Behind Blue Eyes: A Look at the Genetic and Cultural Components that Propelled the Spread of Blue-Eyed Humans

Close-up image of a blue eye

This thoroughly-researched piece is by Sarah Henry, an instructor at Delaware County Community College and tour guide at the Mütter Museum.–KI

I have blue eyes and I have always been interested in exploring my own genetic origins, but I’m not the only one interested in this genetic trait. Countless songs and poems reference people with blue eyes, whether considered a mark of beauty, a representation of sadness, or, in certain cultures, a sign of the oppressor. But blue eyes, so popular in art, are relatively new in human evolution, as new as the invention of writing itself. My interest in this subject was sparked, in part, by a unique archaeological discovery; in 2006, researchers uncovered the world’s oldest confirmed blue-eyed person, dating to approximately 7,000 years ago. This discovery helped to confirm theories regarding the familial relationship of nearly all blue-eyed individuals. This article will exam the genetic origins of blue eyes in humans, the spread of the blue-eyed gene, and the future of this genetic trait.

Genetics: How Do They Work?

The basic explanation of eye-color works like this: a person needs only one dominant brown-eyed gene (from one parent) to be brown-eyed but needs to have two recessive blue-eyed genes (one from each parent) to be blue-eyed. You have probably seen this explanation accompanied by a simple Punnet square (Image 1) in your science textbooks. However, new studies illustrate that the genetics behind eye color are not so straightforward. There are actually two separate genes that control eye color in humans. In his article, “Blue Eye Color in Humans,” Hans Eiberg writes, “Blue/Brown eye-color are known to the public as a school example of inheritance of monogenetic [one gene] inheritance, however, the variation in pigment concentration and the iris suggest the eye color genetics to be far more complex as supported by recent data.” In other words, eye color is controlled not by one gene passed from parent to offspring, but by two genes working in tandem; a more complex chart would take both of these genes into consideration (Image 2).

Punnet Square demonstrating the likelihood of brown or blue eyes.

Image 1

Genetic chart demonstrating the likelihood of brown or blue eye color.

Image 2

 

 

 

 

 

 

 

 

These genes are called OCA2 and HERC2 (represented as O, o, H and h in Image 2). The simplified explanation is that the OCA2 gene controls pigment in the stroma (the tissue and blood vessels) of the iris (the colored part of the eye around the pupil) and the HERC2 gene is needed to help turn on the OCA2 gene to cause it to produce this pigment, resulting in brown eyes. If a person has a non-functioning OCA2 gene, they will always have blue eyes, because the HERC2 gene can’t make the broken OCA2 gene work. Likewise, if a person has a HERC2 gene which doesn’t work, the OCA2 gene will “underachieve,” failing to produce enough pigment to make brown eyes, resulting in blue eyes. These two genes aren’t directly related to each other, yet they affect each other. In this dependent relationship, both of these genes must work to give an individual brown eyes, a genetic relationship known as “epistasis.” Because of this process, it is actually possible (although rare) for two blue-eyed parents to have a brown-eyed child. If one parent passes on a working HERC2 gene and one passes on a working OCA2 gene, rather than the broken version of each, the resulting child could have brown eyes (Image 3). In addition to this more complex explanation of eye color as an inherited trait, this new study also suggests that all blue-eyed people stemmed from a single common ancestor.

Illustration of how dominant and recessive genes work with regard to human eye color

Image 3

How Do We Know All Blue-eyed People Are Related?

Homo sapiens (modern humans) emerged around 200,000 years ago in Africa, but the mutation that causes blue eyes did not appear until sometime around 10,000 years ago. In a study conducted by Professor Hans Eiberg and a team from the University of Copenhagen, researchers examined mitochondrial DNA from 155 blue-eyed subjects from Denmark, two from Jordan, five from Turkey, and 45 brown-eyed candidates, looking at the locus (specific location or position of a gene) responsible for brown or blue eyes. The result was the discovery that more than 97% of blue-eyed people share the single H-1 haplotype (a group of genes within an organism that was inherited together from a single parent). Eiberg and his team write, “A shared haplotype among blue-eyed individuals is almost perfect and suggests the blue color phenotype is caused by a founder mutation.” This means that the vast majority of people with blue eyes share a single inherited genetic mutation, rather than each person with blue eyes possessing a unique mutation. The study also tested seven blue-eyed Mediterranean individuals unrelated to the Danish participants as a control group. They, too, carried the H-1 haplotype. These individuals with the H-1 haplotype all inherited the same switch at the same location in their genetic coding, whereas, brown-eyed individuals have a number of variations in melanin production and DNA, with brown-eyed phenotypes being spread out between haplotypes H-5 and H-10. In short, almost all blue-eyed people came from a single ancestor, which is proven by the possession of the exact mutation at the same location in their genetic coding. That leads us back to the blue-eyed man from the article that sparked this entire investigation.

