Structure of the sodium channel gene SCN11A: evidence for intron-to-exon conversion model and implications for gene evolution.
Exon/intron boundaries in the regions encoding the trans-membrane segments of voltage-gated Na channel genes are conserved, supporting their proposed evolution from a single domain channel, while the exons encoding the cytoplasmic loops are less conserved with their evolutionary heritage being less defined. SCN11A encodes the tetrodotoxin-resistant (TTX-R) sodium channel Nav1.9a/NaN, which is preferentially expressed in nociceptive primary sensory neurons of dorsal root ganglia (DRG) and trigeminal ganglia. SCN11A is localized to human chromosome 3 (3p21-24) close to the other TTX-R sodium channel genes SCN5A and SCN10A. An alternative transcript, Nav1.9b, has been detected in rat DRG and trigeminal ganglion. Nav1.9b is predicted to produce a truncated protein due to a frame-shift, which is introduced by the new sequence of exon 23c (E23c). In human and mouse SCN11A, divergent splicing signals prevent utilization of E23c. Unlike exons 5A/N in genes encoding TTX-sensitive sodium channels, which appear to have resulted from exon duplication, E23c might have evolved from the conversion of an intronic sequence. Although a functional role for Nav1.9b has yet to be established, intron-to-exon conversion may represent a mechanism for ion channels to acquire novel features.
Dib-Hajj
Sulayman D
SD
Department of Neurology, Yale University School of Medicine, New Haven, CT 06510, USA.
Tyrrell
Lynda
L
Waxman
Stephen G
SG
D000595:Amino Acid Sequence; D000818:Animals; D019143:Evolution, Molecular; D005091:Exons / Q000235:genetics*; D006801:Humans; D007438:Introns / Q000235:genetics*; D008969:Molecular Sequence Data; D062558:NAV1.9 Voltage-Gated Sodium Channel; D009479:Neuropeptides / Q000737:chemistry* / Q000235:genetics*; D017386:Sequence Homology, Amino Acid; D015222:Sodium Channels / Q000737:chemistry* / Q000235:genetics*
D062558:NAV1.9 Voltage-Gated Sodium Channel; D009479:Neuropeptides; C491886:SCN11A protein, human; C491885:Scn11a protein, mouse; D015222:Sodium Channels