How ancient DNA is transforming our view of the past

Prof David Reich of Harvard Medical School is one of the leading lights in the field of ancient DNA. His team’s work has cast a new perspective on human history, reconstructing the epic migrations and genetic exchanges that shaped the people of different regions worldwide. Here he explains how this revolution in our understanding unfolded.

If it seems as if there has been an avalanche of recent headlines revealing insights into the travails of our ancient ancestors, you’d be right.

From the fate of the people who built Stonehenge to the striking physical appearance of Cheddar Man, a 10,000-year-old Briton, the deluge of information has been overwhelming.

But this step change in the understanding of our past has been building for years now. It’s been driven by new techniques and technological advancements in the study of ancient DNA – genetic information retrieved from the skeletal remains of our long-dead kin.

At the forefront of this revolution is David Reich of Harvard Medical School in Boston Massachusetts. I met Prof Reich recently at the BBC while he was in the UK to talk about his book Who We Are and How We Got Here, which draws together the most recent scientific results in this field of study.

The Harvard professor, who is 43, was recently highlighted by the journal Nature as one of 10 people who mattered in all of science for his role in transforming the field of ancient DNA from “niche pursuit to industrial process”.

Reich was raised in Washington DC, by parents who were distinguished in their own fields. His mother Tova is a novelist and his father Walter is a professor of psychiatry who also served as the first director of the United States Holocaust Memorial Museum.

“In my family, there was a premium and a strong belief placed on creativity – doing something new and interesting and edgy. Science was seen as the highest thing someone could do,” he says. “I had lots of interests, but the things I was most interested in were history and science.”

Reich says that he “fell in love” with human evolutionary history at the beginning of his PhD in biochemistry, but then moved away from the subject towards medical genetics. He explained: “The technology at the time really wasn’t very good for learning a lot about human history.”

Throughout the 1990s and early 2000s, studies of ancient DNA from our own species were highly contentious because of observations that skeletal remains were easily contaminated by the DNA of living people.

As such, there were always nagging doubts about whether a genetic sequence belonged to the long-dead individual being studied or to an archaeologist involved in excavating the remains, a museum curator who had handled them, or a visitor to the lab where they were being analysed.

However, crucial progress in overcoming these obstacles began in the late 90s with the effort to sequence DNA from Neanderthals, which was led by Professor Svante Pääbo at the Max Planck Institute for Evolutionary Anthropology in Leipzig, Germany.

Pääbo’s group developed a set of protocols to prevent contamination slipping through, including having the same samples sequenced in two laboratories by different teams.

But the field experienced a revolution with the emergence of so-called next-generation sequencing technology. When an organism dies, the DNA in its cells begins to break down – over time it splits into smaller and smaller chunks, as well as accumulating other forms of damage.

It also gets contaminated with vast amounts of microbial DNA from the wider environment. The new sequencing machines could be used to isolate the human genetic material from bacterial DNA and then stitch together the tiny fragments into a readable sequence.

In 2006, Reich and his close scientific collaborator Nick Paterson were invited by Svante Pääbo to join the Neanderthal genome effort. Pääbo had been particularly impressed by a Nature paper they had authored on the complex separation of the human and chimpanzee evolutionary lineages, and thought the techniques they had used would be relevant to the question of whether Neanderthals and modern humans had interbred.

“I was working on the last 10,000 years of human history, reconstructing it on the basis of present-day people, especially in India… it was obvious the ancient DNA techniques that worked in Neanderthals were going to work even better in more recent humans,” Reich explains.

“I talked to Svante and he said: ‘This is very important but it’s not my focus. I’m focused like a laser beam on archaic humans and early modern humans.'”

Reich took a radical decision to completely re-tool his laboratory at Harvard – which had been focused on medical genetics – along the lines of Pääbo’s lab in Leipzig.

“There was a scientist in my laboratory, Nadin Rohland, who had worked in Leipzig (with Svante Pääbo) who knew how to do everything… they helped us to establish this laboratory. It was a big bet that this was a good thing to do.”

