Medical Monday



Already genetic sleuths can determine a suspect’s eye and hair color fairly accurately. It is also possible, or might soon be, to predict skin color, freckling, baldness, hair curliness, tooth shape and age.


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DNA Discovery

Genetically Speaking, Americans Really Are a Melting Pot of Diversity


A new genetic study shows that the U.S. really is a great melting pot. (Wikimedia Commons)

In the outstanding science fiction novel, Lathe of Heaven, racism is solved by turning everyone’s skin color to the same light gray shade. It turns out that if we peel away the skin and pay attention to just the DNA, we might not need this magical solution. At the DNA level, people in the U.S. are more similar than their outward appearance might suggest.

That is the conclusion of a new study that used genetics to trace the ancestry of over 160,000 U.S. customers of 23andMe, a personal genomics company located in Mountain View, CA. The researchers found that most people who self-identified as European-American, Latino or African -American actually had DNA from the one or both of the other groups as well.

For example, people who self-identify as African-American had, on average, 24% European and 0.8% Native American ancestry. And people who self-identify as Latino had, on average, 6.2% African, 18% Native American and 65% European ancestry. Although the numbers were not as large for those who report themselves to be European-American, they still had on average around 0.2% African and 0.2% Native American heritage.

We are all way more similar than our cultural labels might imply.

This doesn’t sound like a lot but if we extrapolate the results with European Americans to the U.S. population, it means that more than 6 million of these folks carry some African ancestry and over 5 million carry some Native American ancestry. We are all way more similar than our cultural labels might imply.

Of course, this doesn’t mean the labels are totally wrong. Another finding is that self-reporting lined up very well with the majority of people’s ancestry. For example, if you are mostly of African ancestry, odds are you have self-identified as such.

This last result does not change the fact that scientists can see in people’s DNA there has been a whole lot of mixing since Europeans and Africans came to the U.S. The U.S. really has been and still is a great melting pot.

Moms Not Dads

Scientists are able to tease out how much of a certain ancestry came from mom’s side of the family and how much from dad’s by comparing a person’s X chromosome with his or her other chromosomes. Remember, men have an X and a Y chromosome and women have two X’s.

By doing such an analysis, the scientists in this study concluded that the non-European ancestry tended to come more from mom’s side of the family. For example, European-Americans might have ten times as many female Native American ancestors as male ones. And African-Americans have four times as many.

There are a couple of possible explanations for this. One obvious one is exploitation. European men may have taken advantage of Native American women meaning that Native American ancestry would flow in from the maternal side of the family.

Another possible explanation has to do with there being more men than women on the frontier. In that situation, many of these men needed to turn to Native American women if they wanted a partner. We can see the results of their successful searches in modern DNA.

Digging Deeper

As companies like 23andMe and AncestryDNA amass more and more genomes in their database, they will be able to parse out everyone’s genomes more and more precisely. For example, in this study the researchers were able to see that the European part of the ancestry of Latinos tended to come from Spain and Portugal as we might expect.

They were also able to see that most of the mixing we see in the U.S. population happened over the last 500 years or so. They are not seeing some ancient mixing of African and European populations back in the Old World. No, they are seeing the results of everyone coming together in the New World.

There is lots more in this study too that you can peruse at your leisure (it is open access which means anyone can read it.) And these sorts of studies are just a start. I can’t wait to learn even more about our ancestry in the future.


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The Truth about DNA

Geneticists Just Discovered a Shocking Truth About Race in White People’s DNA

As it turns out, many white people may not be so “white” after all.

In fact, millions of Americans who consider themselves white actually have mixed-race roots. A study offers yet more evidence that race is no more than a social construct.

Our “hidden” African ancestries. Population genetics scientists from institutions including Harvard University analyzed DNA from thousands of Americans who described themselves as being part of a singular racial group. The results, published in the American Journal of Human Genetics, revealed that almost 4% of participants who identify as white have “hidden” African ancestry.

