The development of digits in vertebrates has long been a topic of intense study in evolutionary biology. Initial research suggested a conserved genetic mechanism across species, were the elimination of certain hox genes in fish seemed to disrupt fin ray formation, hinting at a shared ancestry in digit development.

however, a recent investigation by a US-French team into the regulation of hox genes has revealed a more complex picture. These gene clusters possess regulatory DNA both upstream and downstream, crucial for controlling gene activity. In vertebrates, the upstream regulatory DNA is vital; its deletion leads to inactivity of the entire cluster in the digit-forming region of the limb.

Same Place, Different Reasons

Using CRISPR gene editing, the research team targeted the equivalent upstream region in zebrafish. Surprisingly, unlike the results in mice, deleting this area in fish had minimal impact. While hox gene activity was slightly reduced, the genes remained active in the correct location and at the appropriate time for digit formation. This suggests that while the activity appears similar, the underlying mechanisms differ between fish and mice. “The hox gene activity was slightly reduced, but these genes were still active in the right place at the right time to make digits,” the study noted, indicating that hox activity in digits evolved independently in ray-finned fish and vertebrate lineages.

“the hox gene activity was slightly reduced, but these genes were still active in the right place at the right time to make digits.”

The researchers then investigated the role of the deleted regulatory DNA in fish. They discovered its importance in the developing cloaca, the single orifice in fish responsible for excretion and reproduction, analogous to the rear end in other animals.