Extinct human cousin gave Tibetans advantage at high elevation

Jul 02, 2014
A Chinese researcher collects a blood sample from an ethnic Tibetan man participating in the DNA study. Credit: Beijing Genomics Institute (BGI-Shenzhen)

Tibetans were able to adapt to high altitudes thanks to a gene picked up when their ancestors mated with a species of human they helped push to extinction, according to a new report by University of California, Berkeley, scientists.

An unusual variant of a gene involved in regulating the body's production of hemoglobin – the molecule that carries oxygen in the blood – became widespread in Tibetans after they moved onto the high-altitude plateau several thousand years ago. This variant allowed them to survive despite low oxygen levels at elevations of 15,000 feet or more, whereas most people develop thick blood at , leading to cardiovascular problems.

"We have very clear evidence that this version of the gene came from Denisovans," a mysterious human relative that went extinct 40,000-50,000 years ago, around the same time as the more well-known Neanderthals, under pressure from modern humans, said principal author Rasmus Nielsen, UC Berkeley professor of integrative biology. "This shows very clearly and directly that humans evolved and adapted to new environments by getting their from another species."

This is the first time a gene from another species of human has been shown unequivocally to have helped modern humans adapt to their environment, he said.

Nielsen and his colleagues at BGI-Shenzhen in China will report their findings online July 2 in advance of publication in the journal Nature.

The gene, called EPAS1, is activated when oxygen levels in the blood drop, triggering production of more hemoglobin. The gene has been referred to as the superathlete gene because at low elevations, some variants of it help athletes quickly boost hemoglobin and thus the oxygen-carrying capacity of their blood, upping endurance. At high altitude, however, the common variants of the gene boost hemoglobin and its carrier, , too much, increasing the thickness of the blood and leading to hypertension and heart attacks as well as low-birth-weight babies and increased infant mortality. The variant or allele found in Tibetans raises hemoglobin and red blood cell levels only slightly at high elevation, avoiding the side-effects seen in most people who relocate to elevations above 13,000 feet.

"We found part of the EPAS1 gene in Tibetans is almost identical to the gene in Denisovans and very different from all other humans," Nielsen said. "We can do a statistical analysis to show that this must have come from Denisovans. There is no other way of explaining the data."

Harsh conditions on Tibetan plateau

The researchers first reported the prevalence of a high-altitude version of EPAS1 in Tibetans in 2010, based on sequencing of the genomes of numerous Han Chinese and Tibetans. Nielsen and his colleagues argued that this was the result of natural selection to adapt to about 40 percent lower on the Tibetan plateau. That is, people without the variant died before reproducing at a much higher rate than those with it. About 87 percent of Tibetans now have the high-altitude version, compared to only 9 percent of Han Chinese, who have the same common ancestor as Tibetans.

Nielsen and his colleagues subsequently sequenced the EPAS1 gene in an additional 40 Tibetans and 40 Han Chinese. The data revealed that the high-altitude variant of EPAS1 is so unusual that it could only have come from Denisovans. Aside from its low frequency in Han Chinese, it occurs in no other known humans, not even Melanesians, whose genomes are nearly 5 percent Denisovan. A high quality sequence of the Denisovan genome was published in 2012.

Nielsen sketched out a possible scenario leading to this result: coming out of Africa interbred with Denisovan populations in Eurasia as they passed through that area into China, and their descendants still retain a small percentage – perhaps 0.1 percent – Denisovan DNA. The group that invaded China eventually split, with one population moving into Tibet and the other, now known as Han Chinese, dominating the lower elevations.

He and his colleagues are analyzing other genomes to pin down the time of Denisovan interbreeding, which probably happened over a rather short period of time.

"There might be many other species from which we also got DNA, but we don't know because we don't have the genomes," Nielsen said. "The only reason we can say that this bit of DNA is Denisovan is because of this lucky accident of sequencing DNA from a little bone found in a cave in Siberia. We found the Denisovan species at the DNA level, but how many other species are out there that we haven't sequenced?"

