DNA Sequencing Megathread! Neanderthals, Denisovans and other ancient DNA!

[frunk]

If ancient humans would screw anything even remotely human-looking, I wonder how the populations ever came to drift in the first place. 

Geographic separation.

[The Minsky Moment]

If ancient humans would screw anything even remotely human-looking,

The conclusion I draw from this is that the origins of beer must be far, far older than previously assumed

[jimmy olsen]

If ancient humans would screw anything even remotely human-looking, I wonder how the populations ever came to drift in the first place. 

The Denisovans and the Neanderthals likely did not look that much different from each other. Even the modern humans who ran into the Neanderthals in the middle East 60-70k years ago were built more robustly than present day populations.

http://johnhawks.net/weblog/reviews/neandertals/neandertal_dna/sima-de-los-huesos-dna-meyer-2013.html

The Denisova-Sima de los Huesos connection
Wed, 2013-12-04 23:27 -- John Hawks

I direct your attention to a new paper by Mattias Meyer and colleagues describing a mitochondrial DNA sequence from Sima de los Huesos, Spain (Meyer et al. 2013). It is super awesomely cool work, and I can't wait for the further development as they attempt to get more DNA sequence data from the Sima sample. The recovery of cave bear DNA earlier this year from Sima presaged the current paper, and it seems we are now in a time where we can expect more results from Middle Pleistocene human remains. Very, very good.

Still, there seems to be a widespread confusion about the current result, which shows the Sima mtDNA sequence to be on the same clade as the mtDNA sequences from Denisova, Russia.

I mean, take a look at the quotes from these news articles:

In the New York Times story by Carl Zimmer ("At 400,000 Years, Oldest Human DNA Yet Found Raises New Mysteries"):

    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."

From Ewen Callaway's Nature news article ("Hominin DNA baffles experts"):

    Even Pääbo admits that he was befuddled by his team's latest discovery. "My hope is, of course, eventually we will not bring turmoil but clarity to this world," he says.

I sort of understand the confusion.

For more than a hundred years, scientists have been drawing straight lines connecting different fossils, to try to understand the human family tree. Those straight lines always diverged over time, leading toward increasing specialization and extinction of fossil groups. And for more than twenty-five years, geneticists have been assuming that the lines connecting the genealogy of mtDNA should be the same as the lines connecting the fossils. When those lines were different, geneticists have been happy to toss the fossils out of the human family tree, content to accept the story that the fossil people had become too specialized, too peripheral to be ancestors of today's people.

But the last five years have made clear that both groups -- the fossil scientists drawing straight lines of diverging fossil populations, and the geneticists drawing straight lines of diverging -- were wrong.

Just look at the evidence. Humans today descend in part from Neandertals, even though Neandertal mtDNA is gone. Europeans today are largely different from the Europeans of 10,000 years ago, with a massive mtDNA replacement along with the introduction of Neolithic culture, and at least a second later large-scale replacement of genetic diversity. Earlier Neandertals in Europe have different mtDNA diversity than later Neandertals in Europe. Denisova cave was home to an earlier population of hominins with different mtDNA than the later Neandertals who lived there. Mitochondrial DNA has never been a straight line linking earlier and later populations within a single location. Whenever we look at ancient DNA in hominins, the earlier populations have different mtDNA diversity than the later ones. Moreover, wherever we have ancient mtDNA from other species -- bison, mammoths, cave bears, and others -- we find that later mtDNA sequences do not represent the earlier diversity. The Sima cave bear mtDNA is a direct example of this, but the same phenomenon has happened again and again.

The fossil evidence, we now know, is no different. Paleoanthropologists have widely assumed that the Sima de los Huesos hominins are ancestors of Neandertals. That's a straight line.

There are essentially two reasons for this assumption. One is that Neandertals need ancestors, and the Sima sample seems to be in the right place at the right time -- 300,000 years ago or more, in western Europe.

The other reason is a bit more substantial: the Sima sample exhibits a number of features that are shared with Neandertals but not African fossil humans, and are rare in recent humans. So the sample is not only at the right place and the right time, it sort of looks the part of incipient Neandertals. Jean-Jacques Hublin and others have described this idea as an "accretion" of Neandertal features in European populations over time. Go back far enough in Europe -- say, to the Gran Dolina sample -- and you don't see fossils with Neandertal features. As you proceed forward through the Middle Pleistocene, you start seeing more similarity to Neandertals. Scientists fitted this data to a straight line, projecting a gradual divergence of the European population away from other human populations, eventually becoming Neandertals.

