Scientists Identify First Known Prehistoric Person With Turner Syndrome
Enlarge / The cranium of an individual with mosaic Turner syndrome from an Iron Age site in Somerset, UK. K. Anastasiadou et al. 2024 reader comments 73Turner syndrome is a genetic condition in which a (female) person has only one X chromosome instead of two. Scientists have used a new computational method for precisely measuring sex chromosomes to identify the first prehistoric person with this syndrome dating back some 2,500 years ago, according to a recent paper published in the journal Communications Biology. The team identified four other individuals with sex chromosomes outside the usual XX or XY designations: an early medieval individual with Jacobs syndrome (XYY) and three people from various periods with Klinefelter syndrome (XXY). They also identified an Iron Age infant with Down syndrome.
"It's hard to see a full picture of how these individuals lived and interacted with their society, as they weren't found with possessions or in unusual graves, but it can allow some insight into how perceptions of gender identity have evolved over time," said co-author Kakia Anastasiadou, a graduate student at the Francis Crick Institute.
Added co-author Rick Schulting, an archaeologist at the University of Oxford, "The results of this study open up exciting new possibilities for the study of sex in the past, moving beyond binary categories in a way that would be impossible without the advances being made in Ancient DNA analysis."
According to the authors, the emergence of ancient genomics "has revolutionized our ability to examine human biology over thousands of years, providing insight into phenotypic variation, social stratification, and their impact on health throughout history." When it comes to determining sex identification of ancient remains, genomic data can often overcome some of the limitations of traditional osteological analysis, which is less useful if a skeleton is incomplete or for analyzing non-adult remains. There are several publicly available tools for doing ancient DNA analysis, but they are less useful for detecting extra or missing sex chromosomes.
AdvertisementAnastasiadou et al. Relied on a large database of ancient DNA collected as part of the Thousand Ancient British Genomes project. Their new computational technique involved determining a predicted baseline number of X and Y chromosomes one would expect to see and comparing that to a careful counting of the exact number of X and Y chromosomes present in the samples. They combined this technique with osteological methods.
The skeleton of a young adult female—age was determined based on the wear of the teeth—found at the Charterhouse Warren site in Somerset—was dated back to the Early Iron Age. The genetic analysis showed that some cells had one X chromosome and others had the usual two, known as mosaic Turner syndrome. Women with Turner syndrome generally undergo human growth hormone and estrogen replacement therapy to boost height and trigger the onset of puberty, respectively. The remains included a partial skull, which showed marked pitting in the orbits—evidence of chronic intestinal hemorrhage, often the result of anemia, although there is a possible link with Turner syndrome. Osteological analysis revealed evidence of delayed growth, and the woman was unlikely to have gone through puberty and started menstruating.
The male infant had an extra chromosome 21 (a sign of Down syndrome) and was found at the Wetwang Slack site, buried in the ditch of a square barrow along with an adult female, although the two were not necessarily related since infants were often buried in existing burrows, per the authors. The skeleton with an extra Y chromosome also showed osteological evidence consistent with Jacobs syndrome (male, 46+ years, dated 680 to 890 CE); it was found at the Lincoln Eastern Bypass site in Lincolnshire.
AdvertisementThe three skeletons that showed evidence of Klinefelter syndrome were all buried during different periods according to the burial customs of their day. One skeleton (male, 17–19 years, circa 450 BCE) was found at an Iron Age cemetery site called Wetwang Slack in Yorkshire; another (male, 36–45, 12th–13th century) came from a medieval cemetery under Longwall Quad at Magdalen College, Oxford; and yet another (16–19 years, 18th–19th century) was found at Trinity Burial Ground in Kingston upon Hull. All three skeletons showed signs of delayed puberty and were slightly taller than average for their time, consistent with the genetic evidence showing extra X chromosomes.
These and other disorders of sex development (DSDs) can result in mixed or ambiguous sex-related physical characteristics, although those with milder forms "might not even be aware they have a DSD," they wrote. People with DSDs in the past likely lived according to conventional gender norms, and that seems to be the case with the aforementioned individuals, although none were buried with accompanying grave goods. However, the authors cited a 2022 study regarding a skeleton from early medieval Finland with possible Klinefelter syndrome who was buried with both masculine and feminine grave goods. And some Iron Age females have been found buried with "objects of power" that are usually buried with male individuals.
"Our method is also able to classify DNA contamination in many cases, and can help to analyse incomplete ancient DNA, so it could be applied to archaeological remains which have been difficult to analyze," said co-author Pontus Skoglund, who heads the Ancient Genomics Laboratory at the Crick. "Combining this data with burial context and possessions can allow for a historical perspective of how sex, gender and diversity were perceived in past societies. I hope this type of approach will be applied as the common resource of ancient DNA data continues to grow."
Communications Biology, 2024. DOI: 10.1038/s42003-023-05642-z (About DOIs).
