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

[crazy canuck]

Very interesting if they can trace this to the Bronze Age collapse.

[jimmy olsen]

Very interesting if they can trace this to the Bronze Age collapse.

I read 1177 B.C., The Year Civilization Collapsed relatively recently and I don't remember an epidemic being high up on the list of possible causes. It was combination of climate change leading to famine and migration/invasion.


Anyways, here's a new article. This one on the peopling of the New World

http://www.nytimes.com/2015/10/27/science/dna-of-ancient-children-offers-clues-on-how-people-settled-the-americas.html

DNA of Ancient Children Offers Clues on How People Settled the Americas


OCT. 26, 2015
Carl Zimmer

Researchers have long wondered how people settled the Americas, particularly the path they took to the new territory and the timing of their expansion. Until recently, archaeologists studying these questions were limited mostly to digging up skeletons and artifacts.

But now scientists have begun extracting DNA from human bones, and the findings are providing new glimpses at the history of the first Americans. On Monday, researchers at the University of Alaska and elsewhere published an important addition to the growing genetic archive.

In the Proceedings of the National Academy of Sciences, the researchers reported that they had  recovered DNA from two skeletons of children who lived in Alaska 11,500 years ago. The genetic material is not only among the oldest ever found in the Americas, but also the first ancient DNA discovered in Beringia, the region around the Bering Strait where many researchers believe Asians first settled before spreading through North and South America.

The archaeological site, near Upward Sun River, was discovered in 2010. Excavations there have revealed that between 13,200 and 8,000 years ago, people visited during the summer, catching salmon and hares. They built tentlike structures where they made fires and slept.

In 2011, archaeologists discovered cremated bones on a hearth at the site. Research revealed that the bones belonged to a 3-year-old child. Below the hearth, the team discovered a burial pit containing the skeletons of two other children.

One of the buried children was an infant who died a few months after birth; the other was likely a late-term fetus. After the baby and the fetus died, their bodies were carefully laid atop a bed of red ocher, surrounded by antlers fashioned into hunting darts.

"These things we hardly ever find — it's a very rare window into the worldview of these people," said Ben A. Potter, an archaeologist at the University of Alaska Fairbanks who has led the research at Upward Sun River.

Clearly, the children had been ceremonially buried. But why the two bodies ended up in the same grave is impossible to know. With the consent of Native American tribes that live around the site, Dr. Potter and his colleagues drilled small pieces of bone from the two skeletons and sent them to geneticists at the University of Utah.

The vast majority of our DNA lies in the nucleus of the cell. But the cell's energy factories, called mitochondria, also carry small bits of their own DNA inherited solely from our mothers.

Because each cell can contain hundreds of mitochondria, it is easier to reconstruct their DNA than that of the cellular nuclei. The Utah geneticists focused their search on mitochondrial DNA in the Upward Sun River bones.

They succeeded in recovering mitochondrial DNA from both bone samples. But to their surprise, the genes were markedly different. The infant and the fetus did not share the same mother or even maternal grandmother.

The researchers can only speculate how an infant and a fetus from different mothers ended up in the same grave. They might have had the same father, or they might have belonged to different families who suffered terrible losses at the same time.

But the significance of the DNA found at Upward Sun River extends far beyond the story of two children. It sheds light on how people first moved into the Americas.

In 2007, Ripan Malhi of the University of Illinois and his colleagues proposed a model for this migration, known as the Beringian Standstill. Early Siberians expanded east into Beringia about 25,000 years ago, they proposed, and stayed there for about 10,000 years.

Humans were able to thrive in Beringia because even at the height of the last ice age, the region was not covered by glaciers. It was mainly tundra and shrub land, with scattered stands of trees.

Humans could not expand eastward into the rest of the Americas because they were blocked by glaciers. About 15,000 years ago, as the glaciers retreated, the standstill came to an end.

"It opened up new ecological zones that were being colonized by plants and animals," said Dennis O'Rourke of the University of Utah, a co-author of the new study.

According to the standstill hypothesis, the ancestors of Native Americans would have built up a large degree of genetic diversity in the thousands of years they were confined to Beringia — more so than if these populations had migrated directly from Siberia to the Americas.

