CRISPR Gene-Editing Reveals How Our Fingers And Toes Evolved From Fins


Robin Andrews

Science & Policy Writer

A siamese fighting fish showing off some rather resplendent fin rays on its back. Aroonsak/Shutterstock

At some point during the grand old tale of evolution on Earth, a bunch of aquatic creatures switched from having fins to finger-laden limbs, and – along with a plethora of other adaptations – made it as land-dwelling creatures. This much is known on a fossiliferous scale, but on a cellular level, it’s not so clear how this occurred.

Now, a new Nature study has revealed that much of the same cells that make up fin rays in fish are closely related to the cells that develop into fingers and toes of four-legged terrestrial critters (“tetrapods”). More specifically, the tiny flexible bones found at the tips of these fins are almost certainly the type which, in aquatic ancestors, slowly evolved into the smorgasbord of fingers and toes we can see in lifeforms all over the world today.


“For years, scientists have thought that fin rays were completely unrelated to fingers and toes, utterly dissimilar because one kind of bone is initially formed out of cartilage and the other is formed in simple connective tissue,” Neil Shubin, a professor of organismal biology and anatomy at the University of Chicago, and coordinating author of the study, said in a statement.

“Our results change that whole idea. We now have a lot of things to rethink.”

In order to make this discovery, the researchers turned to a curious organism called the zebrafish. These striped swimmers have incredible tissue regeneration skills, in that they can quickly heal damaged limbs, organs, and even their spinal cords if need be.

They are small, cheap to maintain, quick to grow and their entire life cycle, from development in the egg to the end of their adult life, is visible to researchers. In addition, their entire genome is known to science. Consequently, they are “model organisms,” ones that are often used in developmental biology studies, including this one.


Image in text: Tagged markers in the wrist and digits of a mouse limb (left) compared to the same genetic markers in zebrafish (right). The same genes are responsible for making digits and fin rays. Shubin Laboratory

The researchers in this case used the gene-editing technique CRISPR/Cas to selectively delete genes related to limb-building in their zebrafish, and then continued to breed them with these genes deleted over the course of several years in order to mimic an evolutionary lineage. Along the way, the cells used in limb-building were “tagged” and tracked throughout the zebrafish’s development, from fertilization to the formation of the adult fins.

They found that when so-called Hox genes were removed, their long fin rays were greatly reduced in size and complexity. Additional CT scans revealed that zebrafish lacking genes like these had a greater number of smaller bones making up cartilage fin, and it’s these cartilage developments that would eventually lead to the evolution of fingers and toes.

Essentially, what these zebrafish Hox gene experiments show is that they stayed put during the course of natural evolution, and switched from making fin rays to manufacturing digits as ancestral fish migrated onto the land. Ultimately, this means that our hands, feet, fingers, and toes are far more closely related to the fins of fish than anyone has previously thought.


“[This study is] not saying that fin rays and digits are the same thing,” Kimberley Cooper, a developmental biologist from the University of California, San Diego who was not involved in the study, told The Atlantic. “But there was so much talk about how they are different, and at a fundamental ancient level they’re more similar than we appreciated.”

The humble, useful zebrafish. suchetpong/Shutterstock


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