Explore further: The genetic origins of high-altitude adaptations in Tibetans

More information: Altitude adaptation in Tibetans caused by introgression of Denisovan-like DNA, Nature, dx.doi.org/10.1038/nature13408

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Sean_W
2.6 / 5 (8) Jul 02, 2014
Steal their genes and push them off the mountain. Well done! BWAHAHAHAHAHA!!!!
JVK
1.3 / 5 (16) Jul 03, 2014
Re: "This shows very clearly and directly that humans evolved and adapted to new environments by getting their genes from another species."

Is there a model for that? In all other species ecological variation leads to ecological adaptations via the nutrient-dependent pheromone-controlled conserved molecular mechanisms of amino acid substitutions that differentiate cell types.

If humans evolved by getting their genes from another species, did mutations and natural selection lead to our evolution? I continue to have difficulty following the story line, perhaps because it is preposterous.

Captain Stumpy
4.8 / 5 (16) Jul 03, 2014
I continue to have difficulty following the story line, perhaps because it is preposterous.
@jk
perhaps the difficulty is with your inability to comprehend basic English and learn the basics for things like biology? After all, your own model CREATES MUTATIONS so the problem is NOT the model, it is solely with YOU. remember when I asked
DOES your model make any changes to the nucleotide sequence of the genome of an organism, virus, or extrachromosomal genetic element?
This is a yes or no answer
well... THIS is the DEFINITION of mutation, to which you answered
YES!
--Thanks for asking
which only proves that you DO NOT COMPREHEND the lexicon of your field, nor do you comprehend the basics of your field, likely because you failed out of college. You could NOT learn the basics so now you attack anyone who learns it.

try learning a little yourself. quit attacking mutations and evolution-
BECAUSE YOUR OWN MODEL SUPPORTS EVOLUTION and MUTATION

Sinister1812
5 / 5 (3) Jul 03, 2014
So that's how Bear Grylls became the mountain man.
alfie_null
4.6 / 5 (10) Jul 03, 2014
I continue to have difficulty following the story line

Yes, we know, we know.

Your comportment marks you as a crackpot. Do you acknowledge you are a crackpot? How do you rationalize it? What, do you feel, distinguishes you from other crackpots? Do you believe there is validity in what all crackpots have to say?

Do you believe crackpottery is a good way to advance science? If not, how would you improve the process?
JVK
1.3 / 5 (14) Jul 03, 2014
"As can be expected, the discovered differentially methylated sites were found, not only in gene promoters but also in intragenic regions and in regions potentially harboring enhancers." http://www.ajog.o...abstract

Let's compare epigenetic facts to the pseudoscientific fiction of evolutionary theory in the context of cell type differentiation that links the epigenetic landscape to the physical landscape of DNA in organized genomes in species from microbes to man. How are mutations involved in changes associated with C-section, for example?

http://medicalxpr...tic.html
Returners
2.1 / 5 (7) Jul 03, 2014
There was an experiment on Stan Lee's Super Humans which showed a Tibetan mountaineer who had apparently both very good genes and very experienced in mountain climbing.

In pressure chamber experiments he was able to remain conscious and fully reactive at pressures corresponding to altitudes significantly above the summit of Mt. Everest, by several thousand feet.

That is an example of having both extreme genetic advantage, and extreme personal training.

I think that does qualify him as a "super human" because he may well be the only human alive at that level of this specific type of conditioning.

In spite some some participants being people who only have a high level of skill, the show DID manage to find a few individuals with genetic anomalies or other abilities which cannot be explained through skill and practice, and greatly exceed anything observed in any other human.

In a few cases they were deemed "medically impossible" based on current knowledge, but yet were real....
Returners
2.1 / 5 (7) Jul 03, 2014
Note that normal people with military training to withstand low pressures were not able to remain conscious at levels approaching Everest altitudes, but he went several thousand feet higher.
SoylentGrin
4.3 / 5 (6) Jul 03, 2014
If humans evolved by getting their genes from another species, did mutations and natural selection lead to our evolution?