The fact that two children who died at roughly the same time in the same community shared so few genes is consistent with the idea that the population was prevented from moving into the Americas for thousands of years, Dr. O'Rourke said.

But the two children died after the glaciers melted, he noted, and their settlement "may well be a remnant of that original Beringian group. It may give us a snapshot of that earlier time."

Dr. Malhi, who was not involved in the new study, thought the new DNA was too recent to provide proof of the idea that humans were trapped in Beringia for thousands of years. "It's valuable information, but it's a little bit late to be extremely informative to let us know if the Beringian Standstill hypothesis holds," he said.

More conclusive findings would be possible if scientists found older DNA from people who lived during the Beringian Standstill. Archaeologists are now looking for skeletons from that age, but Dr. Malhi is not holding his breath.

Many of the sites where people lived may now be impossible to reach, because sea levels rose at the end of the ice age.

"There are archaeologists up there looking for such sites," Dr. Malhi said. "But I think it's probably unlikely, largely because a lot of Beringia is now under water."

[crazy canuck]

Very interesting if they can trace this to the Bronze Age collapse.

I read 1177 B.C., The Year Civilization Collapsed relatively recently and I don't remember an epidemic being high up on the list of possible causes. It was combination of climate change leading to famine and migration/invasion.

Yes.  that is why it would be interesting if it could be traced to the collapse.  New information, in an era where there is scant evidence, giving rise to new theories to advance our knowledge and all that.

[MadImmortalMan]

1177 B.C., The Year Civilization Collapsed

Any good?

[The Brain]

1177 B.C., The Year Civilization Collapsed

Any good?

Sure, if you hate civilization.

[crazy canuck]

1177 B.C., The Year Civilization Collapsed

Any good?

Yeah, we talked about it in the books thread.  Great read.  And in the thread there is a link to the author's excellent lecture on the topic.

[jimmy olsen]

I was just quoted by one the head authors of the Homo Naledi discovery. 

I've long championed John Hawks blog and given his work with Lee Berger, I feel vindicated. I was thrilled to see him quote one of my old emails to him in it.

Click here to see accompanying photos and figures. My words are in bold.
http://johnhawks.net/weblog/reviews/denisova/sawyer-2015-denisova-8.html

Another Denisovan from Denisova Cave
18 Nov 2015

Denisova Cave is one of the most fascinating places in the story of human origins. The cave is in the northern wall of the Anuy River valley, within the Altai Krai region of Russia but very near the border with the Altai Republic.

The cave's East Gallery, where excavators still work through part of the Altai summer, feels like a walk-in refrigerator. Archaeologists work inside wearing rugged jackets as they work slowly down through sediments at five degrees Celsius. In the winter, the temperature inside the cave is below freezing. The exceptional cold has made this cave into a time capsule for ancient genetic sequences.

The fossil hominins from the cave are mere scraps, some of them possibly leftovers from hyena meals. But before now three of the bones and teeth have produced genetic sequences, including two from a previously-unknown population that we now call the "Denisovans".

Today there's something new. Another hominin tooth, Denisova 8, has now yielded a partial low-coverage genome, and we can welcome it as a new member of the Denisovan population. Its DNA sequence shows that this tooth is older than the other Denisovan specimens, maybe 60,000 years older. And its DNA increases the diversity of the known sample of Denisovan specimens.

What's important about this? And how does it fit into the already-complicated Denisova family?

The Denisova cast of characters

The story of the hominins from this cave has been fast-moving for the last five years. If you haven't been following closely, it probably seems like a telenovella. Many characters jump out for attention, each with a special, distinctive story.

The first and most famous of the specimens is the distal phalanx from a fifth finger, Denisova 3. When ancient mitochondrial DNA from Denisova 3 was first reported in 2010 by Johannes Krause and colleagues, they found it was very different from any known human or Neandertal—so different that they called this hominin the "X-Woman".

That name didn't last long. Later in 2010, David Reich and colleagues followed up on the mtDNA by sequencing a low-coverage nuclear genome from the specimen. They showed that even though the mtDNA of Denisova 3 last shared an ancestor with us more than a million years ago, the nuclear genome is much less divergent. The "Denisovan" really did belong to a previously unknown population, very different from living humans. But it shared an ancestry with Neandertals within the last half million years.