“For a generation, historians have been writing books about how race is culturally constructed,” said Claudio Saunt, a University of Georgia historian, commenting on the study. “This article uses another tool, DNA analysis, to get at the same question.”

The study: Thousands of customers of 23andMe, a genotyping company, submitted saliva samples for DNA analysis and answered questionnaires about their racial and ethnic identifications. One questionnaire asked participants about geographic ancestral origins while another asked about racial affiliation. Only customers who said they identified with a single racial or ethnic group were included.

The study included 150,000 white participants and several thousand Latinos and African-Americans. They collectively hailed from 48 states. Researchers used participants’ DNA samples to render their genetic profiles and compared the results to their self-reported ancestries.

There’s a link between racial identity and geography. The frequency with which self-identified white participants had African ancestry varied significantly by region. And ancestry patterns appeared to mirror major population shifts tied to historical events in American history.

For example, researchers found white people with African ancestry at much higher rates in southern states. As much as 12% of self-described European Americans from South Carolina and Louisiana had African ancestry. And in other parts of the South, it was about 1 in 10. Researchers estimated that this interracial mixing, which geneticists call “admixture,” started about six generations ago (roughly 180 years) — before African-Americans migrated to the northern states.

Oklahoma, the study revealed, has the highest proportion of self-identified African-Americans with Native American genes. Oklahoma also happens to be where Native Americans and African-Americans first crossed paths, so to speak, when Native Americans walked the Trail of Tears in the 1830s after being forced out of the South.

How people describe themselves, it increasingly seems, has less to do with genetic makeup than the influence of social norms.

“Many Americans claim ancestry they don’t have or don’t claim ancestry that they do,” said Saunt. “In my own state of Georgia, for example, where I teach Native American history, numerous students tell me they have Cherokee ancestry, but in fact whites from Georgia have less indigenous ancestry than whites from just about any other state.”

The study is not without controversy: Personal genotyping companies like 23andMe have come under fire for cherry-picking the genes they analyze (millions out of billions) for participants’ DNA profiles. But, 23andMe codes for genes that are pretty well-established in tracing ancestry, according to a company representative.

And while there’s potentially bias in studying only 23andMe customers, both study authors and other experts in the field said it would be hard for a single research institution, or even a government agency, to perform a study of this magnitude and complexity.

“We needed many, many people,” said lead study author Kasia Bryc, “so it wasn’t possible just a short time ago. 23andMe was the first source that could offer this kind of data.”

Overall, and perhaps most importantly, the findings speak to the thorny relationship between biology and identity.

“Individuals who self-identify as white will respond in diverse ways to genetic testing showing that they have recent African ancestry,” said Saunt. “Some will embrace the findings, and others will deny them, even in the face of the evidence. The insistence on racial purity is part of a long American tradition.  Even before DNA analysis, families repudiated relatives they knew were theirs. That tradition is waning, but it is, unfortunately, far from extinguished.”

Source: ScienceMic

Medical Monday


A 7,700-year-old skeleton of a woman found in Hungary has yielded DNA. Scientists have found that she belonged to a wave of early farmers who moved into Europe from the Near East. Credit Ron Pinhasi


About 50,000 years ago, humans from Africa first set foot in Europe. They hunted woolly mammoths and other big game — sometimes to extinction. Eventually, they began grazing livestock and raising crops.

They chopped down forests and drained swamps, turning villages into towns, then cities and capitals of empires. But even as they altered the Continent, Europeans changed, too.

Their skin and hair grew lighter. They gained genetic traits particular to the regions in which they lived: Northern Europeans, for example, grew taller than Southern Europeans.

Up till now, scientists have learned about evolution on the Continent mostly by looking at living Europeans. But advances in biotechnology have made it possible to begin extracting entire DNA from the bones of ancestors who lived thousands of years ago. Their genomes are like time machines, allowing scientists to see bits of European history playing out over thousands of years.