However, over the last few years, neither of these straight-line reasons has been looking especially good. First, the mtDNA landscape of Neandertals has shifted our knowledge of their population dynamics. Dalen and colleagues (2012) showed that later Neandertals do not have the same diversity as earlier Neandertals in western Europe, and that central Asian Neandertals have more diversity than European ones. From this perspective, the evolution of Neandertals looks less and less like a European phenomenon. Instead, Europe may have been invaded repeatedly by Neandertal populations that were much more numerous elsewhere, such as western or central Asia. I developed that idea last year (Hawks 2012), but in fact it is an old idea going back to the 1950s or earlier.

Now that we know that the last 100,000 years of Neandertal evolution was complex and not centered in western Europe, I don't see why we should assume a straight line between Sima de los Huesos at more than 300,000 years ago and later Neandertals.

Second, the Denisova discoveries have made it clear that other populations existed outside the current visibility of our fossil and archaeological evidence. Why should we assume that these populations looked different from Neandertals? The reality is that we know essentially nothing about the morphology of West or Central Asian hominins of 300,000 years ago. South Asia and Southeast Asia were likewise inhabited throughout this period but we have only the barest hints about the morphology of their inhabitants. These peoples existed just inside the range of archaeological visibility but we lack any but the most rudimentary fossil evidence of them.

To be sure, many people have been assuming that the Denisovans were some kind of East Asian population, for example in China or Southeast Asia. In the process, they have projected the characteristics of the Asian fossil record upon them. That idea has been supported by the existence of Neandertals to the west, and also the sharing of some Denisovan similarity in the genomes of living Australians and Melanesians.

But that's a big assumption. Let's explore an alternative: that the Denisovans we know are in part descendants of an earlier stratum of the western Eurasian population. Although they are on the same mtDNA clade, the difference between Sima and Denisova sequences is about as large as the difference between Neandertal and living human sequences. It would not be fair to say that Denisova and Sima represent a single population, any more than that Neandertals and living people do. But they could share a heritage within the Middle Pleistocene of western Eurasia, deriving their mtDNA from this earlier population.

We know that the Denisovan nuclear genome is much closer to Neandertals than the Denisovan mtDNA. We are still waiting for the long-rumored publication of the idea that Denisovan genomes have a "mystery hominin" element in their ancestry. They could be a mixture of any number of earlier populations. None of these have to be East Asian, and as yet we have no suggestion that this "earlier" element of Denisovan ancestry could be as ancient as the first known habitation of Eurasia, as much as 1.8 million years ago. Maybe the Sima hominins represent this "mystery hominin" population.

Maybe the Denisovans were west Asian Neandertals. It does seem like known genetics of Neandertals may represent something like an earlier iteration of the origin of modern humans -- more African than earlier hominins like the Sima sample, less influenced by Eurasian mixture than the Denisova genome, only a subset of the diversity of surrounding contemporaries. But we have no idea what the Neandertals of the Levant or southwest Asia may have been like genetically -- maybe they were more like Denisovans. This is all basically speculation, which indicates how little we still understand about the dynamics of these populations.

They were complicated. Their relationships cannot be described by drawing straight lines between fossil samples. There were multiple lines of influence among them, small degrees of mixture and large-scale migrations. Europe was far from a slowly evolving population "accreting" Neandertal features over time. The Neandertals we know did not lumber into their doom; they expanded rapidly, multiple times, from non-European origins. They were as dynamic as the Middle Stone Age Africans who would later mix with them and expand across the world.

So I don't find the Sima mtDNA to be the least bit surprising. It's refreshing!

[Jacob]

If this is not racism, I don't know what it is.

I think you got it right in the second half of that sentence.

[jimmy olsen]

By the way, this is likely not the oldest human that will eventually be sequenced. Just six months ago a 700,000 year old horse had it's genome sequenced. A human that far back would likely be an early H. hidelbergenis or a late H. Erectus. A genome of the latter would be absolutely invaluable and it seems it will happen eventually. The field of ancient genomics is progressing at an absolutely astonishing pace.

http://blogs.scientificamerican.com/observations/2013/06/26/horse-fossil-yields-astonishingly-old-genomeare-similarly-ancient-human-genomes-next/

Horse Fossil Yields Astonishingly Old Genome—Are Similarly Ancient Human Genomes Next?