Why is This Stone Age Body in Spain so Important?

In 2006, researchers discovered a 7,000 year old body from the Stone Age in the La Brana cave system in Leon in Northern Spain (Image 4). Genetic testing determined that this man had blue eyes. It was not in itself unusual, but what is remarkable is that he is the earliest known person with blue eyes. Far from being a fair-haired, far-skinned man that we may have expected, his genetics reveal he’s a mixture of other traits. Although he’s closely related to the modern residents of Scandinavia, he also carries the dark-skinned genes of an African, as well as curly dark hair and lactose intolerance (Image 5). So if blue-eyed people originated near the Black Sea and were concentrated in Northern Europe, how did our mystery man end up in Spain?

Artist's rendering of the face of the LaBrana skeleton

Image 4

In order to answer this question, we need to delve into Stone Age migratory patterns. According to Pickrell and Reich, there are two theories of cultural migration: Demographic Stasis vs. Demographic Change. In Demographic Stasis, inhabitants living in a particular region are the descendants of the first people to arrive in that region, meaning the people in a certain area were never integrated into or replaced by people from a second migration. Demographic Change posits that inhabitants of a region descended from people who arrived during periods of technological or cultural change, replacing the previous inhabitants. These periods of change can be tracked by sudden changes of culture in the archaeological record. Essentially, if we can track people by their technology (things like tools and weapons) and implements of culture (things like pottery and jewelry), we can track how people migrated from one place to another and brought their genetic traits with them.

Photograph of the Stone-Age skeleton discovered at La Brana in northern Spain in 2006

Image 5

Specifically, we can see this during the Neolithic (New Stone Age) Revolution, a period of time where humans began to cultivate crops, domesticate animals, and use polished stone tools. Prior to the Neolithic Revolution, almost all the world’s inhabitants subsisted primarily by hunting and gathering, but after the Neolithic Revolution, small pockets of farming emerged, first in the Fertile Crescent, China, and India and then spreading across Eurasia. The Neolithic Revolution occurred between 6,000-10,000 years ago, and because people were better able to procure a steady source of food, the population increased significantly. The technologies which emerged during this time allow archaeologists and researchers to track cultural migration from the northwestern part of the Black Sea region (where the first humans with blue eyes lived) into the rest of Europe. A study of Armenian haplotypes determined, “…hospitable climatic conditions and the key geographic position of the Armenian Highland suggest that it may have served as a conduit for several waves of expansion of the first agriculturalists from the Near East to Europe and the North Caucasus.” People migrated out of the Caucuses (modern-day Georgia, Azerbaijan, and Armenia) and into other parts of Europe (Image 6). Hovhannisyan, et al. write, “Apparently, the population migration of the first farmers from the Levant could have been both by land to Anatolia and the North Caucasus, and by maritime routes via eastern Mediterranean islands towards continental Europe.” Sparked by the population boom created by the Neolithic revolution, people began migrating faster and farther than ever before.

Map of Europe displaying migration patterns for humans with the R1b1a2 (blue-eyed) gene

Image 6

Another study, focusing specifically on the genetics of residents of the Iberian Peninsula (excluding the Basques), indicates a mixture of genetic traits from the Caucuses, Central Asia and North Africa, probably related to migration during the Neolithic Era. A study of eight Bronze Age individuals dated to between 5,500 and 3,500 years ago shows an admixture between existing hunter-gatherer groups and people from later migrations, meaning people who migrated to this area began to blend into the peoples that already lived there by blending both their culture and genetics.

Why Did this Recessive Genetic Trait Survive for Thousands of Years?

