FIGURE 1.

Gene tree of 4 × 6 TM (TM = transmembrane) voltage-gated sodium channel α subunits (Na_v1 and Na_v2), calcium channel α₁ subunits (Ca_v1, Ca_v2, and Ca_v3) and NALCN. Included in the multiple alignment are the 21 human homologs and the 6 homologs from representative protostome invertebrate, pulmonate snail, Lymnaea stagnalis. Basal genes of each class (indicated in bold and ^∗) including apusozoan, Thecamonas trahens (Na_v2), single cell choanoflagellate, Salpingoeca rosetta (Ca_v1 and Ca_v3), placozoan, Trichoplax adhaerens (Ca_v2), and cnidarians (hydrozoan jellyfish), Polyorchis penicillatus (Na_v1). More distant Na Leak Conductance channel (NALCN) serve as the out-group for the phylogenetic tree. Bootstrap values are shown at the nodes. Notably weak branch strength is in the positioning for Ca_v3 T-type channels which is relatively equidistant from sodium channels and other calcium channels. The gene tree illustrate the close kinship amongst Na_v2 and Na_v1 channels and between Ca_v1 and Ca_v2 channels. Amino acid sequences were aligned using MUSCLE 3.7 (Edgar, 2004) within EMBL-EBI web interface (Chojnacki et al., 2017). Gene trees were constructed in PhyML 3.0 (Guindon et al., 2010) using Phylogeny.fr web interface (Dereeper et al., 2008).