The bet paid off in a major way. Reich used his next-generation sequencing tech to power through genome after genome. To date, the lab has retrieved DNA from more than 900 ancient individuals.

The results are helping assemble new narratives for the peopling of our world. In some cases, the results have forced archaeologists and historians to re-visit some long-held ideas, sparking no small amount of debate and controversy.

Reich’s team has helped unravel the tangled web of migration and interbreeding that set down the present-day genetic landscape of Europe. Archaeologists had long suspected that the spread of farming out of the Near East and across Europe was a formative event in the continent’s prehistory.

Reich’s work helped confirm that this meeting of rather distantly related Near East farmers and indigenous hunter-gatherers had been crucial to the mix of ancestry that characterises Europeans, but his team added a third key ingredient to the melting pot.

In a paper published in the journal Genetics in 2012, Reich and his colleagues had spotted that Northern and Central Europeans appeared to have received genetic input from a population related to Native Americans.

Further evidence from ancient DNA would confirm that this distinctive genetic signature had entered Europe for the first time during a mass migration of people from the steppe, on Europe’s eastern periphery.

These nomadic steppe pastoralists, known as the Yamnaya, moved west in the late Neolithic and Bronze Age, around 5,000 years ago. In some areas of Europe, they replaced around 75% of the ancestry of existing populations.

Theories of large-scale migrations had fallen out of favour over the years among some scholars, particularly those for whom the phrase “pots, not people” (that culture tends to spread via the exchange of ideas rather than large-scale movement) had become a mantra.

But successive papers from the Reich group and other teams working on ancient DNA, such as the one led by Eske Willerslev at the University of Copenhagen, showed that mass migrations, with the displacement of earlier populations, were not uncommon in history.

This year, Reich’s team published a sprawling study detailing how an archaeological culture known as the Beaker phenomenon transformed the genetic make-up of western and central Europe. In Britain, the Beakers replaced an astonishing 90% of the existing ancestry. The team isn’t finished with Britain, Reich is now planning to track changes that occurred in the Iron Age and Roman period.

Conflict, innovations such as horse riding, and the spread of diseases like plague to populations with naïve immune systems might all have played a role in some dispersals.

But the reasons behind these replacements remain a question for archaeologists, says Reich. “I think we’re providing data and it vividly portrays the magnitude of these events. Understanding why it happens is a little bit hard for me to say,” he explains.

Reich says that his collaborator Nick Paterson’s background in mathematics has been “absolutely critical” to teasing out the genetic relationships that underlie many key discoveries.

“My laboratory has two lab heads not one, the other is Nick Paterson. I’m not a serious mathematician: I’m numerate, a data analyst, but not a developer of techniques. Nick is a world class mathematician.”

Paterson has an extraordinary biography. Born in 1947 to Irish parents in London, his talents made him a child maths and chess prodigy. A few years after graduating from Cambridge University, he was recruited to work for the UK’s signals intelligence agency GCHQ, where he spent a decade.

After that, he worked for another 10 years at the US equivalent, the National Security Agency (NSA). After leaving the spy world, Paterson worked for the successful New York-based hedge fund Renaissance Technologies, before beginning his collaboration with Reich in 2001.

In the last few years, the Harvard team has also published studies on ancient DNA from Africa, the Middle East and Oceania. Reich is currently finalising a paper on the peopling of South Asia – a longstanding area of interest – which should get published this year. It is likely to be pored over in India, where notions of deep-rooted ancestry are linked to Hindu nationalism.

The Harvard professor recently penned an opinion piece in the New York Times which stirred controversy online, highlighting the lack of consensus on how to frame discussions of human biological variation. In his article, Reich comments: “It is important, even urgent, that we develop a candid and scientifically up-to-date way of discussing any such differences, instead of sticking our heads in the sand and being caught unprepared when they are found.” Some 67 researchers signed an open letter (published by Buzzfeed), objecting to arguments put forward in the op-ed.

For example, the letter says: “Reich critically misunderstands and misrepresents concerns that are central to recent critiques of how biomedical researchers – including Reich – use categories of ‘race’ and ‘population'”.

