The Wonkiness of Pure Bloodlines, and Their Unexpected Upsides

In these modern times, scientists are becoming increasingly diverse in their fields of study. They are not only drawing links towards other scientific fields, but they’re also connecting their work to the social sciences and humanities in a bid to answer some pretty heavy questions about who we are and how we got here.

When I read about these hybrid fields, I can’t help but think we can create even more by making scientific mad libs.

Anthropological geochemistry.

Evolutionary psychology.

Anthrobiogeochemistry.

These are real fields, and they are fascinating.

Anthropological genetics, which combines evolutionary and population genetics with cultural studies to answer questions about the biological drivers of human demographics, such as diversification of agriculture and the spread of disease, is one of these interesting new fields. Anthropological genetics pops up in television shows like Ancient Aliens, Becoming Human, and of course, Secrets of the Dead, a serial in which one episode focused on King Tutankhamen. I watched this particular episode with the realization that my childhood knowledge of King Tut has been radically revised.

Having been tagged with the “Gifted and Talented” label back in elementary school, I was eligible to attend young scholar workshops held at the local high school. One class was a two-day affair on the life and times of King Tut, mixing lecture with an arts and crafts session to create a paper mâché replica of his iconic casket and faceplate.

As my eight-year-old self understood the lecture, Pharaohs were basically living gods (wealth, power, surrounded by good art) and that King Tut took the throne as a young teen after the death of his father. Tut made some heavy changes with the state religion, and died around 18 from a battle injury. He was then mummified and entombed along with a bunch of his stuff, and a millennia later became the subject of arts and crafts projects.

The various depictions found within Tut’s tomb reveal a young man with large eyes, high cheekbones, and full lips — the very image of aristocracy. I couldn’t have told you what a “crush” was at the time, but that’s the best way to describe how I felt.

When it came time to decorate the paper mâché caskets, everything started out just fine, but went quickly went downhill as I got to Tut’s face. I managed to paint one perfect, almond-shaped eye, but the right eye was nowhere near equidistant from the bridge of the nose, which in turn was completely asymmetrical, and I hadn’t left any room for a mouth.

I could’ve tried to fix it, but by this time I was bored by the whole activity and had moved on from my infatuation. I adopted what would become my default “meh” attitude that would take years to overcome, and painted a rough line between the left eye and the bridge of the nose, used more paint to widen the space, added a sort of nose-mouth hybrid, and called it a day.

Years later, a new theory came out suggesting that King Tut probably did not die in battle after all; examination of his skeleton showed that his left foot was clubbed, making it impossible to walk unaided, let alone drive a chariot. Even more recent studies suggested that he had scoliosis, a cleft palate, and rather girlish hips. An artist recreation showed a severe overbite.

Perhaps my rendition was more accurate than I thought.

So what happened to our king that was supposedly created in the image of the gods?

As it turns out, King Tut was severely inbred. We know this because mummy preservation techniques were also ideal for preserving DNA; the subsequent testing of King Tut and others buried within the Valley of the Kings proved that Akhenaten was indeed Tut’s father. However, Queen Nefertiti was not Tut’s mother, nor was the second queen, Kiya. A mummy identified as “The Younger Lady” was a perfect match for Tut’s mother, and oddly enough, his father’s full sister. This was a case of the royals wanting to keep the bloodline pure.

The numerous issues that appear because of inbreeding are a result of genetics. Humans, like many other animals, have two copies of each gene. Small changes in the DNA exist, called alleles. If we have two identical alleles of the same gene, we are considered to be homozygous; two different alleles, we are heterozygous. Blood type, eye color, and hair color are all examples of allelic variation.

When mid-19th century monk Gregor Mendel carried out the first known study in genetic inheritance using peas, he demonstrated that dominant traits are able to mask recessive traits.¹ The specific molecular mechanisms that determine whether a trait is dominant or recessive may be different on a case-by-case basis,² but a common theme is that a recessive allele codes for a nonfunctional protein, or no protein at all. Keep in mind that pea color is a rather innocuous example of a recessive trait. As it is in this cruel world, there are many known recessive genes that cause pretty severe physical problems, which brings us back to inbreeding. Continuous consanguineous pairings increase the frequency of homozygosity and the manifestation of recessive traits, and King Tut’s numerous defects can be attributed to the fact that his parents were brother and sister, inbreeding likely being the norm in the Thutmosid line.

