In 2003, a discovery in a deserted mining town in the Atacama region of Chile caused an international stir. A mummified skeleton had been found, and though human-like in appearance its fully formed skull was profoundly elongated. Bone age was estimated as six to eight years old at the time of death, but the skeleton was only 15 centimetres long.
Now, genome sequencing by researchers in California and Mexico reveals the genetic causes of the skeleton’s developmental abnormalities and provides insight into its age and ancestry.
“This was an unusual specimen with some fairly extraordinary claims put forward,” says senior author Gary Nolan from Stanford University in the US.
Indeed, speculation following its discovery was rampant. Perhaps it was a non-human primate, some suggested, or a human foetus suffering congenital defects, or possibly a child with profound and unprecedented dwarfism. Others believed it was evidence of extraterrestrial life.
Initial DNA testing, conducted by Nolan in 2013, revealed that the skeleton, dubbed ‘Ata’, is indeed of earthly origin, and very much human. The opportunity to follow up with whole genome sequencing was too interesting to pass up.
“It would be an example of how to use modern science to answer the question ‘what is it?’,” Nolan explains.
Ata’s genome was sequenced and compared to those of Homo sapiens, chimpanzees and rhesus macaques, confirming again that the skeleton was indeed human. X and Y chromosome analysis revealed that the specimen was female, while a comparison of the single nucleotide polymorphisms (SNPs) in Ata’s genome with those used as markers for distinct geographical populations suggested her ancestry was Chilean.
Next, the scientists searched for an explanation for her appearance.
According to Nolan, Ata’s “dramatic phenotype could in fact be explained with a relatively short list of mutations in genes known previously to be associated with bone development”.
Specifically, she possessed DNA mutations in several genes associated with bone formation and musculoskeletal development. Mutations in these have been linked to dwarfism, rib anomalies, cranial malformations, scoliosis and other developmental diseases.
There were also mutations in genes associated with two rare diseases, forms of cranial and skeletal dysplasia, which are known to produce severe skull malformations like Ata’s.
Interestingly, researchers also identified five mutations that had never been seen before. The affected genes, including two involved in collagen production and another involved in thyroid function, are known for their roles in development and growth. The mutations would have most certainly disrupted their function.
Together, the results suggest that Ata was most likely a pre-term birth and that, among her other abnormalities, her genetic mutations had caused premature bone formation.
“This is a great example of how studying ancient samples can teach us how to analyse modern day medical samples,” says co-author Atul Butte, of the University of California, San Francisco.