X Y Chromosomes
In the imprinted brain theory, everyone's brain is configured somewhere on a spectrum between hypomentalism and hypermentalism. In hypomentalism, the mechanistic, paternal genes are over-expressed, creating a baby with a larger head who demands more from the mother; this child is more likely to have autism. In hypermentalism, the mentalistic, maternal genes are over-expressed; the baby is likely to have a smaller head, demand less from the mother, and develop psychosis. The normal brain falls somewhere between the two extremes, ensuring that the child exhibits neither autism nor psychosis.
First Prehistoric Person With Turner Syndrome Identified From Ancient DNA
image:
The shaft at the top of the Iron Age deposits (Tony Audsley), where the individual with Turner syndrome was found.
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Francis Crick Institute press release
Under strict embargo: 10:00hrs GMT 11 January 2024
Peer reviewed
Observational study
People
Researchers at the Francis Crick Institute, working with University of Oxford, University of York and Oxford Archaeology, have developed a new technique to measure the number of chromosomes in ancient genomes more precisely, using it to identify the first prehistoric person with mosaic Turner syndrome (characterised by one X chromosome instead of two [XX]), who lived about 2500 years ago.
As part of their research published today in Communications Biology, they also identified the earliest known person with Jacob's syndrome (characterised by an extra Y chromosome - XYY) in the Early Medieval Period, three people with Klinefelter syndrome (characterised by an extra X chromosome - XXY) across a range of time periods and an infant with Down Syndrome from the Iron Age.
Most cells in the human body have 23 pairs of DNA molecules called chromosomes, and the sex chromosomes are typically XX (female) or XY (male), although there are differences in sexual development. 'Aneuploidy' occurs when a person's cells have an extra or missing chromosome. If this occurs in the sex chromosomes, a few differences like delayed development or changes in height can be seen around puberty.
Ancient DNA samples can erode over time and can be contaminated by DNA from other ancient samples or from people handling them. This makes it difficult to accurately capture differences in the number of sex chromosomes.
The team at the Crick developed a computational method which aims to pick up more variation in sex chromosomes. For the sex chromosomes, it involves counting the number of copies of X and Y chromosomes, and comparing the outcome to a predicted baseline (what you would expect to see).
The team used the new method to analyse ancient DNA from a large dataset of individuals collected as part of their Thousand Ancient British Genomes project across British history, identifying six individuals with aneuploidies across five sites in Somerset, Yorkshire, Oxford and Lincoln2. The individuals lived across a range of time periods, from the Iron Age (2500 years ago) up to the Post-Medieval Period (about 250 years ago).
They identified five people who had sex chromosomes which fell outside of the XX or XY categories. All were buried according to their society's customs although no possessions were found with them to shed more light on their lives.
The three individuals with Klinefelter syndrome lived across very different time periods, but they shared some similarities - all were slightly taller than average and showed signs of delayed development in puberty.
By investigating details on the bones, the research team could see that it was unlikely that the individual with Turner syndrome had gone through puberty and started menstruation, despite their estimated age of 18-22. Their syndrome was shown to be mosaic -some cells had one copy of chromosome X and some had two.
Kakia Anastasiadou, PhD student in the Ancient Genomics Laboratory at the Crick, and first author of the study, said: "Through precisely measuring sex chromosomes, we were able to show the first prehistoric evidence of Turner syndrome 2500 years ago, and the earliest known incidence of Jacob's syndrome around 1200 years ago. It's hard to see a full picture of how these individuals lived and interacted with their society, as they weren't found with possessions or in unusual graves, but it can allow some insight into how perceptions of gender identity have evolved over time."
Pontus Skoglund, Group Leader of the Ancient Genomics Laboratory at the Crick, said: "Our method is also able to classify DNA contamination in many cases, and can help to analyse incomplete ancient DNA, so it could be applied to archaeological remains which have been difficult to analyse.
"Combining this data with burial context and possessions can allow for a historical perspective of how sex, gender and diversity were perceived in past societies. I hope this type of approach will be applied as the common resource of ancient DNA data continues to grow."
The team worked with archaeologists from the University of Oxford, the Wells and Mendip Museum, University of York, University of Bradford, Oxford Archaeology, York Osteoarchaeology and Network Archaeology, acknowledging support from Lincolnshire County Council, Magdalen College and Balfour Beatty for National Highways.
Rick Schulting, Professor of Scientific and Prehistoric Archaeology at the University of Oxford, said: "The results of this study open up exciting new possibilities for the study of sex in the past, moving beyond binary categories in a way that would be impossible without the advances being made in ancient DNA analysis."
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Notes to Editors
Reference: Anastasiadou, K. Et al. (2023). Detection of chromosomal aneuploidy in ancient genomes. Communications Biology. 10.1038/s42003-023-05642-z.
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JournalCommunications Biology
Method of ResearchObservational study
Subject of ResearchPeople
Article TitleDetection of chromosomal aneuploidy in ancient genomes.
Article Publication Date11-Jan-2024
