Snake Genomes Reveal Shared Plans for Making Legs, Penises

This is a post about penis enhancers, although not the kind that are advertised on the internet. Let me explain.

Penises and limbs are clearly very different (exaggerated references to third legs aside), but they develop in similar ways. They both involve long bits of tissue that grow out from a small embryonic bud, under the direction of very similar proteins, and molecules. For example, in 1997, Takashi Kondo from the University of Geneva showed that two genes that direct the development of legs in mice are also important for building genitals.

Now, Carlos Infante and Douglas Menke from the University of Georgia has shown that similar enhancers—sequences that switch genes on or off—are also at work in both organs.

Other scientists had already catalogued hundreds of enhancers that control the development of limbs in humans and mice. So Menke’s team wondered: what do these limb enhancers do in a creature without limbs? Have they changed beyond recognition, or become repurposed for other roles, or disappeared entirely?

Infante searched the recently sequenced genomes of three snakes—the boa constrictor, Burmese python, and king cobra—and found counterparts of 65 mammalian limb enhancers. These sequences are still there, and still recognisable, even though their owners have been slithering on their bellies for some 150 million years. So if these enhancers aren’t enhancing limbs, what are they doing instead?

To find out, Infante returned to mice, and found that around half of these enhancers are active in the genitals as well as in limbs. And that turned out to be a general pattern: limb enhancers are also often active in the genitals, but not the eyes, skeleton, or brain. They’re more like all-purpose “appendage enhancers” rather than limb-specific ones, turning on similar suites of genes in arms, legs, and penises alike.

Next, the team focused on just one of these enhancers, known as HLEB. When they deleted it from mouse embryos, the rodents grew up with smaller hips and a smaller baculum or penis bone. An anole lizard’s version of HLEB works equally well in a mouse: stick it in a mouse genome, and it will switch on genes in the rodent’s limbs and genitals. The same can’t be said for the cobra and python versions of HLEB: they can only control the activity of genes in a mouse’s genitals, and not its legs. They retain some of their ancestral functions, but have lost others that are no longer necessary.

Then again, the python HLEB also switches on some genes in the noses of mouse embryos, so perhaps this builder of limbs and penises has evolved a new snake-specific role that no one knows about yet.

PS: “Although the phallus differs from limbs in both form and function…” begins the paper. I’m glad science is around to tell us these things.