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Remember the 40,000 year-old Denisova finger bone that yielded sufficient DNA to speculate that this ancient human, like Neanderthals, interbred with our ancestors? The bone was found in the Altai mountains (Siberia) and is presumed to be a new, now extinct, species of human. A novel technique of DNA sequencing that allows better use of the degraded, single stranded DNA of fossil bones has now been used to get a very complete sequence of the entire genome, and at very "high coverage", meaning each nucleotide or "letter" is read many times, giving confidence to the fidelity of the sequence. The new in-depth data confirm the 2010 findings that this ancient human species, who diverged from our modern human lineage anywhere from 700,000 to 170,000 years ago, did interbreed with H. sapiensand that some of their DNA survives in  contemporary people in Melanesia, who have~6% Denisova DNA in their genomes. Strikingly, Asians do not have any Denisova DNA which is puzzling because the migration to Oceania happened via Asia. This raises the intriguing possibility of more than one wave of migration. We do not know anything about the looks of this ancient hominin, except that now from its DNA we can be pretty confident that it had dark skin and brown eyes and hair. Looking at DNA variants in genes that differ between the Denisovans and modern humans, there are 8 genes associated with brain function or nervous system development, including one gene associated with susceptibility to language disorders in modern humans. The authors speculate that perhaps really important aspects of synaptic transmission may have changed in modern humans.  In addition to yielding great fodder for fun speculation about how different these distant "cousins" were from us, the new technique opens up the possibility of sequencing many more ancient genomes with a greater accuracy. I can't wait.

New DNA Analysis Shows Ancient Humans Interbred with Denisovans

A new high-coverage DNA sequencing method reconstructs the full genome of Denisovans--relatives to both Neandertals and humans--from genetic fragments in a single finger bone

FRAGMENT OF A FINGER: This replica of the Denisovan finger bone shows just how small of a sample the researchers had to extract DNA from.Image: Image courtesy of Max Planck Institute for Evolutionary Anthropology

Tens of thousands of years ago modern humans crossed paths with the group of hominins known as the Neandertals. Researchers now think they also met another, less-known group called the Denisovans. The only trace that we have found, however, is a single finger bone and two teeth, but those fragments have been enough to cradle wisps of Denisovan DNA across thousands of years inside a Siberian cave. Now a team of scientists has been able to reconstruct their entire genome from these meager fragments. The analysis adds new twists to prevailing notions about archaic human history.

"Denisova is a big surprise," says John Hawks, a biological anthropologist at the University of Wisconsin–Madison who was not involved in the new research. On its own, a simple finger bone in a cave would have been assumed to belong to a human, Neandertal or other hominin. But when researchers first sequenced a small section of DNA in 2010—a section that covered about 1.9 percent of the genome—they were able to tell that the specimen was neither. "It was the first time a new group of distinct humans was discovered" via genetic analysis rather than by anatomical description, said Svante Pääbo, a researcher at the Max Planck Institute (M.P.I.) for Evolutionary Anthropology in Germany, in a conference call with reporters.

Now Pääbo and his colleagues have devised a new method of genetic analysis that allowed them to reconstruct the entire Denisovan genome with nearly all of the genome sequenced approximately 30 times over akin to what we can do for modern humans. Within this genome, researchers have found clues into not only this group of mysterious hominins, but also our own evolutionary past. Denisovans appear to have been more closely related to Neandertals than to humans, but the evidence also suggests that Denisovans and humans interbred. The new analysis also suggests new ways that early humans may have spread across the globe. The findings were published online August 30 in Science.

Who were the Denisovans?
Unfortunately, the Denisovan genome doesn't provide many more clues about what this hominin looked like than a pinky bone does. The researchers will only conclude that Denisovans likely had dark skin. They also note that there are alleles "consistent" with those known to call for brown hair and brown eyes. Other than that, they cannot say.

Yet the new genetic analysis does support the hypothesis that Neandertals and Denisovans were more closely related to one another than either was to modern humans. The analysis suggests that the modern human line diverged from what would become the Denisovan line as long as 700,000 years ago—but possibly as recently as 170,000 years ago.

Denisovans also interbred with ancient modern humans, according to Pääbo and his team. Even though the sole fossil specimen was found in the mountains of Siberia, contemporary humans from Melanesia (a region in the South Pacific) seem to be the most likely to harbor Denisovan DNA. The researchers estimate that some 6 percent of contemporary Papuans' genomes come from Denisovans. Australian aborigines and those from Southeast Asian islands also have traces of Denisovan DNA. This suggests that the two groups might have crossed paths in central Asia and then the modern humans continued on to colonize the islands of Oceania.

