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How Tibetans survive life on the 'roof of the world'龙腾网 http://www.ltaaa.com

西藏人是如何在“世界屋脊”上生存的



How the indigenous Tibetan population evolved to live with so little oxygen has been a mystery. Now we are beginning to understand that another species may lie behind their survival.

我们依然不清楚土生土长的西藏人是如何进化到凭那么少的氧气就能活下去的。不过现在我们正逐渐开始明白他们之所以能够活下来可能是因为存在另外的物种。

By Alex Riley
27 February 2017

作者:亚历克斯·理勒
2017年二月27日

Some time in the past, a family sat on the top of the world and gazed at the stars. They lived on the Tibetan Plateau, 4200m (14,100ft) above sea level, in a site now known as Chusang. They called it home.

在一个存在于很久很久以前的时段里,曾有这样一个家庭坐在世界之巅,仰望苍穹的繁星。他们生活在海拔4200米(14100英尺)的青藏高原上一个现在被称作Chusang的地方。他们称它为家。

Although far from the comfort of more lowly climes, this location had its perks. Fuelled by the tectonic forces that raise and support the plateau, a hot spring at the surface provided a welcoming buffer against the chilled air. At night, the family lit fires in a hollow built into the slope, a lonely flicker against the peak of darkness.

虽然较低的海拔所带来的舒适是他们无法享受的,但是这个地方也有它自身的独特优势。抬起并支撑青藏高原的那股地质构造之力为这个地方带来了热能;地表的温泉也为它抵抗寒冷的空气提供了热情的支援。这个家庭将他们的家建在一个斜坡的洞穴中,入夜时分,他们点燃了洞中的几处篝火。火光在黑暗的山顶孤独地闪烁着。

Their fire has long gone out, but the family still left a lasting impression on the world. As they walked and played, 19 hand and foot prints were pressed into the clay-like mud that seeped from the spring and, as they dried, were preserved into the present.

尽管他们点燃的火堆在很久很久以前就熄灭了,但是这个家庭却在这个世界上留下了永恒的印记。当他们行走、玩耍的时候将19个手印和足印留在了从泉眼渗出的、类似黏土的泥土里,随着这些泥土渐渐干涸,那些手印和足印便被保留至今。

Judging by the size of the prints - and the hands and feet that made them - the family group contained six individuals, two of which were children. But who were they? A foraging trip perhaps? Hunting? Or were they simply curious, always searching for lands untouched?

从这些手印和足印的尺寸,以及留下它们的手和脚判断,这个家庭共有六个人,其中两个是儿童。但是他们是谁?也许这是一次寻找食物的征程?狩猎吗?亦或他们仅仅因为好奇,所以经常四处寻找人迹从未到过的土地?

Their marks leave no answers to such questions. All that is known, as shown in a study from January 2017, is that the Chusang prints were made between 12,700 and 7,400 years ago, making it one of the oldest archaeological sites known on the Tibetan Plateau.

他们留下的痕迹无法解答上述那些问题。现在所能了解的都出自一份2017年一月份的研究。该研究认为这个“Chusang痕迹”是在12,700年至7,400年之前留下的,因此这处痕迹也成了青藏高原上最古老的已知考古遗址之一。

But what makes the Chusang family special is their isolatioin. Living at the centre of the plateau, they simply couldn't migrate up and down the mountain with the seasons as other Tibetan people did during this period. They were here year-round, enduring the heavy snowfall, biting winds, and encroaching glaciers of winter.

但是让这个Chusang家庭显得特别的却是他们的孤立状态。虽然生活在青藏高原的中心位置,但是他们完全没有像当时其他的西藏人那样随着季节更替在山上山下之间往返迁徙。他们整年整年地待在这里,忍受着大雪、刺骨的寒风、以及随冬季而来的冰川的侵犯。

Their survival is extraordinary. While the heat of fire could protect them from the cold, the family at Chusang couldn't shelter from an obvious yet insurmountable obstacle of living on the plateau: the air becomes thinner with every step towards the sky. At more than 4,000m (13,000ft) above sea level, each breath contains around a third less oxygen than the same breath far below. But deep inside each of their bodies, within their blood and DNA, an ancient and unique trick to surviving at altitude protected them from the thin air in which they built their home.

