title: Gene structure evolution of the Na+-Ca2+ exchanger (NCX) family.
abstract: BACKGROUND
  The Na+-Ca2+ exchanger (NCX) is an important regulator of cytosolic Ca2+ levels. Many of its structural features are highly conserved across a wide range of species. Invertebrates have a single NCX gene, whereas vertebrate species have multiple NCX genes as a result of at least two duplication events. To examine the molecular evolution of NCX genes and understand the role of duplicated genes in the evolution of the vertebrate NCX gene family, we carried out phylogenetic analyses of NCX genes and compared NCX gene structures from sequenced genomes and individual clones.
  
  
  RESULTS
  A single NCX in invertebrates and the protochordate Ciona, and the presence of at least four NCX genes in the genomes of teleosts, an amphibian, and a reptile suggest that a four member gene family arose in a basal vertebrate. Extensive examination of mammalian and avian genomes and synteny analysis argue that NCX4 may be lost in these lineages. Duplicates for NCX1, NCX2, and NCX4 were found in all sequenced teleost genomes. The presence of seven genes encoding NCX homologs may provide teleosts with the functional specialization analogous to the alternate splicing strategy seen with the three NCX mammalian homologs.
  
  
  CONCLUSIONS
  We have demonstrated that NCX4 is present in teleost, amphibian and reptilian species but has been secondarily and independently lost in mammals and birds. Comparative studies on conserved vertebrate homologs have provided a possible evolutionary route taken by gene duplicates subfunctionalization by minimizing homolog number.
authors.affiliation: Cardiac Membrane Research Laboratory - Kinesiology, Simon Fraser University, Burnaby, BC, Canada. con@sfu.ca
authors.forename: Caly
authors.initials: C
authors.lastname: On
authors.forename: Christian R
authors.initials: CR
authors.lastname: Marshall
authors.forename: Nansheng
authors.initials: N
authors.lastname: Chen
authors.forename: Christopher D
authors.initials: CD
authors.lastname: Moyes
authors.forename: Glen F
authors.initials: GF
authors.lastname: Tibbits
mesh_terms: D017398:Alternative Splicing; D000818:Animals; D030541:Databases, Genetic; D019143:Evolution, Molecular; D005091:Exons; D020440:Gene Duplication; D014644:Genetic Variation; D007438:Introns; D016013:Likelihood Functions; D005810:Multigene Family; D010802:Phylogeny; D017386:Sequence Homology, Amino Acid; D012689:Sequence Homology, Nucleic Acid; D019831:Sodium-Calcium Exchanger / Q000235:genetics*; D013045:Species Specificity; D026801:Synteny
chemical_list: D019831:Sodium-Calcium Exchanger