Recently David Reich, a geneticist at Harvard Medical School, and his colleagues analyzed the genomes of nine ancient Europeans. Eight belonged to hunter-gatherers who lived about 8,000 years ago, seven in what is now Sweden and one in Luxembourg. The ninth came from a farmer who lived 7,000 years ago in present-day Germany.

The scientists compared these genomes with those of living Europeans. As they reported last month in Nature, the study revealed something scientists never knew: Europeans today have genes from three very different populations.

The oldest of these populations were the first Europeans, who appear to have lived as hunter-gatherers. The second were farmers who expanded into Europe about 8,500 years ago from the Near East.

But most living Europeans also carry genes from a third population, which appears to have arrived more recently. Dr. Reich and his colleagues found the closest match in DNA taken from a 24,000-year-old individual in Siberia, suggesting that the third wave of immigrants hailed from north Eurasia. The ancient Europeans that the scientists studied did not share this North Eurasian DNA. They concluded that this third wave must have moved into Europe after 7,000 years ago.

Last week, another team of scientists reported data from an even bigger haul of ancient European genomes — 13, all told. While Dr. Reich and his colleagues studied ancient Europeans separated by hundreds of miles, these scientists focused on just one region in Central Europe called the Great Hungarian Plain.

The people whose genomes the scientists retrieved lived on the plain at various times between 7,700 years ago and 2,800 years ago.

“What’s really exciting here is to have a transect through time,” said Johannes Krause, a co-director of the Max Planck Institute for History and the Sciences in Jena, Germany, who was not involved in the study. “It’s the first time that’s been done.”

Archaeological digs have revealed evidence of farming on the plain as long as 8,000 years ago. People there raised crops like barley, and raised cattle and other livestock. Shards of pottery show that they consumed milk.

The oldest genomes retrieved from human remains in the area — one from a man and one from a woman — date back to the dawn of agriculture on the plain. The woman’s DNA showed that she belonged to the ancient farming population documented by Dr. Reich and his colleagues.

The man, however, did not have the genes of a farmer. He belonged to the oldest population of hunter-gatherers.

“The archaeological information isn’t enough to say whether he was married to a local farmer,” said Ron Pinhasi, an archaeologist at University College Dublin and a co-author of the new study. It may even be that the man’s skull was a trophy of some sort, Dr. Pinhasi added.

Archaeologists have found that early farming culture didn’t change drastically for the next 3,700 years. But about 4,000 years ago, the Bronze Age arrived. People started using bronze tools, trading over longer networks and moving into fortified towns.

Dr. Pinhasi and his colleagues found that the era also brought a sudden shift in human DNA. A new population arrived on the Great Hungarian Plain, and Dr. Reich believes he knows who they were: the northern Eurasians.

“It’s very exciting,” he said. “It documents that by this time in Central Europe, this Eastern influence had already arrived.”

At the start of the Bronze Age, life settled down on the plain for a thousand years. But then came the Iron Age, bringing another shift in culture — and genes.

People began traveling across the plain by horse-drawn chariots and wagons, and the genomes from 2,800 years ago show that the people of the Bronze Age had begun to be supplanted by a new Iron Age population. These are the people most closely related to living Hungarians.

In the new study, Dr. Pinhasi and his colleagues also surveyed individual genes known to have changed over the course of European history.

Today, for example, people in Hungary tend to have light skin and light brown hair, and half of them carry a mutation that lets them digest milk as adults. It took thousands of years for the genes for these traits to appear on the Great Hungarian Plain, the scientists found.

The hunter-gatherer that lived 7,700 years ago, for example, probably had black hair and dark skin, along with blue eyes. His genes suggest that he also probably couldn’t digest milk — not surprising, since he came from a population that didn’t raise livestock.

The ancient farmer woman, on the other hand, probably had dark brown hair and brown eyes. But like the hunter-gatherers, she lacked the genetic mutation for digesting milk.

It is not until 6,400 years ago that the scientists find the first genetic evidence on the Great Hungarian Plain for light brown hair. And the milk mutation appeared even later, just 3,100 years ago.

