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New Insights into the Evolution of Nervous System Proteins

A recent study challenges longstanding assumptions regarding the evolutionary timeline of potassium ion channels, a key family of proteins essential for electrical signaling in the nervous system. This research, spearheaded by scientists at Penn State University, has been released in the Proceedings of the National Academy of Sciences.

The findings indicate that the Shaker family of proteins, which play a critical role in regulating potassium ion flow within cells, existed in single-celled organisms long before the advent of the animal nervous system. This revelation implies that these ion channels did not co-evolve with more complex nervous systems but were pre-existing components in our microbial ancestors.

“Evolution isn’t always a straightforward path towards increased complexity,” remarked Timothy Jegla, an associate professor of biology at Penn State and the study’s lead researcher. He explained that previous perspectives suggested that as animal nervous systems developed complexity, so too did the evolution of ion channels. Contrarily, Jegla’s team found that ancient nerve net structures in some of the simplest living animals displayed a surprising diversity in ion channels.

Ion channels are integral to cellular function, governing how ions traverse cell membranes, a process fundamental to generating the electrical signals that facilitate communication within the nervous system.

The Shaker family is abundant among various animal species, from humans to insects, and specifically governs the efflux of potassium ions to conclude electrical signals known as action potentials. These channels operate similarly to transistors in electronic devices, responding to shifts in electrical fields.

“Many foundational insights into ion channel mechanics stem from studies focused on the Shaker family,” Jegla noted. He emphasized the study’s groundbreaking conclusion that genes coding for these channels, previously thought to be exclusive to animals, are also present in choanoflagellates, which are among the closest living relatives of the animal kingdom.

The research team initially investigated two species of choanoflagellates without success. However, upon expanding their survey to 21 different species, they identified Shaker family genes in three of these micromolecules.

The Shaker family comprises several subfamilies of ion channels distributed throughout the animal realm. The team’s earlier research suggested that comb jellies, possessing rudimentary nerve nets, contained only one subfamily (Kv1). Their findings now indicate that the Shaker family genes found in choanoflagellates are closely aligned with the Kv2, Kv3, and Kv4 types.

“Initially, we believed that Kv2 through Kv4 emerged more recently, but this new data suggests otherwise. Channels akin to Kv2-4 found in choanoflagellates are actually the most primitive type,” Jegla explained. This implies that multiple subtypes existed at the base of the animal evolutionary tree, including Kv1 in comb jellies and the Kv2-4-like channels in choanoflagellates.

Furthermore, it’s suggested that gene loss is a frequent occurrence in evolutionary history—on par with the emergence of new genes. The identification of lost Kv2-4-like genes in descendants such as comb jellies and sponges adds a critical piece to understanding the early evolution of nerve signaling.

The implications of this research extend beyond historical context. Jegla pointed out that many proteins essential for electrical signaling predated the emergence of complex animal nervous systems. “Early animals likely had the capability to construct operational nervous systems by leveraging already existing proteins,” he remarked. Understanding these evolutionary mechanisms may also shed light on contemporary issues related to ion channel dysfunction, including heart arrhythmias and epilepsy.

For further reading: Timothy Jegla et al., “A broad survey of choanoflagellates revises the evolutionary history of the Shaker family of voltage-gated K + channels in animals,” Proceedings of the National Academy of Sciences (2024). DOI: 10.1073/pnas.2407461121

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phys.org