DNA Reveals Presence of Down Syndrome in Ancient Society

Scientists have found six cases of Down syndrome and one case of the very rare Edwards syndrome in the DNA of ancient infants, according to a study published in the journal Nature Communications.

In a global collaborative effort, researchers analyzed DNA samples from the preserved bones of almost 10,000 people, pinpointing six very young individuals with Down syndrome, all from Europe. Their findings not only reveal that infants with Down syndrome were found within several ancient populations, but they shine a light on how those communities cared for people with rare genetic conditions.

“These individuals were buried according to either the standard practices of their time or were in some way treated specially,” lead author Adam Rohrlach, an ancient DNA researcher at the University of Adelaide in Australia, says in a statement. “This indicates that they were acknowledged as members of their community and were not treated differently in death.”

Down syndrome, also called trisomy 21, is a genetic disorder caused by the existence of an extra, third copy of chromosome 21, with the excess genetic material affecting the way the body and brain develop. The condition occurs in approximately 1 in every 700 babies and can cause mental and physical challenges such as learning disabilities and heart disorders.

However, Down syndrome is extremely variable, which makes it a notoriously difficult condition to diagnose in ancient remains. Physical features of Down syndrome, as well as the severity of the condition, differ from person to person. And certain distinct facial features that can indicate Down syndrome, such as almond-shaped eyes, often are not visible in skeletal bones alone.

“You can’t just say, ‘Oh, this change is there, so it’s trisomy 21,’” says Julia Gresky, an anthropologist at the German Archaeological Institute who was not involved in the study, to the New York Times’ Carl Zimmer.

It’s much easier, however, to detect trisomy 21 genetically using ancient DNA, as “an additional chromosome 21 will lead to noticeably more DNA from chromosome 21 being present,” write Rohrlach and study co-author Kay Prüfer in the Conversation.

“While we expected that people with Down syndrome certainly existed in the past, this is the first time we’ve been able to reliably detect cases in ancient remains, as they can’t be confidently diagnosed by looking at the skeletal remains alone,” says Rohrlach in the statement.

Rohrlach and his colleagues created a way to study DNA in ancient remains at scale, developing a methodology to analyze the genetic sequences of thousands of bones that were already logged in a database by the Max Planck Institute for Evolutionary Anthropology in Leipzig, Germany.

The team screened the records of DNA—which dated from the Mesolithic, Neolithic, Bronze and Iron Ages to the mid-1800s—with a computer program that sorted the ancient DNA by chromosome.

“The statistical model identifies when an individual has approximately 50 percent too much DNA that comes from one specific chromosome,” indicating the person carried an extra copy of it, says study co-author Patxuka de-Miguel-Ibáñez, an osteologist at the University of Alicante, in the statement.

Through this process, the researchers found six bones with additional DNA from chromosome 21, the genetic signature for Down syndrome. Three were from babies that likely did not survive to birth, discovered in Iron Age sites in Spain. The other three were from infants under a year old: one found on the Greek island of Aegina dating to 3,300 years ago; one at a Bronze Age site in Bulgaria from 4,800 years ago; and one from Helsinki, Finland, who was buried in a church graveyard dating to the 17th or 18th century.

Researchers also identified an infant with an extra copy of chromosome 18, indicating a condition called Edwards syndrome, at one of the Bronze Age Spanish sites. The baby is believed to have only survived to 40 weeks of gestation and could be the first case of Edwards syndrome found in such ancient remains, according to the statement.

The first case of Down syndrome diagnosed using ancient DNA was identified in 2020. Geneticist Lara Cassidy at Trinity College Dublin and colleagues found that the bones of a 6-month-old boy buried almost 5,500 years ago had high levels of DNA from chromosome 21 preserved in his skeleton. This individual, thought to be the oldest record of Down syndrome, was also examined in the new study and confirmed to have had trisomy 21.

The researchers, however, weren’t able to identify just how common Down syndrome was in ancient society.

“There’s so much uncertainty in the sampling, and in what we could and couldn’t find,” says Rohrlach to the New York Times. “I think it would be a very brave statistician who would try to make too much out of these numbers.”

Researchers did determine a significant similarity among the identified infants, though: They appeared to have been buried with care. In Spain, the three children with Down syndrome and the child with Edwards syndrome were buried either in homes or in special ritual buildings alongside ceremonial objects. That differed from the standard practice of the era, which was cremation.

“We don’t know why this happened,” says study co-author Roberto Risch, an archaeologist from the Autonomous University of Barcelona in Spain, in the statement. “But it appears as if they were purposefully choosing these infants for special burials.”

Though the research found no adult individuals with Down syndrome, the study indicates that infants with the conditions were cared for during their lives, per the Conversation.

The team hopes further analysis of the skeletons confirmed to have Down syndrome could identify a set of common skeletal qualities for individuals with the condition, which scientists can use to diagnose future cases when DNA can’t be recovered from bones. Gresky envisions researchers further using ancient DNA to delve into the history of other genetic conditions, according to the New York Times.

“You just have to look for them, and you have to talk about them,” Gresky tells the publication. “Otherwise, they will stay invisible.”

Catherine Duncan | READ MORE

Catherine Duncan is an intern with Smithsonian magazine.