Reality Check: How does X-Gene inheritance work for the X-Men?



How can mutants have both mutant AND non-mutant children? There are ways!

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. Developmental biologist Yelena Bernadskaya is back for her third and final post on X-Men genetics. Does mutant inheritance make sense?

Sometimes, when a mommy mutant and a daddy mutant love (or hate) each other very much, they have a baby. Will that baby also be a mutant? And will their grandkids be mutants, too? How is the X-Gene passed on? Should there be more girl or boy mutants?

All good questions that we can try to tackle by doing a little family genetics.

Here are the basics. Everyone gets two copies of each gene, one from biological mom and one from biological dad. The copies are called “alleles” and they are not identical — each can code for a different form of the same gene, which will then produce a different physical appearance, or phenotype.

How do you know which allele will actually give you a physical phenotype? Some alleles act like trump cards; they always beat out others and are said to be dominant. You only need one copy of a dominant allele to produce a phenotype. Other alleles can only produce a phenotype when there are two of them, and these are called recessive.

If you have two copies of the same allele, either two of the recessive or two of the dominant, you are said to be homozygous for that allele. If you have one copy of the dominant and one copy of the recessive, you’re heterozygous. Your total collection of all the alleles is your genotype for a given trait. Thus ends the genetics vocabulary lesson.

Image credit: Marvel Comics

The observations

Is the X-Gene dominant or recessive? If a pairing between a mutant and a non-mutant produces a mutant child, we have to assume the X-Gene is dominant. A good example is David Haller, AKA Legion, the son of Charles Xavier and a human woman, Gabrielle Haller. Being a human, Gabrielle could not have contributed a chromosome carrying the X-Gene.

Even if Charles Xavier is homozygous (has two copies) of the X-Gene, he can only contribute one, since we get one copy of each chromosome from mom and one from dad. That makes Legion heterozygous for the X-Gene, and he definitely has mutant powers!

But wait, If the X-Gene is dominant, how do we get mutants from phenotypically non-mutant parents? How does their X-Gene not express itself? It turns out that shutting genes down is a common phenomenon. Cells can turn off specific genes or even whole chromosomes by taking a long string of DNA and compressing it so tight that it becomes inaccessible to the machinery that would normally turn a gene on.

This process is heritable, but because it doesn’t involve any changes in DNA sequence there is a separate term for it, epigenetics. The X-Gene could have ridden along for generations in a condensed, inaccessible state until a triggering event opened it up. After that it behaved as a standard dominant gene.

Knowing whether a gene is dominant or recessive can let us make predictions about how it will be inherited. If everyone with one copy of the X-Gene is a mutant, that means they could secretly be carrying a non-mutant allele,  masked by the dominant X-Gene.

In that case, two heterozygous mutants should be able to produce a non-mutant offspring. This is easiest to see if we use a very simple genetic device called a Punnett Square. You might remember it from basic biology, but here I am, making an X-Men version.

You can see here that one out of four combinations would produce a human child that does not carry an X-Gene at all. However, this hardly ever happens in the X-Men universe, with a famous exception being Graydon Creed, son of Mystique and Sabertooth. So why is the inheritance of the X-Gene so skewed?

Generally, humans have 23 pairs of chromosomes. Of those, 22 aren’t sex-specific. They’re called autosomes, and they segregate according to the Punnett square. The last pair of chromosomes determines (as best it can) your biological sex. These are the sex chromosomes, and because there are two of them, their inheritance is slightly different.

Genes on these chromosomes are considered to be sex-linked, and are inherited in a more sex-specific manner. Genes on the Y chromosome are only passed to male offspring, while genes on the X can be passed to either males or females. This makes some conditions, like red-green colorblindness, the gene for which is on the X chromosome, more common in males.

This is a little counter intuitive. The reason for this skewed inheritance is that the gene for color blindness is a recessive one, and biological females would need two alleles of it to have color blindness, because they have two X chromosomes. This is a fairly rare occurrence.

In biological males there is only one X chromosome and there is nothing to mask the recessive gene, therefore males cannot be silent carriers — if they have that copy of the gene, they will always have color blindness. Again, this is easiest to see in family trees.

Talk about dominant genes. Image credit: Marvel Comics

So let’s talk about the location of the X-Gene. We know it’s not on the Y chromosome, because if it were, there’d be no female mutants, and the Marvel Universe would be a lot more boring. So the X-Gene is on the X chromosome (appropriately enough), and it’s most likely dominant, because pairings between mutants and non-mutants produce mutant offspring (most of the time).

A mutant father would therefore produce all mutant daughters, since he’d have to contribute an X chromosome to them, and a homozygous mutant mother would produce all mutant offspring. In the general population, this would produce roughly an equal number of male and female mutants. There would still be a low incidence of non-mutant offspring if mutants continued to breed with other mutants, as in heterozygous female mutants with human males.

This is still somewhat unsatisfying, since very few non-mutant children are born to mutant parents. There is one final option, though, that could provide a better explanation. Everything we’ve talked about so far assumes that the X-Gene’s location is fixed on a single chromosome in a single position.

The hypothesis

But there are such things as jumping genes(!) that can either change their positions in the genome, or even make multiple copies of themselves, integrating them into different positions in the genome of the single human. These are called “transposable elements,” and they were first discovered in corn by the legendary Barbara McClintock (seriously, go look her up!), which earned her the Nobel Prize in Physiology or Medicine.

Barbara McClintock (Wikimedia Commons)

Transposable elements are large stretches of DNA found in almost all life forms, which have been co-evolving with us for a long time. They comprise approximately 44% of the human genome and have been linked to diseases such as hemophilia and muscular dystrophy. Transposable elements can be very large, allowing them to carry whole genes inside them and even contain instructions for making more copies of themselves.

Having the X-Gene housed on a transposable element would be helpful even to the original Celestials, who could have added instructions for what I’d like to call the X-Element, to make more copies of itself and burrow its way into the genome. They engineered the X-Gene to be dominant, so having even one copy would manifest in mutant powers.

Then basic inheritance did its thing. Having multiple copies of the X-Gene throughout their genome would virtually guarantee that any offspring of a single mutant parent would also be a mutant, making non-mutant offspring very rare, as we do indeed see.

Theoretically, this should allow the X-Gene to eventually spread through the entire human population, as long as its carriers keep breeding. But that’s a whole other issue.