By Kate Wong | June 26, 2013 |  Comments2

Researchers have recovered DNA from a nearly 700,000-year-old horse fossil and assembled a draft of the animal's genome from it. It is the oldest complete genome to date by a long shot–hundreds of thousands of years older than the previous record holder, which came from an archaic human that lived around 80,000 years ago. The genome elucidates the evolution of modern horses and their relatives, and raises the question of whether scientists might someday be able to obtain similarly ancient genomes of human ancestors.

Ludovic Orlando of the University of Copenhagen and his colleagues extracted the DNA from a foot bone found at the site of Thistle Creek in Canada's Yukon Territory in permafrost dating to between 560,000 and 780,000 years ago, which falls within the so-called early Middle Pleistocene time period. They then mapped the fragments of DNA they obtained against the genome of a modern horse to piece together a draft of the ancient horse's genome.

Comparing that sequence to the genomes of a 43,000-year-old horse, a donkey, five modern domestic horses and a modern Przewalski's horse (a type of wild horse native to Mongolia), the researchers were able to gain insights into some key aspects of horse evolution. Their findings indicate that the last common ancestor of the members of the genus Equus—which includes modern horses, donkeys, asses and zebras, along with their extinct relatives–lived some 4 million to 4.5 million years ago, double the estimate suggested by the oldest unequivocal Equus fossils. The results also allowed the team to chart the demographic history of horses over the past two million years, revealing how the population waxed and waned as climate shifted and grasslands expanded and contracted. In addition, the researchers identified several genome regions in modern horses that seem to have been targeted by natural selection acting to promote advantageous gene variants related to immunity and olfaction, as well as a number of genome regions that may have undergone selection related to domestication. A report detailing the study will be published in the June 27 Nature. (Scientific American is part of Nature Publishing Group.)

This is a pretty exciting development (so exciting, in fact, that I'm interrupting my vacation to write about it). And I can't help but think back, as I do whenever a new ancient DNA story breaks, to the first time I ever reported on DNA from deep time. The year was 1997. Researchers had just announced that they had sequenced DNA from a 40,000-year-old Neandertal fossil. Specifically they had sequenced DNA from mitochondria—the cell's energy-producing organelles, which contain their own DNA that is passed on along the maternal line.

The Neandertal mitochondrial genome was a huge breakthrough—and it seemed to settle a long-running debate over Neandertals and the origin of anatomically modern Homo sapiens. But mitochondrial DNA represents only a tiny fraction of an individual's genetic information; the real action is in the DNA that resides in the cell's nucleus—the nuclear genome. The scientists I spoke to back then—geneticists and paleontologists—longed for a nuclear genome from a Neandertal. But they were quite certain that they would never ever get one. Mitochondrial DNA is far more abundant than nuclear DNA, because a cell can contain hundreds of mitochondria, whereas it has just one nucleus. Thus the chances of finding nuclear DNA that has survived the ravages of time is far, far lower than those of obtaining mitochondrial DNA—itself a rarity.

And yet. Fast forward to 2010 and the impossible dream was realized: a draft sequence of a nuclear genome of a Neandertal. More recently the sequencing of nuclear DNA retrieved from an enigmatic finger bone from Denisova Cave in Siberia has revealed a previously unknown kind of human. And scientists have obtained an astonishingly complete Neandertal genome from the same cave site. These ancient nuclear genomes paint a rather different picture of archaic-modern human relations than the early mitochondrial DNA work did, and are providing a wealth of fascinating insights into our own evolution and that of our relatively recently extinct cousins.

This fantastically old horse genome got me thinking about the possibility of recovering DNA from comparably ancient human relatives—ones who roamed the earth long before the Neandertals and the Denisovans. If scientists had such data, what would they try to learn from it? When I asked paleoanthropologist John Hawks of the University of Wisconsin this question, he had this to say:

"Right now the Denisovan and Neandertal genomes have raised a new scenario of population structure for Middle Pleistocene people. They show us that earlier hominins in Eurasia were largely supplanted, possibly with some mixture, by a dispersal of Neandertal and Denisovan ancestors. What was that pre-Neandertal population like? Did it have its own unique events shaping its evolution? How many times did large-scale dispersals of human populations sweep across the Old World? And what happened to African ancestors during this key Middle Pleistocene time period?"

