2014年7月4日 星期五

Tibetans get high-altitude edge from extinct Denisovans' genes 西藏人高原基因來自於遠古滅絕人類






Researchers have known for a while that many people alive today carry genes from human species other than Homo sapiens, the result of ancient interbreeding with Neanderthals and Denisovans. The specifics, though, have not been clear. But in one case they now are, for it is because of these occasional Denisovan ancestors that Tibetans thrive in Tibet http://econ.st/1j0IacI




西藏人高原基因來自於遠古滅絕人類

更新時間 2014年7月3日, 格林尼治標準時間11:47

西藏人
西藏人的高原基因來自於遠古已滅絕的人類
據《自然》期刊報告,現代人從遠古所繼承的一種基因,可以讓他們適應高原的生活。
據悉,這種遠古的人類已經滅絕。這種叫EPAS-1的基因變種可以影響人類血液中的氧氣,在西藏人當中十分普遍。
西藏人長年生活在海拔4000米的高原。
該DNA(脫氧核糖核酸)的序列與一種早已消失了的遠古人類丹尼索瓦人(Denisovans)的DNA相符合。
其實,包括我們自己在內的現代人類的許多人都攜帶已經滅絕了的遠古人類的DNA。
而這些遠古已滅絕的人類曾經和我們的非洲祖先「雜交」。
40萬年前出現的尼安德特人(the Neanderthals)曾生活在歐洲和西亞地區,直到3萬5千年前。
無論是尼安德特人還是丹尼索瓦人都對現代人的DNA有所貢獻。
而現在,研究人員通過研究血紅蛋白找到了EPAS-1基因與丹尼索瓦人之間的聯繫。
比如,當人體在海拔較高的高原時,體內血液中的氧氣水平就比較低,這時候EPAS-1基因就會告訴身體中的其他的基因活躍起來,包括生產額外的紅血球。
而這種EPAS-1基因的變體在西藏人中十分普遍,這可能和他們在數千年前移居到高原生活時所發生的一種自然的基因選擇。
明確證據
該文章的主要作者之一,加州大學的尼爾森教授說,他們找到了明確的證據這種基因來自丹尼索瓦人。
尼爾森告訴BBC,「如果你、我到海拔高緯度時,我們都將立即會經歷各種不同的不良身體反應。我們會喘氣困難,還可能會得高原病。」
「過一陣,我們的身體為了適應這一情況將會生產更多的紅血球。但是由於我們不適應高原環境,我們的身體可能將會製造許多紅血球。」
「我們的血液變得太粘稠,血壓也會升高,這樣就會有中風的危險,如果是孕婦還可能患妊娠毒血症」。
但西藏人就不會有這些問題,他們的身體不會製造過多的紅血球,因此血液也不會粘稠。
尼爾森教授的研究小組在2010年就發現了西藏人身體中的這種EPAS-1基因變體,但是研究人員當時無法解釋它為什麼與從其他現代人類身上找到的DNA序列不一樣。
因此,他們才從更遠古的人類染色體組序列當中去尋找答案。
研究人員把它同尼安德特人相比較,沒有找到匹配,但當同丹尼索瓦人比較時令人吃驚地找到了吻合。
尼爾森教授解釋說,人類祖先與丹尼索瓦人的「雜交」發生在很久以前。
而當西藏人的祖先移居到高原之後,丹尼索瓦人的DNA在他們的身體中產生了基因變體,並喜歡這種環境轉變。之後它便存在於今天大多數的西藏人身上。
尼爾森教授說,這是人類通過與遠古人類「雜交」後獲得的基因適應新環境的一種清楚和直接的例子。
編譯:凱露





Tibetans get high-altitude edge from extinct Denisovans' genes


Scientific ResearchTibetScience
High in the Himalayas, an ancient gene helps Tibetans thrive at altitude
Denisovans are extinct, but their genes live on in Tibetans
Tibetans provide more proof that early humans mated with Neanderthals and Denisovans
Forget climbing Mt. Everest — for most humans, just eking out a living on the harsh Tibetan plateau is challenge enough. But Tibetan people have thrived there for thousands of years, and a new study says it's thanks to a genetic adaptation they inherited from an ancient human relative.
The study, published Wednesday in the journal Nature, identifies a long segment of DNA shared by the extinct people known as Denisovans and modern-day Tibetans. The segment contains the gene scientists think gives Tibetans a lung up over lowlanders at high altitudes.


