Voltage-gated sodium channel gene repertoire of lampreys: gene duplications, tissue-specific expression and discovery of a long-lost gene

Abstract

Studies of the voltage-gated sodium (Nav) channels of extant gnathostomes have made it possible to deduce that ancestral gnathostomes possessed four voltage-gated sodium channel genes derived from a single ancestral chordate gene following two rounds of genome duplication early in vertebrates. We investigated the Nav gene family in two species of lampreys (the Japanese lamprey and sea lamprey) (jawless vertebrates-agnatha) and compared them with those of basal vertebrates to better understand the origin of Nav genes in vertebrates. We noted six Nav genes in both lamprey species, but orthology with gnathostome (jawed vertebrate) channels was inconclusive. Surprisingly, the Nav2 gene, ubiquitously found in invertebrates and believed to have been lost in vertebrates, is present in lampreys, elephant shark () and coelacanth (). Despite repeated duplication of the Nav1 family in vertebrates, Nav2 is only in single copy in those vertebrates in which it is retained, and was independently lost in ray-finned fishes and tetrapods. Of the other five Nav channel genes, most were expressed in brain, one in brain and heart, and one exclusively in skeletal muscle. Invertebrates do not express Nav channel genes in muscle. Thus, early in the vertebrate lineage Nav channels began to diversify and different genes began to express in heart and muscle.

Heterologous functional expression of ascidian Nav1 channels and close relationship with the evolutionary ancestor of vertebrate Nav channels

“…In lamprey, two Nav1 paralogs that conserve ABM (XP_032802055 and XP_032831283 in Fig. 1 B ) are mainly expressed in the nervous system, and other three paralogs that only weakly conserve ABM show different expression patterns ( 27 , 33 , 55 , 56 ). It was also noted that these lamprey Nav1 paralogs are not necessarily grouped with either of mammalian four Nav1 clades: Nav1.1/1.2/1.3/1.7, Nav1.4, Nav1.5/1.8/1.9, and Nav1.6 ( 27 , 55 , 56 ).…”

Eukaryotic Voltage-Gated Sodium Channels: On Their Origins, Asymmetries, Losses, Diversification and Adaptations

“…The replacement of a positively charged lysine residue in the HFS site of Domain II or III with a negatively charged glutamate residue as D EE A differentiate the Na v 2 channels, which are always lacking in sodium ion selectivity ( Zhou et al, 2004 ). Na v 2 channels otherwise closely resemble the Na v 1 channels in structure and are distributed in genomes from single cell eukaryotes and multicellular animals including vertebrates, but not including ray-finned fish or tetrapods, like mammals ( Zakon et al, 2017 ; Figure 8 ). Molecular modeling suggest a much wider and accommodating “DEEA” pore for Na + , K + , and Ca 2+ ions in the absence of a protruding positively charged lysine residue, funneling ions to the side wall containing the carboxylate (D and E) side chains of the HFS site in Na v 2 channels ( Shen et al, 2017 ).…”

“…Na v 2 homologs have also been recorded from arthropods such as cockroach ( Zhou et al, 2004 ), honeybee ( Gosselin-Badaroudine et al, 2016 ) and fruit fly ( Zhang et al, 2011 ) as well as sea anemone (a cnidarian) ( Gur Barzilai et al, 2012 ), the latter of which has four Na v 2 channel homologs. Single Na v 2 channel homologs have been identified in vertebrates species, including cartilaginous fish (Australian ghostshark), lobed-finned fish (coelacanth), and jawless fish (lampreys) ( Zakon et al, 2017 ). All expressed Na v 2 homologs possess slow gating kinetics, and are non-selective channels passing calcium and sodium ions ( Gosselin-Badaroudine et al, 2016 ).…”

“…The diversification of Na v 2 channels particularly within animals lacking true nervous systems (ctenophores, sponges and placozoans) or possessing vestigial nervous systems (tunicates), is suggestive of an expansion of roles for Na v 2 filling of niches in the absence of animals with a mature nervous system. All vertebrate Na v 2 channels identified in non-teleost fish, for example are only expressed outside of the nervous system ( Zakon et al, 2017 ).…”

“…Vertebrates underwent an expansion of Na v 1 channel gene numbers to ten alongside the dramatic changes in body plan that include a greater sophistication of tissues, with different Na v 1.x isoforms expressed at high density in particular tissues such as brain (e.g., Na v 1.6), heart (e.g., Na v 1.5) and skeletal muscle (Na v 1.4) ( Zakon et al, 2017 ).…”