221:Potassium Channels; D015222:Sodium Channels