Svante Pääbo: DNA clues to our inner neanderthal

翻译人员: Lili Liang 校对人员: Chunxiang Qian

What I want to talk to you about

我今天想谈谈

is what we can learn from studying the genomes

从研究现代人和古人类

of living people

基因组的研究中

and extinct humans.

我们能够学到什么

But before doing that,

在此之前

I just briefly want to remind you about what you already know:

我先简短回顾一下你们已有的知识

that our genomes, our genetic material,

我们的基因组 基因物质

are stored in almost all cells in our bodies in chromosomes

几乎存在于人体所有细胞的染色体中

in the form of DNA,

由脱氧核糖核酸（DNA）构成

which is this famous double-helical molecule.

呈双螺旋分子结构

And the genetic information

遗传信息

is contained in the form of a sequence

存在于四种脱氧核苷酸

of four bases

所组成的序列中

abbreviated with the letters A, T, C and G.

这四种脱氧核苷酸分别简称为 A T C G

And the information is there twice --

信息有两组

one on each strand --

每条氢链上各有一组

which is important,

这很重要

because when new cells are formed, these strands come apart,

因为 每当新细胞形成 这些氢链会展开

new strands are synthesized with the old ones as templates

而新的氢链以旧氢链作为模板进行互补配对

in an almost perfect process.

这一过程几乎精准无误

But nothing, of course, in nature

当然 在自然界中

is totally perfect,

事事无绝对

so sometimes an error is made

错误总有发生的时候

and a wrong letter is built in.

而一旦发生 一个错误的字母就会被编进去

And we can then see the result

我们可以等一下会看到

of such mutations

这些突变产生的结果

when we compare DNA sequences

例如拿在座各位的DNA 序列

among us here in the room, for example.

进行比对

If we compare my genome to the genome of you,

如果拿我的基因组与你的基因组相比

approximately every 1,200, 1,300 letters

每1200到1300个字母

will differ between us.

就会出现差异

And these mutations accumulate

这些突变像时间一样

approximately as a function of time.

不断累积

So if we add in a chimpanzee here, we will see more differences.

如果把一只黑猩猩加进来 我们能看到更多差异

Approximately one letter in a hundred

大致每100个字母

will differ from a chimpanzee.

就会出现差异

And if you're then interested in the history

如果你对一段DNA

of a piece of DNA, or the whole genome,

或整个基因组的历史感兴趣

you can reconstruct the history of the DNA

你可以通过观察到的这些差异

with those differences you observe.

对DNA的历史进行重组

And generally we depict our ideas about this history

我们可以通过这个树状图

in the form of trees like this.

来描述这段历史过程

In this case, it's very simple.

在这里 情况非常简单

The two human DNA sequences

这两个人类的DNA序列

go back to a common ancestor quite recently.

可以追溯到较为近期的一位共同祖先

Farther back is there one shared with chimpanzees.

而进一步追溯下去 就找到了他们和黑猩猩的共同祖先

And because these mutations

由于这些突变

happen approximately as a function of time,

多少起到了时间的作用

you can transform these differences

你可以通过这些差异

to estimates of time,

来对时间进行预测

where the two humans, typically,

这两个人类通常

will share a common ancestor about half a million years ago,

在50万年前有共同的祖先

and with the chimpanzees,

而与黑猩猩

it will be in the order of five million years ago.

则在500晚年前有共同的祖先

So what has now happened in the last few years

在过去几年里

is that there are account technologies around

由于有了先进的技术

that allow you to see many, many pieces of DNA very quickly.

你们能够很快地查看许许多多DNA片段

So we can now, in a matter of hours,

我们现在能够在短短几个小时里

determine a whole human genome.

鉴别出一整个人类基因组

Each of us, of course, contains two human genomes --

当然 我们每个人都有两个基因组

one from our mothers and one from our fathers.

一个来自母亲 而另一个来自父亲

And they are around three billion such letters long.

长度约为30亿个字母

And we will find that the two genomes in me,

我们会发现 我的两个基因组

or one genome of mine we want to use,

或者一个基因组

will have about three million differences

在这样的排列中

in the order of that.

有300万个差异

And what you can then also begin to do

现在你可以开始

is to say, "How are these genetic differences

分析这些基因差异

distributed across the world?"

如何分布在世界各地

And if you do that,

如果你这么做

you find a certain amount of genetic variation in Africa.