It is possible that these new genes and others were brought to the plain by successive waves of immigrants. But natural selection probably played a role in making these genes pervasive.

Genetic mutations that enable people to drink milk as adults, for example, could have helped them survive famines. In cow-herding cultures, scientists have found, the milk-drinking mutation led to a 10 percent increase in the number of children.

If that’s true, then for 4,600 years people on the Great Hungarian Plain were milking cows but lacked the ability to digest milk. Dr. Pinhasi suggested that they only used milk at first to make cheese and yogurt, which would have been easier to digest.

Daniel G. Bradley, a geneticist at Trinity College Dublin and co-author of the new study, predicted more unexpected results would emerge as scientists gather more ancient DNA in Europe.

“The past is going to be a different country,” he said, “and it’s going to surprise us.”

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Medical Monday

New forensic tool detects ethnicity and gender in single hair


A cutting-edge technique to identify human hair could one day be helping to catch criminals according to a new study from researchers in Canada.

The tool produces results faster than current DNA analysis techniques used in law enforcement, and in early tests showed a 100% success rate at identifying gender and ethnicity.

The new tool is the work of Diane Beauchemin, a professor in the department of chemistry at Queen’s University in Kingston, Ontario, and MSc student Lily Huang. They describe their proof of concept study in the Journal of Analytical Atomic Spectrometry.

Prof. Beauchemin says her first “foray into forensic chemistry was developing a method of identifying paint that could help solve hit and run cases.” Applying a similar approach to hair analysis was Ms. Huang’s idea, she adds, so they started working on it last year.

Blood samples recovered at a crime scene are often used to identify gender and ethnicity, but blood deteriorates quickly and is prone to contamination.

However, hair is very stable. The reason it is a promising avenue for forensics is because of the unique mix of elements it contains, which varies according to diet, ethnicity, gender the environment and working conditions. They get into the hair from sweat secretions.

The team found they could identify gender from the elements magnesium, sulfur, strontium and zinc. And to discriminate ethnicity they used lithium, molybdenum, sulfur, strontium, chromium, potassium, nickel, zinc and lead.

The process takes just 85 seconds to complete. First they grind up the hair sample, burn it (using a method called electrothermal vaporization), and then analyze the vapor it produces (using inductively coupled plasma optical emission spectrometry).

Current forensic methods used to analyze hair are time-consuming and use corrosive solvents and reagents, Prof. Beauchemin told Chemistry World.

Method is robust and can be used universally

Ms. Huang says the method is “very robust and can be used universally. One of our samples even included dyed hair and the test was 100% accurate. The test was able to distinguish East Asians, Caucasians and South Asians.”

a hand picking a strand of hair from a hairbrush
Current forensic methods used to analyze hair are time-consuming and use corrosive solvents and reagents.

The team is already talking to law enforcement agencies about the next step in using the new method.

And the researchers are also planning to develop the method so it can pinpoint exactly where in the world a hair sample is from, as well as add more ethnicities and age to the repertoire.

To extend the repertoire of variables the method can identify means measuring more elements, but Prof. Beauchemin says this would not take more time, because their detection is simultaneous.

In 2010, Medical News Today learned how researchers are working on a method of forensic identification using hand bacteria. The method uses the fact that when we handle objects we leave behind bacterial communities that are uniquely identifiable.

Source: Medical News Today

Medical Monday



All his life, Neil Schwartzman searched for his biological family. He was adopted in 1960 at 10 days old, and he never knew where he came from. At first, he looked for answers by going to social services in his hometown of Montreal, Quebec, and trying to access adoption records. “There was nothing in the file,” he said. “Everything I did ended up being a dead end.” As he approached middle age, in 2008, he had just about given up. That’s when he heard about the direct-to-consumer genetic testing service 23andMe.

Unlike previous inquiries about his origins, this one occurred at the molecular level. He spit in a tube and sent it off to 23andMe’s California headquarters for analysis. For about $100, they sent back information about his genealogy (biological relatives), ancestry (lineage and geographic origins), and — this was before a 2013 Food and Drug Administration crackdown — his health, including genetic predispositions for various diseases and behavioral traits. Schwartzman said he didn’t expect much from his foray into personal DNA testing. He just signed up “as a last-ditch effort to try to get some medical information for myself.”

