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

<p>Abstract</p> <p>Background</p> <p>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 <it>NCX </it>gene, whereas vertebrate species have multiple <it>NCX </it>genes as a result of at least two duplication events. To examine the molecular evolution of <it>NCX </it>genes and understand the role of duplicated genes in the evolution of the vertebrate <it>NCX </it>gene family, we carried out phylogenetic analyses of <it>NCX </it>genes and compared <it>NCX </it>gene structures from sequenced genomes and individual clones.</p> <p>Results</p> <p>A single <it>NCX </it>in invertebrates and the protochordate <it>Ciona</it>, and the presence of at least four <it>NCX </it>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 <it>NCX4 </it>may be lost in these lineages. Duplicates for <it>NCX1</it>, <it>NCX2</it>, and <it>NCX4 </it>were found in all sequenced teleost genomes. The presence of seven genes encoding <it>NCX </it>homologs may provide teleosts with the functional specialization analogous to the alternate splicing strategy seen with the three <it>NCX </it>mammalian homologs.</p> <p>Conclusion</p> <p>We have demonstrated that <it>NCX4 </it>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.</p

The sodium-calcium exchanger (NCX): temperature adaptation and evolutionary history

The sodium-calcium exchanger (NCX) is an important regulator of intracellular calcium and is highly conserved across species. NCX among different species that live in diverse environments demonstrate adaptation to different conditions while maintaining a relatively high degree of identity. For further understanding of NCX temperature sensitivity, we characterized NCX gene sequences from a wide variety of genomes for analyses. However, these analyses did not lead to specific predictions of temperature sensitivity among the various homologs of NCX. By comparing NCX orthologs with different temperature dependencies yet with high genotype conservation, ten amino acids were predicted as being primarily responsible for the variation in phenotype. Mutation of these ten amino acids and activity measurement over a range of temperatures resulted in a significant change in its temperature sensitivity. Further work to elucidate the changes in NCX function at different temperatures is required to establish the specific mechanisms underlying NCX temperature dependence