Phylogeneticrelationshipsofvoltagegated sodium channel α subunitsThenine sodium channel amino acid sequences were alignedand compared for relatedness using a maximum parsimonyprocedure that measured their evolutionary distance bycalculating the number of nucleotide changes required forthechangeincodonateachpositionThe phylogenetictree is consistent the designationof thesesodium channels as a single family.Nay1.1, Nay1.2, Nay1.3,andNay1.7arethe most closely relatedgroupbythisanalysis.Allfour of these sodium channels are highly tetrodotoxin-sensitiveand broadly expressed inneurons.Theirgenes are all located onhumanchromosome2g23-24,consistentwithacommonevolutionaryorigin
Phylogenetic relationships of voltage‐ gated sodium channel subunits The nine sodium channel amino acid sequences were aligned and compared for relatedness using a maximum parsimony procedure that measured their evolutionary distance by calculating the number of nucleotide changes required for the change in codon at each position. The phylogenetic tree is consistent the designation of these sodium channels as a single family. NaV1.1, NaV1.2, NaV1.3, and NaV1.7 are the most closely related group by this analysis. All four of these sodium channels are highly tetrodotoxin-sensitive and broadly expressed in neurons. Their genes are all located on human chromosome 2q23–24, consistent with a common evolutionary origin
Sodiumchannelsexpressedinadult DRGineuronBlue,neurofilament,amarkerofmediumandlargeneuronsGreen,redperipherin,aspecificsmallneuronmarkerRed,sodiumchannel isoformsNav1.1,Nav1.6,Nav1.7,Nav1.8andNav1.9
Sodium channels expressed in adult DRG neuron Na Blue, neurofilament, a marker of medium and large neurons Green, redperipherin, a specific small neuron marker Red, sodium channel isoforms Nav1.1, Nav1.6, Nav1.7, Nav1.8 and Nav1.9
Amino acid seguence similarity of voltagegated sodium channel α subunitsrNav1.1rNav1.2rNav1.3rNav1.7rNav1.4rNav1.6rNav1.5rNav1.8rNav1.95252015100AminoAcidSequenceDifferences(%)Williamet al.2oo9,Voltage-GatedSodiumChannelsintroductorychapter
Amino acid sequence similarity of voltagegated sodium channel subunits William et al. 2009, Voltage-Gated Sodium Channels, introductory chapter
Phylogeneticrelationships ofvoltagegated sodium channel α subunitsNaV1.5,NaV1.8,NaV1.9 are also closely related,and their aminoacid sequencesaregreaterthan64%identicaltothoseofthefoursodiumchannelsencodedonchromosome2.These sodium channels are tetrodotoxin-resistant tovaryingdegrees, due to changes in amino acid sequence at a singleposition in domain l, and they are highly expresses in heartanddorsal root ganglion (DRG)neurons.Theirgenes are located onhumanchromosome3p21-24,consistentwithacommonevolutionaryoriginTheisoforms Nay1.4,expressed primarily in skeletal muscle,andNay1.6,expressedprimarilyintheCNS,aresetapartfromtheseothertwocloselyrelatedgroupsofsodiumchannelgenes
Phylogenetic relationships of voltagegated sodium channel subunits NaV1.5, NaV1.8, NaV1.9 are also closely related, and their amino acid sequences are greater than 64% identical to those of the four sodium channels encoded on chromosome 2. These sodium channels are tetrodotoxin-resistant to varying degrees, due to changes in amino acid sequence at a single position in domain I, and they are highly expresses in heart and dorsal root ganglion (DRG) neurons. Their genes are located on human chromosome 3p21–24, consistent with a common evolutionary origin. The isoforms Na V1.4, expressed primarily in skeletal muscle, and Na V1.6, expressed primarily in the CNS, are set apart from these other two closely related groups of sodium channel genes
Phylogeneticrelationships ofvoltagegated sodium channel α subunitsThe chromosome segments carrying the sodium channel genesareparalogoussegmentsthat contain many setsof relatedgenes, including the homeobox (HOX) gene clusters. Thesesegmentsweregeneratedbywholegenomeduplicationeventsduringearlyvertebrateevolution.Thecomparisonsofaminoacidsequenceidentity,phylogeneticrelationship,and chromosomalrelationshipleadtotheconclusion that all nine members of the sodium channel familythathave been functionally expresses are members of a singlefamily of proteinsand have arisenfromgeneduplications andchromosomal rearrangements relatively recently in evolution
Phylogenetic relationships of voltagegated sodium channel subunits The chromosome segments carrying the sodium channel genes are paralogous segments that contain many sets of related genes, including the homeobox (HOX) gene clusters. These segments were generated by whole genome duplication events during early vertebrate evolution. The comparisons of amino acid sequence identity, phylogenetic relationship, and chromosomal relationship lead to the conclusion that all nine members of the sodium channel family that have been functionally expresses are members of a single family of proteins and have arisen from gene duplications and chromosomal rearrangements relatively recently in evolution