A pair of University of Florida researchers says they know why snakes no longer walk the Earth: The enhancer of a gene known as the Sonic hedgehog got turned off.

A separate study found the enhancer DNA is actually missing.

Professor Martin Cohn of the UF College of Medicine and doctoral candidate Francisca Leal say the off switch involved a trio of mutations that changed the way genetic information ultimately is transcribed. Their research was published in Wednesday’s edition of Current Biology.

The genetic change means the Sonic hedgehog gene, which also controls the development of many organs, flickers only briefly when the embryo is only 24 hours old and then goes out at the point when limbs develop. Surprisingly, snakes still have the rest of the machinery it takes to make limbs.

Cohn and Leal studied python embryos, noting they form leg buds, but the process breaks down before they can get beyond that stage. The pythons actually develop full “pre-cartilaginous” leg skeletons but they degrade before the baby snakes hatch, leaving only the remnants of a femur, the research found.

"It was absolutely mind-blowing because this was like development of a cryptic leg skeleton in an embryo," Cohn told NPR.

"This surprising conservation and the specific modifications in the snake genome are a clear testament of their ancestry. Snakes clearly evolved from limbed ancestors and their genomes demonstrate this," she told Phys.org.

Boas also retain rudimentary legs, but other snakes lose the ability altogether. Cobras and vipers show extensive decay of the Sonic hedgehog limb enhancer, the researchers said.

Snakes first started losing their legs 100 million years ago. Fossil records show snakes with legs as recently as 90 million years ago, and some scientists say it is possible legs re-evolved in other snakes.

Cohn said the research could point the way to discovering the transcription factor binding sites in mice or even humans.

Another study published in Cell indicates snakes may lack a key stretch of DNA. Researchers at Lawrence Berkeley National Laboratory inserted snake DNA into mice that developed truncated limbs as a result.

Lead author and geneticist Axel Visel and colleagues studied published snake genomes, also looking at the Sonic hedgehog and a piece of DNA known as ZRS — Zone of Polarizing Activity Regulatory Sequence. When the researchers inserted ZRS from other vertebrates and even fish into mice, the rodents developed normal limbs; when snake ZRS was inserted, the limbs were truncated.

"Using these new genomic tools, we can begin to explore how different evolutionary versions of the same enhancer affect limb development and actually see what happens," Visel told Phys.org. "We used to be mostly staring at sequences and speculating about molecular evolution, but now, we can really take these studies to the next level."

Research published last year in Science Advances found snakes lost their limbs when they began to live and hunt in burrows.

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