How did the blue-eyed gene persist if there’s no overt evolutionary advantage to possessing it? One argument would be that those original groups of people who possessed blue eyes produced offspring with other blue-eyed people in their own group, leading to a population where blue eyes were the norm. However, there are both objective and subjective benefits to possessing blue eyes. Subjectively, possessing blue eyes may just make one individual more sexually attractive to another. Objectively, blue eyes filter light differently than dark eyes (dark eyes, like dark skin, possess more pigment which can protect those organs from sun damage), which make them especially advantageous in the low light of Northern European winters. Because people with light eyes are more sensitive to light, they can see better in areas that lack sufficient sunlight for large portions of the year. Conversely, while light sensitivity (photophobia) proved useful in a world prior to electricity, it actually opens blue-eyed people up to a host of medical problems including an increased risk of macular degeneration, which can ultimately lead to blindness because light eyes are worse at filtering out harmful UV light.

What is the future of blue eyes?

At the turn of the 20th century, 50 percent of people living in the United States had blue eyes. Now, however, people are more likely than ever to marry outside of their ethnic group, leading to more genetically diverse offspring and a decline in blue eyes due to the dominance of the brown-eyed genes. Currently, in the U.S., only 17 percent of the population (1 in 6) has blue eyes and only between 5-8% of people worldwide possess the trait. (Green eyes are even more rare, but they are a topic for another article.)  Even though they are new in human history, blue eyes are already on the decline.

Whether used to convey beauty, as one writer notes about the poetry of Longfellow and Romanticism, “It delighted in sentimental musings amid the ruins, in pathetic legend, in dreamy pictures of monks and harpers and knights and radiant maidens with soft blue eyes” or to convey sadness like in the Who song “Behind Blue Eyes,” where Roger Daltry sings, “No one knows what it’s like/ To be the bad man/ To be the sad man/ Behind blue eyes,” or as Kristina Richardson writes in her article regarding the perception of blue eyes in the Islamic Middle Ages, “My preliminary archival work suggests the Medieval Muslim male writers overwhelmingly accepted the characterization of blue and green eyes as unattractive and deviant,” a line of thinking fueled by the brutality of European crusaders who raped, pillaged and murdered in an attempt to reclaim the Holy Land. Blue eyes have been a notable trait in literature across cultures for centuries. Though the future of blue eyes is unclear, nearly all living and dead blue-eyed individuals share a familial relationship through a single genetic mutation. If you have blue eyes or know someone with blue eyes, they are more than likely related to that 7,000 year old man whose remains that researchers found in a remote cave in Spain.

Sources

A. Hoyhannisyan, Z. Khachatryan. M. Haber, P. Hrechdakian, et all. Different waves and directions of Neolithic migrations in the Armenian Highland. Investigative Genetics 5 (2014).

B. Starr. “Eye Color.” TheTech. TheTech, 14 October 2004. <http://genetics.thetech.org/ask/ask59>

B. Starr. “How Blue Eyed Parents Can Have Brown Eyed Children: Two Different Ways to Get Blue Eyes.” TheTech. <http://genetics.thetech.org/how-blue-eyed-parents-can-have-brown-eyed-children>

F.L. Patty. Sidelights on American Literature. “The Shadow of Longfellow.” Century Company, 1922: p. 237.

H. Eiberg, J. Troelsen, M. Nielsen, A. Mikkelsen, J. Mengel-From, K.W. Kjaer, L. Hansen. Blue eye color in humans may be caused by a perfectly associated founder mutation in a regulatory element located within the HERC2 gene inhibiting OCA2 expression. Human Genetics 123 (2008): 177-187.

I. Lazaridis, et all. Ancient human genomes suggest three ancestral populations for present-day European. Nature 513 (18 September 2014): 409-413.

K. Richardson. “Blue eyes in Islamic Middle Ages.” Medievalists. Medievalists, 16 February 2014. <http://www.medievalists.net/2014/02/16/blue-eyes-islamicate-middle-ages/>

J. Bryner. “One Common Ancestor Behind Blue Eyes.” LiveScience. LiveScience, 31 January 2008. <http://www.livescience.com/9578-common-ancestor-blue-eyes.html&gt;

J.K. Pickrell and D. Reich. Toward a new history and geography of human genes informed by ancient DNA. Trends in Genetics Vol. 30, No. 9 (Sept 2014): 377-389.

