Snakes Co-opt Defunct Leg Genes to Enhance Penises

The same genes used for growing legs in reptiles and mammals perform a very different function in snakes.

If you sold all your home gym equipment, would you just leave your basement empty? No, you’d repurpose it as a tv room or a guest room. That’s exactly what Evolution does when it comes to genes. The ancestors of modern snakes stopped growing limbs over 80 million years ago, but instead of scrapping the whole genetic framework, snakes slowly repurposed the genes for another organ — the most important body part of all, as some men might suggest — snakes use these leftover leg genes as penis enhancers.

These genetic enhancers are strips of DNA that regulate the expression of other genes. Scientists already know that an intricate network of enhancers tightly control embryonic development so that the embryo doesn’t end up with two legs on the same side of the body, or different-sized arms, for example.

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Carlos Infante and Douglas Menke from the University of Georgia wanted to better understand how the enhancers have evolved to create such a wide range of limb sizes and shapes among vertebrates. They started with snakes as an example of extreme limb evolution, and began digging around in the genome to see what had happened in the 80 million years since snakes lost their legs.

To their surprise, the same enhancers on which reptiles and mammals depend for proper limb development are alive and well in snakes. Normally, any DNA that is no longer used for a crucial body part tends to accumulate tons of random mutations because natural selection no longer cares about keeping it intact. The fact that these enhancers had not accumulated mutations, despite losing their apparent purpose, meant they must still be doing something important.

So the team went back to mice to get a closer look at what the enhancers do besides grow arms and legs. It turns out about half the enhancers previously identified as limb-inducing were also active in genital development — specifically, in building the phallus that develops into a male penis or a female clitoris. In retrospect, it doesn’t seem that shocking, since limbs and phalluses are both appendages and would require similar proteins and mechanisms to direct their growth.

But the enhancers from the snake genome weren’t identical to the appendage enhancers inherited from the common ancestor of mammals and reptiles. The team spliced these snake enhancers into the DNA of mouse embryos to see how they operated in a system where legs were still an option. The snake DNA had lost its power to activate the genes for mouse hindlimbs, and focused only on genes involving gonads — they had basically become phallus-specific enhancers.

Menke hypothesizes that this secondary function for leg genes and enhancers popped up when internal fertilization appeared and created a demand for external genitals. The team plans to further investigate how these enhancers specialize their action on genes for either limbs or genitals, and how they regulate the formation of different genital shapes among reptiles and mammals. After all, no matter how similar legs and penises can look in some instances, there’s a lot of morphological distinction under the surface.