他们的生存显得很不平凡。虽然火的热量保护这个Chusang家庭免遭严寒的伤害,但是因为他们生活在青藏高原上,所以他们还是无法避开一个众所周知且无法克服的障碍:每向天空走一步,空气就会变得更稀薄。在海拔超过4000米(13,000英尺)的地方吸进的每一口空气的含氧量,只抵得上在远远不及这个海拔的地方吸进同样一口空气的三分之一。但是在他们留下的躯体的最深处,在他们的血液和DNA中,存在着一种让他们能生活在这个海拔高度的古老而独特的魔力。正是这种魔力在他们建立家园的地方保护着他们免遭稀薄空气的伤害。



Humans have occupied the Tibetan Plateau for housands of years - but the secrets to their survival are only just being discovered by scientists (Credit: Getty Images)

人类在青藏高原上已经住了几千年了——但是他们能够在此生存下去的秘密却只能由科学家来揭开(感谢Getty图片供图)

Any mountain climber will be able to describe the shortness of breath that normally comes with altitude. It's not that the air has a lower percentage of oxygen - it's around 21% wherever you stand in the world. But air pressure decreases the further you walk or fly from the sea's surface, allowing the gas molecules to spread out in all directions, and lung can only stretch so far to compensate.

任何一个登山者都可以描述通常伴随海拔而来的呼吸短浅。这并非指空气的含氧量降低了——不论你身处地球的何处,氧气始终占空气的21%左右。不过,在海平面能够向四面八方扩散的空气分子,随着你或走或飞地离海平面越来越远,其压力就会降低,为此你的肺就只能向外伸展(对大气压下降)作出补偿。

There are ways to deal with this change in pressure, however. Over many hundreds of generations, people living on the Andean altiplano that extends from Peur into Bolivia, have evolved barrel-shaped chests that increase the volume of each of their breaths. And since the late 1800s, scientists have known that their blood is pumped full of red blood cells and haemoglobin, the oxygen-carrying molecules, that they contain.

但是还是存在几种对付气压改变的方法的。从秘鲁到玻利维亚,安第斯山脉绵延不绝,在那里生活的人经过数百代之后,终于进化出了桶状的胸腔,这样便可以增加他们每次呼吸的空气的体积。科学家们从19世纪末就已经知道他们的血液中充满了专司携带氧气的红细胞和血红蛋白。

When the air is thin, the blood thickens to increase the amount of oxygen it can shepherd to cells around the body. This hematopoietic (literally, "blood" and "to make" in Greek) response is also found in anyone who decides to hike up a mountain. "Compared at altitude to Andean highlanders, we are pretty similar," says Cynthia Beall, an anthropologist from Case Western Reserve University in Ohio. "Not completely, but the general response is the same."

因为血液帮全身细胞代为照管氧气,所以当空气稀薄的时候,它就会变稠以增加含氧量。这种造血反应在任何决定登山的人的体内都会找到。辛西娅·比尔是俄亥俄州西储大学的一名人类学家,她说:“我们与安第斯高原的海拔高度很接近。虽然并非一模一样,但是总的反应是相同的。”

And since virtually all research on high-altitude populations was focused in the Andes, haematopoiesis was seen as a universal response to low oxygen levels for nearly two centuries. It was only in the late 1970s and early 80s, after hiking to seven villages in Nepal, that Beall started to find that Tibetans didn't fit this theory.

因为所有针对高海拔居民的研究几乎都集中于安第斯山区人,所以近两百年以来造血反应都被看作是一种对低氧级别的普遍反应。直到比尔于二十世纪70年代晚期和80年代早期登上尼泊尔境内的七座村庄之后,她才开始意识到这个理论不适用于西藏人。



Researchers were initially surprised to find that Tibetans apparently lack the physiological adaptations that are necessary for life at altitude (Credit: Getty Images)

刚开始研究人员惊讶地发现西藏人明显缺乏那种为了在那个海拔生活所必须的生理适应性。(感谢Getty图片供图)

Firstly, they lacked the barrel-shaped chests, but seemed to breath at a faster rate than Andeans. And second, in the autumn of 1981 Beall and her colleagues found that Tibetans have surprisingly low haemoglobin levels, often within the range of what is normal for people who live at sea level. Although they live on the so-called "roof of the world", their physiological state seemed surprisingly similar to those who had never left its floor.