J. Mengel-From, C. Borsting, J. J. Sanchez, Hans Eiberg, Neils Morling. Human eye colours and HERC2, OCA2 and MATP. Forensic Science International: Genetics 4 (2010): 323-328.

S. Connor. “Revealed: First Ol’ Blue Eyes is 7,000 years old and was a caveman living in Spain.” IndependentUK. IndependentUK, 26 January 2014. <http://www.independent.co.uk/news/science/revealed-first-ol-blue-eyes-is-7000-years-old-and-lived-in-a-cave-9086310.html>

T. Günther, C. Valdiosera, H. Malmström, I Urena, et all. Ancient genomes link early farmers from Atapuerca in Spain to modern-day Basques. PNAS 112 (2015): 11917-11922

University of Copenhagen. “Blue-eyed humans have a single, common ancestor.” ScienceDaily. ScienceDaily, 31 January 2008. <www.sciencedaily.com/releases/2008/01/080130170343.htm>.

CEPI Curiosities: Chevalier Jackson Chewed Up and Spit Out

CEPI Curiosities: Tales from Medical History's Strange Side

Welcome again, fellow historico-medico philes for the latest installment of CEPI Curiosities. This time around, we round out our series of guest-authored pieces with Karabots Junior Fellows intern Paul Robbins’ third and final post. If you haven’t seen his previous two articles on Chang and Eng and FOP (fibrodisplasia ossificans progressiva), I recommend you go and do that. In the meantime, here’s Paul’s take on Chevalier Jackson and his collection of swallowed objects.

Chevalier Jackson was born on November 4, 1865, in Pittsburgh, PA. He was a Philadelphia otolaryngologist and a Fellow of The College of Physicians of Philadelphia. Chevalier Jackson created a method to remove swallowed objects from the human lungs. He is most known for his collection of swallowed objects gathered over a career that continued for almost 75 years. Dr. Jackson’s collection includes 2,374 swallowed objects.

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Dr. Chevalier Jackson

It was said that Chevalier Jackson had a cold, cruel, and lonely childhood. He had his own laboratory at the age of four where worked with wood and sharp tools. As a child he had no intimate friends and few companions; unlike other boys his age Chevalier did not find interest in physical activities such as football, baseball, or dancing. Jackson was bullied as a child; he was bullied so much that at one point he was thrown into a trench and was found unconscious by a dog.

X-Ray of patient who swallowed safety pin

Chevalier Jackson went to Thomas Jefferson University and received a MD. He also went to England to study laryngology which is the branch of medicine that deals with the larynx and its diseases. After his college years, he went on and became a otolaryngologist. A otolaryngology is the study of diseases of the ear and throat. Dr Jackson’s specialty was the removal of objects from people’s throats. His most frightening procedure was when he had to extract three open safety pins from a nine-month-old baby.

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He kept and took careful records of each swallowed object as an example for other otolaryngologists while performing bronchoscopy. Bronchoscopy is a procedure in which a hollow tube called a bronchoscope is injected into your airways to provide a view of the tracheobronchial tree. More than 80% of his patients were under the age of 15. Dr Jackson’s collection of over 2,000 swallowed objects consists mostly of safety pins, toys, coins, medals, and buttons.

Dr. Jackson practiced his techniques for extracting swallowed objects on a doll named Michelle. Michelle had a child sized esophagus which made it extremely easier for him to practice his techniques on her. Once, Jackson even demonstrated an emergency tracheotomy on Michelle; the scar on her mouth is still shown. Michelle helped Chevalier Jackson gain confidence to operate and try his new ideas on real children. Because of Michelle, Jackson was able to save the lives of over 98% of the children he treated.

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If you’d like to learn more about Chevalier Jackson, his whole collection is located in carefully-arranged drawers in the Mütter Museum in Philadelphia.

 

How CEPI Youth Spent their Summer Vacation, Part 2: The Teva Pharmaceuticals Internship Program

The 2016 cohort of the Teva Pharmaceuticals Internship program pose with Teva employees and hold certificates of completion for completing their summer internship

As the summer winds down to a close, it’s back to school season here in Philadelphia as students make their way back into the classrooms. For the students in CEPI’s youth programs, summer was a busy time full of networking, career building, and learning outside the classroom. Yesterday, we focused on the Karabots Junior Fellows Program. Today we feature the highlights of the students in the Teva Pharmaceuticals Internship Program.

