Genetics in Game of Thrones: Those Crazy Inbred Targaryens

Viserys and Daenerys Targaryen

I wanted to shift gears a little bit and finally stop talking so much about Robert Baratheon. And a lot of the most interesting genetic wackiness in Game of Thrones surrounds an entirely different family: the Targaryens. The Targaryen words are “fire and blood”, which to me means their two most important traits are (1) dragons and (2) inbreeding, although not necessarily in that order. The Targaryens keep their bloodline “pure” by marrying brother to sister pretty much whenever they can. But what would happen if a family really did that? Wouldn’t they be, well, insane and deformed?

A piglet with severe congenital deformities

The stereotype is that brother-sister mating takes you from “adorable piglet” to “circus hawks call it an alien” in no time at all. But this piglet isn’t necessarily inbred.

Inbreeding essentially does one thing – it reduces the genetic diversity in a population. If mom and dad are more similar genetically, a kid will be less likely to be heterozygous for any trait than non inbred individuals, and that in turn means that they’re more likely to express recessive traits: things like, say, exceptionally pale hair color. And the reality is that this picture of inbreeding (funny hair and eye color but basically normal) isn’t our standard stereotype of inbreeding. In part, that’s because one generation of inbreeding after many generations of outcrosses operates differently than many generations of sustained inbreeding.

So let’s talk about the first generation of inbreeding. To be clear, this isn’t Daenerys Targaryen we’re talking about any more, it’s Joffrey Baratheon. The Lannisters spent generations marrying into other families before Cersei decided that her brother was her one true love. And this is, to an extent, where Martin gets it wrong: we don’t see any obvious congenital abnormalities in the young “Baratheon” children, and the one character we know who had a stillborn, and tragically deformed, child was Daenerys – after marrying Kahl Drogo, who most likely didn’t have a drop of Targaryen blood.

Daenerys Targaryen and Kahl Drogo

I mean, until very recently it would have required the Khalasar to cross an ocean, which we know they really don’t like. And you’d figure the “Dothraki invasion of Westeros a few years back” would be a thing that Martin would have mentioned.

Why would this be? Well, like I said before, inbreeding is potentially dangerous because it increases your chances to be homozygous for dangerous alleles. For that to happen, both the mother and father must have been heterozygous for the allele. And in families, that happens two ways: first, maybe grandpa was a mutant, and happened to pass his mutant allele on to both mom and dad. The mutation was poisonous but you couldn’t see it in a heterozygote, and since it was unique to grandpa there wasn’t much risk of getting a homozygote unless someone went and had kids with their brother or sister. Everyone has about 1000 new mutations, and because most mutations are silent in a heterozygote a trait like this can linger in a family for a few generations, so there’s a nontrivial chance of a family-specific mutation causing problems for inbred individuals. That’s a story that’s fairly easy to understand.

A pedigree describing why inbreeding causes an increased risk for genetic disorders

You wouldn’t even know which mutations run in your family until you started uncovering them by inbreeding. Or until you sequenced your genome.

But if every family’s inbreeding hits different genes, then every family’s inbreeding would look different. And that’s not what we see. There are some commonalities to inbred individuals across not only families but species. It’s called inbreeding depression and it’s the things I mentioned before: miscarriages, small babies, immune system problems, and the like. The best in-universe example is actually Lysa Arryn: she had one child and many miscarriages, and the child she did have was sickly, small, and weak. This isn’t because of a mutation that happened a few generations ago, it’s because of a mutation that happened a very long time ago, in a gene that’s just incredibly variable across individuals and taxa. Maybe even someplace where we actively select for variation, instead of any particular allele. I bet you can see where I’m going with this: some place like the immune system. It’s easy to see how immune problems can cause a kid to be sickly. But how could immune system problems lead to a small kid, or a miscarriage?

Japanese Spitz puppies (hopefully this makes up for the piglet from earlier)

You can see something related to this in dogs and cats, too: purebred animals have a tendency towards health problems while mixed breed animals seem to be healthier.

The answer lies in the placenta. The placenta is a battleground between the mother and the child, where fetal cells physically invade into maternal tissue and reorganize it in order to direct blood full of oxygen and nutrients to the developing embryo. A malformed placenta will lead to miscarriage. A small placenta that doesn’t effectively funnel nutrients to the fetus will lead to a small child. And metabolic changes that happen during development can stick with you for your entire life: so a starved baby will grow more slowly and will be a very small adult. It’s possible that some neurological problems could be linked to the placenta as well: the placenta is an important source of neuroactive hormones and signalling molecules before they are produced by the developing brain. But how is the placenta controlled by the immune system? The placenta, it turns out, is full of white blood cells. Obviously, if maternal white blood cells attacked the growing placenta or fetus, the fetus can’t develop. Even more so, white blood cells from the mother help reorganize the maternal cells that make up half of the placenta. Changes in the immune system can profoundly alter placental development, and with it things like fertility, survival, size, and cognitive development.

A diagram of the placenta from Gray's Anatomy

The placenta is actually a really fascinating organ in general: it is the site of a complex negotiation between the mother’s body and the growing fetus.

So, what makes subsequent generations different? Well, a lot of the really terrible mutations will get weeded out quickly. If at that first generation mom and dad share 50% of their genes (as in a brother-sister pairing), then two things happen: there’s a 25% chance that at any gene, a kid will be a homozygote. And that kid’s brothers and sisters will share more than 50% of their DNA, too; more like 75%. After a few generations, you get to the point where every individual is homozygous at every gene, and every individual is essentially genetically identical. We haven’t seen this in human populations because such sustained close inbreeding is incredibly rare. But we do see it in laboratory animal populations. And those populations aren’t horribly deformed. They’re a bit smaller, and weaker, and in some cases stupider than their wild counterparts, and a cross between two strains that can add back variation into the genome will result in a hardier animal, but the inbred individuals get on pretty much all right.

Laboratory mice

These mice are probably all genetically identical because they’re so inbred. And they have that beautiful white-blonde Targaryen hair, too.

How does this relate back to Daenerys and the other Targaryens? Well, a bunch of traits that are usually recessive in human populations are present in the Targaryen family with startling frequency: platinum-blond hair, and blue (or purple) eyes, for instance. A bunch of Targaryen kings were sickly or weak, which makes sense with what I mentioned above about the immune system. And unlike families like the Freys, who seem to revel in their fertility, the Targaryens rarely have more than two or three kids in a generation. And there’s a history of madness as well, which might have as much to do with the stresses of ruling and social pressures towards lighting things on fire as it does with inbreeding. But in general, the Targaryens seem to be basically plausible as an inbred royal family. Probably because there are plenty of inbred royal families in our history for Martin to draw on.

Maybe he got the creepiness from there too. Or maybe that’s something that’s all Martin.

Previous posts: Forensic Science, Baratheon Hair Color

Elizabeth is a PhD Candidate studying Genetics in the San Francisco Bay Area. She specializes in the epigenetics of mammalian development. In her free time, she is an aerialist, a dancer, a clothing designer, and an author. You can find her on tumblr at madgeneticist.tumblr.com, on twitter at @lysine_rich, and also on facebook or google+.
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