DNA from a medieval skeleton in Portugal reveals XXY chromosomes

This article was originally published by the Australian Broadcasting Cooperation (ABC). We have reposted it here in its entirety to allow access for non-Australians and also to preserve information specific to the community.

When Portuguese archaeologists unearthed the skeleton of a remarkably tall man who lived more than 1,000 years ago, they assumed he was too tall to be a local.

Standing around 1.8 metres, he would have been around a head taller than other adults of the time.

But DNA extracted from his bones revealed not only was he from the region, he was also born with a genetic condition known as Klinefelter syndrome.

Those with the condition are born with an extra X chromosome and tend to be taller than average.

It affects one in 600 male births today.

The diagnosis by researchers in Portugal and Australia was reported in The Lancet.

João Teixeira, ancient DNA and evolutionary biologist at the Australian National University and co-author of the study, said it was the oldest confirmed case of Klinefelter syndrome so far.

Key points:

  • Researchers analysed the DNA and bones of a 1,000-year-old skeleton excavated from modern-day Portugal 
  • They found the individual had a genetic condition which meant they were born with an extra X chromosome
  • The diagnosis explains some of the skeleton’s features, such as its unusual height and wide pelvis
The individual was buried in an oval-shaped grave with arms crossed over their chest (Supplied Sophia Tereso)

“We’re interested in developing this [technique] further and applying it to other archaeological specimens to look not only for Klinefelter syndrome cases, but also other [conditions like it].

“This could help give us an idea about the frequency of these genetic conditions through time.”

Site of historical importance

The statuesque skeleton was one of a few dozen excavated from the mountainous medieval archaeological site of Torre Velha in north-eastern Portugal, between 2012 and 2015.

In Roman times, it was the site of a settlement that sat at the junction of roads connecting cities across the Iberian Peninsula.

“We’re interested in looking at this place because of all the different peoples that inhabited it, and to understand the different migrations of people, from the Romans to the Germanic tribes to the establishment of Portugal,” Dr Teixeira said.

When people’s remains were discovered, they were carbon-dated to find out when they died, and their DNA extracted and sequenced.

DNA analysis on ancient specimens isn’t always possible. Long strands of DNA, which are twisted up as chromosomes in our cells, tend to fall apart and get chopped up by bacteria after we die.

Sometimes there are simply not enough long strands left to elicit much meaningful information.

Still, DNA that’s thousands of years old can yield a wealth of information about a person, such as their ancestry and biological sex.

Biological sex is determined by our sex chromosomes, which come in two types: X and Y. We usually inherit an X from our mother or an X or Y from our father.

Genetic females are typically XX while males are XY.

When Dr Teixeira and his colleagues scrutinised DNA from the tallest Torre Velha skeleton, which was thought male from the shape of the bones, they found something unexpected.

“The amount of DNA fragments mapping to the X chromosome was compatible with a female, but then we had as much mapping to the Y as you have for males,” Dr Teixeira said.

“We were intrigued.”

Statistically, the individual was all but confirmed to be XXY — Klinefelter syndrome. This happens when an egg or a sperm contains an extra X chromosome.

And when Dr Teixeira’s colleagues closely examined the skeleton, they could see signs of the condition in the bones too.

First up, the individual’s height stood out, Dr Teixeira said, “and 1,000 years ago, 1.8m was seriously tall”.

The skeleton also had other potential Klinefelter symptoms such as broader-than-usual hips, and teeth that were worn more on one side than the other, perhaps because the person had an underbite.

The bigger picture

Pairing genetic findings with skeletal evidence strengthens the study’s findings, according to Sally Wasef, who works with ancient DNA at Queensland University of Technology and was not involved with the work.

“It’s really interesting that you can tell, from ancient DNA, the existence or not of a medical condition,” Dr Wasef said.

“But without [archaeological evidence], you’re only looking at a single piece of a puzzle, and trying to work out what the whole picture looks like.”

Dr Teixeira said the technique could be used to glean information about extra or missing chromosomes in situations where DNA samples were degraded, such as forensic investigations.

It could also be used to look for genetic conditions such as Down syndrome, which is caused by the presence of an extra copy of chromosome 21, through human history.

And as for how far back they could go?

That depends on the quality of the DNA. If a specimen is left undisturbed in the frozen Arctic, its DNA will be in much better shape than another in the hot, humid tropics.

“But if you find a really well-preserved specimen from 30,000 years ago, I think you could do it,” Dr Teixeira said.

Sourced from ABC (Australia)