The researchers add: “This doesn’t mean that genetic variation is unimportant; it is, but it does not follow racial lines. History has taught us the many ways that studies of human genetic variation can be misunderstood and misinterpreted.”

Asked about the criticisms, the Harvard professor told me: “I’m actually very pleased to be part of introducing this discussion. I think that scientists have been anxious about discussing differences among populations in public fora, even though all the work that we do is about differences among populations and learning about their history. The anxiety is about possible misuse of that data – for good reason.”

He stressed the need for scientists to take charge of the narrative, lest they hand the initiative to those with less benign intentions. “The thing I have felt very strongly, increasingly over time, is that the fact that scientists are too afraid to speak up about these topics means that the vacuum… gets filled by people who don’t really know the scientific facts,” he explains.

Prof Reich says that science itself shouldn’t be considered immune from the influence of longstanding assumptions. “I think there’s a huge opportunity for interpretational bias. I think that the genetic data are very seriously constraining the models that are possible right now,” he says.

But, he adds: “There’s some advantage to coming at it from the outside… arguably, there’s something to be said for a non-Jewish European person studying Jewish population history, or a person from Africa studying East Asian population history… in my lab, I’ve pushed people to work on areas that are not their own background.”

Looking to the future, Prof Reich sees huge potential for uncovering as yet unknown human movements and gene exchange in different parts of the world.

“I think Africa is a place that’s deeply under-represented. There are maybe only 20 genome sequences in what is the most diverse place in the world – the place with the deepest and most complex human history,” said Prof Reich.

“That compares to more than 1,000 genomes from Europe right now, which is an important but small corner of the world.”

He adds: “There’s so much to do.”

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Who We Are and How We Got Here by David Reich is published by Oxford University Press.

Iron Age study targets British DNA mystery

A project to sequence DNA from about 1,000 ancient remains could resolve a genetic mystery involving people from south-east Britain.

A recent study showed that the present-day genetic landscape of Britain was largely laid down by the Bronze Age.

But Prof David Reich told the BBC that this wasn’t the end of the story.

During the Iron Age or Roman Period, the DNA of people in the south-east diverged somewhat from that of populations in the rest of the Britain.

Prof Reich, from Harvard Medical School in Boston, told BBC News: “We are initiating an effort to follow up on this observation – and more generally to provide a fine-grained picture of population structure of Iron Age and Roman Britain – using a study that will be on a scale of 1,000 newly reported British samples.”

Read the full interview with David Reich

This, he explained, “would be far larger than any previously reported dataset”.

For comparison, the total global data-set of DNA sequences from ancient human remains currently stands at about 1,400 individuals.

The migration of people associated with the Beaker culture from continental Europe into Britain at the end of the Neolithic period (around 4,000 years ago) remains the most significant event to shape the genetics of subsequent populations on the island.

The Beakers are intimately associated with the introduction of metal-working to Britain. They largely replaced the existing population of farmers who had built Stonehenge and other impressive monuments around the country.

But at some point after the Bronze Age, groups in the south-east appear to have mixed with a population similar to those Stonehenge builders who inhabited Britain before the Beakers arrived.

Most people from south-east Britain still trace most of their ancestry to the Beaker people, but the later mixing event had a bigger impact than Medieval Anglo-Saxon migrations – traditionally seen as the foundation point of English history.

Prof Reich said his team currently had three working hypotheses to explain the result. While the Beakers replaced around 90% of the ancestry in Britain, it’s possible that a pocket (or pockets) of Neolithic farmers held out in isolation somewhere for hundreds of years.

During the Iron Age (which began around 3,000 years ago), they mixed back in with the general population, diluting the Beakers’ genetic background with a type of ancestry that’s now stronger around the Mediterranean than in Northern or Central Europe.

Alternatively, the genetic data may be hinting at a separate migration from continental Europe during the Iron Age – perhaps one that brought Celtic languages into Britain.

The third possibility is that scholars have simply underestimated the genetic impact of the Roman occupation, which lasted in Britain from AD 43 until 410. Roman settlers from the Italian peninsula would have traced a large proportion of their ancestry to Neolithic farmers like those that inhabited Britain before the arrival of the Beaker people.