Now, lest we get ahead of ourselves, it must be noted that the horse fossil was found in permafrost, which no doubt contributed to the preservation of the DNA. So will scientists have to find a Middle Pleistocene human on ice (or ice-cold soil) to have any hope of getting a genome out of it? Not necessarily. The Denisova specimens weren't preserved in permafrost and their ancient DNA is first class. Still, they are far younger than the horse fossil. But according to ancient DNA expert Hendrik Poinar of McMaster University in Canada, the key to DNA preservation is dry conditions. "While cold and dry is best, warm and dry will still work," he explains.

Poinar additionally noted that he is certain that researchers will eventually recover genomes even older than this 700,000-year-old (give or take) one. Which brings me to my final thought. When I learned of the horse genome, the first thing I thought was: what does this mean for Australopithecus sediba, the two million-year-old fossil species unearthed in at the site of Malapa in South Africa a few years ago. It has been held up as a candidate for the long-sought ancestor of our genus, Homo. These fossils are exquisitely preserved and may even contain organic material. Some of the remains are completely encased in rock, visible only with computed tomography and other imaging techniques. Might scientist be able to extract DNA from these fossils—and might that DNA be sufficiently well preserved to yield a genome? "I think DNA from Malapa is very possible and an exciting prospect," Poinar says.

In fact, efforts are already under way to recover DNA from the A. sediba fossils, "We are in the process of looking and there are specimens presently being investigated," says paleoanthropologist Lee Berger of the University of the Witwatersrand, who is leading the recovery and analysis of the fossils from Malapa. "It is of course unlikely in a [two million-year-old] fossil," he notes, "nevertheless, Malapa has as good a chance as anywhere if the impossible is going to prove possible."

I'm going to resume my vacation now. But I'll be daydreaming about genomes from our long-vanished cousins. The future of ancient DNA research has never looked brighter.

[The Brain]

a 700,000 year old horse

Time for the glue factory.

[Ed Anger]

Neigh

[jimmy olsen]

Looks like there's no party like a Denisovan cave party!

More big news from Denisova, analysis by Zimmer and Hawks.

http://www.nytimes.com/2013/12/19/science/toe-fossil-provides-complete-neanderthal-genome.html?pagewanted=1&_r=0

Toe Fossil Provides Complete Neanderthal Genome
Published: December 18, 2013

By CARL ZIMMER
Published: December 18, 2013

Scientists have extracted the entire genome of a 130,000-year-old Neanderthal from a single toe bone in a Siberian cave, an accomplishment that far outstrips any previous work on Neanderthal genes.

The accuracy of the new genome is of similar quality to what scientists would achieve if they were sequencing the DNA of a living person.

"It's an amazing technical accomplishment," said Sarah A. Tishkoff, an expert on human evolution at the University of Pennsylvania, who was not involved in the research. "Twenty years ago, I would have thought this would never be possible."

The new Neanderthal genome, which is described in the current issue of Nature, is part of an extraordinary flurry of advances in studying ancient human DNA. Earlier this month, for example, scientists reconstructed a small segment of genes from a 400,000-year-old fossil in Spain, setting a record for the oldest human DNA ever found.

While the Spanish DNA only provided faint, tantalizing clues about human evolution, the new Neanderthal genome is more like a genetic encyclopedia, rich with new insights. The Neanderthal to whom the bone belonged was highly inbred, for example, offering a glimpse into the social lives of Neanderthals.

The new Neanderthal genome also contains evidence of more interbreeding between ancient human populations than previously known.

The authors of the new study also compared the Neanderthal genome to modern human DNA to better understand what makes our own lineage unique. They have come up with a list of mutations that evolved in modern humans after their ancestors branched off from Neanderthals some 600,000 years ago.

"The list of modern human things is quite short," said John Hawks, a paleoanthropologist at the University of Wisconsin who was not involved in the study.

Neanderthals have intrigued scientists ever since their first fossils were found in 1856. Experts argued whether they were part of our own species or a separate one. Since the initial discovery, researchers have found remains of these heavy-browed, solidly built humans from Spain to Central Asia. Their fossil record now stretches from about 200,000 years ago to about 30,000 years ago.

Some of these fossils still hold fragments of Neanderthal DNA. In 1997, Svante Paabo of the Max Planck Institute for Evolutionary Anthropology and his colleagues extracted a snippet from a 40,000-year-old Neanderthal fossil. In 2010, after gathering more DNA from fossils, Dr. Paabo's team published a rough draft of the entire Neanderthal genome.

