Secondary mutations and power suppression — can the X-Men’s gene expression be controlled?

Our genetics expert has the surprising answer.

Since their debut in 1963, the X-Men have sworn to protect a world that hates and fears them, but here at AiPT! we’ve got nothing but love for Marvel’s mighty mutants! To celebrate the long-awaited return of Uncanny X-Men, AiPT! brings you UNCANNY X-MONTH: 30 days of original X-Men content. Hope you survive the experience…AiPT! Science is going all-in for Uncanny X-Month, with the most detailed look at X-Men biology anywhere, EVER. To follow up on her first post on the X-Gene, developmental biologist Yelena Bernadskaya is back to talk about how mutations can be brought on, or even suppressed. 

The natural method

If you were a mutant in the Marvel Universe, you’d probably not know it for a long time. For the majority of mutants, the change happens around the same time as puberty. Why is that? What’s so different about our bodies during puberty that can set off these chain reactions that can completely transform an individual? The answer is pretty obvious.

Hormones! In essence hormones are just chemical signals that tell the body to do stuff. They control things like our sleep/wake cycles, metabolism, and the onset of sexual maturity, i.e. puberty.

Cells have receptors that can recognize different types of hormones, bring those hormones inside the cell, and then activate genes that will carry out different functions. This process is a type of chemical induction that can happen naturally when our bodies make the hormones, or it can be induced artificially by introducing the hormones into the body. As long as the synthetic hormone is chemically identical to the real thing, your body will not be able to tell the difference.

Since the X-Gene often activates around the time of naturally occurring puberty, we can speculate that it is indeed responsive to hormones. But sometimes it can be triggered artificially by stressing the host in different ways, which tells us that we can have some level of control over it, if only we could figure out the particulars of some of the triggers.

How can we do that? How precisely can we control this activity and can we switch it on and off at will? I’m happy to say that in this area we are pretty far ahead. Scientists can control expression of genes with drugs, temperature, and even just by shining lights on things.

A new calling? Image credit: Marvel Comics

The unnatural method

Controlling gene expression with drugs is very similar to controlling them with hormones. The drug will bind to a receptor, which will then send a message through secondary chemicals that will turn on specific target genes. We can easily control this by choosing when the drug is administered. Pretty straightforward so far.

The problem is that you can’t isolate the effects of this type. If you only want to target a person’s right hand, giving him a drug intravenously is not helpful, because it will be distributed to the rest of the body.

Scientists who work with model organisms (animals close enough to human beings in certain respects to stand in for them during testing) have spent a lot of time developing ways to control the turning on and turning off of genes. This is important because mutating some genes can be lethal very early in development, but the same genes can have another function later in life.

How do you find these late functions if every time you mess with the gene you end up killing your organism? Turns out you can just warm them up a bit! Some gene mutations result in a protein that is temperature sensitive.

And if you add a little pressure? Image credit: Marvel Comics

When a protein becomes temperature-sensitive it can only function at a specific, usually low, temperature. If an animal with this mutation is shifted to a restrictive, usually higher, temperature that protein loses its function.

This enables scientists to look at the function of genes essential for early survival much later in life. A lot of mutants like this have been made in the small roundworm Caenorhabditis elegans, a common genetic model organism.

More recent methods have taken the ability to induce gene expression even further. We can do it by shining a light on cells or organisms, because light is just energy, and that energy can cause proteins to change their shape.

You have cells in your eyes that already do this, the photoreceptor cells (rods and cones). A photosensitive protein called rhodopsin changes conformation (the arrangement of atoms) when it senses blue light.

By studying how photosensitive proteins in these cells change conformation when they’re exposed to light, scientists have been able to engineer synthetic genes that now make proteins that respond to those energy supplies. Then they can make the proteins do different things, like go to specific parts of the cell, or bind up a bunch of other proteins.

Don’t believe me? Check out this fly embryo where the researchers are able to WRITE the name of the protein they study just by shining a light on it in the shape of the letters.

Johnson et al, 2017

They do this by taking a protein that fluoresces under short range wavelengths, like a blacklight, and tagging it with another protein that can drag things to the membrane. When they shine a high intensity light on it, there’s enough energy to make the protein change shape and expose the tag, which then relocates the fluorescent protein to the membrane.

Pop quiz:  Who remembers what a transcription factor is? It’s a type of protein that can activate genes, and it needs to get to the nucleus to do that. Scientists have fused these transcription factors to light responsive proteins that can drag the transcription factor into the nucleus when you shine a light on it.

Once in the nucleus, the transcription factor can do its job and turn on genes.  This gives the scientists really close control of when and also where gene activation is induced. If this were possible in a human, and they want to target just a hand, they can have a person stick their hand in a box with a black light in it.

The Marvel method

If you can turn genes on this way, can you also shut them off? As it turns out, yes you can! Transcription repressors are a group of proteins that can turn genes off. Most of them work at the level of DNA and can displace the transcription factors or make the DNA housing a certain gene physically inaccessible.

For the X-Gene, it means that we can actually have some reasonable amount of control about when it gets turned on, or maybe even ways to tease out latent, secondary mutations (thank you, Grant Morrison).

Image credit: Marvel Comics

Perhaps more interestingly to characters like the Morlocks or Rogue in the ’90s, this also creates the potential of being able to suppress their mutant powers by shutting off the expression of the X-Gene. Or maybe powers can potentially be changed, if they’re shut off in some organs and turned on in others.

Now that we know if mutant powers could be controlled, stay tuned to Uncanny X-Month for two essays from philosophers asking whether they should be or not, later this week. Only on AiPT! Comics!