Humans have fingers because fish needed cloaca

The transition from fins to limbs is one of the most important events in vertebrate evolution. It explains how animals that once lived in water eventually walked on land. Scientists have been studying how this change happened by focusing on a group of genes called the Hox clusters. These genes shape the body plan of all vertebrates. The HoxA and HoxD clusters in particular are essential for forming limbs in four-limbed animals. Yet fish also have similar Hox genes even though they don’t have fingers.

This similarity has been a puzzle — and one a new paper in Nature has answered. Scientists from France, Switzerland, and the US have reported that one of humans’ most defining features is built on an ancient foundation.

The scientists worked with zebrafish, a common laboratory species whose genes are well understood. They focused on two large stretches of DNA that flank the HoxD cluster. In mice, these regions, called 3DOM and 5DOM, control whether HoxD genes are switched on in different parts of a developing limb. The team deleted these regions in zebrafish. Then, by comparing normal and altered fish embryos, and tracking where and when certain Hox genes became active, they could test whether the same DNA stretches controlled fin development.

They also examined tissue structures like the cloaca, an opening used for digestion and reproduction, to see whether gene activity was linked to these organs as well. In parallel, they studied mouse embryos to trace whether the same regulatory elements were at work in the urogenital system of mammals.

The experiments revealed a surprise. When scientists removed the 3DOM region in zebrafish, Hox gene activity in the front part of developing fins was erased, confirming that this regulatory system existed before limbs evolved. But deleting the 5DOM region had little effect on fin development; instead, however, it caused the loss of gene expression in the cloaca. In mice, the same 5DOM region was found to drive Hox activity in the urogenital sinus, a structure that develops from the cloaca.

These results suggested that the regulatory system crucial for fingers in tetrapods wasn’t originally designed for limbs but controlled the formation of cloacal tissues.

The findings are a reminder that evolution can innovate by recycling existing components to serve new purposes, and also deepen researchers’ understanding of the genetic links between fins, limbs, and reproductive organs.

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