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European women twice as likely to be blonde as men, study says

Women from European descent are twice as likely to be naturally blonde as men, according to new research.

The largest ever genetic study on pigmentation looked at nearly 300,000 people of European descent.

It found 124 new genes that play a major role in determining human hair colour variation.

The report’s authors say they are not sure why there are so many more blonde women than men, calling it an “intriguing mystery”.

The study which is published in Nature Genetics, builds on previous genetic studies that had only identified a dozen or so hair colour genes.

The data was supplied by the UK Biobank, American DNA testing company 23andMe and the International Visible Trait Genetics Consortium and their study partners in the Netherlands, Australia and Italy.

They chose people of European descent because of their variety in hair colours.

They found men were three times as likely as women to have black hair.

Prof Tim Spector, joint lead author, from Kings College London, told the BBC they were not expecting to find so many more blonde women than men.

“It’s a mystery and it’s intriguing because it wasn’t what we were looking for. We thought it was a bias but it wouldn’t go away and it’s found in every sub-group of every population we saw,” he said.

“It’s a curious mystery because it’s a very big effect – to see two and threefold effects both in a whole variety of American populations and European ones was quite amazing.”

The researchers say it opens up a whole new area of research to discover why, but Prof Spector has some theories.

“We thought it might have something to do with the attraction of women for darker skinned men and vice versa – but we don’t think the genes are any different. We think the genes are being expressed differently – so for some reason the blonde genes that may be there at birth are persisting in females and disappearing in males.”

So blonde women are just as likely to give birth to blonde boys as blonde girls, but the boys are not keeping their genetically blonde hair when they grow up.

The changing of the expression of genes – switching them off and on – is known as epigenetics.

Prof Spector said it could be other genes that are affecting the process and there are examples of this in mice studies where chemicals, stress and hormones were found to affect the way some of the pigment genes work.

“But some of it could be for evolutionary reasons because blonde women are more likely to be successful with men and men are more likely to be more successful with women if they’re dark-haired rather than light-haired.

“A lot of this is speculation – but it opens up a whole new area of research to try and work out why genes might be expressed differently in men and women and what the motive is – and whether this is a recent cultural change.”

The discovery of 124 genes connected to hair colour also revealed some links to cancers such as skin, testicular, prostate and ovarian.

Other pigment genes they found affected the chances of having Crohn’s disease and other forms of bowel disease.

The researchers, who include experts at Erasmus MC University Medical Centre in Rotterdam, hope their discoveries will help improve the understanding of these diseases and help develop new drugs to target these genes.

The genes also make it easier and more accurate to predict hair colour from DNA, which could help in forensic science for solving crimes, they add.

More than half your body is not human

More than half of your body is not human, say scientists.

Human cells make up only 43% of the body’s total cell count. The rest are microscopic colonists.

Understanding this hidden half of ourselves – our microbiome – is rapidly transforming understanding of diseases from allergy to Parkinson’s.

The field is even asking questions of what it means to be “human” and is leading to new innovative treatments as a result.

“They are essential to your health,” says Prof Ruth Ley, the director of the department of microbiome science at the Max Planck Institute, “your body isn’t just you”.

No matter how well you wash, nearly every nook and cranny of your body is covered in microscopic creatures.

This includes bacteria, viruses, fungi and archaea (organisms originally misclassified as bacteria). The greatest concentration of this microscopic life is in the dark murky depths of our oxygen-deprived bowels.

Prof Rob Knight, from University of California San Diego, told the BBC: “You’re more microbe than you are human.”

Originally it was thought our cells were outnumbered 10 to one.

“That’s been refined much closer to one-to-one, so the current estimate is you’re about 43% human if you’re counting up all the cells,” he says.

But genetically we’re even more outgunned.

The human genome – the full set of genetic instructions for a human being – is made up of 20,000 instructions called genes.

But add all the genes in our microbiome together and the figure comes out between two and 20 million microbial genes.