At the same time, Reich and colleagues sampled the mtDNA from a second hominin specimen. This one, Denisova 4, is a third molar, or "wisdom tooth" representing a different individual from the finger bone. The mtDNA of this tooth is not identical to the finger, but it does belong to the same highly divergent lineage.

In 2012, Mattias Meyer and colleagues did more work on the Denisova 3 sample, ultimately yielding a very high coverage genome. From this genome it was possible to show that Denisova 3 came from a very endogamous population, one that had been small for a very long time.

Then, in 2014, Kay Prüfer and colleagues sequenced the DNA from another Denisova Cave specimen. This one, a toe bone, came from a similar archaeological level as the original Denisova 3 sequence, although it lay a bit lower in the sequence and therefore is probably a bit older. This toe bone produced another high-coverage genome, the second from the site. And unlike the other two Denisova specimens, this toe belonged to a Neandertal.

That's quite a trick, telling Neandertals from previously unknown populations based on fingers and toes. Anthropologists would never attempt such a thing from the bones themselves. Or, maybe more accurately, some anthropologists would make extravagant claims from the finger and toe bones, and they would be fools.

But a whole genome gives millions of bits of evidence about relationships. The two Denisova mtDNA sequences stand apart from any known Neandertal or modern human. The nuclear genome of Denisova 3 differs from any known Neandertal or modern human at millions of base pairs. Still, that Denisova 3 genome has large stretches of DNA shared with the Neandertal toe bone, indicating that the Neandertal population interbred with the ancestors of the Denisovan individuals at some point.

And the Neandertal toe bone itself was highly inbred—as homozygous across its whole genome as people whose parents are half-siblings.

It's a Paleolithic telenovella.
Denisova 8

Now, Susanna Sawyer and colleagues report this week in Proceedings of the National Academy of Sciences on the genetic data from a third Denisovan individual, Denisova 8. And they add nuclear genetic sequence, at low coverage, from the Denisova 4 tooth.

Denisova 8 is another tooth, again, likely a third molar. The two teeth are morphologically different from each other, with little indication that they reflect a single gene pool, except that the teeth are both quite large relative to most later Pleistocene humans.

One of the main genetic results is that the two molars (Denisova 4 and 8) clearly group with the original pinky (Denisova 3) genome in their nuclear and mitochondrial DNA. However, Denisova 8 is an outlier to the other two, more different from them in mtDNA sequence than any Neandertals are from each other, and somewhat more different in the nuclear genome than would be typical for Neandertals.

Part of that difference is due to the age of Denisova 8. Its mtDNA branch is shorter than the other two specimens. It is missing evolutionary history that is present in Denisova 3 and Denisova 4, enough to suggest that Denisova 8 lived some 60,000 years earlier in time than those other two. The nuclear genome is consistent with such an age estimate, although the low-coverage sequence is not really sufficient to give an any accuracy on its own. So one reason why Denisova 8 increases the diversity of the Denisova sample is that it lacks tens of thousands of years of genetic drift that was shared in the ancestry of the later specimens.

Still, when we look at the variation in the two low-coverage genomes from Denisova 4 and 8 in comparison with the high-coverage Denisova 3 genome, all the Denisovans together seem to have been just a bit less inbred than Neandertals. Sawyer and colleagues provide a measure of genetic difference between genomes that is scaled to the difference between humans and chimpanzees. To accomplish this measurement, they take the preserved sequence that overlaps between two low-coverage genomes (or high-coverage genomes), examine every site within the overlapping sequence where either of the two hominin sequences differs from the chimpanzee genome, and examine the fraction of times that the two hominin sequences are discrepant from each other. This gives a measure of difference between the two genomes relative to their difference from chimpanzees.

For the Denisovan genomes, this difference averages 2.9 percent. For Neandertal genomes compared to each other, the difference averages 2.5 percent. So Denisovans are a bit more diverse than Neandertals by this measure.

For human populations, the differences range between 4.2 and 9.5 percent. The least diverse pair of individuals are Karitiana people from South America. This highly endogamous human group is still half again as diverse as Denisovans.

