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In this month’s ‘Science Notes’, we examine a recent paper that has developed a new method to identify ‘aneuploidies’ – conditions characterised by an atypical number of chromosomes – among a large array of individuals from Europe, spanning the Iron Age to the post-medieval period.
While sometimes it is possible to sequence the whole genome of an ancient individual, frequently (due to varying degrees of preservation) they can only be partially sequenced. These are known as ‘low-coverage’ genomes. In such cases, chromosomal abnormalities remained largely undetected in the archaeological record. Now a study by an international team of researchers has developed a method to allow for the ‘screening’ of any potential aneuploidies, even within ‘low-coverage’ genomes.
Their approach is a computational one, so that in the future aneuploidies can be detected using simple statistics. A similar method has been used previously to determine the sex of an individual by comparing the proportion of genetic sequences that align with the Y chromosome with those that align with the X chromosome. Until now, however, this technique had not been developed any further in order to detect any potential differences in the number of X and/or Y chromosomes present or, indeed, any differences among the autosomes (the first 22 pairs of chromosomes).
To start, using previously published genomes, the team established an ‘autosomal baseline’ (which they called Na) – that is, the typical sum of sequences matching the first 22 pairs of chromosomes. The researchers then calculated the number of sequences aligning to chromosome X and those aligning to chromosome Y, and divided them by Na to get the Rx and Ry estimates, respectively. Finally, they estimated the expected values for Na, Rx, and Ry, and compared them with the published genomes to establish average distributions for each value.
To test their method, the team searched through the ‘1,000 ancient British genomes’ dataset, currently being generated by the Ancient Genomics team at the Francis Crick Institute, for any potential outliers from their established ‘norm’. They quickly found some. Three individuals – one medieval, from Magdalen College, Oxford; one post-medieval, from the Trinity Burial Ground in Kingston upon Hull (above); and one from the Iron Age chariot burial site of Wetwang in East Yorkshire – were found to have Rx values typical of a female (so with two XX chromosomes) but they also had an Ry value typical of a male (so with XY chromosomes). This suggests that these individuals could have had two X chromosomes as well as a Y, an aneuploidy known as Klinefelter syndrome. Another medieval individual – from an 8th-century burial found during works for the Lincoln Eastern Bypass – had the highest observed Ry value of all analysed individuals, suggesting that this person might have had an additional copy of the Y chromosome, and hence might have been XYY, a condition known as Jacobs syndrome. Interestingly, three of these four individuals displayed osteological characteristics that indicate they may have been taller than the average male in their respective burial sites – something that is common among XXY and XYY individuals today.
In addition to these four individuals, the team identified a person from the Iron Age site of Charterhouse Warren in Somerset with an Rx value suggesting that they only had one copy of the X chromosome and an Ry value suggesting that they did not have a Y chromosome – meaning they were X0, a condition known as Turner syndrome. Further analysis, however, showed that their Rx value was higher than 375 XY individuals, which would mean that there were some additional X chromosomes present. This seems to suggest that this person may have had what is known as mosaic Turner syndrome, a condition where the majority of cells in the body have X0 chromosomes, but a few have the more typical XX. This individual also displayed evidence of an arched palate, a characteristic frequently associated with Turner syndrome.
The final aneuploidy the team detected was among the autosomal chromosomes. This was achieved by identifying individuals with sequences above the ‘autosomal baseline’. In this way, they were able to identify a newborn male with Down’s syndrome, also from Wetwang Slack.
The team then turned to the archaeological record to see if any of these individuals appear to have been treated differently in death – and, on the whole, each seems to have been buried in ways typical of the rest of the cemetery from which they came. It should be noted, though, that many people with these syndromes do not appear different from the general population, and it could be that the people from this study were able to lead ‘typical’ lives. Burial practices cannot reveal everything about a person’s life, however, and it will be interesting to see – as this method is used more widely – what it might reveal about the experiences of people with these conditions in the ancient past.
Text: Kathryn Krakowka
