July 02, 2014

Altitude adaptation in Tibetans came from Denisovans

This is somewhat strange given that Denisova cave is not at high altitude.

Nature (2014) doi:10.1038/nature13408

Altitude adaptation in Tibetans caused by introgression of Denisovan-like DNA

Emilia Huerta-Sánchez et al.

As modern humans migrated out of Africa, they encountered many new environmental conditions, including greater temperature extremes, different pathogens and higher altitudes. These diverse environments are likely to have acted as agents of natural selection and to have led to local adaptations. One of the most celebrated examples in humans is the adaptation of Tibetans to the hypoxic environment of the high-altitude Tibetan plateau1, 2, 3. A hypoxia pathway gene, EPAS1, was previously identified as having the most extreme signature of positive selection in Tibetans4, 5, 6, 7, 8, 9, 10, and was shown to be associated with differences in haemoglobin concentration at high altitude. Re-sequencing the region around EPAS1 in 40 Tibetan and 40 Han individuals, we find that this gene has a highly unusual haplotype structure that can only be convincingly explained by introgression of DNA from Denisovan or Denisovan-related individuals into humans. Scanning a larger set of worldwide populations, we find that the selected haplotype is only found in Denisovans and in Tibetans, and at very low frequency among Han Chinese. Furthermore, the length of the haplotype, and the fact that it is not found in any other populations, makes it unlikely that the haplotype sharing between Tibetans and Denisovans was caused by incomplete ancestral lineage sorting rather than introgression. Our findings illustrate that admixture with other hominin species has provided genetic variation that helped humans to adapt to new environments.

Link

29 comments:

Mike Keesey said...

The one place we've found Denisovans is probably not the only place they ever lived. Thinking so would be like living in 1857 and assuming that Neandertals only lived in Kleine Feldhofer Grotte.

In fact a lot of Ice Age animals have origins in the Tibetan plateau: https://news.usc.edu/63909/high-altitude-tibet-was-the-cradle-of-evolution-for-cold-adapted-mammals-new-study-finds/

ron quiroriano said...

That is a very interesting turn of events.
So only Tibetans carry the high altitude adaptation that evolved in denisovans, while not found in other populations.
Does that not put some constraints on how AMH dispersed in east Asia and the Americas

Vincent said...

Very interesting. I think there's a link between Y-DNA D-M174 in Tibetans and this "Denisovan-like" gene. D-M174 and DE-M145 are probably the earliest AMH in Asia, it is normal to assume that their carriers may have interbred with Denisovans (and Neanderthals, of course).
Before anyone mentions them to attack my hypothesis, the Andamanese Islanders are very probably descended from a source population in India that bifurcated: one population went northward into Tibet and North-East Asia (D1a, D1b, D1c), the other went westward and then southward into the Andaman Islands and Southeast Asia. I don't know for sure if this is also the case for Andamanese people, but recently the FTDNA project of haplogroup D by Ray Banks reports the discovery of a new sub-clade, D4 (now D2) in a pair of relatives previously thought to be D* from Cebu Island, Philippines. Maybe the Andamanese are also D2, who knows.

n/a said...

Wat?

That would only be remotely strange if you thought "Denisovans" were restricted to the eponymous site. Based on patterns of archaic admixture in modern humans, it's always been obvious "Denisovans" must have been more widespread, with SE Asia being the likely major location of admixture. Comparisons of the ancient DNA with the archaic segments in modern humans also indicate a great deal of divergence between the Denisova cave population and the population that actually contributed "Denisovan" admixture.

aniasi said...

Do you know if there are any other studies looking at Denisovan DNA in other populations? I think the most remarkable thing here is that Denisovan admixture has been found outside of an Aboriginal Southeast Asian population.

andrew said...

Also stunning that it is found in a population with otherwise almost non-detectable Denisovan admixture, in a population that likely didn't arrive in Tibet until after the Denisovan population was extinct.

Most plausibly, one would imagine a modern human with Denisovan admixture from SE Asia making his way to the proto-Tibetan population, and leaving an undetectable contribution to the Tibetan gene pool except for his fitness enhancing genes which he owed to Denisovan admixture in his distant ancestors thousands of years later.

Given the fact that some West Eurasian uniparental hgs apparently made their way to West Eurasia by back migration, this scenario isn't as far fetched as it might seem.

terryt said...

"this gene has a highly unusual haplotype structure that can only be convincingly explained by introgression of DNA from Denisovan or Denisovan-related individuals into humans".

That makes complete sense. After all Denisovans had lived for a very long time at extreme northern latitudes and so had plenty of time to adapt to high altitude as well.

"Our findings illustrate that admixture with other hominin species has provided genetic variation that helped humans to adapt to new environments".

I believe we have just begun to scratch the surface here. So far we have genetic signatures from just two archaic populations and so we don't yet know what we are looking for in the case of other archaic populations.

Kes said...

I knew it! Yetis were Denisovans!

...

Seriously though, this is a bit of a surprise. Or maybe the connection is some mountain-adapted Homo Erectus group (and Denisovans are simply the closest proxies for which we have data?)