Why do you think it's either/or? Many factors have gone into how all species have evolved.
Punctuated equilibrium vs. slow changes? Both have occurred. Viral insertion vs. selective mating? Both again. Gene drift vs. point mutations? Both, many times.
cjn
4.3 / 5 (6) Jul 03, 2014
Re: "This shows very clearly and directly that humans evolved and adapted to new environments by getting their genes from another species."
JVK: ...If humans evolved by getting their genes from another species, did mutations and natural selection lead to our evolution? I continue to have difficulty following the story line, perhaps because it is preposterous.


They didn't find these genes just lying around, or from eating some Tibetan fruit -the population picked up this gene by mating with the Denisovan species. Probably not with consent from both parties.
JVK
1 / 5 (12) Jul 03, 2014
De novo gene creation is nutrient-dependent and associated with the epigenetic effects of food odors. Frugivory in bats and their adaptive radiations are the example that directly links vitamin C via quantum physics and quantum biology to a single base pair change and amino acid substitutions that differentiate the cell types of all individuals of all species (except those that have mutated into existence). Which species do you claim mutated into existence via natural selection. What was selected?
Rute
5 / 5 (1) Jul 04, 2014
I'd like to know how large a degree of the regional non-neutral phenotypic variation among people around the world comes from these genes inherited from Neanderthals and Denisovans and the unnamed sister species in Africa (possible others as well). Clearly there have been genetic exchanges of important quality like this study shows.
verkle
1 / 5 (6) Jul 05, 2014
I thought the definition of species was that different species cannot effectively mate with each other. If the Denisovans were a different species, how could they interbreed? I would counclude they were a sub-species, and in fact very human.
TheGhostofOtto1923
4 / 5 (4) Jul 05, 2014
I thought the definition of species was that different species cannot effectively mate with each other. If the Denisovans were a different species, how could they interbreed? I would counclude they were a sub-species, and in fact very human
Do lions and tigers belong to different species even though they can still mate? Did god include them separately on the ark as all the pictures show or did he just use one species of protocat and then force them into different niches afterward which made them change their coloration and also hate each other?

Perhaps you need to do a little research on species.

"The species problem is a mixture of difficult related questions that often come up when biologists define the word "species"."
http://en.wikiped..._problem
cjn
3.7 / 5 (6) Jul 05, 2014
I thought the definition of species was that different species cannot effectively mate with each other. If the Denisovans were a different species, how could they interbreed? I would counclude they were a sub-species, and in fact very human.


They are not "human" by definition. The pre-homo-sapiens sapiens hominid species deviated from our line through emigration events before our the modern human species was in its current form. There were [likely] multiple "Out of Africa" events which allowed waves of the then-current dominant hominid species to exit out of the African continent and populate other areas of Eurasia. The did not continue to evolve the same way as the populations which remained in Africa once they departed. Thus, once the lasted Out of Africa event happened, we were quite distinct from the populations we ended up displacing.
TheGhostofOtto1923
3 / 5 (4) Jul 05, 2014
They are not "human" by definition.
Uh yes they were.

"Denisovans or Denisova hominins /dəˈniːsəvə/ are a Paleolithic-era species of the genus Homo or subspecies of Homo sapiens."

-You did not know this because you didnt bother to look it up.
cjn
4.2 / 5 (5) Jul 05, 2014
-You did not know this because you didnt bother to look it up.


Apparently, someone didn't read the full entry. I'll share it with you:

"Denisovans or Denisova hominins /dÉ�ˈniːsÉ�vÉ�/ are a Paleolithic-era species of the genus Homo or subspecies of Homo sapiens. In March 2010, scientists announced the discovery of a finger bone fragment of a juvenile female who lived about 41,000 years ago, found in the remote Denisova Cave in the Altai Mountains in Siberia, a cave which has also been inhabited by Neanderthals and modern humans. Two teeth and a toe bone belonging to different members of the same population have since been reported.

Analysis of the mitochondrial DNA (mtDNA) of the finger bone showed it to be genetically distinct from the mtDNAs of Neanderthals and modern humans."
antigoracle
1.7 / 5 (6) Jul 05, 2014
Extinct human or elusive Yeti??
JohnGee
5 / 5 (4) Jul 05, 2014
Haha you moron.
TheGhostofOtto1923
3 / 5 (4) Jul 05, 2014
Apparently, someone didn't read the full entry. I'll share it with you
Okay so let's put the 2 together.