Another example: Charles II of Spain (b.1661), nicknamed “Lo Hechizado” (The Hexed). Charles II had severe physical and mental disabilities; he was epileptic, had an abulic personality, and drooled constantly due to a severe pronunciation of the lower jaw and a rather large tongue. The final blow was infertility, resulting in the replacement of the doomed Hapsburg line by the French Bourbons following his death. As the story goes the Spanish royals ceased outbreeding after 1550; from then on everyone in the family married close relatives with expected results. Calculations of the genetic structure of Charles II show that his frequency of homozygosity was higher than that of a hypothetical offspring of a brother-sister pairing.³

These examples regarding royal lineages are extreme cases that demonstrate how damaging high frequencies of inbreeding can be. However, royal lineages alone do not account for all of the maintenance of genetic diseases caused by recessive alleles, and the presence of a genetic disease does not mean that the afflicted party is a result of inbreeding. If particular alleles are damaging to human mortality, why have they not simply become extinct?

One reason recessive alleles persist is due to the fact that a heterozygous carrier becomes less susceptible to other maladies and presents overall good health. This phenomenon is called “heterozygote advantage.”

The sickle cell anemia/malaria relationship is an example of heterozygote advantage. Sickle cell anemia is a blood disorder affecting individuals with two abnormal copies of the “sickle type” hemoglobin gene (HgbS/HgbS). Abnormal hemoglobin forms strands, forcing red blood cells to warp into a crescent or sickle shape, which results in their clumping within our circulatory system. Afflicted individuals have poor circulation, susceptibility to spleen disorders, and have a high risk of stroke. The tradeoff here is that individuals carrying one or more copies of HgbS, when infected, show only mild symptoms of malaria which is known historically as one of our deadliest diseases. There are several hypotheses as to why heterozygous individuals are less affected by malaria, centering on the observation that these individuals carry a lower pathogen load.^{4 5}

A second example of heterozygote advantage concerns cystic fibrosis and cholera. Cystic fibrosis occurs when an individual has two copies of a recessive allele that codes for a defective chloride channel (CTFR), affecting the regulation of fluids in our body. Afflicted individuals suffer from build-up of thick mucus which is ideal for microbial colonization, resulting in dangerous and chronic lung and sinus infections. Despite the recessive and debilitating nature of cystic fibrosis, the mutant allele still persists in human populations. The reasoning behind this is that people who carry a copy of the defective CTFR allele are more likely to survive cholera.

Most of us that grew up in the 1990s remember cholera as one of the diseases that picked off virtual family members in the Oregon Trail computer game. Infection occurs after ingestion of bacterium Vibrio cholera, which makes its way into our intestinal tract and secretes a toxin (choleragen) ,that indirectly results in permanent opening of our chloride channels, which in turn results in an uncontrolled loss of bodily fluids in a terribly undignified way; A person afflicted with cholera may produce between 20 to 50 liters of diarrhea daily, with death soon resulting from dehydration. The consensus is that heterozygous individuals have fewer chloride channels to be stuck on OPEN, so fluid loss is less severe, leading to a higher chance of survival.

These are just two known examples of heterozygote advantage known, with thousands more yet to be discovered.⁵ It is difficult to predict what nature will throw at us, so having a full arsenal of diverse genes is a safe bet. In the end, there is only so pure your bloodline can get before your family is scraped out of history, and your legacy is reduced to historians publishing unflattering CGI recreations of you.

¹ Mendel, GJ. (1866) “Experiments Concerning Plant Hybrids.” Proceedings of the Natural History Society of Brünn pp3–47

⁵ Withrock et al., (2015). “Genetic diseases conferring resistance to infectious diseases.” Genes and Diseases 2:247-254