Ancient DNA Reveals Prehistoric Cases of Chromosomal Disorders

An innovative method for accurately determining chromosome counts in ancient genomes has been produced from a collaboration between scientists at the Francis Crick Institute, the University of Oxford, the University of York and Oxford Archaeology.

This technique has led to the discovery of the earliest known case of a prehistoric female with mosaic Turner syndrome, a condition marked by having a single X chromosome instead of the usual pair (XX) in some cells. The individual lived approximately 2,500 years ago and was unearthed during an excavation at Charterhouse Warren in Somerset. The work was published in Communications Biology.

Ancient aneuploidy

The researchers also highlighted individuals with a range of other chromosomal disorders, including the earliest known person to have Jacob’s syndrome – where cells have an extra Y chromosome – and an infant born with Down syndrome from the Iron Age, over 2,500 years ago. 

Analysis also identified three individuals with Klinefelter syndrome, who have an additional X chromosome (XXY) from multiple eras.

Usually, human cells contain 23 pairs of chromosomes, including the sex chromosomes, which are usually XX (female) or XY (male). A small number of people have differences in sexual development, in which their sex chromosome count is altered.  Aneuploidy refers to a chromosomal anomaly involving an extra or missing chromosome, leading to developmental delays or physical changes in puberty.

Identifying such changes in ancient DNA samples is challenging, as the genetic materials can degrade over time or become contaminated.

Crick Institute researchers developed a computational approach to detect variations in sex chromosomes more accurately. This involves comparing the observed counts of X and Y chromosomes against expected baselines.

Earliest evidence

Utilizing this method, researchers analyzed DNA from a comprehensive dataset as part of the Thousand Ancient British Genomes project. This led to the identification of 6 individuals with aneuploidy across 5 digs in Oxford, Somerset, Yorkshire and Lincoln, spanning from the Iron Age to about 250 years ago.

“Through precisely measuring sex chromosomes, we were able to show the first prehistoric evidence of Turner syndrome 2,500 years ago, and the earliest known incidence of Jacob’s syndrome around 1,200 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,” said Kakia Anastasiadou, PhD student in the Ancient Genomics Laboratory at the Crick and first author of the study.

The study also revealed that the three individuals with Klinefelter syndrome, despite living in different periods, shared certain characteristics such as above-average height and signs of delayed puberty.

“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,” said Rick Schulting, professor of scientific and prehistoric archaeology at the University of Oxford.

Reference: Anastasiadou K, Silva M, Booth T, et al. Detection of chromosomal aneuploidy in ancient genomes. Commun Biol. 2024;7(1):1-9. doi:10.1038/s42003-023-05642-z

This article is a rework of a press release issued by the Francis Crick Institute. Material has been edited for length and content.