No one knew the Denisovans ever roamed the Earth until four years ago, when scientists sequenced the DNA of a finger bone unearthed in a cave in the Altai Mountains of southern Siberia. The genome exhibited similarities to that of modern humans and our extinct Neanderthal relatives, but it was different enough to be considered a distinct species.
Like Neanderthals, Denisovans mated with their human contemporaries, scientists soon discovered. People of Melanesian descent who today inhabit Papua New Guinea share 5% of their genetic makeup with the Denisovans.
Now it appears that Tibetans can also trace part of their ancestry to this mysterious group.


In the new study, scientists collected blood samples from 40 Tibetans and sequenced more than 30,000 nucleotides on a segment of DNA containingEPAS1, the gene that makes Tibetans so well-suited for life at high altitude. Then the scientists compared that sequence with those of 1,000 individuals representing the 26 human populations in the Human Genome Diversity Panel. They found the high-altitude gene in only 2 of the 40 Han Chinese people in the panel and no one else.
“Natural selection by itself could not explain that pattern,” said Rasmus Nielsen, a computational biologist at UC Berkeley and an author of the study. “The DNA sequence was too different from anything else we saw in other populations.”
So they investigated whether the gene might have been imported from extinct Neanderthals or Denisovans, and, bingo, they found a match.
But how did the gene end up in the genome of modern Tibetans? The scientists used computer models to test two different hypotheses. Were Denisovans and Tibetans descended from a common ancestor that gave the gene to both? Or did humans acquire the gene by mating with Denisovans?


Early humans and Denisovans probably diverged around half a million years ago, and it’s very unlikely that the gene could be maintained in both populations for so long, Nielsen said.
“By the process of recombination, DNA segments become shorter and shorter and shorter,” he said. “But here we have a very long segment that is shared. That’s very unlikely, statistically.”
Alternatively, the gene could have entered the Tibetan gene pool more recently via sex. Once transferred, the gene would have spread rapidly in the Tibetan population because of the merciless selective pressures of high-altitude living.
“Genetically, Han Chinese and Tibetans are very similar throughout the genome,” Nielsen said. “But for this particular gene, they are extremely differentiated from each other, which is something you only see with very strong or very recent selection.”


The reason Tibetans need EPAS1 is that their mountainous home — a crease of buckled crust thrust upward by the tectonic collision of India and Asia — lies about 15,000 feet above sea level, on average. Up there, the air contains 40% less oxygen than it does at low elevations.
Although previous studies had identified the importance of EPAS1, scientists still don’t know exactly what the gene does. They know only that it leads to lower levels of hemoglobin — the oxygen-toting protein in blood — in Tibetans who live at high altitude compared with people from low elevations who have acclimatized.
“That may sound counterintuitive,” said Nielsen — after all, wouldn’t you want more oxygen, and thus, more hemoglobin to deliver it? But people without the gene tend “overreact” at altitude.


“As we acclimatize, we’ll start to produce a lot of red blood cells,” he said, speaking for himself and other non-Tibetans. Too many, in fact. “That will expose us to various diseases like hypertension, increased risk of stroke and preeclampsia. There are very negative fitness effects of having too many red blood cells, and the Tibetans avoid them.”
So how do Tibetans get more oxygen? Presumably they don’t, Nielsen said, and scientists are still trying to understand the physiological mechanisms that allow them to cope.
But one thing is now clear: They owe their extraordinary fitness to a rogue gene introduced into the human genome from their long-lost cousins.
Abigail Bigham, an anthropologist at the University of Michigan who was not involved in the study, said now the search for Denisovan DNA should extend to other groups not represented in the Human Genome Diversity Panel.
“When they looked in Han Chinese, they saw it in only two individuals,” Bigham said. “But other populations in Central Asia or East Asia — there are 49 other ethnic minorities in China that have different genetic backgrounds — would have been interesting to look at as well.”
In any case, she said, the new study adds to a growing body of work that has reshaped the way scientists think about human evolution and our relationship to our extinct relatives.
For a long time, most scientists believed Neanderthals and Denisovans had nothing to do with modern humans. Now they realize that these species are responsible for introducing some of the genetic diversity that allowed people to adapt to unique environments.
“We’ve come full circle,” Bigham said. “Not only has there been interbreeding, but in fact that interbreeding has led to important functional changes in the human genome.”
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