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Differential evolution of voltage-gated sodium channels in tetrapods and teleost fishes
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Pharmacology.
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Pharmacology.
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Pharmacology.
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Pharmacology.
2011 (English)In: Molecular biology and evolution, ISSN 0737-4038, E-ISSN 1537-1719, Vol. 28, no 1, p. 859-871Article in journal (Refereed) Published
Abstract [en]

The voltage-gated sodium channel (SCN) alpha subunits are large proteins with central roles in the generation of action potentials. They consist of approximately 2,000 amino acids encoded by 24-27 exons. Previous evolutionary studies have been unable to reconcile the proposed gene duplication schemes with the species distribution and molecular phylogeny of the genes. We have carefully annotated the complete SCN gene sequences, correcting numerous database errors, for a broad range of vertebrate species and analyzed their phylogenetic relationships. We have also compared the chromosomal positions of the SCN genes relative to adjacent gene families. Our studies show that the ancestor of the vertebrates probably had a single sodium channel gene with two characteristic AT-AC introns, the second of which is unique to vertebrate SCN genes. This ancestral gene, located close to a HOX gene cluster, was quadrupled along with HOX in the two rounds of basal vertebrate tetraploidizations to generate the ancestors of the four channels SCN1A, SCN4A, SCN5A and SCN8A. The third tetraploidization in the teleost fish ancestor doubled this set of genes and all eight are still present in at least three of four investigated teleost fish genomes. In tetrapods the gene family expanded by local duplications before the radiation of amniotes, generating the cluster SCN5A, SCN10A and SCN11A on one chromosome and the cluster SCN1A, SCN2A, SCN3A and SCN9A on a different chromosome. In eutherian mammals a tenth gene, SCN7A, arose in a local duplication in the SCN1A gene cluster. The SCN7A gene has undergone rapid evolution and has lost the ability to cause action potentials - instead it functions as a sodium sensor. The three genes in the SCN5A cluster were translocated from the HOX-bearing chromosome in a mammalian ancestor along with several adjacent genes. This evolutionary scenario is supported by the adjacent TGF-beta receptor superfamily (comprised of five distinct families) and the CSRNP gene family as well as the HOX clusters. The independent expansions of the SCN repertoires in tetrapods and teleosts suggest that the functional diversification may differ in the two lineages.

Place, publisher, year, edition, pages
2011. Vol. 28, no 1, p. 859-871
Keyword [en]
Voltage-gated sodium channel, AT-AC intron, HOX, TGF-beta receptor, activin receptor, CSRNP (cysteine-serine-rich nuclear protein)
National Category
Medical and Health Sciences
Identifiers
URN: urn:nbn:se:uu:diva-129518DOI: 10.1093/molbev/msq257ISI: 000285418600080PubMedID: 20924084OAI: oai:DiVA.org:uu-129518DiVA, id: diva2:344158
Available from: 2010-08-18 Created: 2010-08-18 Last updated: 2017-12-12Bibliographically approved

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Widmark, JennyOcampo Daza, DanielLarhammar, Dan

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