Scientists identify first known prehistoric person with Turner syndrome

Turner 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.

Anastasiadou 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.

The 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).