Humans share limb regeneration genes with gar fish

Gar fish. (Credit: Solomon David)

Gar, a toothy, freshwater fish, can reveal many evolutionary secrets—even possible genetic blueprints for limb regeneration in people, researchers report.

Scientists knew that salamanders can regrow full limbs after amputation. Ingo Braasch, an assistant professor of integrative biology at Michigan State University, and his team, however, were the first to study how gar and other fish regenerate entire fins. More importantly, the researchers focused on how they rebuild the endochondral bones within their fins, which are the equivalent of human arms and legs.

“Gars are often considered ‘dinosaur fish’ because of their ancestor-resembling body type,” Braasch says. “They’re becoming a popular, new research organism for biomedical research, largely in part because the gar genome is quite similar to the human genome.”

Ingo Braasch holds a gar fish (limb regeneration concept)
Evolution and gars—freshwater fish with toothy snouts—are so intricately intertwined that Ingo Braasch created a vanity license plate, highlighting his dedication to this research—”Garwin.” (Credit: Michigan State)

Garfish has been called a “bridge species,” as its genome is similar to both zebrafish—often used as a genetic model for human medical advances—and humans. Gar evolve slowly and have kept more ancestral elements in their genome than other fish. This means that along with serving as a bridge species to people, gar also are great connectors to the deep past.

So, by studying how fish regenerate fins, Braasch’s team pinpointed the genes and the mechanisms responsible that drive the regrowth. When they compared their findings to the human genome, they made an interesting observation.

gar fin
Ingo Braasch has shown that gar, a toothy, freshwater fish, can reveal many evolutionary secrets—even possible genetic blueprints for limb regeneration in people. (Credit: Michigan State)

“The genes responsible for this action in fish also are largely present in humans,” Braasch says. “What’s missing, though, are the genetic mechanisms that activate these genes in humans. It is likely that the genetic switches that activate the genes have been lost or altered during the evolution of mammals, including humans.”

2 gar fish
Ingo Braasch studies the evolution of genomic and morphological relationships among vertebrate animals—connecting the past with the present—using gars as genetic models. (Credit: Solomon David)

Evolutionary speaking, this suggests that the last common ancestor of fish and tetrapods, or four-legged vertebrates, had already acquired a specialized response for appendage regeneration, and that this program has been maintained during evolution in many fish species as well as salamanders, he adds.

Continuing research into these key genes and missing mechanisms could eventually lead to some revolutionary medical advances.

“The more we study these commonalities among vertebrates, the more we can home in on prime targets for awakening this program for regenerative therapies in humans,” Braasch says. “Such direct biomedical advances remain in the distant future, but studies of fin regeneration in fish will continue to reveal much about the regenerative potential of vertebrates.”

The research appears in Proceedings of the National Academy of Sciences.

Additional researchers from Michigan State, Universidade de Federal do Para, Instituto Tecnologico Vale, Laboratorio de Biologia Molecular, James Madison University, and Leibniz Institute for Evolution and Biodiversity Science also contributed to this research.

Source: Michigan State University