首先,他们没有桶状胸腔,而且呼吸频率似乎也比安第斯山区人快。其次,比尔和她的同事们于1981年秋天吃惊地发现西藏人的血红蛋白水平并不高,这个血红蛋白水平于那些生活在海平面的人而言都算正常范围之内。而且令人称奇的是虽然他们住在所谓的“世界屋脊”,但是他们的生理状态似乎与那些从未离开地面的人差不多。

"At first, this was anxiety inducing," says Beall. "You think, 'Oh gosh, did I meaure the wrong people? Did I do the wrong measurements? Is there something I'm missing?'" But after returning to Tibet and Nepal many times since, collecting more data from more villages, she only found support for her initial results: at high altitude, low-oxygen environments, Tibetan people reduce the amount of oxygen their blood can carry.

“这个结果在刚开始的时候足以引发焦虑,”比尔说。“你会想,‘哦,老天爷,我是不是搞错对象了?我的测量方式是不是错了?我遗漏什么了吗?’”但是在她后来又多次返回西藏和尼泊尔,从更多的村落收集更多的数据之后,她只找到对她最初研究结果的支持,即在高海拔且低氧的环境中,西藏人降低了他们的血液能携带的氧气水平。

How could this be? What at first appears to be highly paradoxical - not to mention potentially dangerous - actually makes a lot of sense, protecting Tibetan people from some of the nastier side effects of the high-life.

怎么会这样呢?最初看来是极其荒谬的东西(先不谈它的潜在危险性)其实还是非常有意义的,因为它让西藏人免受高原生活中一些比较令人讨厌的副作用影响。

One benefit, for instance, is reduced wear and tear on their blood vessels. "If you have high levels of haemoglobin your blood tends to be more viscous, and that can have a lot of damaging effects, " says Tatum Simonson from the University of California in San Diego. "You're basically pumping this very thick, concentrated blood throughout your system. Your heart is on overdrive."

举个例子:有一个优点便是他们血管的磨损被减轻了。来自加州大学圣迭戈分校的泰特姆·西蒙森说:“如果你血液中的血红蛋白处于一个高水平,那么你的血液就更粘稠,这极具破坏性。你基本上就是在将这种粘稠浓缩的血液在你的循环系统中泵进泵出。于是你的心脏便过载了。”



Tibet attracts millions of tourists, but while native Tibetans can easily cope with low oxygen conditions, visitors may suffer from mountain sickness (Credit: Getty Images)

虽然西藏吸引着数百万的旅游者,但是旅游者却不能像西藏本地人那样轻松应对低氧条件,从而患上高山病(感谢Getty图片供图)

A possible outcome of this added stress on the entire circulatory system is chronic mountain sickness, or CMS. First described in 1925 by the Peruvian doctor Carlos Monge Medrano, CMS (also known as Monge's disease) can afflict people who have lived happily at high altitude for years. "It's not clear that triggers the onset," says Beall. "But people become breathless, they become cyanotic [their lips and extremities turn blue], they can't work, they can't sleep well - they're very ill."

附加在整个循环系统上的这种压力可能带来慢性高山病,或称作CMS。秘鲁医生卡洛斯·蒙格·梅德拉诺于1925年首次描述了CMS(因此该病又被称作蒙格氏病)。CMS让那些多年生活在高海拔地区的人本来可以很幸福的生活痛苦不堪。“还不清楚病因是什么,”比尔说。“但是人们喘不上气,脸部发绀【就是他们的嘴唇和手足变成了蓝色】,他们无法工作也睡不好——他们感觉非常难受。”

As with short-term altitude sickness, the remedy for CMS is a slow descent into thicker, more oxygenated air. But it is no cure. Fluid may have already built up in the lungs (a high altitude pulmonary oedema, or Hape) or in the brain (a high altitude cerebral oedema, or Hace), or the thick blood may be congested in other vital organs. The worst-case scenario is death.