In early May 2011, several years after enrolling, he was pleasantly surprised: an email arrived from another anonymous 23andMe user saying she thought Schwartzman might be a half-brother.

The 23andMe website prompted him with a question about whether he wanted to find out more about the nature of their DNA relationship. He consented. Soon, he said, “We began to realize that my mother had a baby that she never disclosed to anyone.” That baby was Schwartzman. “The whole thing was swept under the rug until — fast forward 50, 51 years ahead — and there I am.”

Because of this “technological magic,” as Schwartzman put it, he was reunited with his family with more ease than any other search he had undertaken. He was able to fulfill that deep, universal longing we all have to understand our origins.

“It was nice to finally share this commonality with the rest of the world. It was very emotionally satisfying.”

Within a few weeks, he flew to California to meet his older sister, Jolie Pearl. They had their first meeting in a crowded restaurant in San Francisco’s theater district. They were the first ones at the restaurant, and they talked until the place closed. During that same visit, on an emotional day he will never forget, he was reunited with his biological mother in Oakland, California. On the way there, he asked his sister what kind of flower his mom would like. They decided on a potted orchid.

His mother, who was already confused with dementia, gave Schwartzman a book, “a random gift she pulled up at last minute,” he said. “It certainly wasn’t a typical reunion you see on TV, where the music swells up and everyone is carried away on gossamer wings.” Still, he said, “It was the welcome completion of a quest I had had for 50 years. It confirmed that I wasn’t placed on the earth by aliens, that I had a mother.”  

The reunion went well enough that the family met again, once in California and once in Montreal. “It was nice to finally share this commonality with the rest of the world,” Schwartzman said. “It was very emotionally satisfying.”

At the time, Schwartzman and Pearl were the poster children for 23andMe’s “DNA relatives” program. Their story — and a picture of them staring at each other at a fork in a railway track — is still featured on the company web page about adoptees. They were, it seemed, among the many now finding family and having joyful reunions as a result of personal genetic testing. “It was the start of a relationship,” 23andMe writes of Schwartzman’s discovery. Then, Schwartzman hailed 23andMe as “an example of the miracle of modern science.” Pearl called the reunion “the best thing.”

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Medical Monday

Single letter of DNA ‘defines hair color’

Changing just one letter of genetic code is enough to generate blonde hair in humans, according to a new analysis from researchers at the Howard Hughes Medical Institute in Chevy Chase, MD.

David Kingsley, of the Howard Hughes Medical Institute, has been studying the evolution of sticklebacks – the small fish that moved from the seas to colonize lakes and streams at the end of the last Ice Age – for the last 10 years.

Using the sticklebacks’ adaptive responses to different habitats as a case study, Kingsley and his colleagues have been able to identify molecular-level changes responsible for driving evolution. More recently, they have turned their attention to see how evolutions in the stickleback might apply to other species, such as humans.

The research that led Kingsley’s team to investigate the genetic code responsible for hair color initially concerned changes in stickleback pigmentation. As part of a 2007 study, they found that a change in the same gene had driven pigmentation changes in different populations of sticklebacks around the world.

Interestingly, they found that this genetic change was not unique to the stickleback.

Same gene in sticklebacks and humans controls pigmentation

“The very same gene that we found controlling skin color in fish showed one of the strongest signatures of selection in different human populations around the world,” Kingsley says.

magnifying glass and DNA
The genome “is littered with switches,” the researchers suspect.

Different versions of this gene – called “Kit ligand” – in humans are associated with differences in skin color. In both fish and humans, Kingsley found, the genetic changes thought to be responsible for pigmentation differences take place in regulatory elements of the genome.

“It looked like regulatory mutations in both fish and humans were changing pigment,” Kingsley says.

