Our fingers may owe their existence to a long-forgotten feature of ancient fish. New research suggests that the genetic switch behind digit formation originally helped build a fish’s cloaca more than 380 million years ago.
How does fish DNA connect to human digits?
Scientists from Switzerland and the United States have found that the DNA sequence responsible for forming fingers and toes in humans was first used for a very different purpose. The same regulatory system, known as a DNA switch, once guided the formation of the cloaca, a multi-purpose opening used for excretion and reproduction in early fish species. Denis Duboule, a developmental geneticist at the University of Geneva, said this is a clear example of how evolution repurposes existing tools, as reported by ScienceAlert. “Rather than building a new regulatory system for the digits, nature has repurposed an existing mechanism, initially active in the cloaca,” he said.
What did researchers discover in the genetic code?
The study focused on a group of genes called Hoxd, which control digit formation in tetrapods, the four-limbed animals that include humans. Scientists compared genomes of zebrafish and mice, examining the DNA switches near these genes. While zebrafish lack digits and some Hoxd genes, they still retain the genetic landscape associated with those switches. Using fluorescent markers, researchers found that in mouse embryos the switches were active in developing digits, while in zebrafish they lit up in the cloaca.
Additional CRISPR-Cas9 technology experiments gave some further hints. When researchers knocked out this regulatory area, mouse embryos were unable to develop fingers and toes properly. In zebrafish, the cloaca was not formed correctly, whereas the fins developed normally. These observations suggest that the original purpose of the genetic landscape was related to cloaca development, which was only later repurposed to form digits as animals transitioned onto land.
Why is this finding significant for the study of evolution?
The study explains the way evolutionary mechanisms remodel existing genetic components for new functions instead of constructing them anew. As tetrapods emerged from aquatic ancestors, the genetic system once vital for a fish’s cloaca was co-opted to shape limbs and digits. Aurélie Hintermann, a geneticist involved in the study, told ScienceAlert that the cloaca and digits share a key trait. “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,” she explained.
This study offers new insight into one of evolution’s most enduring mysteries: how animals developed limbs with digits from their finned ancestors. It also highlights how nature reuses existing genetic mechanisms to create new structures, demonstrating that innovation often comes from adaptation rather than invention.
The research, published in Nature, opens the door to further studies on how other biological features may have evolved from ancient functions, reshaping our understanding of life’s history on Earth.
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