对于短期的海拔不适应,CMS的治疗方法就是慢慢下降到空气不那么稀薄且含氧量较高的地方。不过疾病并不会因此而治愈,因为肺部或是脑部可能已经有水分开始堆积(高海拔肺水肿,或称作高原肺水肿;或者高海拔脑水肿,或称作高原脑水肿),还有一种情况就是粘稠的血液可能充塞在其它器官中。最糟糕的情况就是死亡。

In the Peruvian Andes, up to 18% of the population CMS at some point in their lives. But on the Tibetan Plateau that number is rarely above 1%.

在秘鲁的安第斯山区,超过18%的人口在其生命中的某个时候会得CMS。但是在青藏高原上,这个比例几乎不超过1%。

Certainly thin blood helps reduce CMS risk, but it's certainly not the only reason Tibetan people can live happily at such extremes. In 2005, for instance, Beall and her colleagues found that Tibetans exhale more nitric oxide compared to people living in the Andes and at sea level. Originally described as a relaxation factor, this gas leads to a widening of blood vessels in the lung and around the body, known as vasodilation. With more space, blood flow - and oxygen transport - can increase.

虽然血红蛋白含量低的血液确实有助于降低罹患CMS的风险,但是这却不是西藏人能幸福地生活在如此极端条件下的唯一原因。下面以2005年比尔及其同事的发现为例:与生活在安第斯山区的人以及生活在海平面的人相比,西藏人呼出更多的一氧化氮。一氧化氮以舒张血管著称,所以通常被认为是一种能让肺部及全身血管扩张的松弛因子。因为有了更多的空间,所以血流增加了,同时也就输送了更多的氧气。

And, as Simonson suggests, what if Tibetans simply don't require as much oxygen as other people? What if their muscles are just more efficient with their usage, for instance? "Perhaps they are already so well tuned that they don't need more red blood cells and haemoglobin to bind more oxygen," she says. Her work is now exploring this possibility.

不过(也有其他的假设),就如西蒙森所讲的那样,比如西藏人就是不像其他人那样需要那么多的氧气呢?或者西藏人能更有效地使用他们的肌肉呢?“也许他们很能适应环境以致于不需要更多的红细胞和血红蛋白去捆绑更多的氧气,”她说。她目前的工作就是探索这种可能性。



Very rapid genetic changes may have allowed ancient populations to survive and thrive in this environment (Credit: Getty Images).

极其快速的遗传物质的改变可能是允许古时候的人在这种环境中生存兴盛的原因(感谢Getty图片供图)。

Although she has visited the Tibetan Plateau several times for her research, Simonson surveys the history of this region back in her laboratory. As a geneticist, she can scour the genomes (the entire DNA sequence of an individual) of Tibetan people to find what underlies their unique adaptations to the high life.
虽然西蒙森因为研究的原因去过几次青藏高原,但是她还是在实验室里调查了这个地区的历史。作为一个遗传学家,为了找到究竟是什么奠定了西藏人对高原生活独特的适应性,她可以搜遍各地寻找西藏人的染色体组(个体完整的DNA序列)。

In 2010, by comparing the genomes of 30 Tibetan people to those from a Han Chinese population living in Beijing, simonson could identify those genes that were associated with living at high-altitude. This is easier than it sounds. Since the two populations are closely related but only one has lived at altitude for thousands of years, any major differences between the genomes are likely to underlie adaptations to this change in environment, such as an atmosphere thin on oxygen.

2010年,通过将30个西藏人的染色体组与一名生活在北京的汉族人的染色体组相比,西蒙森找到了那些与高海拔生活相关联的遗传物质。这件事做起来比听起来容易。因为藏族人和汉族人是近亲,但是其中只有一个民族在高海拔地区生活了数千年,所以他们的染色体组之间的主要差异很可能便构成其适应环境改变(比如空气中的含氧量变少)的基础。

Simonson's lab wasn't the only one attempting this. In the space of two weeks in 2010, a total of three research groups each published a study that found a handful of genes that were markedly different between the two populations. Of note, two genes called EPAS1 and EGLN1 stood out from the crowd, and, importantly, were already known to modulate the haemoglobin levels in blood.

