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Call For Papers: Comparative Genomics

Genomic organization, expression, and phylogenetic analysis of Ca²⁺ channel β4 genes in 13 vertebrate species

¹ Department of Biology, Colorado State University, Fort Collins, Colorado
² College of Veterinary Medicine, Cornell University, Ithaca, New York

The Ca²⁺ channel β-subunits, encoded by CACNB genes 1–4, are membrane-associated guanylate kinase (MAGUK) proteins. As auxiliary subunits of voltage-gated Ca²⁺ channels, the β-subunits facilitate membrane trafficking of the pore-forming 1 subunits and regulate voltage-dependent channel gating. In this report, we investigate whether two zebrafish β4 genes, β4.1 and β4.2, have diverged in structure and function over time. Comparative expression analyses indicated that β4.1 and β4.2 were expressed in separable domains within the developing brain and other tissues. Alternative splicing in both genes was subject to differential temporal and spatial regulation, with some organs expressing different subsets of β4.1 and β4.2 transcript variants. We used several genomic tools to identify and compare predicted cDNAs for eight teleost and five tetrapod β4 genes. Teleost species had either one or two β4 paralogs, whereas each tetrapod species contained only one. Teleost β4.1 and β4.2 genes had regions of sequence divergence, but compared with tetrapod β4s, they exhibited similar exon/intron structure, strong conservation of residues involved in 1 subunit binding, and similar 5' alternative splicing. Phylogenetic results are consistent with the duplicate teleost β4 genes resulting from the teleost whole genome duplication. Following duplication, the β4.1 genes have evolved faster than β4.2 genes. We identified disproportionately large second and third introns in several β4 genes, which we propose may provide regulatory elements contributing to their differential tissue expression. In sum, both mRNA expression data and phylogenetic analysis support the evolutionary divergence of β4.1 and β4.2 subunit function.

zebrafish; β-subunit; heart; nervous system; development; splicing; expression; membrane-associated guanylate kinase