你会发现一定数量的基因变异发生在非洲

And if you look outside Africa,

如果你看非洲以外

you actually find less genetic variation.

你找到相对较少的基因变异

This is surprising, of course,

这让人大吃一惊

because in the order of six to eight times fewer people

这是因为非洲以外的人口数量

live in Africa than outside Africa.

比非洲的人口多了6至8倍

Yet the people inside Africa

但是非洲人

have more genetic variation.

拥有更多的基因变异

Moreover, almost all these genetic variants

更值得注意的是 几乎所有非洲以外的

we see outside Africa

基因变异

have closely related DNA sequences

都与非洲境内的DNA序列

that you find inside Africa.

关系非常密切

But if you look in Africa,

但如果你看非洲境内

there is a component of the genetic variation

基因变异的组成

that has no close relatives outside.

在非洲以外并没有近亲

So a model to explain this

所以这个模式说明

is that a part of the African variation, but not all of it,

来自非洲的一部分变异

[has] gone out and colonized the rest of the world.

走出了非洲 走向了世界

And together with the methods to date these genetic differences,

再通过使用追溯这些基因差异的手段

this has led to the insight

我们得到这样一个结论

that modern humans --

即现代人

humans that are essentially indistinguishable from you and me --

本质上基本相同的你和我

evolved in Africa, quite recently,

都是在10万至20万年前

between 100 and 200,000 years ago.

在非洲出现并演进的

And later, between 100 and 50,000 years ago or so,

之后 在大约10万到5万年前

went out of Africa

他们走出了非洲

to colonize the rest of the world.

走向了世界

So what I often like to say

我常说

is that, from a genomic perspective,

从基因组的层面上看

we are all Africans.

我们都是非洲人

We either live inside Africa today,

现代人要么生活在非洲

or in quite recent exile.

要么就是以前从非洲走出来的

Another consequence

现代人近期起源的

of this recent origin of modern humans

另一个结果

is that genetic variants

是基因变异

are generally distributed widely in the world,

在世界上广泛分布

in many places,

到很多地方

and they tend to vary as gradients,

至少从总体上看

from a bird's-eye perspective at least.

基因变异的走势成斜线状

And since there are many genetic variants,

既然存在如此多的基因变异

and they have different such gradients,

它们的变化率也不同

this means that if we determine a DNA sequence --

这意味着如果我们鉴别出一个DNA序列

a genome from one individual --

即某个人的基因组

we can quite accurately estimate

我们就可以非常准确地推算出

where that person comes from,

这个人来自何方

provided that its parents or grandparents

假设这个人的父母或祖父母

haven't moved around too much.

基本都留在一个地方

But does this then mean,

但是这就意味着

as many people tend to think,

比如说 许多人认为

that there are huge genetic differences between groups of people --

不同大洲的人

on different continents, for example?

其基因存在巨大差异吗？

Well we can begin to ask those questions also.

我们也在问这些问题

There is, for example, a project that's underway

有一个正在进行的项目

to sequence a thousand individuals --

在为一千个人的基因组排序

their genomes -- from different parts of the world.

这些人来自世界各地

They've sequenced 185 Africans

他们为来自非洲的两个种群的

from two populations in Africa.

185人进行了基因组排序

[They've] sequenced approximately equally [as] many people

他们也在欧洲和中国也找了同样多的人

in Europe and in China.

对其基因组进行排序

And we can begin to say how much variance do we find,

现在可以说我们找到了多少差异了

how many letters that vary

也就是其中一个序列

in at least one of those individual sequences.

有多少字母是不同的

And it's a lot: 38 million variable positions.

这个数字很大 3千8百万个差异

But we can then ask: Are there any absolute differences

我们会为 非洲人和非非洲人种

between Africans and non-Africans?

是否存在绝对的差异

Perhaps the biggest difference

也许我们许多人所认为的

most of us would imagine existed.

最大差异曾经存在过

And with absolute difference --

我所谓的

and I mean a difference

绝对差异是指

where people inside Africa at a certain position,

当所有非洲人 在基因序列中

where all individuals -- 100 percent -- have one letter,

某个特定位置上都有同样一个字母

and everybody outside Africa has another letter.

而所有非非洲人种 在这个位置上都有另一个字母

And the answer to that, among those millions of differences,

而在这几百万个差异中

is that there is not a single such position.

没有任何一个位置有这种情况

This may be surprising.

这听起来不可思议

Maybe a single individual is misclassified or so.