西蒙森的实验室并非唯一一个进行这项尝试的实验室。2010年的两周时间里,一共就有三家研究机构各自发表了他们的研究成果,称他们在这两大族群之间找到几个明显不同的基因。值得注意的是,这其中有两个被命名为EPAS1和EGLN1的基因显得尤为突出,因为它们调节血液中的血红蛋白水平,重要性可见一斑。

"The really wonderful part was everyone finding the same thing," says Beall, who was involved in one of the three studies. "In genomic studies, there are so many instances where one study found an association [between a trait and a gene] and it wasn't possible to replicate it," says Beall. "And in this case, right off the bat, we had replication. It's real."

参与上述三个研究之一的比尔说:“最精彩的部分在于每个人都找到了同样一件东西。在染色体组研究中经常存在虽然一个研究【在一个特征与一个基因之间】找到了关联,但是却没办法复制它的情况。不过在本例中我们成功复制了,所以说它是真实存在的。”

The field of human genomics is made easier by the nature of our species as a whole: at the level of DNA, of genomes, we are very similar." On average, there aren't big differences between different populations," says Rasmus Nielsen from University of California in Berkeley." The genetic variants that are most different between different groups are variants that code for things like hair colour and eye colour and skin colour."

因为从基因组和DNA这个层面来讲我们是非常相似的,所以一般而言,我们这个物种的天性让人类基因组学领域更容易被研究。“在不同种族之间几乎不存在较大的差异,”加州大学帕克莱分校的拉斯马森·尼尔森说。“存在于不同族群之间的差异最大的遗传变异是那些给头发眼睛皮肤颜色编码的遗传变异体。”

Our differences are slight and are held at the surface. Under the skin, deep in our DNA, we are nearly identical. From this sea of similarity, important genetic changes between populations can be seen as small but steep islands breaking the surface of the genome. But after looking more closely at the EPAS1 gene from the Tibetan genomes, Nielsen not only found it was a steep change, but it was a unique one too. After searching through the aptly named 1,000 Genomes Project, he couldn't find anything quite like it elsewhere. "The DNA sequence that we saw in Tibetans was simply too different, " Nielsen says.

我们的不同之处可以被忽略,而且它们都在表面。透过皮肤,深入我们的DNA,我们几乎是完全一样的。与汉藏两族人之间像海一样多的相似处相比,几个重要的基因变化只能被认为是从海底升起的、刺破染色体组表面的小却陡峭的岛屿。但是尼尔森在更加严密的检查这个来自西藏人染色体组的EPAS1遗传因子之后,发现这个遗传因子不仅是一个陡峭的改变,还是一个独一无二的改变。在查遍“1000染色体组计划”(名字非常符合内容) 之后,尼尔森也没能在别处找到与这条遗传因子非常相似的东西。不管是什么都没有找到。尼尔森说:“我们在西藏人染色体组中看到的这个DNA序列简直太不一样了。”

It was as if Tibetans had inherited the gene from another species. And, in fact, that's exactly what had happened.

这就仿佛西藏人从另外一个物种获得了这条基因一样,不过事实也的确如此。



The life-saving genetic variants that help Tibetans to survive at altitude may come from an ancient (now extinct) species of human (Credit: Getty Images)

这条帮助西藏人在高海拔生存的救命的基因变异可能来自一支古老的人类(现已灭绝)(感谢Getty图片供图)

Before its publication in 2010, Nielsen had worked on the Neanderthal genome project with the doyen of ancient DNA Svante Paabo, a geneticist from the Max Planck Institute for Evolutionary Anthropology in Leipzig, Germany. He knew our species had bred with these close evolutionary cousins, and scoured their DNA for the source of the Tibetan-specific EPAS1 gene. No match.

