Evolution and divergence of sodium channel genes in vertebrates

Abstract

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)]}.

Gene Duplications and Evolution of Vertebrate Voltage-Gated Sodium Channels

“…Our tree was not significantly better at explaining the molecular data than the topologies of Plummer and Meisler (1999), Goldin (2002) or Lopreato et al (2001) (Table 3).…”

“…1). For example, results from Plummer and Meisler (1999) and Lopreato et al (2001) are distinct from other studies in that they both support the hypothesis that two early wholegenome duplications in vertebrates (known as the 2R hypothesis, (e.g., Amores et al 1998;Ohno 1970;Sidow 1996) led to four SCNA genes in the most recent ancestor of teleosts and tetrapods (Teleostomi).…”

“…1;Plummer and Meisler 1999;Goldin et al 2000;Lopreato et al 2001;Goldin 2002;Piontkivska and Hughes 2003). Because the topology of mammalian SCNA phylogeny from Goldin (2002) is identical to that from Plummer and Meisler (1999), these two trees were treated as a single hypothesis.…”

“…Phylogenetic analysis has been previously applied to SCNA genes to determine the evolutionary history of the vertebrate SCNA gene family (Goldin 2002;Goldin et al 2000;Lopreato et al 2001;Piontkivska and Hughes 2003;Plummer and Meisler 1999).…”

“…Amores et al (1998) proposed that the larger number of zebrafish hox and associated genes arose during a genome-wide duplication event unique to teleosts (see also Meyer and Schartl 1999;Wittbrodt et al 1998;Vandepoele et al 2004). Interestingly, Lopreato et al (2001) suggested that, in teleosts, this genome-wide duplication event contributed to SCNA gene family evolution.…”