The Vampire Monologs: Ancient DNA and the un-dead?

Tuesday's news stories reveal that Bulgaria rather than Romania (Transylvania) has provided us with some skeletal remains of what are being claimed to have been vampires.  According to a story on the BBC, "Archaeologists in Bulgaria have found two medieval skeletons pierced through the chest with iron rods to supposedly stop them from turning into vampires."  Fortunately, once living, and then not-so living, they were thus driven, so to speak, from the un-dead to the really, truly dead.   We all (or at least young, nubile ladies with accessible necks) should be relieved at this news.  But it also portends  important science, if done carefully.

Vampire skeleton. Source: BBC

We're told by Bram Stoker in the classic 1897 Dracula that vampires are recruited from the living by other vampires. I don't recall if it's explained how the first vampire came to not-be.  Nor how the legendary vampires are mainly males.  I'll leave that to others to study.

What's actually relevant for MT readers is the genetic questions posed by these discoveries.  The skeletons are recent enough that the bones will contain DNA that is in good enough condition to be sequenced.  Normally this would be called 'ancient DNA' (denoted aDNA), but a more relevant term for these rather recently un-deceased would be vDNA.  What will it show?  Will we be able to find the gene 'for' vamping?  How will the scientists do this?

Source: Flickr CC photo by Mugley

Vampires pose serious problems for evolutionary genetics, that are too intricate to go into in a mere blog post, and I plan to write about this in the near future, and report the findings to the NY Times rather than this puny blog outlet.  But there are some less grandiose issues posed by vDNA.  First, what would one expect to see?  

The sequence should show clear similarity to modern eastern Europeans.  Overall, there should be no particular trait that would reveal the vampire status of the individual.  Indeed, if vampires are randomly recruited, what we need to know is whether some people (like Mina Harker) were genetically susceptible to being vamped, or not.  If not, of course we have the conundrum that, since we're routinely informed (by the NY Times and the major journals) that everything human must have a genetic cause.  So we must assume some genetic difference.

This is a challenge, because we now know that any two copies of the human genome--even the two that you carry--differ by millions of nucleotides.  Therefore, to find the vampire susceptibility variation we might be looking for a family of genes, call them Vam1, Vam2,..., and so on that are responsible.  Since all genes are already known from human DNA sequence, we must simply have mislabeled these genes.  Many genes' functions are not known, and the Vam genes must be among them.  However, why do they even exist if only some women ever become vamps (not to mention male vampires)?  This poses one of the key evolutionary questions raised by vampirehood, since our view of evolution is that it has no foresight, so Vam genes can't have evolved for their future adaptive value in the Caucasus.

This suggests that there aren't really any Vam genes after all.  Instead we must search for variation in known genes that yield susceptibility to being vamped.  It's easy to imagine how that could be. For example, genes conferring long, luscious necks on women, or that make a woman want to wear low-necked blouses, could easily have the allure that is needed for them to be among the Chosen.

Vampire, Edvard Munch

But we don't know the genes 'for' necks (or low-neck shirt wearing), and what GWAS have clearly shown without doubt is that such traits are complex with many contributing genes.  As a result, we need to identify many places in the genome, where variants will generally only contribute a minor amount.  As we know with other disorders like diabetes, heart disease, and the genetically based Gullibility Predilection to believing that Everything is Genetic (the high frequency GPEG allele), we need large samples to find the critical variants in the sea of millions of rare but useless variants each of us carries.  Rather than Vam genes, what we seek are, shall we call them, genetic V-ariants.

That means, of course, that we must first of all do whole-genome sequencing and collect very large case-control samples to ferret out the V-ariant elements, and therein lie two V-ery serious challenges!

First, how on earth will we find enough cases?  We need to find the skeletons (or undead cadavers in current dungeon coffin residences) of a huge number of vampires--these days, the state of the art requires that we ascertain hundreds of thousands!  But how on (or under the) earth, this side of the Styx, could we find such a horde?  We need to compare their un-dead vDNA with that of the not-yet-dead DNA of living people.  We can't just dig up graveyards, or rummage around everybody's  basement, because how would we know which corpses were, or might have been, vampires?  This exemplifies the second challenge, which is how can we even obtain adequate controls?

Reading vDNA: a real problem in genetic cryptography!
You might be aware (most geneticists don't seem to be) that while controls are defined as being unaffected by the trait in question, many of them will  become future cases--that is their DNA is susceptible even if classified as 'unaffected' or 'normal'.  That means that until we know who will become un-dead in the future, we don't know whose DNA doesn't contain V-ariants!

A typical GWAS kind of approach, to salvage this situation, might be to select as controls only women who typically wear turtlenecks.  They might be the least likely to carry the susceptibility variants (if indeed susceptibility is linked to making ones neck alluringly available).  Otherwise, how do we match our cases with adequate controls?

If it turns out, as it surely will, that hundreds or thousands of genes in vDNA as in living DNA contain V-ariants, then we will face the horrible, or horrifying, problem that most of us carry some of the V-ariants, but we can't really know who.  A geneticist, even the usual type seeking attention, may be reluctant to stick her neck out with only weak evidence.  So as we walk and work among the living, we have no way to know if, at the end of the day as the phrase goes, we'll later walk among the un-dead...