Marshall Christian R, Fox Joanne A, Butland Stefanie L, Ouellette B F Francis, Brinkman Fiona S L, Tibbits Glen F
Department of Molecular Biology and Biochemistry, Simon Fraser University, Burnaby, Canada.
Physiol Genomics. 2005 Apr 14;21(2):161-73. doi: 10.1152/physiolgenomics.00286.2004. Epub 2005 Mar 1.
The Na+/Ca2+ exchanger (NCX) is a member of the cation/Ca2+ antiporter (CaCA) family and plays a key role in maintaining cellular Ca2+ homeostasis in a variety of cell types. NCX is present in a diverse group of organisms and exhibits high overall identity across species. To date, three separate genes, i.e., NCX1, NCX2, and NCX3, have been identified in mammals. However, phylogenetic analysis of the exchanger has been hindered by the lack of nonmammalian NCX sequences. In this study, we expand and diversify the list of NCX sequences by identifying NCX homologs from whole-genome sequences accessible through the Ensembl Genome Browser. We identified and annotated 13 new NCX sequences, including 4 from zebrafish, 4 from Japanese pufferfish, 2 from chicken, and 1 each from honeybee, mosquito, and chimpanzee. Examination of NCX gene structure, together with construction of phylogenetic trees, provided novel insights into the molecular evolution of NCX and allowed us to more accurately annotate NCX gene names. For the first time, we report the existence of NCX2 and NCX3 in organisms other than mammals, yielding the hypothesis that two serial NCX gene duplications occurred around the time vertebrates and invertebrates diverged. In addition, we have found a putative new NCX protein, named NCX4, that is related to NCX1 but has been observed only in fish species genomes. These findings present a stronger foundation for our understanding of the molecular evolution of the NCX gene family and provide a framework for further NCX phylogenetic and molecular studies.
钠钙交换体（NCX）是阳离子/Ca2+反向转运体（CaCA）家族的成员，在多种细胞类型中维持细胞内Ca2+稳态方面发挥着关键作用。NCX存在于多种生物中，并且在物种间具有较高的整体同源性。迄今为止，在哺乳动物中已鉴定出三个独立的基因，即NCX1、NCX2和NCX3。然而，由于缺乏非哺乳动物的NCX序列，对该交换体的系统发育分析受到了阻碍。在本研究中，我们通过从Ensembl基因组浏览器可获取的全基因组序列中鉴定NCX同源物，扩展并丰富了NCX序列列表。我们鉴定并注释了13条新的NCX序列，包括来自斑马鱼的4条、来自日本河豚的4条、来自鸡的2条，以及来自蜜蜂、蚊子和黑猩猩的各1条。对NCX基因结构的研究以及系统发育树的构建，为NCX的分子进化提供了新的见解，并使我们能够更准确地注释NCX基因名称。我们首次报道了在非哺乳动物生物中存在NCX2和NCX3，由此提出了一个假说，即在脊椎动物和无脊椎动物分化时期左右发生了两次连续的NCX基因复制。此外，我们发现了一种推定的新NCX蛋白，命名为NCX4，它与NCX1相关，但仅在鱼类基因组中被观察到。这些发现为我们理解NCX基因家族的分子进化提供了更坚实的基础，并为进一步的NCX系统发育和分子研究提供了框架。
