Fins to fingers: Ancient fish had the genes

Chemical enhancement shows the activity of genes associated with limb development in a mouse embryo. Implanting such embryos with fish DNA failed to produce digits, a study showed
(Denis Duboule / University of Geneva; Federal Technical Institute, Lausanne)

Fish don’t have fingers, but they could.

That conclusion, drawn by a team of researchers in Switzerland, casts new light on the evolution of four-legged land vertebrates, suggesting that a flick of a switch could have repurposed the bony radials of fins to become the fingers and toes of land-based animals.

The DNA programming architecture necessary to create such digits was present in the ancient genome of fish, before the emergence of amphibians, according to the researchers, who published their findings Tuesday in the online journal PLOS Biology.

“The basics of the regulatory mechanism are there in the fish,” said geneticist Denis Duboule of the University of Geneva and Federal Institute of Technology in Lausanne. “Everything is there, you just need to click it, and then it goes into the genes.”


Virtually since Darwin published “On the Origin of Species,” scientists have debated how fish could have evolved to walk on land. Paleontologists sought evidence of a transition from the bony spines of fish fins to the complex of fingers and toes in feet and hands. There have been tantalizing finds, including Tiktaalik, a prehistoric fish with shoulder and pelvis characteristics of a tetrapod, or four-legged animal.

Modern genetics since has added evidence to supplement the fossil record. Several labs have isolated genes known as HOX clusters that control limb formation in vertebrates.

Those genes have an odd habit, based on the way they interact with adjacent DNA. They direct the formation of the large bones of the arm, or proximal side of the appendage. But at some point, they switch to forming digits, the distal side.

“If you have this complex of genes, on one side there is sort of a control tower for the forearm, and on the other side there is a control tower for the digits,” said Duboule. “This is what we call enhancers: regulatory sequences which control gene expression.”

Duboule and his colleagues reasoned that if both sets of regulatory DNA sequences were present in fish, then perhaps fish fins were the genetic and evolutionary equivalent of the hands and feet of tetrapods. Evolutionary biologists call such equivalence a homology.

“We went into fish, and to my big surprise I must say, the two control towers are there,” Duboule said.


The researchers next took a snippet of zebrafish DNA and implanted it in mice embryos. None of them showed any sign of developing fingers and toes.

“We realized that by taking either the one on the right or the one on the left, we got the same result: They both made forearms,” Duboule said. “So there is no way we can see, so far, that these control towers work in making digits. Our conclusion, therefore, is that everything you need to make digits is there in the fish, but it’s not properly used.”

Strictly speaking, fin radials and digits are not homologous, even though the limb genes appear identical, the study concluded.

Duboule suggested that the regulatory DNA was “hijacked” and repurposed.

“We share our genes with all vertebrates, and the genes have been used and reused and reused,” Duboule said.

Embryonic development could offer a clue to such evolutionary tinkering, Duboule said.

“Our limbs, our arms and our legs, grow from the tip in ebryogenesis – they don’t grow from the bottom,” Duboule said.

A growth factor driving forearm development then could have inadvertently tripped the mechanism that switched these bimodal genes into digital mode.

“Maybe the art of digits involves not the evolution of a whole new set of control mechanisms, but maybe making them active in the patterning of the new structure,” said University of Chicago paleontologist Neil Shubin, who has worked on Tiktaalik fossils and was not involved in the Swiss study.

“We’re going to learn a lot about this over the next couple of years as people start to look at other kinds of fish fins,” said Shubin, whose bestselling book “Your Inner Fish,” explores the common ground between aquatic ancestors and their terrestrial descendants.

“What happens when we get the genomes of all these other living species that are kind of closer to Tiktaalik in the evolutionary tree?” Shubin said. “This is going to open up an exciting time in the field of evolutionary biology, for both geneticists and paleontologists, because we’re asking the same question using different tool kits.”

Researchers are thwarted not only by the lack of genome data for other fish, but the challenges of creating a transgenic fish model, as they routinely do with mice. That would allow them to produce the laboratory equivalent of a walking fish.

“It’s not the end of the argument,” Duboule said. “The end of the argument is the day you can produce a fish with digits - the day where people can sit around the table and say: Hey, these are digits.”