Gene Structure Evolution of the Na+-Ca2+ Exchanger (NCX) Family

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. Invertebrateshave a single NCX gene, whereas vertebrate species have multiple NCX genes as a result of at leasttwo duplication events. To examine the molecular evolution of NCX genes and understand the roleof duplicated genes in the evolution of the vertebrate NCX gene family, we carried out phylogeneticanalyses of NCX genes and compared NCX gene structures from sequenced genomes and individualclones.Results: A single NCX in invertebrates and the protochordate Ciona, and the presence of at leastfour NCX genes in the genomes of teleosts, an amphibian, and a reptile suggest that a four membergene family arose in a basal vertebrate. Extensive examination of mammalian and avian genomesand 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 encodingNCX homologs may provide teleosts with the functional specialization analogous to the alternatesplicing strategy seen with the three NCX mammalian homologs.Conclusion: We have demonstrated that NCX4 is present in teleost, amphibian and reptilianspecies but has been secondarily and independently lost in mammals and birds. Comparative studieson conserved vertebrate homologs have provided a possible evolutionary route taken by geneduplicates subfunctionalization by minimizing homolog number.