"Paleolithic-era species of the genus Homo or subspecies of Homo sapiens... showed it to be genetically distinct from the mtDNAs of Neanderthals and modern humans."

-Is your limited knowledge of genetics able to equate the 2 or does it need to be expanded a bit (a lot?) Apparently 'distinct' is a word with many meanings. Sorry I will defer to the authors of the above study, who are actual scientists.
Returners
1 / 5 (6) Jul 06, 2014
Do lions and tigers belong to different species even though they can still mate? Did god include them separately on the ark as all the pictures show or did he just use one species of protocat and then force them into different niches afterward which made them change their coloration and also hate each other?


The answer to that is unclear.

There is a commandment (to the Jews) which says, in modern language, "not to breed your cattle with a diverse kind." However, that was more of a symbolic, religious symbol just meaning that you shouldn't mix good and bad, sort of like how their sacrifice required the spotless lamb to symbolize a sinless redeemer, the Christ.

However, it is clear that whatever God's intentions, he gave free will to everything, so things are what they are at this point.

It's pretty clear that some organisms interbreed, and some diverge. There's actually an alleged example of a minor divergence recorded in the Bible.
TheGhostofOtto1923
3.7 / 5 (6) Jul 06, 2014
he gave free will to everything, so things are what they are at this point
Yah tell me again how you're not religious Lrrkrrr. You're a Christ-ian.

As to 'free will for everything', does god give the rain the option not to fall? The plants to grow? Are you saying that when lions hate tigers this is just a choice, a form of feline bigotry?
that was more of a symbolic, religious symbol just meaning that you shouldn't mix good and bad
Of course. Another metaphor. So when god said 'don't make graven images', that was a metaphor as well. What about the other commandments? Were they metaphors for a more comprehensive list somewhere?

There is no mt Sinai - was that a metaphor as well? And there was no exodus, no 2M Jews in goshen, no genocidal Joshuan rampage. They must have been metaphors too I guess.

What makes YOU think YOU have the authority to decide what is metaphor and what is not? Oh yeah - you're the guy who rewrites physics to suit his theist preconceptions.
TheGhostofOtto1923
4.2 / 5 (5) Jul 06, 2014
The answer to that is unclear.
No the answer to that is very clear. There WAS no flood. Evidence tells us this. What - did god obliterate all the evidence and replace it with totally convincing counter evidence? Did he do the same with the jewish kingdoms, the first people, and creation itself?

Why does your god LIE to you in order to find out how much you TRUST him?? Perhaps because he is the creation of liars. Perhaps he is just a metaphor for totally human authority and blind obedience.
JVK
1 / 5 (6) Jul 07, 2014
http://phys.org/n...ull.html

"...you can't rely on one anatomical feature or one piece of DNA..."

You can rely on the fact that nutrient-dependent pheromone-controlled amino acid substitutions differentiate cell types and link ecological variation to ecological adaptations without all the pseudoscientific nonsense of evolutionary theories. If cause and effect were not so clearly linked via animal models to humans, theorists might continue to try to make their case.

See instead: http://www.ncbi.n...24693353

Captain Stumpy
5 / 5 (7) Jul 08, 2014
all the pseudoscientific nonsense of evolutionary theories
Mutations are pathological; they do not create new species
@jk
you consider MUTATION a pseudoscientific nonsense part of evolution theory
did mutations and natural selection lead to our evolution? I continue to have difficulty following the story line, perhaps because it is preposterous
well according to you
In my model, selection of nutrients and their metabolism to species-specific pheromones enables speciation
as well as when I asked
DOES your model make any changes to the nucleotide sequence of the genome of an organism, virus, or extrachromosomal genetic element?
This is a yes or no answer
THIS is the DEFINITION of MUTATION- to which you answered
YES!
--Thanks for asking
so...in your own words
YOUR MODEL IS PREPOSTEROUS
YOUR MODEL CANNOT CREATE NEW SPECIES
YOUR MODEL IS PSEUDOSCIENCE AND CANNOT BE A PART OF EVOLUTION

YOUR words, mensa-boy
are you illiterate or stupid?
JVK
1 / 5 (6) Jul 08, 2014
http://phys.org/n...tml#nwlt

"Roughly 50 percent of the insertions were population unique."