Crimson Guard said...

Tibetan type appears to be a composite of some kind:

http://i58.tinypic.com/f1h5dt.png
http://i60.tinypic.com/2llbtc3.png

"Races: A Study..." By Carleton Coon

eurologist said...

It appears that this admixture must have taken place before the separation of Tibetans and Han, but at a point when at least partial Mongoloid features were already evolved or (more likely) introgressed - perhaps via the same admixture. Given findings so far in northern China, I would date this to before 45,000 ya, and it also supports a northern migration route (and before the Siberian y-DNA Q and R migrations).

Grey said...

cool

About Time said...

I wouldn't be surprised if many or even most major physical adaptations in humans are from archaics living in diverse environments with less technology than sapiens.

f9d6dd44-03a6-11e4-9110-971a6bcebb66 said...

Maybe Chna just recently got rid of all the Denisovan descendants behind the curtain. How would we know? Does it look like it?

Is it at all possible the Denisovan Hominim was a forgery?

Geopolitical events ad many questions to these claims.
Some of these claims have too much weight on geopolitics to dismiss possibility of forgeries.
Technology makes forgeries impossible to detect especially at the highest national levels that would be involved in these cases.

Raimo Kangasniemi said...

There's speculation that in Denisova's this ability might have helped them to adapt to cold climates.

safar bikram adhikari said...

I have a query....
An article published in the Journal of the Near eastern studies (1959, Vol. 18) presents some evidence of a black population in the region of the south eastern corner of the Black sea and later to Caucasus region farther north. These Kassite did not migrate towards South with main bodies of Kassites but settled in the region of India and do you believe that these same Kassites were the Kusshians, who once ruled in Tarim Basin (present day Xinjiang region, China)and their capital being Kashgar ?

Chad Rohlfsen said...

I haven't followed the Denisovan/Neanderthal links very well, but I have something that I'm pondering. Is it possible that Denisovans are a Basal population that broke off from say, Heidelbergensis. Neanderthals are then derived and split into a Western and Eastern Eurasian group. The Eastern group being this unknown hominid in East Eurasia.

terryt said...

"Or maybe the connection is some mountain-adapted Homo Erectus group (and Denisovans are simply the closest proxies for which we have data?)"

I think that is very likely correct.

"this admixture must have taken place before the separation of Tibetans and Han, but at a point when at least partial Mongoloid features were already evolved or (more likely) introgressed - perhaps via the same admixture".

That is also likely correct. The EDAR370A mutation (which is certainly associated with much of the 'Mongoloid' phenotype) looks to have originated somewhere near the northeast Tibet/China border region and spread from there. The mutation covered in the present paper could easily have entered the modern human gene pool at the same time and place. However the EDAR mutation is said to have appeared in modern hujmansd around 35,000 years ago. That is considerably more recent than the 'before 45,000 ya.' you propose.

"it also supports a northern migration route (and before the Siberian y-DNA Q and R migrations)".

I have been convinced for many years that the distribution and phylogeny of both Y-DNA C and mt-DNA N indicates a northern route eastward for those haplogroups.

"I wouldn't be surprised if many or even most major physical adaptations in humans are from archaics living in diverse environments with less technology than sapiens".

Most likely so. Razib has even coined a term for it, 'multiregionalism':

http://www.unz.com/gnxp/a-vindication-of-multi-regionalism-in-adaptation-not-ancestry/

Obviously not mutiregionalism in the old sense of 'regional continuity' though.

"In fact a lot of Ice Age animals have origins in the Tibetan plateau: https://news.usc.edu/63909/high-altitude-tibet-was-the-cradle-of-evolution-for-cold-adapted-mammals-new-study-finds/"

Nice find. Quote:

"the team’s new fossil assemblage offers an alternative scenario, which the authors call the “out of Tibet” hypothesis. It argues that some of the Ice Age megafauna (which in North America include the woolly mammoth, saber-toothed cat, giant sloths and others) used ancient Tibet as a “training ground” for developing adaptations that allowed them to cope with the severe climatic conditions. These Tibetan ancestors were thus pre-adapted to cold climates during the Ice Age (2.6 to .01 million years ago)".

Recently it was discovered that many hair samples considered to ne 'Yeti' are actually from a bear closely related to the modern polar bear:

http://www.sci-news.com/genetics/science-bigfoot-yeti-hair-samples-match-dna-paleolithic-polar-bear-known-mammals-02044.html

eurologist said...

Vincent,

I agree with you - as I have always said, y-DNA haplogroup D (& DE) looks like a remnant population; the first AMH population in Asia, and the first one to admix with heidelbergensis and erectus-like or erectus-admixed populations.

German Dziebel said...

@Eurologist

"I agree with you - as I have always said, y-DNA haplogroup D (& DE) looks like a remnant population; the first AMH population in Asia, and the first one to admix with heidelbergensis and erectus-like or erectus-admixed populations."

FYI: Ust-Ishim, the oldest modern human DNA plus the one that shows admixture with Neandertals at greater proportion that the rest of modern humans is not DE or D or E.

