On Caly, Marshall Christian R, Chen Nansheng, Moyes Christopher D, Tibbits Glen F
Cardiac Membrane Research Laboratory - Kinesiology, Simon Fraser University, Burnaby, BC, Canada.
BMC Evol Biol. 2008 Apr 30;8:127. doi: 10.1186/1471-2148-8-127.
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.
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.
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.
钠钙交换体（NCX）是细胞溶质钙水平的重要调节因子。其许多结构特征在广泛的物种中高度保守。无脊椎动物有一个单一的NCX基因，而脊椎动物由于至少两次复制事件而有多个NCX基因。为了研究NCX基因的分子进化并了解复制基因在脊椎动物NCX基因家族进化中的作用，我们对NCX基因进行了系统发育分析，并比较了来自已测序基因组和单个克隆的NCX基因结构。
无脊椎动物和原索动物海鞘中有一个单一的NCX，而硬骨鱼、一种两栖动物和一种爬行动物的基因组中存在至少四个NCX基因，这表明一个由四个成员组成的基因家族出现在基础脊椎动物中。对哺乳动物和鸟类基因组的广泛研究以及共线性分析表明，NCX4可能在这些谱系中丢失。在所有已测序的硬骨鱼基因组中都发现了NCX1、NCX2和NCX4的复制基因。七个编码NCX同源物的基因的存在可能为硬骨鱼提供了类似于哺乳动物三个NCX同源物通过可变剪接策略实现的功能特化。
我们已经证明NCX4存在于硬骨鱼、两栖动物和爬行动物物种中，但在哺乳动物和鸟类中已次生且独立丢失。对保守的脊椎动物同源物的比较研究通过最小化同源物数量提供了基因复制亚功能化可能采取的进化途径。
