biostudies-literatureLi XHHS | National Institutes of HealthNINDS NIH HHSNIGMS NIH HHSE1010-9https://www.ebi.ac.uk/biostudies/studies/S-EPMC4352839biostudies-literatureUnknown112(9)We examined the origins and functional evolution of the Shaker and KCNQ families of voltage-gated K(+) channels to better understand how neuronal excitability evolved. In bilaterians, the Shaker family consists of four functionally distinct gene families (Shaker, Shab, Shal, and Shaw) that share a subunit structure consisting of a voltage-gated K(+) channel motif coupled to a cytoplasmic domain that mediates subfamily-exclusive assembly (T1). We traced the origin of this unique Shaker subunit structure to a common ancestor of ctenophores and parahoxozoans (cnidarians, bilaterians, and placozoans). Thus, the Shaker family is metazoan specific but is likely to have evolved in a basal metazoan. Phylogenetic analysis suggested that the Shaker subfamily could predate the divergence of ctenophorProceedings of the National Academy of Sciences of the United States of AmericaMajor diversification of voltage-gated K+ channels occurred in ancestral parahoxozoans.PMC4352839R01 GM093116NS069842R01 NS069842Liu HAnishkin ATrigg LMKamel BMartindale MQvan Rossum DBLi XJegla TMedina MRhodes SASassic JKDiatta FHSimmons DKChu Luo JfalseMajor diversification of voltage-gated K+ channels occurred in ancestral parahoxozoans.We examined the origins and functional evolution of the Shaker and KCNQ families of voltage-gated K(+) channels to better understand how neuronal excitability evolved. In bilaterians, the Shaker family consists of four functionally distinct gene families (Shaker, Shab, Shal, and Shaw) that share a subunit structure consisting of a voltage-gated K(+) channel motif coupled to a cytoplasmic domain that mediates subfamily-exclusive assembly (T1). We traced the origin of this unique Shaker subunit structure to a common ancestor of ctenophores and parahoxozoans (cnidarians, bilaterians, and placozoans). Thus, the Shaker family is metazoan specific but is likely to have evolved in a basal metazoan. Phylogenetic analysis suggested that the Shaker subfamily could predate the divergence of ctenophor2015-01-01T00:00:00Z2015 Mar2026-04-29T19:25:14.58Z2019-03-27T01:47:47ZS-EPMC43528392569174010.1073/pnas.1422941112