Arvid Eriksson said...

What about the asian version of the "ATP-binding cassette C11 gene" that gives dry earwax and is associated with reduced body odor / sweat? Could this also be come from Denisovans?

eurologist said...

"However the EDAR mutation is said to have appeared in modern hujmansd around 35,000 years ago. That is considerably more recent than the 'before 45,000 ya.' you propose."

Terry,

I know - but that date is ridiculously late. We have "Aurignacian-associated" Central Siberians by 50,000 - 45,000 ya, and "Gravettian-associated" Siberians all the way to the East by 35,000 ya --- none of them originally with Mongoloid features, and most likely none of them with y-DNA haplogroup DE/D.


"FYI: Ust-Ishim, the oldest modern human DNA plus the one that shows admixture with Neandertals at greater proportion that the rest of modern humans is not DE or D or E."

German,

What is it, then? AFAIK it has not officially been published, yet.

In the thread were many of us tried to guess Ust-Ishim's y-DNA haplogroup in advance, I think I voted for P or Q.

terryt said...

"FYI: Ust-Ishim, the oldest modern human DNA plus the one that shows admixture with Neandertals at greater proportion that the rest of modern humans is not DE or D or E".

Don't keep us in suspense, German. Tell us what it is. Or are you making things up again?

Vincent said...

"FYI: Ust-Ishim, the oldest modern human DNA plus the one that shows admixture with Neandertals at greater proportion that the rest of modern humans is not DE or D or E".

There is no evidence for this, and the haplogroups you mentioned are as possible as C, CF, CT, although I think C is more probable because it is likely that Ust-Ishim was the ancestor of Kostenki 14 (who was C IMO)

terryt said...

"that date is ridiculously late. We have 'Aurignacian-associated' Central Siberians by 50,000 - 45,000 ya, and 'Gravettian-associated' Siberians all the way to the East by 35,000 ya --- none of them originally with Mongoloid features, and most likely none of them with y-DNA haplogroup DE/D".

Because none of them originally had Mongoloid features it is virtually certain they did not have the particular EDAR mutation. In other words 'Mongoloid features' north of northern China postdate the earliest human presence in the region. And the cultures you list predate the development of Mongoloid features. The introgression of the Denisovan 'survival' gene must postdate those culture as well. And don't forget diploid DNA is almost completely independent of haploid DNA although usually any spread of diploid DNA would be carried at least partly by the expansion of some haplogroup(s). Any introgression into modern humans would have been into pre-existing modern haplogroups in the region. Therefore it is quite possible that members of a particular hapligroup could both have and lack particular a-DNA.

"In the thread were many of us tried to guess Ust-Ishim's y-DNA haplogroup in advance, I think I voted for P or Q".

Like Vincent I voted for C. Although I am sure it was neither C1 nor C2 at that time. Although:

"it is likely that Ust-Ishim was the ancestor of Kostenki 14 (who was C IMO)"

I can find no reference to Kostenki 14 being Y-DNA C. The nearest I've seen is that it was mt-DNA U2 and probably Y-DNA R1a.

German Dziebel said...

@Eurologist

"What is it, then? AFAIK it has not officially been published, yet.

In the thread were many of us tried to guess Ust-Ishim's y-DNA haplogroup in advance, I think I voted for P or Q."

It's not P or Q.

@terryT

"Don't keep us in suspense, German. Tell us what it is. Or are you making things up again?"

I never make things up. I just know what you don't know.

@Vincent

"There is no evidence for this, and the haplogroups you mentioned are as possible as C, CF, CT, although I think C is more probable because it is likely that Ust-Ishim was the ancestor of Kostenki 14 (who was C IMO)."

It's not C.

Vincent said...

"I can find no reference to Kostenki 14 being Y-DNA C. The nearest I've seen is that it was mt-DNA U2 and probably Y-DNA R1a."

In fact it is my personal hypothesis on the basis of physical anthropological evidence, you wouldn't find any reference to that. R1a? Extremely unlikely, it is too young. But I wouldn't be surprised if he had D either.

Vincent said...

"Analyses of the relationship of the Ust-Ishim individual to present-day humans show that he is closely related to the ancestral population shared between present-day Europeans and present-day Asians."

https://mcidublin.conference-services.net/reports/template/onetextabstract.xml?xsl=template/onetextabstract.xsl&conferenceID=3958&abstractID=811773

If this doesn't favour a CF-derived haplogroup, I don't know what does.

terryt said...

"I never make things up. I just know what you don't know".

If you know why are you being so evasive?

German Dziebel said...

@TerryT

"If you know why are you being so evasive?"

For the same ethical reason as before: the paper hasn't been officially published yet and I don't want to leak anything specific from it. And I don't want to make private conversations public. We just have to be patient. It's not going to be earth-shattering when it comes to Y-DNA. It's the presence of the longest (among modern human populations) Neandertal chunks in Amerindians, as can be seen in Paabo's presentation on Ust-Ishim, that's interesting to ponder.