Rapid evolution of a voltage-gated sodium channel gene in a lineage of electric fish leads to a persistent sodium current

摘要

Most weakly electric fish navigate and communicate by sensing electric signals generated by their muscle-derived electric organs. Adults of one lineage (Apteronotidae), which discharge their electric organs in excess of 1 kHz, instead have an electric organ derived from the axons of specialized spinal neurons (electromotorneurons [EMNs]). EMNs fire spontaneously and are the fastest-firing neurons known. This biophysically extreme phenotype depends upon a persistent sodium current, the molecular underpinnings of which remain unknown. We show that a skeletal muscle–specific sodium channel gene duplicated in this lineage and, within approximately 2 million years, began expressing in the spinal cord, a novel site of expression for this isoform. Concurrently, amino acid replacements that cause a persistent sodium current accumulated in the regions of the channel underlying inactivation. Therefore, a novel adaptation allowing extreme neuronal firing arose from the duplication, change in expression, and rapid sequence evolution of a muscle-expressing sodium channel gene. Author summary The electrical properties of excitable cells, such as those in muscle and nervous tissue, were enabled in large part by the evolution of voltage-gated ion channel genes. The regulated conduction of ions through these channels results in the propagation of electrical signals, facilitating communication between cells. Here, we investigated how voltage-gated sodium (Na_(v)) channels contributed to the evolution of a novel electric organ system in the Apteronotids—a lineage of weakly electric fish. This organ is developmentally derived from motor neurons and used for communication between individual fish, as well as for probing their nocturnal environment. We used transcriptomic data to show that the gene encoding a broadly conserved muscle-specific sodium channel was duplicated in an ancestral fish. One duplicated gene copy subsequently gained expression in the spinal cord, where the electric organ is located. Through evolutionary analysis and biophysical experiments, we demonstrate that sequence changes in this new sodium channel transformed its function to cause novel electrical properties that can facilitate spontaneous high-frequency action potentials. This study shows that duplicate genes can gain highly novel expression patterns and quickly adapt to contribute to the phenotypic evolution of novel organ systems.