The insertions are nutrient-dependent and pheromone-controlled in all species, which means the insertions are not random, not linked to mutations, not naturally selected, and cannot automagically result in the unconstrained evolution of biodiversity.

Instead, it means that ecological variation results in ecological adaptations via conserved molecular mechanisms in species from microbes to man.

"Evolution canyon" is the place where animals "...have been able to adapt and survive in such close, but extremely different, ecologies."

It should be called "ecological adaptation canyon" so that social scientists are not confused about how ecological variation and ecological adaptation contribute to biodiversity, since mutations and natural selection do not contribute to the insertions.
JVK
1 / 5 (6) Jul 08, 2014
"Small intranuclear proteins also participate in generating alternative splicing techniques of pre-mRNA and, by this mechanism, contribute to sexual differentiation in at least two species, Drosophila melanogaster and Caenorhabditis elegans (Adler and Hajduk, 1994; de Bono, Zarkower, and Hodgkin, 1995; Ge, Zuo, and Manley, 1991; Green, 1991; Parkhurst and Meneely, 1994; Wilkins, 1995; Wolfner, 1988). That similar proteins perform functions in humans suggests the possibility that some human sex differences may arise from alternative splicings of otherwise identical genes."

-- From our 1996 Hormones and Behavior review article http://www.hawaii...ion.html

JVK
1 / 5 (6) Jul 08, 2014
There is only one model for the differentiation of cell types (sex differences and all other individual differences in all species). It is my model. Those who continue to believe that cell type differences "evolved" must learn the difference between evolution and ecological adaptations.

Fruit fly research may reveal what happens in female brains during courtship, mating
www.sciencedaily....2424.htm

Excerpt: "...our study opens the possibility that analogous neuroendocrine systems control sexual receptivity from flies to vertebrates," adds senior author Dr. Barry Dickson, who was also a co-author on the Current Biology paper published by Dr. Vosshall.

I don't know why people are ignoring what is known about cell type differentiation in species from microbes to man and wondering about possibilities that involve conserved molecular mechanisms.
anonymous_9001
5 / 5 (4) Jul 08, 2014
Is alternative splicing also responsible for the differentiation seen in Lenski's populations?
Captain Stumpy
5 / 5 (7) Jul 08, 2014
There is only one model for the differentiation of cell types (sex differences and all other individual differences in all species). It is my model
@jk
but you argue AGAINST your own model, so how can YOUR model be correct? you say
The insertions are nutrient-dependent and pheromone-controlled in all species, which means the insertions are not random, not linked to mutations, not naturally selected, and cannot automagically result in the unconstrained evolution of biodiversity.
Instead, it means that ecological variation results in ecological adaptations via conserved molecular mechanisms in species from microbes to man
but you also said YOUR MODEL CREATES MUTATIONS, which was proven and which IS TRUE, therefore EITHER:
1- you are a complete idiot
2- you don't know what you are talking about
3- you are WRONG

from what you've posted thus far, it is ALL THREE.
Captain Stumpy
5 / 5 (6) Jul 08, 2014
It should be called "ecological adaptation canyon" so that social scientists are not confused about how ecological variation and ecological adaptation contribute to biodiversity, since mutations and natural selection do not contribute to the insertions.
@jk
so... what you are saying here is that YOUR MODEL is WRONG, because I asked
DOES your model make any changes to the nucleotide sequence of the genome of an organism, virus, or extrachromosomal genetic element?
This is a yes or no answer
to which you answered
YES!
--Thanks for asking
so, IN YOUR OWN WORDS
mutations and natural selection do not contribute to the insertions
therefore YOUR MODEL IS WRONG and YOU ARE TRYING TO PROVE IT
I don't know why people are ignoring what is known
maybe because you don't know what is going on? you contradict yourself time and again, and you also LIE BLATANTLY
you try to prove a magical sky-fairy religious dogma rather than science...