Both the Denisovans and Neandertals were very endogamous relative to today's people, even just comparing to Europeans today. That endogamy must reflect something about the ancient population structure of these archaic people. One consequence of the endogamy — as two preprints by Graham Coop's lab and Rasmus Nielsen's lab show — is that Neandertals may have carried a load of slightly deleterious genetic variants. When the Neandertals and Denisovans mated with the more diverse population that dispersed from Africa in the Late Pleistocene, some of these deleterious genetic variants may have been slowly weeded out of the modern human population by purifying selection.

How big were the Denisovans' teeth?

We don't know very much about what Denisovans may have looked like, with only a fingertip and two wisdom teeth to go on. So it's tempting to take these slim data and make something more out of them than we probably should.

With two teeth, we at least can measure their sizes. They're big. Bigger than most living humans, bigger than any Neandertals, as big as some third molars of Australopithecus.

We can't make too much out of the large size of these third molars, because similarly large teeth do occasionally occur among Upper Paleolithic people. The supplementary material to Sawyer and colleagues' paper gives a brief review, noting that the Oase 2 skull has such a large third molar, as does a tooth from a partial juvenile dentition of a probable Neandertal from Obi-Rakhmat, Uzbekistan.

    Two Late Pleistocene specimens are comparably large in size, the M3s of the early Upper Paleolithic modern human Oase 2 and the M2/3 of Obi-Rakhmat 1 (14, 15). Oase 2 does not show large extra cusps, but instead strong crenulation (16). Obi-Rakhmat shows a large extra cusp, but mesially, not distally (Main text, Figure 1), and a large number of accessory cusps possibly due to gemination (17).

The Oase 2 specimen is the earliest modern human known from Europe. This is not the same individual as the Oase 1 mandible, but it may be relevant that the Oase 1 specimen had more Neandertal ancestry than any known living person, and that Neandertal ancestry was quite recent, possibly within four generations.

Is it odd that we have large third molars in some individuals in Eastern Europe and Central Asia, including the Denisovans? I think to answer this we will need a larger sample of fossil humans from other places. There is at least one Chinese third molar specimen from Xujiayao that approaches the size of these large teeth. Perhaps the Chinese specimen is a Denisovan, or maybe this is one morphological extreme that is distributed among Late Pleistocene populations.

The thing is, if there was one piece of morphological evidence I would throw away and pay no attention to above all others, it's the morphology of the third molar. It is just enormously variable among living humans and living primates. I wouldn't trust it to tell us about relationships of hominin groups.

OK, so maybe I would trust the third molar above the pinky finger.

UPDATE (2015-11-18): I've known about these results for a long time, as the authors kindly shared them with me. But I forgot that the results were also previously a part of the documentary "Sex in the Stone Age", until I found a letter from a reader in my archives:

   

I just watched the National Geographic documentary "Sex in the Stone Age" and was surprised by the reference to the discovery of a 2nd Denisovan tooth, one whose mitochondrial DNA was distinct enough from that of the mtDNA in the finger and original tooth to indicate that the Denisovan population had as much genetic diversity as H. Sapiens currently has today. This is interesting, since if I recall correctly, Neanderthals had low levels of genetic diversity, with evidence of replacement of their western European population by an Eastern population. This perhaps indicates that the Denisoans had a larger population than that of the Neanderthals. I don't recall reading about this find on your website or anywhere else.

At the time I gave some context to that report from the documentary but had little more to say.

What's interesting about this week's publication is that the nuclear genome and mtDNA have contrasting patterns. The genetic variation within Denisovans is best assessed across the nuclear genome, and they are low in a similar way as Neandertals.

Still, the Neandertal sample covers a very large geographic area, from Spain to the Altai. Our intuition might lead us to expect that extensive range to encompass more variation than three Denisovan individuals from a single site. But the Denisovan genomes cover a longer time than the low-coverage Neandertal genomes, and across such a time they may actually sample very different populations. If we had a Neandertal low-coverage genome as early as Denisova 8, their variation might look different.

To me, the core observation is that both these populations were highly endogamous compared to any living human groups. I'll have a bit more to say about the mtDNA discrepancy shortly...
Reference

Sawyer S, Renaud G, Viola B, Hublin J-J, Gansauge M-T, Shunkov MV, Derevianko AP, Prüfer K, Kelso J, Pääbo S. 2015. Nuclear and mitochondrial DNA sequences from two Denisovan individuals. Proceedings of the National Academy of Sciences, USA (early edition) doi:10.1073/pnas.1519905112

[Malthus]

Heh, that's pretty awesome. 