Prof Sarkis Mazmanian, a microbiologist from Caltech, argues: “We don’t have just one genome, the genes of our microbiome present essentially a second genome which augment the activity of our own.

“What makes us human is, in my opinion, the combination of our own DNA, plus the DNA of our gut microbes.”

Listen to The Second Genome on BBC Radio 4.

Airs 11:00 BST Tuesday April 10, repeated 21:00 BST Monday April 16 and on the BBC iPlayer

It would be naive to think we carry around so much microbial material without it interacting or having any effect on our bodies at all.

Science is rapidly uncovering the role the microbiome plays in digestion, regulating the immune system, protecting against disease and manufacturing vital vitamins.

Prof Knight said: “We’re finding ways that these tiny creatures totally transform our health in ways we never imagined until recently.”

It is a new way of thinking about the microbial world. To date, our relationship with microbes has largely been one of warfare.

Microbial battleground

Antibiotics and vaccines have been the weapons unleashed against the likes of smallpox, Mycobacterium tuberculosis or MRSA.

That’s been a good thing and has saved large numbers of lives.

But some researchers are concerned that our assault on the bad guys has done untold damage to our “good bacteria”.

Prof Ley told me: “We have over the past 50 years done a terrific job of eliminating infectious disease.

“But we have seen an enormous and terrifying increase in autoimmune disease and in allergy.

“Where work on the microbiome comes in is seeing how changes in the microbiome, that happened as a result of the success we’ve had fighting pathogens, have now contributed to a whole new set of diseases that we have to deal with.”

The microbiome is also being linked to diseases including inflammatory bowel disease, Parkinson’s, whether cancer drugs work and even depression and autism.

Obesity is another example. Family history and lifestyle choices clearly play a role, but what about your gut microbes?

This is where it might get confusing.

A diet of burgers and chocolate will affect both your risk of obesity and the type of microbes that grow in your digestive tract.

So how do you know if it is a bad mix of bacteria metabolising your food in such a way, that contributes to obesity?

Prof Knight has performed experiments on mice that were born in the most sanitised world imaginable.

Their entire existence is completely free of microbes.

He says: “We were able to show that if you take lean and obese humans and take their faeces and transplant the bacteria into mice you can make the mouse thinner or fatter depending on whose microbiome it got.”

Topping up obese with lean bacteria also helped the mice lose weight.

“This is pretty amazing right, but the question now is will this be translatable to humans”

This is the big hope for the field, that microbes could be a new form of medicine. It is known as using “bugs as drugs”.

Goldmine of information

I met Dr Trevor Lawley at the Wellcome Trust Sanger Institute, where he is trying to grow the whole microbiome from healthy patients and those who are ill.

“In a diseased state there could be bugs missing, for example, the concept is to reintroduce those.”

Dr Lawley says there’s growing evidence that repairing someone’s microbiome “can actually lead to remission” in diseases such as ulcerative colitis, a type of inflammatory bowel disease.

And he added: “I think for a lot of diseases we study it’s going to be defined mixtures of bugs, maybe 10 or 15 that are going into a patient.”

Microbial medicine is in its early stages, but some researchers think that monitoring our microbiome will soon become a daily event that provides a brown goldmine of information about our health.

Prof Knight said: “It’s incredible to think each teaspoon of your stool contains more data in the DNA of those microbes than it would take literally a tonne of DVDs to store.

“At the moment every time you’re taking one of those data dumps as it were, you’re just flushing that information away.

“Part of our vision is, in the not too distant future, where as soon as you flush it’ll do some kind of instant read-out and tells you are you going in a good direction or a bad direction.

“That I think is going to be really transformative.”

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Illustrations: Katie Horwich

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Exercise benefits to the brain ‘may be passed on’

Physical and mental exercise has been found to be beneficial for our brains, but scientists have now found it could also improve the learning ability of our children.

In a mouse study, researchers found the benefits gained from these activities were passed on to their offspring, despite not altering their DNA.

Further research is needed to see if this replicates in humans.

The German study is being published in the journal Cell Reports.

