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1 Department of Molecular Biology and Biochemistry, Simon Fraser University, Burnaby, BC, Canada; BC Research Institute for Children's & Women's Health, Cardiovascular Sciences, Vancouver, BC, Canada; Cardiac Membrane Research Laboratory, Simon Fraser University, Burnaby, BC, Canada
2 UBC Bioinformatics Centre, University of British Columbia, Vancouver, BC, Canada
3 Department of Molecular Biology and Biochemistry, Simon Fraser University, Burnaby, BC, Canada
* To whom correspondence should be addressed. E-mail: tibbits{at}sfu.ca.
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 - NCX1, NCX2, NCX3 - have been identified in mammals. However, phylogenetic analysis of the exchanger has been hindered by the lack of non-mammalian 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 thirteen new NCX sequences, including four from zebrafish, four from Japanese pufferfish, two from chicken, and one 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.
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