在发现这条基因的消息于2010年公布之前,尼尔森和古代DNA研究老前辈斯文特·帕玻一起为“穴居人基因组计划”工作。斯文特·帕玻是德国莱比锡麦克斯·布兰卡进化人类学研究所的遗传学家。他清楚我们这个物种曾与这些进化关系近的远亲杂交过。他也为了找到西藏人的这条特殊的EPAS1基因的源头而搜寻对比过他们的DNA。但结果是不匹配。

Although disappointing, it wasn't all that surprising. Neanderthals are only known to have mated with the ancestors of modern-day Europeans, leaving a legacy of 1-5% Neanderthal DNA in their genomes. For people of Asian ancestry Nielsen instead looked to Denisovans, another branch of the human family tree.

对这个结果虽然感到失望,但是它并不让人吃惊。穴居人是唯一能被找到与现代欧洲人的祖先交配过的。他们还在现代欧洲人的基因组中留下了1-5%的DNA。为了寻找具有亚洲系谱的人类,尼尔森转而检查人类系谱图的另一个分支丹尼索尔人。

Discovered in the Altai Mountains in Siberia, they are known only from two teeth, a tiny finger bone, from which Paabo and his colleagues published a rough genome in 2012. The results demostrated that populations form Papua New Guinea, Australia, and a few regions of southeast Asia had inherited between 1-6% of their genomes from Denisovans.

丹尼索尔人被发现与西伯利亚的阿尔泰山脉,而且仅存两颗牙齿和一根小指骨,不过凭此帕玻和他的同事们于2012年发表一组粗糙的基因组。这个基因组证明巴布亚新几内亚、澳大利亚以及东南亚少数地区的人从丹尼索尔人那里继承了1%到6%的基因。

It was a case of third time lucky. "There was a complete match," he says. "It's so hard to believe that it could possibly be true. But it is." Between 50,000 and 30,000 years ago, some Denisovans and the ancient ancestors of Tibetan and Han Chinese people had sex, merged their genomes, shuffled the genes like a deck of cards, and produced children who would grow up to have offspring of their own.

幸运第三次降临。“完全匹配,”他说。“我都不敢相信这是真的。但是它的确是真的。”在距今5万至3万年这段时间里,一些丹尼索尔人和西藏人以及汉人的古老祖先交配过,并融入了他们的基因组,就像洗牌一样插入他们的基因,然后制造能长大并生养自己后代的孩子。

Over the next tens of thousands of years, this gene seems to have conferred little benefit to Han Chinese people and is only found in roughly 1% of the population today. But for all those intrepid groups that moved up onto the Tibetan Plateau, including the Chusang family, it helped make every breath easier, every heartbeat less dangerous. On the Tibetan Plateau, 78% of the population has this version of EPAS1, a gene that separates them from those far below, but connects them to the past.

又过了好几万年,这条基因似乎不再为汉族人带来什么益处了,因为今天携带这条基因的汉族人只占人口的大约1%。但是对所有那些向青藏高原转移的勇敢无畏的族群(这其中也包括Chusang家庭)而言,它让每一次呼吸更轻松、每一次心跳少一些危险。在青藏高原上,78%的西藏人携带EPAS1。正是这条基因将西藏人与远在下面的人区分开来,但又将他们与过去连在一起。

Over 50,000 years in the making, this story still doesn't have an ending. Although its origin is known, those areas that make EPAS1 in Tibetans unique are still largely unchartered. The specific change (or changes) that leads to reduction in haemoglobin content is still unknow. "All the geneticists say it's in an area that's very hard to sequence," says Beall. The new explorers, those of mountains of data and genomes, still have a long journey ahead of them.

又用了5万年发展,这个故事依然没有结束。虽然我们已经知道了它的起源,但是那些让EPAS1在西藏人中间变得独一无二的大部分区域还是不规则。导致血红蛋白含量减少的改变细节还不清楚。“遗传学家们能说的只有它存在于一个很难对其排序的区域中,”比尔说。一条漫长的路途依然摆在那些在数据和基因组的高山上攀登的新登山者。

Alex Riley is a writer based in Berlin, Germany. He tweets as @riley__alex.

亚历克斯·理勒是以德国柏林为基地的作家。推特号:@riley_alex