This Is Why Snakes Have No Legs

It’s all because of something called the Sonic hedgehog gene.
October 24, 2016, 10:00pm

There's a story in the Bible of how the snake lost its legs for leading Adam and Eve to eat the apple in the garden of Eden. But scientists now have new insight into why snakes no longer have legs.

University of Florida professor of molecular genetics and microbiology Martin Cohn, Ph.D., and Ph.D. candidate Francisca Leal, found that a series of genetic mutations impacting the Sonic hedgehog gene likely caused snakes to lose their limbs around 100 million years ago during the Upper Cretaceous period. They published their findings in the journal Current Biology in late October.


According to fossil records, snakes had a complete set of forelimbs and hindlimbs about 150 million years ago. As shown in the video, if you look carefully at the python, you can see the remnants of one of its legs, a tiny black claw sticking out by his vent. So where'd they go?

"These transient embryonic legs give us a window in the evolutionary history of snakes by showing us that they have retained a remarkable amount of machinery needed to make limbs," Cohn said. "What these results suggest is that the legs were not completely lost, in that the even python embryos start to form the skeletal elements of the entire leg, but the distal parts degenerate."

The Sonic hedgehog gene is a key gene that signals limb development, and according to the new study, a trio of mutations that appeared roughly 100 million made the gene much less likely to be expressed. Together, the mutations got rid of the region of the gene known as the transcription factor binding sites, where proteins and DNA bind together. During normal limb formation, the enhancer, or part of the DNA responsible for gene expression, acts as a genetic "switch" that goes on, but the mutations eradicated that switch.

By comparing the DNA of snakes and lizards, Cohn and Leal found that while some snakes, such as cobras or vipers, are totally without a hint of previous limbs, pythons and boa constrictors have tiny limb rudiments left over.


"The results tell us that python limb development progresses much further than we knew before," Cohn said in a press release. "They make embryonic legs but the cells don't complete the process of skeletal development."

So while pythons have three deletions in the the limb-specific enhancer of the hedgehog gene (known as the ZRS), nearly identical ZRS degradation was also present in the boa constrictor, Cohn told Motherboard. "In advanced snakes, which are completely legless (no rudiments at all), we found much more extensive mutations/degradation of the ZRS than we saw in either python or boa," he said.

In addition to studying the Sonic hedgehog gene, the researchers also studied the enhancers of the Hoxd genes, which dictate the formation of fingers and toes. Surprisingly, the Hoxd enhancers did not show degradation, said Cohn. In fact, they even showed a late stage of the Hoxd expression, which would typically be associated with developing fingers and toes.

"We found that python embryos begin to develop not only a femur, but also a tibia, fibula, and footplate," Cohn told me. However, those structures degenerate before they fully become distinct, since they're transitory and only present at embryonic stages. "These results tell us that pythons have retained a lot more of the leg than we appreciated," he said, "but the structures are transitory."

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