In July CEPI welcomed the newest cohort of Teva interns with an intensive four-day-a-week, four-week summer program. During the entire month, they took part in activities related to issues connected to violence, forensics, and healthcare. CEPI also welcomed Matilda David and Miriam Iken, two students participating in the University of Pennsylvania’s Bridging the Gaps Program, who helped us carry out our programming.

During Week 1, we introduced our new Teva interns to the College of Physicians of Philadelphia as well as each other. Highlights from their first week included tours of the Mütter Museum and the Historical Medical Library; meeting with a Teva alum who shared her experiences in the program; and a series of games, team-building exercises, and CEPI’s home-grown room escape activity: “Dr. Mütter’s Secret Specimen.”

Week 2 brought a focus at the historical, social, and cultural factors that lead to violence. Michael Nairn, a professor of Urban Studies at the University of Pennsylvania led the interns through a history of race relations in Philadelphia and the evolution of the city’s neighborhoods. Barb Fox discussed the upcoming June 5th Memorial (memorializing the victims of a fatal building collapse at 22nd and Market on June 5, 2013). Jon Goff, who currently serves as the College of Physicians of Philadelphia’s Advancement Information Manager, shared his experience serving in the Peace Corps. Other topics and activities included a discussion of intimate partner violence and a trip to the Karabots Pediatric Care Center of the Children’s Hospital of Philadelphia to meet with a panel of medical professionals.

During Week 3, the focus shifted toward forensic science. The fellows met with forensic experts and took place in a series of hands-on activities to strengthen their deductive and investigative powers. Crime scene expert Gladys “GG” Siebert walked them through a real-life (simulated) crime scene in the Benjamin Rush Medicinal Plant Garden; they took part in blood spatter analysis with Drexel Biology professor Susan Gurney.  Forensic expert Kimberlee Moran taught them how to take and examine fingerprints, and Mütter Museum Director (and formerly an F.B.I.-trained police investigator) Robert Hicks addressed the challenges of analyzing eyewitness testimony. Dr. Hicks literally threw himself into the role and was the victim of a simulated attack (similar to one he did with the Karabots Junior Fellows this past spring) and had the students attempt to recreate the event and identify the assailant. They also traveled to Drexel University’s Center City Physical Therapy Lab to learn about the physical impact of violence and how injury victims recover. They also studied topics related to family therapy and violence prevention.

Students in the Teva Pharmaceuticals Internship program practice taking vitals on a medical dummy at the Drexel University Physical Therapy Labs

The fourth and final week focused on coping and community action, and the interns explored ways to face violence in their communities. They met with Tieshka Smith, creator of #RacismisaSickness, a multi-medium exhibit addressing the impact of police violence. They journeyed to Eastern State Penitentiary to discuss the impact of prisons in America (and see the site’s new exhibit on the subject: Prisons Today: Questions in the Age of Mass Incarceration) They also expanded their cultural horizons as they met with Teva alums Binta and Adunia who shared their experiences living and growing up in Africa. Finally, they made preparations for their future by meeting with STEM-related professionals from internship benefactor Teva Pharmaceutical Industries, Ltd. They also helped develop a toolkit for coping with and combating violence in their communities (the toolkit is scheduled to debut as part of the second annual Pennsylvania Teen Health Week, January 9-13, 2017).

We have a wide array of activities lined up for both of our youth programs, so be sure to check back here to see what the upcoming school year has in store for the healthcare professionals and community leaders of the future!

How CEPI Youth Spent Their Summer Vacation, Part I: The Karabots Junior Fellows

The Karabots Junior Fellows pose in front of the statue of Benjamin Franklin at the Franklin Institute

As the summer winds down to a close, it’s back to school season here in Philadelphia as students make their way back into the classrooms. For the students in CEPI’s youth programs, summer was a busy time full of networking, career building, and learning outside the classroom. Today’s article is the first of a two-part series spotlighting the achievements of two of our youth programs. Our first focus is on the Karabots Junior Fellows Program.