Using improved methods, the scientists were able to reconstruct the genome from another trove of DNA from an 80,000-year-old finger bone retrieved by a team of Russian explorers from a cave called Denisova.

Much to their surprise, the genome belonged to a separate lineage of humans that had not been known from the fossil record before. The scientists called these mysterious people the Denisovans.

By comparing the rough drafts of the Denisovan and Neanderthal genomes to modern human DNA, Dr. Paabo and his colleagues found clues to how we're all related. Modern humans, Neanderthals and Denisovans all descended from a common ancestor that lived several hundred thousand years ago. The ancestors of modern humans then branched away on their own lineage. It wasn't until later that Neanderthals and Denisovans split apart from each other.

The researchers also discovered some Neanderthal and Denisovan DNA in the genomes of living humans.

Dr. Paabo and his colleagues concluded that modern humans interbred with both Neanderthals and Denisovans before those two lineages became extinct.

The scientists then developed better methods for reconstructing ancient DNA. They were able to create a new version of the Denisovan genome that was extremely accurate and complete.

There was just one catch: the latest reconstruction methods demanded a lot of ancient DNA, which is a rare thing to find in fossils. But when Dr. Paabo and his colleagues studied more bones from Denisova, they hit the jackpot again, discovering an abundance of DNA in a toe bone.

"We thought it would be a Denisovan toe," said Dr. Paabo, "but it very clearly was a Neanderthal."

The scientists were able to reconstruct the new Neanderthal genome even more accurately than the Denisovan one.
(Page 2 of 2)

The crisp focus of the new genome is yielding new discoveries about Neanderthals. For example, Dr. Paabo and his colleagues can distinguish the origin of each piece of DNA — whether it came from the Neanderthal's mother or father. With an X chromosome from each parent, the toe belonged to a female.

A closer look at these two sets of DNA revealed that the Neanderthal female was extremely inbred. Her two parental sets of genes were identical for long stretches. Such similarity can only come about when close relatives have children.

"We don't know if this is typical of all Neanderthals, or just this population in Siberia," said Dr. Paabo. It will take more high-caliber Neanderthal genomes to settle that question.

The new genome reveals not just inbreeding but interbreeding. The accompanying diagram summarizes the flow of DNA between human lineages over the past half million years, based on a comparison of the new Neanderthal genome with other Neanderthal DNA sequences, the Denisovan genome and the genomes of

Dr. Paabo and his colleagues were able to detect not one, but two injections of Denisovan DNA into the modern human gene pool.

Intriguingly, the Denisovan genome also contains hints of even more exotic interbreeding. A few percent of their DNA appears to have originated from a more distant branch of our evolutionary tree.

Dr. Paabo said it was possible that the branch was a species known as Homo erectus, which lived across much of the Old World from 1.8 million to about 50,000 years ago.

Dr. Tishkoff thinks this is a possible explanation of the data, but not the only one. She thinks it is possible that the same pattern could have emerged if the ancestors of humans, Neanderthals and Denisovans in Africa became separated from each other early on, evolving different DNA sequences.

Despite all the flowing DNA, Neanderthals, Denisovans and modern humans did not become one big genetic blur. After Denisovan and Neanderthal DNA made its way into the modern human gene pool, most of it gradually disappeared. And modern humans took their own evolutionary path.

By comparing their high-quality ancient genomes to human genomes, Dr. Paabo and his colleagues are drawing up a list of mutations that are unique to our own lineage. "I would say it is a definitive list," said Dr. Paabo.

Dr. Paabo is intrigued by some mutations that affect genes involved in the development of the brain. But he sees the list as only a starting point for research.

"What lies ahead is to understand which of these is important," said Dr. Paabo. "That's totally up in the air."

http://johnhawks.net/weblog/reviews/neandertals/neandertal_dna/altai-neandertal-genome-2013.html

The Altai Neandertal
December 18, 2013

It is notable that we now have evidence for interbreeding among every kind of hominin we have DNA from, and some we don't.

Neandertals and humans. Denisovans and humans. Neandertals and Denisovans. Some living sub-Saharan Africans and one or more unknown ancient populations. Denisovans and one or more unknown, even more ancient populations. They were all mixing.

The picture of Pleistocene human evolution has come rapidly into focus during the last two years. Before the last 30,000 years, the world was full of human populations that were around twice as different from each other as the most diverse recent human groups. Some of these ancient groups grew at the expense of others, but the "losers" over the long term still survived within the genomes of the "winners".