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Abstract of original publication:

A High-Coverage Genome Sequence from an Archaic Denisovan Individual

  1. Matthias Meyer1,*,
  2. Martin Kircher1,*,
  3. Marie-Theres Gansauge1
  4. Heng Li2
  5. Fernando Racimo1,
  6. Swapan Mallick2,3
  7. Joshua G. Schraiber4
  8. Flora Jay4
  9. Kay Prüfer1
  10. Cesare de Filippo1
  11. Peter H. Sudmant6,
  12. Can Alkan4,5
  13. Qiaomei Fu1,7
  14. Ron Do2
  15. Nadin Rohland2,3
  16. Arti Tandon2,3
  17. Michael Siebauer1,
  18. Richard E. Green8
  19. Katarzyna Bryc3
  20. Adrian W. Briggs3
  21. Udo Stenzel1
  22. Jesse Dabney1
  23. Jay Shendure6,
  24. Jacob Kitzman6
  25. Michael F. Hammer9
  26. Michael V. Shunkov10
  27. Anatoli P. Derevianko10
  28. Nick Patterson2,
  29. Aida M. Andrés1
  30. Evan E. Eichler6,11
  31. Montgomery Slatkin4
  32. David Reich2,3,*,
  33. Janet Kelso1,
  34. Svante Pääbo1,

+Author Affiliations

  1. 1Department of Evolutionary Genetics, Max Planck Institute for Evolutionary Anthropology, D-04103 Leipzig, Germany.
  2. 2Broad Institute of Massachusetts Institute of Technology and Harvard, Cambridge, MA 02142, USA.
  3. 3Department of Genetics, Harvard Medical School, Boston, MA 02115, USA.
  4. 4Department of Integrative Biology, University of California, Berkeley, CA 94720, USA.
  5. 5Department of Computer Engineering, Bilkent University, 06800 Ankara, Turkey.
  6. 6Department of Genome Sciences, University of Washington School of Medicine, Seattle, WA 98195, USA.
  7. 7CAS-MPS Joint Laboratory for Human Evolution, Institute of Vertebrate Paleontology and Paleoanthropology, Chinese Academy of Sciences, 100044 Beijing, China.
  8. 8Jack Baskin School of Engineering, University of California, Santa Cruz, CA 95064, USA.
  9. 9Arizona Research Laboratories, Division of Biotechnology, University of Arizona, Tucson, AZ 85721, USA.
  10. 10Palaeolithic Department, Institute of Archaeology and Ethnography, Russian Academy of Sciences, Siberian Branch, 630090 Novosibirsk, Russia.
  11. 11Howard Hughes Medical Institute, Seattle, WA 98195, USA.

+Author Notes

  •  Present address: Department of Genome Sciences, University of Washington, Seattle, WA 98195, USA.

  1. To whom correspondence should be addressed. E-mail: (M.M.); (D.R.); (S.P.)
  1. * These authors contributed equally to this work.


We present a DNA library preparation method that has allowed us to reconstruct a high-coverage (30X) genome sequence of a Denisovan, an extinct relative of Neandertals. The quality of this genome allows a direct estimation of Denisovan heterozygosity, indicating that genetic diversity in these archaic hominins was extremely low. It also allows tentative dating of the specimen on the basis of “missing evolution” in its genome, detailed measurements of Denisovan and Neandertal admixture into present-day human populations, and the generation of a near-complete catalog of genetic changes that swept to high frequency in modern humans since their divergence from Denisovans.

And a GREAT blog post from John Hawks on this article. Read it ALL, it's fascinating (maybe a bit technical).

Denisova at high coverage

Thu, 2012-08-30 15:25 -- John Hawks

Science today has released the new paper on the Denisova high-coverage genome by Mattias Meyer and colleagues from Svante Pääbo's group (abstract link, until I can get the doi working). There is a lot of material in the supplements of the new paper, and it will take some time to work through implications.

The basics are quite simple: The paper confirms the initial interpretation of the genome by David Reich and colleagues [1] in most respects. The mixture with a whole-genome sample from Papua New Guinea is estimated at 6% Denisovan ancestry. Confirming the later paper by Reich and colleagues [2], the new analysis finds no significant evidence of Denisovan ancestry in a mainland south Chinese (Han Dai) individual, and can exclude it down to a very small fraction:

However, in contrast to a recent study proposing more allele sharing between Denisova and populations from southern China, such as the Dai, than with populations from northern China, such as the Han (17), we find less Denisovan allele sharing with the Dai than with the Han (although non-significantly so, Z = –0.9) (Fig. 4B) (table S25). Further analysis shows that if Denisovans contributed any DNA to the Dai, it represents less than 0.1% of their genomes today (table S26).

