Evolution of Voltage‐Gated Sodium Channels


Voltage‐gated sodium channels play important roles in the nervous system by enabling propagation of action potentials along axons. It has been suggested that sodium channels evolved from calcium channels before the split of animals and choanoflagellates, as deduced from studies of sequence motifs important in the ion selectivity of sodium and calcium channels. The sodium channel α gene was subsequently duplicated in the two whole‐genome duplication events (2R) in early vertebrate evolution, resulting in four genes. Several local duplication events in tetrapods later resulted in the total set of ten sodium channel α genes present in today's humans. In teleosts, another whole‐genome duplication event (3R) doubled the ancestral vertebrate set from four to eight. The high number of sodium channel gene duplicates in both tetrapods and teleosts probably reflects their great importance in the evolution of the vertebrate nervous system.

Key Concepts:

  • Sodium channels evolved from calcium channels and were present in the common ancestor of animals and choanoflagellates.

  • One α subunit voltage‐gated sodium channel gene (SCNA) quadrupled in two whole‐genome duplication events early in vertebrate evolution.

  • The ancestral vertebrate set duplicated again in the teleost‐specific whole‐genome duplication to generate eight genes.

  • One of the genes was duplicated to three adjacent genes (SCN5A, 10A and 11A) in the amniote lineage after the divergence of amphibians.

  • One of the other tetrapod genes duplicated to four adjacent genes (SCN3A, 2A, 1A and 9A) before the radiation of amniotes, 310 Mya. After the split of metatheria and eutheria (150 Mya), an additional gene, SCN7A, arose through yet another local duplication in the same region.

Keywords: whole‐genome duplication; vertebrate evolution; sodium channel; nervous system; vertebrate; teleost fish

Figure 1.

Evolutionary history of the sodium channel α gene family (SCN) in tetrapods and teleosts. One ancestral sodium channel gene, located on the same chromosome as a HOX‐cluster, was duplicated in two rounds of genome doublings. The tetrapod lineage underwent local duplications leading to the present repertoire of 10 SCNA genes in human. In the teleost lineage, a third genome doubling occurred, leading to a total set of eight SCNA genes in zebrafish. The number or letter in each box represents the subtype of SCNA gene or HOX‐cluster. Each line represents one chromosome with its chromosome number shown on the side. The number below each box shows the chromosomal position in Mb. Stars mark two genes in zebrafish positioned according to database version Zv7. The triplet SCN5A, SCN10A and SCN11A and the quartet SCN3A, SCN2A, SCN1A, as well as SCN9A are present in amniotes whereas SCN7A, the most recent local duplicate, is only present in eutherian mammals. Note that the human SCNA triplet is not linked to the HOXA cluster in mammals due to a translocation.



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Widmark, Jenny, and Larhammar, Dan(Jun 2013) Evolution of Voltage‐Gated Sodium Channels. In: eLS. John Wiley & Sons Ltd, Chichester. http://www.els.net [doi: 10.1002/9780470015902.a0024936]