Our current cohort of the Karabots Junior Fellows Program was extremely busy during the summer. Many spent part of their summer taking part in internships where they assisted various departments of the College of Physicians of Philadelphia. Regular readers have seen the fruits of some of their efforts in the form of articles for CEPI Curiosities on the difference between venom and poisons, the lives of Chang and Eng Bunker, and the story of Harry Eastlack and his battle with FOP (fibrodysplasia ossificans progressiva). Other internships included developing educational and public programs, creating social media content, cataloging specimens in the Mütter Museum collection, designing materials for library researchers, inventorying stock in the Museum Store, transcribing videos on the Mütter Museum’s YouTube channel to make them accessible to more viewers, and strengthening donor relations. On August 2, the College of Physicians hosted a version of Murder at the Mütter, our annual forensic-science themed murder mystery event, for students in the Franklin Institute’s STEM Scholars Program. The event was developed, promoted, and implemented by several of our Karabots Interns.

Evidence from the Karabots Interns' Murder at the Mütter event, including a cell phone, fingerprint and footprint samples, and a bloody shirt

Evidence from the Karabots Interns’ Murder at the Mütter event

During the middle of August, the Fellows reconvened as a group to share their summer experiences together and take part in a two-week series of healthcare and medical-themed activities. This year’s theme was “Many Bodies, One Health.” Based in part on the One Health Initiative, a program designed to encourage coordination between public health officials, environmental experts, and human and veterinary healthcare professionals to prepare for possible future zoonotic disease outbreaks, our programming focused on bodily systems and emphasized the similarities, differences, and overall interconnectedness of humans and animals. Over their two weeks they studied the structure and function of parts of the body, such as the heart, brain, eyes and ears, through examining models and performing dissections. Among other activities they also learned how to lead healthier lives with lessons on aerobic exercise, yoga, self-hypnosis, and nutrition (the latter they learned from nutrition student and KJF alum Sarah Lumbo). The Fellows met with healthcare professionals at the Children’s Hospital of Philadelphia’s Karabots Pediatric Care Center and the Physical Therapy Department at Drexel University’s College of Nursing and Health Professions and hosted experts from the Penn SUMR Scholars Program; they also met with animal guests, including a therapy dog, several pet snakes, and a talkative bird.

Three Karabots Junior Fellows dissect a sheep's brain

As a way of tracking their progress, we periodically had them write down something that had learned which they then added to our “Bodies of Knowledge,” images of human and animal bodies from medical works posted on our bulletin board. Over the course of the two weeks, they managed to fill these bodies with facts related to anatomy, physiology, and personal health. They left the session with newfound knowledge to better prepare them for their futures in medicine.

Students in the Karabots Junior Fellows program stick notes containing facts they learned during their two week summer session on a bulletin board containing anatomical images of a human and horse, adding to their "bodies of knowledge"

Be sure to check back in tomorrow as we examine what our Teva Pharmaceuticals Interns were up to this summer.

Pizza and Public Health: The Karabots Fellows Meet the SUMR Scholars

Students from the Karabots Junior Fellows and SUMR Scholars programs pose on the marble staircase at the College of Physicians of Philadelphia

A few weeks ago our fourth cohort of the Karabots Junior Fellows Program met for a two-week series of lessons and activities (an article going into more detail about their endeavors is forthcoming). In what has become a welcome tradition, our students got the chance to meet with students from Penn’s SUMR internship program. Short for Summer Undergraduate Minority Research program, the internship program run by the University of Pennsylvania’s Leonard Davis Institute of Health Economics (LDI) offers paid internships to undergraduates interested in pursuing health sciences research projects. SUMR pays especial focus to underrepresented minority groups.

On August 18, the SUMR scholars came to the College of Physicians of Philadelphia to meet with the Karabots Fellows. After some introductions they toured the Mütter Museum, where the Fellows gave mini-tours of objects in the Museum they had selected to research and develop presentations.

Afterwards, the SUMR scholars and Karabots Fellows convened in the Ashhurst conference room to have pizza and discuss careers in healthcare. For more on the visit from the SUMR scholars’ perspective be sure to check out Hoag Levins and Megan Pellegrino’s recent blog post on their visit.

The Karabots Junior Fellows and Penn's SUMR Scholars network around a table at the College of Physicians of Philadelphia