也许这是因为个别人被分错组了

So we can relax the criterion a bit

那我们就把标准放松一些

and say: How many positions do we find

看看我们在95%的非洲人样本中

where 95 percent of people in Africa have

能够找到多少个这样的位置

one variant,

一个变量是

95 percent another variant,

95% 另一个变量

and the number of that is 12.

我们得到的数字是12

So this is very surprising.

这真的很神奇

It means that when we look at people

这意味着我们看到

and see a person from Africa

一个来自非洲的人

and a person from Europe or Asia,

和一个来自欧洲或亚洲的人

we cannot, for a single position in the genome with 100 percent accuracy,

从单个序列位置来看 我们无法

predict what the person would carry.

100%准确判断这个人携带的基因组的序列

And only for 12 positions

而通过12个序列位置判断

can we hope to be 95 percent right.

我们也只能期望95%的准确率

This may be surprising,

这令人意外

because we can, of course, look at these people

我们从外表上看

and quite easily say where they or their ancestors came from.

很容易就知道他们或其祖先从哪里来

So what this means now

这意味着

is that those traits we then look at

那些显而易见的特征

and so readily see --

包括

facial features, skin color, hair structure --

面部特征 肤色 毛发结构

are not determined by single genes with big effects,

都不是由单个其重大作用的基因决定的

but are determined by many different genetic variants

而是许多不同基因变体共同作用的结果

that seem to vary in frequency

而在世界不同的地方

between different parts of the world.

这些变体变化呈现不同频率

There is another thing with those traits

关于这些特征的另外一点

that we so easily observe in each other

我们能够不费吹灰之力就能分辨彼此

that I think is worthwhile to consider,

我认为这点非常值得思考

and that is that, in a very literal sense,

那就是

they're really on the surface of our bodies.

这些特征都体现在我们体表

They are what we just said --

这些都是

facial features, hair structure, skin color.

面部特征 毛发结构 肤色

There are also a number of features

在食物的新陈代谢方面

that vary between continents like that

以及对抗病菌的

that have to do with how we metabolize food that we ingest,

免疫系统方面

or that have to do

不同人种的

with how our immune systems deal with microbes

相关特征

that try to invade our bodies.

也有不同

But so those are all parts of our bodies

但这些都属于身体特征

where we very directly interact with our environment,

直接与环境互动

in a direct confrontation, if you like.

也可以说是与自然亲密接触

It's easy to imagine

不难想象

how particularly those parts of our bodies

身体这些部位

were quickly influenced by selection from the environment

能够很快被自然选择所影响

and shifted frequencies of genes

并改变相关的

that are involved in them.

基因频率

But if we look on other parts of our bodies

如果我们看看那些

where we don't directly interact with the environment --

不直接接触外界环境的部位

our kidneys, our livers, our hearts --

如肾脏 肝脏 心脏

there is no way to say,

就完全不可能

by just looking at these organs,

通过观察这些器官

where in the world they would come from.

来判断人种

So there's another interesting thing

由此可推断出

that comes from this realization

另外一个有趣的观点

that humans have a recent common origin in Africa,

那就是人类的共同祖先来自非洲

and that is that when those humans emerged

他们出现在

around 100,000 years ago or so,

距今10年以前

they were not alone on the planet.

但他们不是唯一的人类种群

There were other forms of humans around,

当时还有其他人类种群

most famously perhaps, Neanderthals --

最著名的要数尼安德特人

these robust forms of humans,

这些体魄强健的人类

compared to the left here

在左边

with a modern human skeleton on the right --

与右边的现代人骨架相对比

that existed in Western Asia and Europe

他们自千百年前就一直生活在

since several hundreds of thousands of years.

西亚和欧洲地区

So an interesting question is,

这里有个问题很有意思

what happened when we met?

我们两种人相遇的时候 发生了什么

What happened to the Neanderthals?

尼安德特人后来怎么了

And to begin to answer such questions,

为了回答这些问题

my research group -- since over 25 years now --

我的研究组 从25年前

works on methods to extract DNA

就一直在对从生活在几万年前的

from remains of Neanderthals

穴居人以及古生物的

and extinct animals

遗骸中提取其DNA的方法

that are tens of thousands of years old.

进行研究

So this involves a lot of technical issues

提取DNA

in how you extract the DNA,

并将它转换成可以进行排序的形式

how you convert it to a form you can sequence.

