Archaeologists uncover sex chromosome abnormalities

A look at an excavation in England where a medieval person with an XXY chromosome anomaly was found. © Oxford Archaeology

They once lived with one X or Y chromosome too many or too few - and with the associated consequences: Using ancient DNA from bone finds, a research team has identified people who had various forms of chromosomal abnormalities that affected their sexual and physical influenced development. In the future, this new analysis option could shed light on how past societies dealt with “unusual” people, say the scientists.

What makes people male or female? This question depends on which aspect of the complex issue of human gender identity you are dealing with. However, the so-called genetic or chromosomal gender is considered a kind of basis. It is defined by the typical combination of sex chromosomes in a person's cells. The basis for the development of female sexual characteristics is two X chromosomes, while for males it is the combination of an X and a Y chromosome. But not all people have either an XX or XY pairing. Disturbances in the distribution of sex chromosomes can occur during early stages of development. As a result, some people may have too many or too few X or Y chromosomes.

Forms and consequences

One of the most common forms of these so-called sex chromosomal aneuploidies is an XXY combination. People affected by this so-called Klinefelter syndrome usually develop male sexual characteristics. But reduced testosterone production can lead to delayed puberty and the development of feminine traits. In addition, those affected are often taller than average. The latter also applies in the case of an XYY combination – the so-called Jacobs syndrome. Due to the additional Y chromosome, otherwise mostly normal male characteristics develop.

Another case of sex chromosome anomaly is the so-called Turner syndrome. Those affected only have a single X chromosome. As a result, they usually develop as female. However, reduced estrogen production can lead to a failure in the development of typically female characteristics and to infertility. In addition, the people often remain noticeably small.

As the research team led by Kyriaki Anastasiadou from the Francis Crick Institute in London reports, it has previously been difficult to detect chromosomal abnormalities in DNA samples that come from archaeological finds. The traces of genetic material obtained are often severely degraded. However, sex chromosome anomalies are an aspect that can be informative for research into ancient societies, especially in the case of Klinefelter and Turner syndromes. The authors write: “The anomalies can lead to disorders of sexual development, which manifest themselves in mixed or ambiguous gender-related physical characteristics. This can affect society’s perception of one’s own gender or gender.”

Detection method developed

That's why the researchers have developed a special procedure that expands the possibilities for identifying chromosomal abnormalities. The number of copies of the non-sex chromosomes in a DNA sample is recorded. This then results in an expected value for the number of sex chromosomes. If there is an unusually high or low value in the case of the genetic traces of X or Y, an anomaly can be assumed. The researchers say that this approach also works with DNA that is quite severely degraded.

To test their method, they applied it to a large data set collected as part of the so-called Thousand Ancient British Genomes project. The genetic information comes from hundreds of human remains found at various locations in Great Britain. The individuals lived in different periods of the past - from the early Iron Age to modern times.

Successful test

As the researchers report, they identified five people whose sex chromosomes were outside the XX or XY categories. They were also able to compare the results with characteristics of the respective skeletons. The team diagnosed mosaic Turner syndrome in one person: the analyzes showed that their body was partially affected by a lack of the second X chromosome, which occurs frequently. The bones of those affected have been dated to around 500 BC. According to the results of the examination of her skeletal remains, she died between the ages of 18 and 22. Still, there were no signs of puberty and she was unusually small. These features therefore match the well-known symptoms of this form of sex chromosome anomaly.

The team also identified three individuals with Klinefelter syndrome from different eras. The XXY combination was also reflected in findings on their skeletons, the team reports: There was evidence of unusual development during puberty and the people were above average height. The individual in whom the researchers identified an XYY anomaly also had a stature typical of this form: the man from the early Middle Ages was an impressive 1.84 meters tall.

As the researchers write, they were unable to detect any abnormalities in the burial method of all five individuals identified that would indicate a special perception or treatment of the people in question. But according to them, this would be possible in other cases, which creates potential for evaluating the rapidly growing genomic data from archaeology. Senior author Pontus Skoglund from the Francis Crick Institute concludes: “Combining this data with the burial context can provide a historical perspective on how gender assignments and diversity were perceived in earlier societies,” says the scientist.

Source: The Francis Crick Institute, Communications Biology, doi: 10.1038/s42003-023-05642-z

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