JVK
1 / 5 (5) Jul 09, 2014
Is alternative splicing also responsible for the differentiation seen in Lenski's populations?


Is there any other model for that?

I wrote: "There is only one model for the differentiation of cell types (sex differences and all other individual differences in all species). It is my model. Those who continue to believe that cell type differences "evolved" must learn the difference between evolution and ecological adaptations."

See: Nutrient-dependent pheromone-controlled ecological adaptations: from atoms to ecosystems

http://figshare.c...s/994281
Captain Stumpy
5 / 5 (5) Jul 09, 2014
I wrote: "There is only one model for the differentiation of cell types (sex differences and all other individual differences in all species). It is my model
@jk
you have also written
Biological facts continue to refute the pseudoscientific nonsense of mutation-initiated natural selection and evolved biodiversity
and when I asked
DOES your model make any changes to the nucleotide sequence of the genome of an organism, virus, or extrachromosomal genetic element?
This is a yes or no answer
This is the DEFINITION of MUTATION- to which you answered
YES!
--Thanks for asking
so to say that there is only one model, and it is yours is FRAUD and a blatant LIE
OR
you don't know what you are talking about, which is essentially the same thing
Your condemnation of mutation, when your own model causes mutations, only proves that you are not CAPABLE of making:
1- an honest statement
2- a logical statement
3- a logical decision based upon your work, let alone anyone else's
Captain Stumpy
5 / 5 (4) Jul 09, 2014
Is there any other model for that?
@jk
I would say Lenski's

and HE is FAR MORE REPUTABLE than you
He doesn't make fraudulent claims or blatantly LIE on public comment sites
anonymous_9001
5 / 5 (6) Jul 10, 2014
Is there any other model for that?


I'll take that as a "yes" to my question. Unfortunately for you, prokaryotes don't utilize splicing, so your explanation for how Lenski's E. coli adapted is impossible. If you knew anything about biology, you would have known that I was asking you a loaded question and was leading you right into a trap, with which I got you hook, line, and sinker.
anonymous_9001
5 / 5 (4) Jul 11, 2014
Still waiting on a follow up post. Should be interesting to see Kohl try to explain how an organism incapable of splicing utilizes splicing to adapt.
JVK
1 / 5 (3) Jul 24, 2014
If you knew anything about biology, you would have known that I was asking you a loaded question and was leading you right into a trap...


If you knew anything about the conserved molecular mechanisms of cell type differentiation that I have detailed in my published works, you would not keep posting as an anonymous fool and probably would not post anything at all. For example, light-induced amino acid substitutions appear to link cell type differentiation from plants to algae via photosynthesis.

If cell type differentiation in E. coli is not due to alternative splicings of pre-mRNA and amino acid substitutions, you could either cite the source for your claim, or explain how the cell types differentiate (heat?). Claims that cell type differentiation occurs due to mutations and natural selection have become so ridiculous that no informed molecular biologist makes them.

So, who is filling your head with nonsense. Is it still PZ Myers, or is it some other atheist blogger?
anonymous_9001
5 / 5 (3) Jul 31, 2014
If cell type differentiation in E. coli is not due to alternative splicings of pre-mRNA and amino acid substitutions, you could either cite the source for your claim


The source for my claim? Are you seriously asking me for a source stating that bacteria don't splice? That's a defining characteristic of prokaryotes that separates them from eukaryotes.
Captain Stumpy
5 / 5 (2) Jul 31, 2014
If cell type differentiation in E. coli is not due to alternative splicings of pre-mRNA and amino acid substitutions, you could either cite the source for your claim


The source for my claim? Are you seriously asking me for a source stating that bacteria don't splice? That's a defining characteristic of prokaryotes that separates them from eukaryotes.
@anonymous_9001
in other words... jk does not know what he is talking about!
IMAGINE THAT!
heck... he cannot even comprehend that his own model causes mutations (to which he admits, by the way)

THIS is why so many educated biologists like you, Anonymous_9001, call jk a crackpot!
Even if you don't have a degree, at least you know enough about biology to spot the looney in the midst.

THANKS for the great work, ANON! keep it up!

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