The process of selection on human genes spanned these different human populations, as genes of adaptive value were exchanged between them, long surviving their progenitor populations. Each of the groups shared genetic variation from their common ancestors, but some local populations were markedly restricted in variation by inbreeding. All in all, humans of the past had a population structure rather like today's chimpanzees, although ancient humans were slightly more alike across a much larger geographic range.

Last spring we heard that the Max Planck Institute for Evolutionary Anthropology had successfully sequenced a high-coverage genome from a hominin toe bone found at Denisova Cave, Russia. In the announcement they made clear that this genome was substantially different from the existing high-coverage genome from Denisova. That first genome, from the bone of a pinky finger, represented a previously-unknown human population, quite different from Neandertals. This new genome, from the Denisova toe bone, is much more similar to the genomes of other Neandertals already known from Vindija, El Sidrón, Feldhofer and Mezmaiskaya. That seems like enough to call the toe a Neandertal.

Yet this week's paper makes clear that this genome is not just another Neandertal. Kay Prüfer and colleagues (2013) describe several kinds of analyses on the high-coverage data. The most important of these analyses establish the pattern of similarities and differences between this genome and others, allowing us to test some hypotheses about the relationships of Neandertals, Denisovans and modern humans.

At the moment, I am just going to present and explain a few of the major conclusions of the study. The paper itself is only 7 pages long, but the supplementary data stretch across 248 dense pages of text and figures. It's much more than a dissertation's worth of information, and it is going to take some time for me to completely digest. There will be much more to discuss over the next few weeks. Further papers that use these data are in the pipeline, with some interesting additional results. This is good work and I am excited by it, but I am going to present some notes of caution as well. I think some interpretations are likely to shift as we learn more.

Here are the major insights of the present study:

    The new genome appears to represent an individual that has fewer new derived mutations than the Denisovan high-coverage genome. The research suggests this as a means of "molecular dating" of the specimens, proposing that the Denisovans lived in Denisova cave after this Neandertal population.

    The Denisovan high-coverage genome includes portions that reflect ancestry from Neandertals.

    The new genome groups with previously known Neandertals in a genome-wide cluster analysis, but represents a more divergent population of Neandertals than those yet described. Under a model where genetic differences reflect a branching population history, the "Altai Neandertal" population seems to have diverged from other Neandertals sometime between 77,000 and 114,000 years ago.

    The high-coverage Neandertal genome shares many derived mutations with sub-Saharan Africans, while the high-coverage Denisova genome shares fewer. If these archaic populations were equally related to Africans, they would have the same number of shared derived mutations with Africans. Prüfer and colleagues infer that the Denisovan genome had ancestors who belonged to a yet more ancient hominin population. They suggest this population represents around 4 percent of the ancestry of Denisovans, and that it diverged from the common ancestors of Neandertals and sub-Saharan Africans sometime around a million years ago. The confidence intervals on both estimates are large.

    The new genome has many extended runs of homozygosity, consistent with inbreeding. The study concludes that the parents of this individual were likely 1/4 degree relatives -- such as uncle/niece or half-sibling mating.

    A comparison of the archaic human genomes with the 1000 Genomes Project samples shows only 96 amino-acid-coding changes shared by nearly all of the 1094 recent humans but absent from Denisovan and Neandertal genomes. A larger number (over 3000) of mutations that "possibly affect gene regulation" are also near fixed in recent humans. These are potentially interesting because they may be related to recent behavioral or anatomical evolution of modern humans.

    The paper reports on new sequencing of the Mezmaiskaya Neandertal to 0.5x coverage. This genome is substantially closer to recent humans than are the other Neandertal genomes. Presumably the population of Neandertals that accounts for present-day Neandertal genes in living people was closer to the Mezmaiskaya Neandertal than others.

    The high-coverage Neandertal and Denisova sequences allow a new estimate of the amount of Neandertal and Denisovan ancestry in human populations. Neandertal ancestry of living non-Africans is now estimated between 1.5 and 2.1 percent. This is lower than previous estimates, a discrepancy that the paper does not explain.

    The paper finds significant evidence for Denisovan ancestry of mainland Asian and Native American populations. The Denisovan fraction in these populations is small, only around two tenths of a percent on average, but the ancestry is spread throughout these populations into the New World.