Exercise is recommended to keep the mind sharp in the over-50s and doing puzzles and brain training exercises has been found to delay the onset of dementia and reduce the risk of diseases such as Alzheimer’s.

Researchers from the German Centre for Neurodegenerative Diseases (DZNE) found that when they exposed mice to a stimulating environment in which they also had plenty of exercise, their offspring which they had later also benefitted.

The younger mice achieved better results in tests that evaluated their learning ability than the control group.

They also had improved synaptic plasticity – which is a measure of how well nerve cells communicate with each other and the cellular basis for learning.

They found this in the hippocampus, the area of the brain that is important for learning.

This phenomenon is known as epigenetic inheritance.

What is epigenetics?

  • Epigenetics is a growing field trying to understand how the environment interacts with genes.
  • Previously it was believed that acquired skills don’t modify the DNA sequence so therefore can’t be passed on to children.
  • But in recent years scientists have found that in some circumstances lifestyle factors such as stress and trauma in parents can affect the next generation.
  • For example, a poor diet increases the risk of disease in ourselves but also raises the risk in our children.
  • This phenomenon is known as “epigenetic” inheritance, as it is not associated with changes in DNA sequence.

    They found the benefits were conveyed through the RNA molecules that are contained in sperm, along with paternal DNA.

    “Presumably, they modify brain development in a very subtle manner improving the connection of neurons. This results in a cognitive advantage for the offspring,” said Prof André Fischer from DZNE.

    The researchers say that whether their findings are translatable to people needs to be determined.

    Prof Marcus Pembrey, from Great Ormond Street Institute of Child Health, said the research was an “important step” in unravelling “what, if anything, contributes to an individual’s intelligence beyond genetic inheritance and learning after birth”.

    He added: “If this system of the offspring inheriting a ‘head start’ applies to humans, it might help to explain the so-called Flynn effect, where the population IQ in industrial societies has risen every decade for the last century.”

    Prof Simon Fishel, of the private Care Fertility group, said it was a “fascinating study” providing “further increasing evidence of how we conduct our lives before we conceive our children may have consequences for our offspring”.

    He said it “opens up further the enthralling study of a ‘transgenerational inheritance’ and added: “However, there is much work to do to understand if this study can not only be replicated in mice, but other mammalian species too, and ultimately in humans.”

Why some cancers are ‘born to be bad’

A groundbreaking study has uncovered why some patients’ cancers are more deadly than others, despite appearing identical.

Francis Crick Institute scientists developed a way of analysing a cancer’s history to predict its future.

The study on kidney cancer patients showed some tumours were “born to be bad” while others never became aggressive and may not need treating.

Cancer Research UK says the study could help patients get the best care.

“We don’t really have tools to differentiate between those that need treatment and those that can be observed,” said researcher and cancer doctor Samra Turajlic.

One cancer could kill quickly while a patient with a seemingly identical cancer could live for decades after treatment.

It means uncertainty for both the patient and the doctor.

Kidney cancer

It is most common in people in their 60s and 70s. Symptoms include:

  • Blood in your pee
  • Persistent pain in the lower back or side
  • Sometimes a lump or swelling in your side

    The work, published in three papers in the journal Cell, analysed kidney cancers in 100 patients.

    The team at the Crick performed a sophisticated feat of genetics to work out the cancer’s history.

    It works like a paternity or ancestry test on steroids.

    As cancers grow and evolve, they become more mutated and, eventually, different parts of the tumour start to mutate in different ways.

    Researchers take dozens of samples from different parts of the same tumour and then work out how closely related they are.

    It allows scientists to piece together the evolutionary history of the whole tumour.

    “That also tells us where the tumour might be heading as well,” said Dr Turajlic.

    Chance to change care

    The researchers were able to classify kidney cancer into one of three broad categories:

    • Born to be bad
    • Benign
    • Intermediate

      The “born to be bad” tumours had rapid and extensive mutations and would grow so quickly they are likely to have spread round the body before they are even detected.

      Surgery to remove the original tumour may delay the use of drugs that can slow the disease.

