On October 24th, 2017 we learned about

The strange but important reasons for your body’s Sonic Hedgehog gene

After a week of playing Acapella Science’s Evo-Devo in the car to my kids, I thought it would be worth walking through the song to try and explain what it’s talking about. The song is dense, packing in a ton of information about the relationship between individual animal’s growth and species’ evolutionary change. As far as I could tell, my four- and eight-year-old followed along as well as could be expected:

Genes provide instructions to build specific body parts. Got it!
Changing when those instructions are used can put anatomy in new locations. Ok!
That’s Sonic the Hedgehog, a video game character known for collecting gold rings and magic gems. What?

The glimpse of SEGA’s Sonic the Hedgehog is brief and unexplained in the song’s video, and my kids certainly weren’t the first people to be confused by the character’s inclusion in a discussion of genetics. As it turns out, Sonic is included as a reference to a specific gene pathway named after the video game character, much to the chagrin of scientists and doctors ever since its discovery. This is largely because the Sonic Hedgehog gene turned out to be an incredibly crucial ingredient in embryonic development, and mutations can lead to serious and often lethal health problems. Nobody wants to hear about a sassy video game mascot when facing life and death health problems, and as you’d imagine, the name was originally picked with a completely different context in mind.

Figuring out names for fruit fly genes

To try and make sense of this, we need to first back up to fruit flies. Drosophila melanogaster is a fruit fly species commonly used in laboratory experiments due to it’s relatively simple genome, manageable size, and quick life cycles. The flies reproduce and grow up quickly, allowing scientists to make changes to their genes then quickly see the effects of those alterations in action as the next batch of flies grows up. As an effect of a specific gene was isolated, researchers would give them names that described their function. An example is antennapedia, which is a gene that regulates when flies grow legs and antennae, as both types of anatomy are grown from the same underlying genetic instructions. Decreasing antennapedia’s functionality leads to legs growing from the fly’s face, while exaggerated versions of the gene will cause all the fly’s legs to grow as antennae.

At some point, researchers added a bit of irreverence to their naming conventions. This was a fun way to liven up hours spent raising deformed flies, but also helped these names stick in people’s memories. Strings of prefixes and quantities may be accurate and inoffensive, but they won’t help you remember that a certain gene mutation can cause a fly to develop without a heart in the same way the name “Tinman” can. Mutations in the “Out Cold” gene lose coordination in low temperatures. “Groucho Marx” mutations cause an excess of facial bristles. The list of silly names is long, but a group that has risen to prominence is the “hedgehog” genes, a name picked because mutations cause fly larvae to sprout unusually dense coverings of hair-like denticles on the backs while growing shorter and squatter overall, looking a lot like a hedgehog.

From “hedgehog” genes to human health

The hedgehog genes proved to be complex and important to various lines of research. To differentiate between them, specific variations were named after types of hedgehogs, including Indian hedgehog and desert hedgehog. This seemed fine until Dr. Robert Riddle found a new variation in 1991, and opted to name his hedgehog after the video game character which was debuting in the United States around that time. In that moment, it probably made sense, carrying on both the hedgehog group name and the tradition of adding humor to a gene’s name. The name certainly didn’t consider what this particular gene meant to an organism’s health, or that 75 percent of fruit fly disease genes also turn up in mammals like humans, meaning it was going to be relevant to a much wider audience.

Ideally, the Sonic Hedgehog gene pathway created proteins that regulate what anatomy gets built where in a developing embryo. Higher concentrations of these proteins at one end of an embryo lead to different outcomes than lower concentrations elsewhere, allowing it to serve multiple purposes in a developing body. Many of these functions are associated with making mirrored anatomy— you have two lungs, two lobes in your brain, etc. Eyes, for example, initially grow as a single “eye field” in the middle of an animal’s face, but the Sonic Hedgehog signalling gets the body to split that tissue into two distinct eyes. When these functions are disrupted, one result is holoprosencephaly (HPE). Mild cases of HPE may lead to a single, fused incisor instead of the usual two front teeth, but more severe cases often lead to stillborn offspring, cycloptic eyes and underdeveloped brains. This is one example of when a doctor doesn’t want to be discussing a fictional blue hedgehog, although bizarrely there is a small, unintentional connection between the character and HPE— Sonic is usually drawn with one giant sclera containing two pupils, rather than two distinct eyeballs. By some total fluke of character design, it appears that Sonic himself may be displaying symptoms of HPE.

Calls to stop controversial gene names

With all the confusion and controversy surrounding the Sonic Hedgehog gene, it seems like it should have been the last “silly” name that could be tied to a medical condition. It certainly stands out, but it certainly wasn’t the last time fictional characters were attached to a gene’s name. Beatrix Potter’s Mrs. Tiggy-Winkle is the namesake for another hedgehog gene, making studies like “Sonic Hedgehog and Tiggy-Winkle Hedgehog Cooperatively Induce Zebrafish Branchiomotor Neurons” a reality instead of just word salad. Not every silly name get through though, as Pokemon USA threatened to sue researchers who wanted their gene discovery to be dubbed the Pokemon gene, as the company understandably didn’t want their characters becoming associated with cancer. Future discoveries are likely to receive duller names as well, thanks to nomenclature committees looking to crack down on joke names that are more likely to reach the public’s ear than in the past. Theoretically, hearing about a disorder based on the “LFNG O- fucosylpeptide 3-beta-N-acetylglucosaminyltransferase” gene should somehow be more dignified than learning about problems with Sonic, especially if you’re more of a Mario fan.

My four-year-old asked: I don’t have a bad [Sonic Hedgehog] gene, do I?

There’s no sign of that. The Sonic Hedgehog gene is really only active in embryos, since it’s needed to help properly assemble anatomy in the correct arrangement. Once you’re done growing, its primary job is done. That said, it may also play a role in some regenerative functions, having been associated with hair regrowth in rats, among other things.

Source: The sonic hedgehog gene by Anna Perman, The Guardian