    The Denisovan ancestry of living populations of New Guinea represents a substantially different genetic background than the Denisova high-coverage genome. The divergence between the Siberian Denisovan high-coverage genome and the Denisovan intermixture with humans is greater than the divergence between any living groups of humans with each other.

We can now see that the original description of the Denisovan genome in 2010 and follow-up analyses in 2011 were based on a number of inaccurate assumptions. The current high-coverage data have added a lot of precision to some analyses, but several of the changes in this new research have actually come from the adoption of new assumptions and more refined models.

Some of the conclusions in this paper will not last long as more ancient genomes are sequenced. We have recently seen with the publication of the Sima de los Huesos mtDNA that many assumptions about the Denisova population are questionable ("The Denisova-Sima de los Huesos connection").

Some examples:

    Why should we assume that the Denisovan ancestry includes only a single "mystery population"? The Sima de los Huesos result shows that several populations may have been in a position to mix with the ancestors of Denisovans.

    Why should we assume that the Denisovans were a single population? The genetic differences among "Denisovan" groups by our current definition were greater than those between any two human groups today.

    This current paper is noncommittal about the rate of mutations that should be applied to the ancient genomes, which leads to an uncertainty of more than a factor of two in the date estimates presented. This is unfortunate because the uncertainty prevents the DNA from shedding light on the relationships of pre-Neandertal, Neandertal and modern human fossil remains. But the uncertainty is real, as the relevant mutation rates remain a matter of debate ("A longer timescale for human evolution", "What is the human mutation rate?").

At any rate, the new genome has tremendous value for the further study of how we evolved. As I continue to study the supplements of the paper, I will be updating on several areas of interest.

[Queequeg]

IDK how people ever doubted that Neanderthals and Humans mixed while Madds Mikkelsen exists. 

[jimmy olsen]

IDK how people ever doubted that Neanderthals and Humans mixed while Madds Mikkelsen exists.

A quick google search and I don't really see anything Neanderthalish about in appearance. 

EDIT: By the way, seems like Neanderthals practiced patrilocality, which is the fancy term for the men staying with the groups they're born into and the women moving (or are traded to) a new group.

Also, some heavy duty cannibalism
http://www.nytimes.com/2010/12/21/science/21neanderthal.html?_r=0

Bones Give Peek Into the Lives of Neanderthals
El Cidrón Research

REMAINS The bone fragments of the family were retrieved at El Cidrón.
By CARL ZIMMER
Published: December 20, 2010

Deep in a cave in the forests of northern Spain are the remains of a gruesome massacre. The first clues came to light in 1994, when explorers came across a pair of what they thought were human jawbones in the cave, called El Sidrón. At first, the bones were believed to date to the Spanish Civil War. Back then, Republican fighters used the cave as a hide-out. The police discovered more bone fragments in El Sidrón, which they sent to forensic scientists, who determined that the bones did not belong to soldiers, or even to modern humans. They were the remains of Neanderthals who died 50,000 years ago.

Today, El Sidrón is one of the most important sites on Earth for learning about Neanderthals, who thrived across Europe and Asia from about 240,000 to 30,000 years ago. Scientists have found 1,800 more Neanderthal bone fragments in the cave, some of which have yielded snippets of DNA.

But the mystery has lingered on for 16 years. What happened to the El Sidrón victims? In a paper this week in The Proceedings of the National Academy of Sciences, Spanish scientists who analyzed the bones and DNA report the gruesome answer. The victims were a dozen members of an extended family, slaughtered by cannibals.

"It's an amazing find," said Todd Disotell, an anthropologist at New York University. Chris Stringer of the Natural History Museum of London said the report "gives us the first glimpse of Neanderthal social structures."

All of the bones were located in a room-size space the scientists dubbed the Tunnel of Bones. They were mixed into a jumble of gravel and mud, which suggests that the Neanderthals did not die in the chamber. Instead, they died on the surface above the cave.

Their remains couldn't have stayed there for long. "The bones haven't been scavenged or worn out by erosion," said Carles Lalueza-Fox of Pompeu Fabra University in Barcelona, a co-author of the new paper. Part of the ceiling in the Tunnel of Bones most likely collapsed during a storm, and the bones fell into the cave.

No animal bones washed into the Tunnel of Bones along with the Neanderthals'. In fact, the only other things scientists have found there are fragments of Neanderthal stone blades. And when the scientists closely examined the Neanderthal bones, they found cut marks — signs that the blades had been used to slice muscle from bone. The long bones had been snapped open. From these clues, the scientists concluded that the Neanderthals were victims of cannibalism. Scientists have found hints of cannibalism among Neanderthals at other sites, but El Sidrón is exceptional for the scale of evidence.

