Evolution and divergence of sodium channel genes in vertebrates

Invertebrate species possess one or two Na(+) channel genes, yet there are 10 in mammals. When did this explosive growth come about during vertebrate evolution? All mammalian Na(+) channel genes reside on four chromosomes. It has been suggested that this came about by multiple duplications of an ancestral chromosome with a single Na(+) channel gene followed by tandem duplications of Na(+) channel genes on some of these chromosomes. Because a large-scale expansion of the vertebrate genome likely occurred before the divergence of teleosts and tetrapods, we tested this hypothesis by cloning Na(+) channel genes in a teleost fish. Using an approach designed to clone all of the Na(+) channel genes in a genome, we found six Na(+) channel genes. Phylogenetic comparisons show that each teleost gene is orthologous to a Na(+) channel gene or gene cluster on a different mammalian chromosome, supporting the hypothesis that four Na(+) channel genes were present in the ancestors of teleosts and tetrapods. Further duplications occurred independently in the teleost and tetrapod lineages, with a greater number of duplications in tetrapods. This pattern has implications for the evolution of function and specialization of Na(+) channel genes in vertebrates. Sodium channel genes also are linked to homeobox (Hox) gene clusters in mammals. Using our phylogeny of Na(+) channel genes to independently test between two models of Hox gene evolution, we support the hypothesis that Hox gene clusters evolved as (AB) (CD) rather than {D[A(BC)]}.