Neuronal communication in animals depends on complex electrical signals shaped by large suites of functionally diverse voltage-gated ion channels. While these channels are based on molecular designs that first evolved in prokaryotes, it has long been assumed that the neuronal signaling requires functionally unique gene families that will have evolved specifically within the animal lineage. The recent explosion of sequence data from diverse eukaryotes, including most protozoan lineages, has provided the opportunity to revisit these assumptions. We re-examined the evolutionary origins of two animal-specific families of voltage-gated K+ channels, Shaker and KCNQ, that together set neuronal action potential threshold, duration and frequency. We find that both have protozoan origins. The KCNQ lineage is traceable to the common ancestor of all eukaryotes and the animal channels were inherited directly from our opisthokont ancestors. In contrast, the Shaker family, which encodes many of the canonical neuronal K+ currents, surprisingly may have first evolved in cryptophyte algae and entered the animal lineage via horizontal gene transfer. Protozoan lineages appear to contain the vast majority of ion channel sequence diversity, and it now appears that most of the evolutionary events that shape the distinctive structure/function relationships of our neuronal ion channel families likely occurred in protozoans.
“Training in molecular and cellular biology, molecular evolution, biophysics and neuroscience. First started looking at the evolution of neuronal signaling molecules including ion channels for a term paper in my senior year evolution class as an undergrad. In grad school I showed that Shaker family K+ channels were present and functionally conserved in a jellyfish, the first evidence that cnidarian and bilaterian nervous systems would share a common molecular basis for neuronal signaling. As a postdoc I gained skills in ion channel biophysics and took that into the biotech industry to pursue drug discovery at Icagen Inc. and later the Genomics Institute of the Novartis Research foundation where I worked for the 2021 Nobel prize winner Ardem Patapoutian on sensory ion channels and signaling mechanisms. I then returned to academics at the Scripps Research Institute and came to Penn State to get the opportunity to return to looking at the molecular evolution of neuronal signaling in the genomic age. Undergrad: Degree in Biology from Carleton College, Northfield MN Grad: Degree in Neuroscience from Washington University, St. Louis MO. Trained with Dr. Larry Salkoff who discovered many of the neuronal K+ channel families the hard way – when you had to figure out how to identify the genes without any sequence data! Postdoc: Rick Aldrich (recently retired National Academy member) who characterized the molecular mechanisms by which voltage-gated ion channels activate and inactivate. Biotech experience: Ion Channel Drug Discovery at Icagen Inc, Characterization of sensory ion channels and signaling mechanisms at GNF with Ardem Patapoutian (2021 Nobel Prize).”