      The benign tumours are at the complete opposite and are likely to grow so slowly they may never be a problem to patients and could just be monitored.

      The intermediate tumours were likely to initially spread to just one other location in the body and could be treated with surgery.

      Michael Malley, 72, from London, took part in the trial at the Royal Marsden Hospital after being diagnosed with kidney cancer.

      He said: “Clearly studies like these are really important for understanding how kidney cancer evolves over time, and I hope this one day leads to better treatments for patients like me.”

      There is still the challenge of figuring out how best to tailor treatments to each tumour type, and even how to perform such tests in a hospital rather than a research lab.

      The tools used in this study are being investigated in other cancers, including lung cancer.

      Dr Turajlic says: “We’ve no doubt they will be applicable to other types of cancer.”

      The studies also revealed that the earliest mutations that lead to kidney cancer were happening up to half a century before the cancer was detected.

      Sir Harpal Kumar, the chief executive of Cancer Research UK, said the study was “groundbreaking”.

      He added: “For years we’ve grappled with the fact that patients with seemingly very similar diagnoses nevertheless have very different outcomes.

      “We’re learning from the history of these tumours to better predict the future.

      “This is profoundly important because hopefully we can predict the path a cancer will take for each individual patient and that will drive us towards more personalised treatment.”

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Origin of ‘six-inch mummy’ confirmed

Tests on a six-inch-long mummified skeleton from Chile confirm that it represents the remains of a newborn with multiple mutations in key genes.

Despite being the size of a foetus, initial tests had suggested the bones were of a child aged six to eight.

These highly unusual features prompted wild speculation about its origin.

Now, DNA testing indicates that the estimated age of the bones and other anomalies may have been a result of the genetic mutations.

Details of the work have been published in the journal Genome Research.

In addition to its exceptionally small height, the skeleton had several unusual physical features, such as fewer than expected ribs and a cone-shaped head.

The remains were initially discovered in a pouch in the abandoned nitrate mining town of La Noria. From there, they found their way into a private collection in Spain.

Some wondered whether the remains, dubbed Ata after the Atacama region where they were discovered, could in fact be the remains of a non-human primate. A documentary, called Sirius, even suggested it could be evidence of alien visitations.

Genetic investigation

The new research puts those ideas to rest.

A scientific team analysed the individual’s genome – the genetic blueprint for a human, contained in the nucleus of cells.

They had already used this to confirm that the individual was human. Now, the team has presented evidence that Ata was a female newborn with multiple mutations in genes associated with dwarfism, scoliosis and abnormalities in the muscles and skeleton.

“What was striking and caused us to speculate early on that there was something strange about the bones was the apparent maturity of the bones (density and shape),” said Garry Nolan, a professor of microbiology and immunology at the Stanford University School of Medicine in California.

He told BBC News: “There was proportionate maturation of the bones, making the body look more mature despite the fact that the specimen was itself small. This discrepancy drove much of the research. So, we believe that one or more of the mutated genes was responsible for this.”

The results revealed four new single nucleotide variants (SNVs) – a type of genetic mutation – in genes that were known to cause bone diseases, like scoliosis or dislocations, as well as two more SNVs in genes involved in producing collagen.

Ata also had 10 pairs of ribs, rather than 12 – a feature that has never been seen in humans before.

“We actually believe the girl was stillborn or died immediately after birth,” said Prof Nolan.

“She was so badly malformed as to be unable to feed. In her condition, she would have ended up in the neonatal ICU.”

However, access to advanced medical care was probably unavailable in the remote Chilean region where she was found. The skeleton’s intact condition suggests it may be no more than 40 years old.

Future benefit

Prof Nolan began the scientific investigation of Ata in 2012, when a friend called saying he might have found an “alien”.

He explained: “While this started as a story about aliens, and went international – it’s really a story of a human tragedy. A woman had a malformed baby, it was preserved in a manner and then “hocked”, or sold.”

The scientists said that future studies of Ata had the potential to improve our understanding of the underlying basis of genetic skeletal disorders – with the potential to help others.

