The reason we humans have fingers today may all be thanks to a fish's clacker.
New research into the origins of digit formation shows that the DNA switch controlling finger and toe development got its humble start regulating the formation of fish cloacas, 380 million years ago.
It's a beautiful illustration of nature's "waste not, want not" ethos in action: why build new genetic tools from scratch when existing ones can be repurposed for the job?
Related: Wild New Study Suggests Buttholes Once Had a Very Different Purpose
"The fact that these genes are involved is a striking example of how evolution innovates, recycling the old to make the new," says developmental geneticist Denis Duboule of the University of Geneva in Switzerland.
"Rather than building a new regulatory system for the digits, nature has repurposed an existing mechanism, initially active in the cloaca."
The question of how tetrapods, or four-limbed animals, evolved digits from our fishy ancestors is one scientists have sought to answer for some time now. One school of thought proposes that digits derived from fins, but it's not the only possible explanation for our wiggly, dextrous appendages.
The development of tetrapod digit formation is encoded in genes called Hoxd that form part of a large regulatory landscape. The team of US and Swiss researchers compared fish and mouse genomes, in particular looking at the regions next to the Hoxd genes that contain the DNA switches that control them.
Zebrafish do not have digits, and they're missing some Hoxd genes, the researchers found. However, they still have the genetic regulatory landscape adjacent to their remaining Hox genes with the DNA switches. This raised the question about what function that landscape originally performed.
So, the researchers tagged some of these switches in both mice and zebrafish embryos with fluorescent markers to light up the tissues that express the genes. For mouse embryos, the switches lit up in the digits, but for the zebrafish, it was the cloaca.
The next step was to determine what deleting these elements using CRISPR-Cas9 would do – and once again, the results were quite clear. In mice with the deleted regulatory region, their fingers and toes failed to develop correctly. In zebrafish, it was the cloaca that didn't form according to plan – not the fish's fins.
These results, the researchers say, suggest that the original role of the regulatory landscape was to aid in the development of fish cloacas, the multi-purpose orifice used for excretion and reproduction.
The research suggests that, as tetrapods evolved from aquatic ancestors, that landscape was put to new use.
"The common feature between the cloaca and the digits is that they represent terminal parts," says geneticist Aurélie Hintermann, who worked with the University of Geneva during the research and is now at the Stowers Institute in the US.
"Sometimes they are the end of tubes in the digestive system, sometimes the end of feet and hands, i.e., digits. Therefore, both mark the end of something."
More research needs to be done to explore this connection, and other things that may have changed during the course of the evolution of life on Earth, but one thing seems apparent.
You'll never think of fish fingers quite the same way again.
The research has been published in Nature.