The research was published in the Proceedings of the National Academy of Sciences.

“We often think of evolution as a one-way street toward greater complexity, but that’s often not what happens in nature,” said Timothy Jegla, an associate professor of biology in the Penn State Eberly College of Science and leader of the research team. “For example, it was thought that as different types of animals evolved and nervous systems became more complex, ion channels emerged and diversified to match that complexity. But our research suggests that’s not the case. We’ve previously shown that the oldest living animals, those with simple nerve nets, have the highest diversity of ion channels. This new finding adds to the growing evidence that many of the building blocks for nervous systems were already present in our protozoan ancestors — before nervous systems even existed.”

Ion channels are located in the membranes of cells and regulate how charged particles called ions move in and out of the cell, a process that results in the electrical signals that form the basis of communication in the nervous system. The Shaker family of ion channels is found in a wide range of animals, from humans to mice to fruit flies, and specifically regulates how potassium ions flow out of the cell to terminate electrical signals called action potentials. These channels can open or close based on changes in the electrical field, much like transistors in computer chips.

“Much of what we know about how ion channels work at the molecular level comes from mechanistic studies of the Shaker family of ion channels,” Jegla said. “We previously thought that the Shaker family of voltage-gated potassium channels was found only in animals, but now we see that the genes encoding this family of ion channels were present in several species of animals’ closest living relatives, a group of single-celled organisms called choanoflagellates.”

The researchers had previously looked for these genes in two species of choanoflagellates, but were unable to find them. In the current study, they expanded their search to 21 species of choanoflagellates and found evidence of Shaker family genes in three of these species.

Several subfamilies, or types, of ion channels within the Shaker family are present across the animal kingdom. The research team previously found that comb jellies—animals with a relatively simple “nerve net” (thought to be similar to the very first animal nervous system)—have only one of these types, called Kv1. This led the team to believe that the common ancestor of animals likely had only Kv1, with other types evolving later. However, Jegla and colleagues found that the Shaker family genes in choanoflagellates were more closely related to types Kv2, Kv3, and Kv4.

“We thought that types 2 through 4 had evolved on a more recent timeline, but our new research suggests that the Kv2-4-like channels found in choanoflagellates are in fact the oldest subtype,” Jegla said.

Furthermore, this finding indicates that multiple subtypes were present at the base of the animal family tree, including Kv1, which is found in comb jellies, and the Kv2-4-like channels, which are found in choanoflagellates.

“The genes for Kv2-4-like genes were lost in the living descendants of the earliest animal groups like comb jellies and sponges, so the only reason we know they were present in the earliest animals is because of the choanoflagellates,” Jegla added. “Gene loss is common in evolution — about as common as the evolution of new genes — although it can be hard to detect. Now that genetic sequencing is cheap enough that scientists can sample species widely, rather than just looking at a few representative species, we can detect many more of these gene losses, and that will change our view of how many of our own gene families first evolved.”

This work also adds to the growing evidence that many elements of the nervous system were present before the nervous system as a whole emerged, Jegla noted.

“Most of the functionally important proteins that we use in electrical signaling, which underlie neuronal communication and neuromuscular movement, are all based on proteins that existed before animals,” Jegla said. “It seems that animals were able to put together a functioning nervous system very early in their evolution simply because most of the necessary proteins were already there.”

Jegla added that understanding how these ion channels evolved helps us understand how they function, which in turn could have implications for treating conditions associated with ion channel dysfunction, such as cardiac arrhythmias and epilepsy.

In addition to Jegla, the research team includes Benjamin Simonson, a doctoral student in the molecular, cellular and integrative biosciences program at Penn State’s Huck Institutes of the Life Sciences and the Eberly College of Science, who recently defended his dissertation, and David Spafford, an associate professor of biology at the University of Waterloo, who specializes in choanoflagellate physiology. Funding from the Penn State Department of Biology and the Huck Institutes of the Life Sciences supported this work.