“Analysing a puzzling sample like the Ata genome can teach us how to handle current medical samples, which may be driven by multiple mutations,” said Atul Butte, director of the Institute for Computational Health Sciences at the University of California, San Francisco.

“When we study the genomes of patients with unusual syndromes, there may be more than one gene or pathway involved genetically, which is not always considered.”

Prof Nolan says further research into Ata’s precocious bone aging could one day benefit patients. “Maybe there’s a way to accelerate bone growth in people who need it, people who have bad breaks,” he said. “Nothing like this had been seen before. Certainly, nobody had looked into the genetics of it.”

He added: “I think it should be returned to the country of origin and buried according to the customs of the local people.”

Origin of ‘six-inch mummy’ confirmed

Tests on a six-inch-long mummified skeleton from Chile confirm that it represents the remains of a newborn with multiple mutations in key genes.

Despite being the size of a foetus, initial tests had suggested the bones were of a child aged six to eight.

These highly unusual features prompted wild speculation about its origin.

Now, DNA testing indicates that the estimated age of the bones and other anomalies may have been a result of the genetic mutations.

Details of the work have been published in the journal Genome Research.

In addition to its exceptionally small height, the skeleton had several unusual physical features, such as fewer than expected ribs and a cone-shaped head.

The remains were initially discovered in a pouch in the abandoned nitrate mining town of La Noria. From there, they found their way into a private collection in Spain.

Some wondered whether the remains, dubbed Ata after the Atacama region where they were discovered, could in fact be the remains of a non-human primate. A documentary, called Sirius, even suggested it could be evidence of alien visitations.

Genetic investigation

The new research puts those ideas to rest.

A scientific team analysed the individual’s genome – the genetic blueprint for a human, contained in the nucleus of cells.

They had already used this to confirm that the individual was human. Now, the team has presented evidence that Ata was a female newborn with multiple mutations in genes associated with dwarfism, scoliosis and abnormalities in the muscles and skeleton.

“What was striking and caused us to speculate early on that there was something strange about the bones was the apparent maturity of the bones (density and shape),” said Garry Nolan, a professor of microbiology and immunology at the Stanford University School of Medicine in California.

He told BBC News: “There was proportionate maturation of the bones, making the body look more mature despite the fact that the specimen was itself small. This discrepancy drove much of the research. So, we believe that one or more of the mutated genes was responsible for this.”

The results revealed four new single nucleotide variants (SNVs) – a type of genetic mutation – in genes that were known to cause bone diseases, like scoliosis or dislocations, as well as two more SNVs in genes involved in producing collagen.

Ata also had 10 pairs of ribs, rather than 12 – a feature that has never been seen in humans before.

“We actually believe the girl was stillborn or died immediately after birth,” said Prof Nolan.

“She was so badly malformed as to be unable to feed. In her condition, she would have ended up in the neonatal ICU.”

However, access to advanced medical care was probably unavailable in the remote Chilean region where she was found. The skeleton’s intact condition suggests it may be no more than 40 years old.

Future benefit

Prof Nolan began the scientific investigation of Ata in 2012, when a friend called saying he might have found an “alien”.

He explained: “While this started as a story about aliens, and went international – it’s really a story of a human tragedy. A woman had a malformed baby, it was preserved in a manner and then “hocked”, or sold.”

The scientists said that future studies of Ata had the potential to improve our understanding of the underlying basis of genetic skeletal disorders – with the potential to help others.

“Analysing a puzzling sample like the Ata genome can teach us how to handle current medical samples, which may be driven by multiple mutations,” said Atul Butte, director of the Institute for Computational Health Sciences at the University of California, San Francisco.

“When we study the genomes of patients with unusual syndromes, there may be more than one gene or pathway involved genetically, which is not always considered.”

Prof Nolan says further research into Ata’s precocious bone aging could one day benefit patients. “Maybe there’s a way to accelerate bone growth in people who need it, people who have bad breaks,” he said. “Nothing like this had been seen before. Certainly, nobody had looked into the genetics of it.”

He added: “I think it should be returned to the country of origin and buried according to the customs of the local people.”