But tracking down specific regulatory elements in the whole genome is like finding a needle in the proverbial haystack. “We have to be kind of choosy about which regulatory elements we decide to zoom in on,” Kingsley acknowledges.

As well as encoding a protein that develops pigment-producing cells, however, Kit ligand has many other functions. For example, it influences the behaviors of blood stem cells, sperm or egg precursors and neurons in the intestine.

The team was interested in seeing whether they could isolate the regulatory changes in Kit ligand responsible for hair color without affecting any of the gene’s other functions.

‘Switching on’ Kit ligand’s hair color-determining powers

To do this, a research specialist in Kingsley’s team – Catherine Guenther – cut out segments of human DNA in the implicated region and linked each piece to a reporter gene. When these genes correctly “switch on,” they produce a distinctive blue color.

Next, Guenther introduced these pieces of switched-on DNA into mice. This allowed the team to further narrow the scope of their search until they had isolated a single piece of DNA that switched on the gene activity for developing hair follicles.

Further examining the DNA in that regulatory segment, the team found that it was just a single letter of genetic code that differed between people who have different hair colors.

The versions of this DNA associated with different hair colors were then each tested on the Kit ligand gene using cultured cells. The “blonde” switch reduced the activity of the gene by about 20%, which led the researchers to conclude they had identified a critical component of the DNA sequence.

Mice were then engineered to have a Kit ligand gene placed under either the genetic switches for blonde or brunette hair. Kingsley explains the results:

“Sure enough, when you look at them, that one base pair is enough to lighten the hair color of the animals, even though it is only a 20% difference in gene expression. This is a good example of how fine-tuned regulatory differences may be to produce different traits. The genetic mechanism that controls blonde hair doesn’t alter the biology of any other part of the body. It’s a good example of a trait that’s skin deep – and only skin deep.”

Their work with switching on different hair colors has led the team to suspect that the genome “is littered with switches.” Kingsley thinks that the various activities of Kit ligand, as well as other genes, may be adjusted by very subtle DNA tweaks.

As well as leading to a better understanding of the molecular mechanisms involved in human diversity, Kingsley hopes that this work may lead to improving human resistance to many common diseases.

“The trick is,” he says, is finding “which switches have changed to produce which traits.”

Source: Medical News Today

Medical Monday


DNA: The Basics

We each have 23 pairs of chromosomes. Each chromosome holds packages of DNA, which contains genes passed down from your parents and holds potential keys to everything from your hair color to your risks of certain illnesses. Within the DNA are many types of genetic variants, including one called single nucleotide polymorphisms, There are about 10 million SNPs in the human genome, and some have been found to predict risk of diseases or have a regulatory effect on a gene’s function.

Source: Prevention

Medical Monday


Actress Vanessa Williams Explains How DNA Powers Her Family Tree



Vanessa Williams



Most of us are curious about our family lineage. For Vanessa Williams, who recently took part in the show “Who Do You Think You Are” and explored her family’s history, the task was both surprising and informative. Here, she talks about what she learned and how she plans to use that information.
How did you become interested in finding out about your lineage?

I’ve always been interested, but I was introduced to [one of the websites that help people research their family backgrounds] before I even did a show called “Who Do You Think You Are,” so I signed up as a member to document my own family tree, and my DNA analysis was done as a part of doing the show.

We ended up doing two stories on my father’s side. One of my great-great-grandfathers was a soldier in the Civil War, and the other was born a slave but ended up being an educator and principal, and one of the first black legislators in Tennessee back in 1885. The stories are rich and informative and intriguing, but also as an African American, you don’t always have the luxury to know exactly where your ancestors are from.

What did you find out about your DNA?

My DNA breaks down as follows: I’m 23% from Ghana, 17% from the British Isles, 15% from Cameroon, 12% Finnish, 11% Southern European, 7% Togo, 6% Benin, 5% Senegal and 4% Portuguese.