As the researchers examined bone fragments, they tried to match them to each other. Some loose teeth fit neatly into jawbones, for example. "The whole thing was quite complicated. In fact, it was a mess," said Dr. Lalueza-Fox.

After spending years on these anatomical jigsaw puzzles, Dr. Lalueza-Fox and his colleagues could identify 12 individuals. The shape of the bones allowed the scientists to estimate their age and sex. The bones belonged to three men, three women, three teenage boys and three children, including one infant.

Once the scientists knew who they were dealing with, they looked for DNA in the bones. The cold, damp darkness of El Sidrón has made it an excellent storehouse for ancient DNA. Dr. Lalueza-Fox and his colleagues have published a string of intriguing reports on their DNA. In two individuals, for example, they found a gene variant that may have given them red hair. They launched an ambitious project to find DNA in the teeth of all 12 individuals. In one test, they were able to identify a Y chromosome in four. The scientists had already identified all four of them as males — the three men and one teenage boy — based on their bones.

The scientists then hunted for mitochondrial DNA, which is passed from mothers to their children. They looked for two short stretches in particular, called HVR1 and HVR2, that are especially prone to mutate from generation to generation. All 12 Neanderthals yielded HVR1 and HVR2. The scientists found that seven of them belonged to the same mitochondrial lineage, four to a second, and one to a third.

Dr. Lalueza-Fox argues that the Neanderthals must have been closely related. "If you go to the street and sample 12 individuals at random, there's no way you're going to find seven out of 12 with the same mitochondrial lineage," he said. "But if you go to the birthday party for a grandmother, chances are you'll find brothers and sisters and first cousins. You'd easily find seven with the same mitochondrial lineage."

All three men had the same mitochondrial DNA, which could mean they were brothers, cousins, or uncles. The females, however, all came from different lineages. Dr. Lalueza-Fox suggests that Neanderthals lived in small bands of close relatives. When two bands met, they sometimes exchanged daughters.

"I cannot help but suppose that Neanderthal girls wept as bitterly as modern girls faced by the prospect of leaving closest family behind on their 'wedding' day," said Mary Stiner, an anthropologist at the University of Arizona.

Linda Vigilant, an anthropologist at the Max Planck Institute for Evolutionary Anthropology in Germany, considers the research "a nice start." But she challenges Dr. Lalueza-Fox's claim that the Neanderthals must be immediate family because they belong to the same mitochondrial lineage. In her own work on wild chimpanzees, she finds that some chimpanzees with identical HVR1 and HVR2 are not closely related.

The best way to settle the debate, said Dr. Vigilant, is to find more Neanderthal DNA to which the El Sidrón genes can be compared. "It is exciting to think that we might actually be able to tackle the question in the near future," said Dr. Vigilant.

Dr. Lalueza-Fox thinks it may be possible to draw a detailed genealogy of the El Sidrón Neanderthals in the next few years. He also hopes to get a better idea of how they died. The stone blades may provide a clue. They were made from rocks located just a few miles away from the cave. The victims might have wandered into the territory of another band of Neanderthals. For their act of trespass, they paid the ultimate price.

[Razgovory]

Actually since the claims are being rewritten every year it seems it's extremely unclear what exactly is going on.

[jimmy olsen]

Actually since the claims are being rewritten every year it seems it's extremely unclear what exactly is going on.

Which claims?

[Razgovory]

Actually since the claims are being rewritten every year it seems it's extremely unclear what exactly is going on.

Which claims?

For instance a study showing that humans and Neanderthals did not interbreed with humans and one that showed they did interbreed with humans was released in one year.

[The Brain]

Actually since the claims are being rewritten every year it seems it's extremely unclear what exactly is going on.

Which claims?

For instance a study showing that humans and Neanderthals did not interbreed with humans and one that showed they did interbreed with humans was released in one year.

As always the truth is somewhere in the middle.

[jimmy olsen]

Actually since the claims are being rewritten every year it seems it's extremely unclear what exactly is going on.

Which claims?

For instance a study showing that humans and Neanderthals did not interbreed with humans and one that showed they did interbreed with humans was released in one year.

The first study was a on a limited stretch of the genome and the later one was based on the whole genome. Not complicated.