[The Brain]

[jimmy olsen]

The Anatolian hypothesis is triumphant! The Neolithic farmers of Europe were primarily descended from Anatolian settlers.

http://dienekes.blogspot.kr/2015/11/neolithic-farmers-from-greece-and.html

Neolithic farmers from Greece and Anatolia

A couple of new papers appeared this week. First, an article in Nature on natural selection in ancient Europe includes a sample of Anatolian Neolithic farmers and concludes that the European Neolithic farmers were descended from them with a bit of extra European hunter-gatherer admixture. Second, a new preprint on the bioRxiv includes Neolithic samples from northern Greece and finds that they too resemble the Anatolian and European farmers. I think it is time to declare the problem of "Neolithization of Europe" done. It took less than 4 years to solve it with ancient DNA. Here is a (non-exhaustive) list of papers in historical review:

Keller et al. (2012): Iceman (5kya) looks Sardinian! Was this a fluke?
Skoglund et al. (2012): No, because... Swedish farmer (5kya) looked Sardinian too! When did these "Sardinians" come to Europe?
Lazaridis et al. (2014): No later than an LBK farmer from Germany (7kya) but what about western Europe?
Haak, Lazaridis et al. (2015): Spanish early farmers from northern Spain looked Sardinian too
Olalde, Schroeder et al. (2015): Ditto for Mediterranean Spain! So where did they all come from?
Mathieson et al. (2015): Anatolia!
Hofmanová, Kreutzer et al. (2015): via Greece!

Iain Mathieson et al.

Ancient DNA makes it possible to observe natural selection directly by analysing samples from populations before, during and after adaptation events. Here we report a genome-wide scan for selection using ancient DNA, capitalizing on the largest ancient DNA data set yet assembled: 230 West Eurasians who lived between 6500 and 300 BC, including 163 with newly reported data. The new samples include, to our knowledge, the first genome-wide ancient DNA from Anatolian Neolithic farmers, whose genetic material we obtained by extracting from petrous bones, and who we show were members of the population that was the source of Europe's first farmers. We also report a transect of the steppe region in Samara between 5600 and 300 BC, which allows us to identify admixture into the steppe from at least two external sources. We detect selection at loci associated with diet, pigmentation and immunity, and two independent episodes of selection on height.

Early farmers from across Europe directly descended from Neolithic Aegeans

Zuzana Hofmanová, Susanne Kreutzer et al.

Farming and sedentism first appear in southwest Asia during the early Holocene and later spread to neighboring regions, including Europe, along multiple dispersal routes. Conspicuous uncertainties remain about the relative roles of migration, cultural diffusion and admixture with local foragers in the early Neolithisation of Europe. Here we present paleogenomic data for five Neolithic individuals from northwestern Turkey and northern Greece, spanning the time and region of the earliest spread of farming into Europe. We observe striking genetic similarity both among Aegean early farmers and with those from across Europe. Our study demonstrates a direct genetic link between Mediterranean and Central European early farmers and those of Greece and Anatolia, extending the European Neolithic migratory chain all the way back to southwestern Asia.

[Jaron]

Tim, you are famous!

[Queequeg]

The Anatolian hypothesis is primarily linguistic.  And it's rubbish. 

[jimmy olsen]

The Anatolian hypothesis is primarily linguistic.  And it's rubbish.

Who do you think speaks a language? Who spreads it?

It's people of course.

The farmers of Anatolia colonized Europe, overwhelming the natives with the numbers and assimilating them. They doubtlessly brought their language with them.

[Queequeg]

That would be ancestral to Pelasgian or Etruscan, NOT Indo-European.  Indo-European has NO relationship with any of the NUMEROUS attested autochthonous languages of Anatolia prior to the invasion of the Hittites, and has a relatively clear relationship with the Uralic and NW Caucasian language groups. 

[Razgovory]

Tim, I don't think you understand what the Anatolian Hypothesis is.  It has to do with the homeland of Proto-Indo Europeans not where farming came from.