Now, I can’t wait to go to Ghana and Cameroon and Togo and Senegal — it’s a great opportunity to see why the customs resonate with you. I love to travel and I love to explore, and I have to admit that I was always jealous of people who knew their cultural background. Both my family and myself came out with light eyes, so obviously there is a recessive gene here. Not knowing what that was just made me very curious.

How did it feel to find out about all these different parts of your lineage?

It’s fascinating! The first person I called was my mother, and I sent her my results and copied all my kids so they know where half of their genetic makeup is from. I wish that my father was still alive, because he was a huge history buff and interested in genealogy as well. It allows a greater sense of history for the family and a bit of pride as well.

Why do you think this information is important? Is it just for your own knowledge or to do plan to use it for health purposes as well?

I remember my mother told me that when my brother was a baby, they identified some blood issue with him, and they asked her if she had any relatives from Italy because this particular blood characteristic was consistent with someone from Italy. My mother said, “No, no, nothing like that.” Well, now come to find out 45 years later and obviously we have the same genetic makeup that Southern European is 11% of our makeup.

How did your family react to all this information?

They loved it. They really can’t wait to go on our world tour of where we’re from. The biggest surprise was Finland. How did that happen? Who is Finnish? That is definitely going to be one of my trips coming up. It’s all surprising, really interesting and it’s really incredible.

Source: LA Times

DNA Breaking News

At 400,000 Years, Oldest Human DNA Yet Found Raises New Mysteries

Javier Trueba, Madrid Scientific Films

    Scientists have found the oldest DNA evidence yet of humans’ biological history. But instead of neatly clarifying human evolution, the finding is adding new mysteries.

    In a paper in the journal Nature, scientists reported Wednesday that they had retrieved ancient human DNA from a fossil dating back about 400,000 years, shattering the previous record of 100,000 years.

    The fossil, a thigh bone found in Spain, had previously seemed to many experts to belong to a forerunner of Neanderthals. But its DNA tells a very different story. It most closely resembles DNA from an enigmatic lineage of humans known as Denisovans. Until now, Denisovans were known only from DNA retrieved from 80,000-year-old remains in Siberia, 4,000 miles east of where the new DNA was found.

    The mismatch between the anatomical and genetic evidence surprised the scientists, who are now rethinking human evolution over the past few hundred thousand years. It is possible, for example, that there are many extinct human populations that scientists have yet to discover. They might have interbred, swapping DNA. Scientists hope that further studies of extremely ancient human DNA will clarify the mystery.

    “Right now, we’ve basically generated a big question mark,” said Matthias Meyer, a geneticist at the Max Planck Institute for Evolutionary Anthropology in Leipzig, Germany, and a co-author of the new study.

    Hints at new hidden complexities in the human story came from a 400,000-year-old femur found in a cave in Spain called Sima de los Huesos (“the pit of bones” in Spanish). The scientific team used new methods to extract the ancient DNA from the fossil.

    “This would not have been possible even a year ago,” said Juan Luis Arsuaga, a paleoanthropologist at Universidad Complutense de Madrid and a co-author of the paper.

    Finding such ancient human DNA was a major advance, said David Reich, a geneticist at Harvard Medical School who was not involved in the research. “That’s an amazing, game-changing thing,” he said.

    Since the 1970s, Spanish scientists have brought out a wealth of fossils from the cave dating back hundreds of thousands of years. “The place is very special,” said Dr. Arsuaga, who has found 28 nearly complete skeletons of humans during three decades of excavations.

    Based on the anatomy of the fossils, Dr. Arsuaga has argued that they belonged to ancestors of Neanderthals, which lived in western Asia and Europe from about 200,000 to 30,000 years ago.

    When Dr. Meyer and his colleagues drilled into the femur, they found ancient human DNA inside, just as they had hoped.

    “Our expectation was that it would be a very early Neanderthal,” Dr. Meyer said.

    But the DNA did not match that of Neanderthals. Dr. Meyer then compared it to the DNA of the Denisovans, the ancient human lineage that he and his colleagues had discovered in Siberia in 2010. He was shocked to find that it was similar.

