Ancient genomes reveal Down Syndrome in past societies
Burials show that children with Down Syndrome and Edwards Syndrome were recognized as members of their communities
IMAGE:
REMAINS OF INDIVIDUAL “CRU001”, A BOY WHO DIED AT OR SHORTLY BEFORE BIRTH AND WAS BURIED IN ALTO DE LA CRUZ.
view moreCREDIT: © GOBIERNO DE NAVARRA/J.L. LARRION
For many years, researchers at MPI-EVA have been collecting and analyzing ancient DNA from humans who lived during the past tens of thousands of years. Analyzing these data has allowed the researchers to trace the movement and mixing of people, and even to uncover ancient pathogens that affected their lives. However, a systematic study of uncommon genetic conditions had not been attempted. One of those uncommon conditions, known as Down Syndrome, affects nowadays around one in 1,000 births.
To their surprise, Adam “Ben” Rohrlach and colleagues identified six individuals with an unusually high number of DNA sequences from Chromosome 21 that could only be explained by an additional copy of Chromosome 21. One case from a church graveyard in Finland was dated to the 17th to 18th century. The remaining five individuals were much older: dating to between 5,000 and 2,500 years before present, they were found at Bronze Age sites in Greece and Bulgaria, and Iron Age sites in Spain. In all cases, the researchers were able to obtain a wealth of additional information about the remains and the burials.
Burials within settlements and with grave goods
While individuals with Down Syndrome can live a long life today, often with the help of modern medicine, this was not the case in the past. Indeed, age estimates from skeletal remains showed that all six individuals died at a very young age, with only one child reaching around one year of age. The five prehistoric burials were all located within settlements and in some cases accompanied by special items such as coloured bead necklaces, bronze rings or sea-shells. “These burials seem to show us that these individuals were cared for and appreciated as part of their ancient societies,” says Rohrlach, the lead author of the study.
Although the study was aimed at finding cases of Down Syndrome, the researchers also discovered an individual with a different condition. Among the approximately 10,000 tested DNA samples, one individual had an unexpectedly high fraction of ancient DNA sequences from Chromosome 18 that showed that she carried three copies of this chromosome. Three copies of Chromosome 18 are known to cause Edwards Syndrome, a condition associated with more severe health issues than Down syndrome. With an incidence of less than one case in 3,000 births, Edwards Syndrome also occurs much less often than Down Syndrome. This find, too, was made at one of the Spanish Iron Age sites, leaving the researchers with a mystery to solve. “At the moment, we cannot say why we find so many cases at these sites,” says Roberto Risch, an archaeologist of the Universitat Autònoma de Barcelona working on intramural funerary rites, “but we know that they belonged to the few children who received the privilege to be buried inside the houses after death. This already is a hint that they were perceived as special babies.”
As the number of DNA samples from ancient individuals continues to increase, the authors plan to further expand their research in the future. “What we would like to learn is how ancient societies reacted to individuals that may have needed a helping hand or were simply a bit different,” says Kay Prüfer, who coordinated the sequence analysis.
Aerial view of the Early Iron Age settlement of Alto de la Cruz, Navarra, during the 1989 excavation campaign.
Reconstruction of the Early Iron Age settlement of Las Eretas, Navarra.
CREDIT
© Iñaki Diéguez/Javier Armendáriz, Museo Las Eretas, Navarra
JOURNAL
Nature Communications
ARTICLE TITLE
Discovery of cases of Trisomy 21 and Trisomy 18 among 9,855 Historic and Prehistoric Individuals
ARTICLE PUBLICATION DATE
20-Feb-2024
Ancient DNA reveals Down syndrome in past human societies
IMAGE:
REMAINS OF INDIVIDUAL “CRU001”, WHO THE RESEARCHERS DISCOVERED HAD DOWN SYNDROME. THE REMAINS WERE FOUND AT A SITE IN SPAIN DATING TO THE IRON AGE. PHOTOGRAPH FROM THE GOVERNMENT OF NAVARRE AND J.L. LARRION.
view moreCREDIT: PHOTOGRAPH FROM THE GOVERNMENT OF NAVARRE AND J.L. LARRION.
By analysing ancient DNA, an international team of researchers have uncovered cases of chromosomal disorders, including what could be the first case of Edwards syndrome ever identified from prehistoric remains.
The team identified six cases of Down syndrome and one case of Edwards syndrome in human populations that were living in Spain, Bulgaria, Finland, and Greece from as long ago as 4,500 years before today.
The research indicated that these individuals were buried with care, and often with special grave goods, showing that they were appreciated as members of their ancient societies.
The global collaborative study, led by first author Dr Adam “Ben” Rohrlach of the University of Adelaide, and senior author Dr Kay Prüfer of the Max Planck Institute for Evolutionary Anthropology, involved screening DNA from approximately 10,000 ancient and pre-modern humans for evidence of autosomal trisomies, a condition where people carry an extra (third) copy of one of the first 22 chromosomes.
“Using a new statistical model, we screened the DNA extracted from human remains from the Mesolithic, Neolithic, Bronze and Iron Ages all the way up to the mid-1800s. We identified six cases of Down syndrome,” says Dr Rohrlach, a statistician from the University of Adelaide’s School of Mathematical Sciences.
“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.”
Down syndrome occurs when an individual carries an extra copy of chromosome 21. The researchers were able to find these six cases using a novel Bayesian approach to accurately and efficiently screen tens of thousands of ancient DNA samples.
“The statistical model identifies when an individual has approximately 50 per cent too much DNA that comes from one specific chromosome,” says Dr Patxuka de-Miguel-Ibáñez of the University of Alicante, and lead osteologist for the Spanish sites.
“We then compared the remains of the individuals with Down syndrome for common skeletal abnormalities such as irregular bone growth, or porosity of the skull bones, which may help to identify future cases of Down syndrome when ancient DNA can’t be recovered.”
The study also uncovered one case of Edwards syndrome, a rare condition caused by three copies of chromosome 18, that comes with far more severe symptoms than Down syndrome. The remains indicated severe abnormalities in bone growth, and an age of death of approximately 40 weeks gestation.
All of the cases were detected in perinatal or infant burials, but from different cultures and time periods.
“These individuals were buried according to either the standard practices of their time or were in some way treated specially. This indicates that they were acknowledged as members of their community and were not treated differently in death,” says Dr Rohrlach.
“Interestingly, we discovered the only case of Edwards syndrome, and a noticeable increase in cases of Down syndrome, in individuals from the Early Iron Age in Spain. The remains could not confirm that these babies survived to birth, but they were among the infants buried within homes at the settlement, or within other important buildings,” says Professor Roberto Risch, co-author and archaeologist from The Autonomous University of Barcelona.
“We don’t know why this happened, as most people were cremated during this time, but it appears as if they were purposefully choosing these infants for special burials.”
The research has been published in the journal Nature Communications and was part of a large collaborative project involving researchers from the University of Adelaide, including Dr Adam “Ben” Rohrlach, Dr Jonathan Tuke and Associate Professor Bastien Llamas, as well as researchers from across the world, including at the Max Planck Institute for Evolutionary Anthropology in Germany where the data was generated.
JOURNAL
Nature Communications
METHOD OF RESEARCH
Data/statistical analysis
SUBJECT OF RESEARCH
People
ARTICLE TITLE
'Cases of trisomy 21 and trisomy 18 among historic and prehistoric individuals discovered from ancient DNA'
ARTICLE PUBLICATION DATE
20-Feb-2024