That is a mystery to be explained. How did Asians end up lacking any evidence of Denisovan ancestry, when the peoples of Sahul (Australia and New Guinea) have six percent? It's nutty! The early modern humans who were the ancestors of present Sahulian peoples surely came from Asia, and they surely mixed with Denisovans there somewhere, right? But today there's no sign that present Asian peoples descended from those early Asian peoples.

We must, I think, conclude that there was at least one, and possibly several episodes of massive population movement across South and Southeast Asia.

I have recently completed a review of the analogous problem for Neandertals in Europe -- late and early Neandertals themselves appear to have been a dynamic population. I'm now working on a review of the situation in Southeast Asia. We may fundamentally have to look at the archaeological record in a new, and much more dynamic, way than has been the case.

Neandertal gene flow

To me at the moment, this is the most interesting paragraph of the new paper:

Interestingly, we find that Denisovans share more alleles with the three populations from eastern Asia and South America (Dai, Han, and Karitiana) than with the two European populations (French and Sardinian) (Z = 5.3). However, this does not appear to be due to Denisovan gene flow into the ancestors of present-day Asians, since the excess archaic material is more closely related to Neandertals than to Denisovans (table S27). We estimate that the proportion of Neandertal ancestry in Europe is 24% lower than in eastern Asia and South America (95% C.I. 12–36%). One possible explanation is that there were at least two independent Neandertal gene flow events into modern humans (18). An alternative explanation is a single Neandertal gene flow event followed by dilution of the Neandertal proportion in the ancestors of Europeans due to later migration out of Africa. However, this would require about 24% of the present-day European gene pool to be derived from African migrations subsequent to the Neandertal admixture.

This is a very interesting result, partially because it is the opposite of what we are finding. As I explained earlier this year, we are finding Europeans to share more Neandertal alleles than Asians do. The difference in our results has been much smaller than 24%; really only an increase of less than 0.5% on the whole genome, or maybe 10% relative to the overall amount in Europe (which is on the order of 3%).

My initial reaction to this difference is that it reflects the sharing of Neandertal genes in Africa. Meyer and colleagues filtered out alleles found in Africa, as a way of decreasing the effect of incomplete lineage sorting compared to introgression in their comparison. But if Africans have some gene flow from Neandertals, eliminating alleles found in Africans will create a bias in the comparison. If (as we think) some African populations have Neandertal gene flow, that probably came from West Asia or southern Europe. So as long as the present European and Asian (and Native American) samples have undergone a history of genetic drift, or if (as mentioned in the quote) they mixed with slightly different Neandertal populations, this bias will tend to make Asians look more Neandertal and Europeans less so.

Anyway, this demands further investigation. The Denisova genome makes a more compelling outgroup for these kinds of comparisons, because it is much closer to us than chimpanzees are. But it isn't really an outgroup because it shares alleles by descent with Neandertals. So it takes some clever genetics to compare the distributions of derived alleles in these genomes in terms of introgression versus incomplete lineage sorting.

Read the rest here

This information is great, a part of our ancestors lives on in us.

"This is an extinct genome sequence of unprecedented accuracy," says Matthias Meyer, the lead author of the study. "For most of the genome we can even determine the differences between the two sets of chromosomes that the Deniosovan girl inherited from her mother and father." From this the researchers can tell that genetic variation of the Denisovans was lower than in present-day humans. This is likely due to that an initially small Denisovan population that grew quickly while spreading over a wide geographic range. "If future research of the Neandertal genome shows that their population size changed over time in similar ways, it may well be that a single population expanding out of Africa gave rise to both the Denisovans and the Neandertals," says Svante Pääbo, who led the study.

The researchers furthermore generated a list of about 100,000 recent changes in the human genome that occurred after the split from the Denisovans. Some of these changes affect genes that are associated with brain function and nervous system development. Others possibly affect the skin, the eye and dental morphology. "This research will help determining how it was that modern human populations came to expand dramatically in size as well as cultural complexity while archaic humans eventually dwindled in numbers and became physically extinct," says Svante Pääbo.

Earlier this year, the Leipzig researchers had already made the entire Denisovan genome sequence available to the broader public by publishing it online.

Just to think that I have an inexplicable ancestor in the family tree!

Isn't it amazing?

"This information is great, a part of our ancestors lives on in us."

Also living on in us are remnants of the DNA that fought the diseases that afflicted them. I'm impressed.


Carl Zimmer in the New York Times:

ScreenHunter_440 Dec. 04 20.22Scientists 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.

More here.

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