    “Everybody had a hard time believing it at first,” Dr. Meyer said. “So we generated more and more data to nail it down.”

    The extra research confirmed that the DNA belonged on the Denisovan branch of the human family tree.

    The new finding is hard to reconcile with the picture of human evolution that has been emerging in recent years based on fossils and ancient DNA. Denisovans were believed to be limited to East Asia, and they were not thought to look so Neanderthal-like.

    Based on previously discovered ancient DNA and fossil evidence, scientists generally agreed that humans’ direct ancestors shared a common ancestor with Neanderthals and Denisovans that lived about half a million years ago in Africa.

    Their shared ancestors split off from humans’ lineage and left Africa, then split further into the Denisovans and Neanderthals about 300,000 years ago. The evidence suggested that Neanderthals headed west, toward Europe, and that the Denisovans moved east.

    Humans’ ancestors, meanwhile, stayed in Africa, giving rise to Homo sapiens about 200,000 years ago. Humans then expanded from Africa into Asia and Europe about 60,000 years ago. They then interbred not only with Neanderthals, but with Denisovans, too. Later, both the Denisovans and Neanderthals became extinct.

    “Now we have to rethink the whole story,” Dr. Arsuaga said.

    Dr. Arsuaga doubts that Denisovans were spread out across so much of the Old World, from Spain to Siberia, masquerading as Neanderthals.

    One alternative explanation is that the humans of Sima de los Huesos were not true Neanderthals, but belonged to the ancestors of both Denisovans and Neanderthals.

    It is also possible that the newly discovered DNA was passed to both Neanderthals and Denisovans, but eventually disappeared from Neanderthals, replaced by other variants.

    “It got lost in one lineage but made its way in the other,” suggested Jean-Jacques Hublin, a Max Planck paleoanthropologist who was not involved in the research.

    Beth Shapiro, an expert on ancient DNA at the University of California, Santa Cruz, favors an even more radical possibility: that the humans of Sima de los Huesos belong to yet another branch of humans. They might have been a species called Homo erectus, which originated about 1.8 million years ago and became extinct within the last few hundred thousand years.

    “The more we learn from the DNA extracted from these fossils, the more complicated the story becomes,” Dr. Shapiro said.

    This complicated story has come to light only because of advances over the past 20 years in retrieving ancient DNA.

    When an organism dies, its DNA breaks down into smaller and smaller fragments, while also becoming contaminated with the DNA of other species like soil bacteria. So piecing the fossil DNA together is a bit like putting together a jigsaw puzzle created by a sadist.

    In 1997, Svante Paabo of the Max Planck Institute and his colleagues, who had pioneered the techniques for retrieving DNA fragments, published a snippet of DNA from a Neanderthal fossil dating back about 40,000 years. They and other scientists then built on this success by searching for bits of DNA from other Neanderthals.

    In 2006, a team of French and Belgian researchers obtained a fragment of Neanderthal DNA dating back100,000 years, which until now held the record for the oldest human DNA ever found.

    Meanwhile, using improved methods, Dr. Paabo, Dr. Meyer and their colleagues assembled a rough draft of the entire Neanderthal genome in 2010.

    That discovery shed light on how Neanderthals and humans’ ancestors split from a common ancestor hundreds of thousands of years ago. It also revealed that Neanderthals and humans interbred about 50,000 years ago.

    At about the same time as that discovery, Russian collaborators sent the Max Planck team 80,000-year-old fossils they had found in a cave in Siberia called Denisova. When the German scientists sequenced the entire genome from the finger bone of a girl, it turned out to be neither human nor Neanderthal, but from a separate lineage, which Dr. Paabo and his colleagues named Denisovans.

    Dr. Meyer is hopeful that he and his colleagues will be able to get more DNA from the Spanish fossil, as well as other fossils from the site, to help solve the puzzle they have now stumbled across. “It’s extremely hard to make sense of,” Dr. Meyer said. “We still are a bit lost here.”

    Source: The New York Times