Researchers from Michigan State University and the University of Texas at Austin have made a shocking discovery.
In a study published June 1 in the journal Scientists progress, the team explained how small genetic changes allow weakly electric fish to evolve their electric organs. The findings could have broader implications for human health and disease.
Jason Gallant, associate professor at MSU. Credit: Gregory Kohuth
As a result of these genetic changes, the fish took tiny protein motors that typically cause muscles to contract and repurposed them to generate electrical signals in a new organ. These proteins and their associated genetic components are found in all species of vertebrates, including humans.
“What really strikes me is that these esoteric fish allow us to understand something profound about how our own genomes work,” said Jason Gallant, associate professor of integrative biology in MSU’s College of Natural Science.
“It’s exciting because we can see how a small change in the gene can completely change where it’s expressed,” said Harold Zakon, professor of neuroscience and integrative biology at the University of Texas at Austin.
The pintail is a weakly electric fish that has helped researchers uncover clues to the evolutionary history of the electric organ. Credit: Jason Gallant
Weakly electric fish are fish that use weak electrical signals in a manner similar to birdsong, to communicate with other electric fish and share important information, including their sex and species. They are related to the most well-known highly electric fish, such as electric eels, which can generate enough energy to stun prey or zap predators.
Evolution took advantage of a quirk in fish genetics to develop electrical organs. All fish have duplicate versions of the same gene that produces tiny muscle motors called sodium channels. The electric fish deactivated a copy of the sodium channel gene in the muscle, activated it in other cells and voila: a new organ was born.
This big part of the story was known. The new research helps show exactly how it happened.
The team discovered a short section of DNA in the sodium channel gene that controls whether the gene is expressed in a given cell. The researchers found that, in electric fish, this control region is either impaired or completely absent. And the implications go far beyond the evolution of electric fish.
“This control region is found in most vertebrates, including humans,” Zakon said. “So the next step in terms of human health would be to look at this region in human gene databases to see how much variation there is in normal healthy people and whether certain deletions or mutations in this region might lead to reduced expression of sodium channels, which could lead to disease.
“Electric fish are really important biomedical models,” Gallant said. “That’s why some of the oldest textbooks in the field feature engravings of electric eels.”
In humans and other vertebrates, there is very little wiggle room when it comes to sodium channels and similar proteins called ion channels. In fact, there are conditions such as epilepsy that may have their roots in mutations or other channel deviations.
Zebrafish are not electric fish, but like humans and most other vertebrates, they have sodium channels in their muscles, which fluoresce green in this image. Credit: Mary Swartz/Johann Eberhart/University of Texas at Austin.
Fish have a lot more flexibility due to their duplicate genes, allowing electric fish to do amazing things with their ion channels, like evolve an electrical organ. Understanding how and why these adaptations work allows researchers to discover and explore general biological principles.
“Electric fish are masters at playing with what is usually a very strongly constrained biophysical system,” Gallant said. “They have become this evolutionary laboratory that allows us to better characterize and understand ion channels.”
That’s why the National Science Foundation awarded Gallant a $1.5 million grant in 2017 to better understand electric fish genetics and firmly establish fish as model organisms. With grant work and this new Science Advances publication — which was also supported by the NSF — the team is empowering other members of the research community to ask questions and find answers with electric fish.
“It’s the coming of age of the electric fishing system and a preview of the attractions to come,” Gallant said.
“You can choose to study genetics and molecular biology in any number of systems, but the mysteries presented by electric fish are the things that get me out of bed in the morning,” he said. “They are like living Pokémon. Each is so different from the other, and inside each is a discovery to be made. We hope MSU will be remembered as the birthplace of the electric fishing system.
While Gallant and his collaborators at UT Austin are helping other researchers explore the mysteries of nature with electric fish, they have their own questions that they will continue to explore.
Electric fish native to Africa (like this gray elephantfish) and South America (like the rust-colored knifefish) evolved along different paths to reach the same destination – having an electric organ. Credit: Jason Gallant
For example, there are two groups of electric fish in the world: one from Africa and the other from South America. The researchers found that electric fish from Africa had mutations in the sodium channel control region, while electric fish from South America lost it entirely. So how did these two different groups of electric fish arrive at the same solution to grow an electric organ – losing expression of a sodium channel gene in muscle – via two different pathways? As Gallant says, “it’s gold in the hills”.
“If you rewind the tape of life and play, would it play the same way or find new ways to move forward? Would evolution work the same way over and over again? said Galant. “Electric fish are trying to answer this question because they have repeatedly developed these incredible traits. In this article, we attempted to understand how these sodium channel genes were repeatedly lost in electric fish. It was really a collaborative effort.”
The study’s first author was Sarah LaPotin, a research technician in Zakon’s lab at the time of the research and currently a doctoral student at the University of Utah. In addition to Gallant and Zakon, the study’s other lead author was Johann Eberhart, professor of molecular biosciences at UT Austin.