Molecular evolution of voltage-sensitive ion channel genes: on the origins of electrical excitability

We have analyzed nucleic acid and amino acid sequence alignments of avariety of voltage-sensitive ion channels, using several methods forphylogenetic tree reconstruction. Ancient duplications within this familygave rise to three distantly related groups, one consisting of the Na+ andCa++ channels, another the K+ channels, and a third including the cyclicnucleotide-binding channels. A series of gene duplications produced atleast seven mammalian homologues of the Drosophila Shaker K+ channel;clones of only three of these genes are available from all three mammalianspecies examined (mouse, rat, and human), pointing to specific genes thathave yet to be recovered in one or another of these species. TheShaw-related K+ channels and the Na+ channel family have also undergoneconsiderable expansion in mammals, relative to flies. These expansionspresumably reflect the needs of the high degree of physiological andneuronal complexity of mammals. Analysis of the separate domains of thefour-domain channels (Ca++ and Na+) supports their having evolved by twosequential gene duplications and implies the historical existence of afunctional two-domain channel.