需要用到纷繁复杂的技术

You have to work very carefully

工作的时候要高度谨慎

to avoid contamination of experiments

以免把你的DNA

with DNA from yourself.

与试验中的DNA混在一起

And this then, in conjunction with these methods

通过使用这些方法

that allow very many DNA molecules to be sequenced very rapidly,

我们能够在很短的时间里将许多DNA分子排序

allowed us last year

我们在去年

to present the first version of the Neanderthal genome,

成功将首个尼安德特人基因组排序

so that any one of you

所有人

can now look on the Internet, on the Neanderthal genome,

现在都能在网络上看到

or at least on the 55 percent of it

我们到目前为止重建的

that we've been able to reconstruct so far.

尼安德特人55%的基因组

And you can begin to compare it to the genomes

你可以开始把它

of people who live today.

和现代人类的基因组作对比

And one question

有一个问题

that you may then want to ask

你可能会问到

is, what happened when we met?

那就是 我们碰面时 发生了什么

Did we mix or not?

我们交汇过吗

And the way to ask that question

研究这个问题

is to look at the Neanderthal that comes from Southern Europe

就要把来自南欧的尼安德特人基因组

and compare it to genomes

与现代人的基因组

of people who live today.

相比对

So we then look

接下来

to do this with pairs of individuals,

我们一对对地进行比对

starting with two Africans,

先比对两个非洲人

looking at the two African genomes,

观察这两个非洲人的基因组

finding places where they differ from each other,

找出它们的差异

and in each case ask: What is a Neanderthal like?

每次比对都要问 尼安德特人的情况呢

Does it match one African or the other African?

它是否与其中一个非洲人相匹配

We would expect there to be no difference,

我们认为这两个非洲人之间没有差异

because Neanderthals were never in Africa.

因为尼安德特人从未去过非洲

They should be equal, have no reason to be closer

他们应该是一样的 其中一个非洲人

to one African than another African.

不会比另一个非洲人与尼安德特人更相近

And that's indeed the case.

而事实正是如此

Statistically speaking, there is no difference

数据说明

in how often the Neanderthal matches one African or the other.

尼安德特人和两个非洲人的差距是一样的

But this is different

但是这又不同了

if we now look at the European individual and an African.

这次我们比对的是欧洲人和非洲人

Then, significantly more often,

尼安德特人与欧洲人

does a Neanderthal match the European

相匹配的情况

rather than the African.

远胜于与非洲人的匹配

The same is true if we look at a Chinese individual

我们在比对中国人和非洲人的时候

versus an African,

情况也是这样的

the Neanderthal will match the Chinese individual more often.

尼安德特人与中国人匹配的程度更高

This may also be surprising

这也让人惊奇

because the Neanderthals were never in China.

因为 尼安德特人从来没有去过中国

So the model we've proposed to explain this

我们提出的解释是

is that when modern humans came out of Africa

当现代人在10万年前

sometime after 100,000 years ago,

走出非洲时

they met Neanderthals.

他们碰上了尼安德特人

Presumably, they did so first in the Middle East,

他们可能首先到了中东

where there were Neanderthals living.

那里正是穴居人生活的地方

If they then mixed with each other there,

如果他们曾在那里交汇过

then those modern humans

那么那些现代人

that became the ancestors

后来成为了非洲以外

of everyone outside Africa

人类的祖先

carried with them this Neanderthal component in their genome

就携带了尼安德特人的基因

to the rest of the world.

并把它传播到了世界各地

So that today, the people living outside Africa

于是 今天 生活在非洲以外的人们

have about two and a half percent of their DNA

有2.5%的DNA

from Neanderthals.

来自穴居人

So having now a Neanderthal genome

我们现在有了一个穴居人基因组

on hand as a reference point

作为一个参照点

and having the technologies

又有了研究古代遗骸

to look at ancient remains

并从中提取DNA的

and extract the DNA,

技术

we can begin to apply them elsewhere in the world.

我们可以在世界其它地区采用这些技术

And the first place we've done that is in Southern Siberia

我们首先在南西伯利亚

in the Altai Mountains

阿尔泰山

at a place called Denisova,

一个叫做德尼柔娃（Denisova）的地方

a cave site in this mountain here,

这是一个溶洞

where archeologists in 2008

考古学家在2008年

found a tiny little piece of bone --

发现了一小片骨头

this is a copy of it --

这是骨头的复制品

that they realized came from the last phalanx

他们发现这是

of a little finger of a pinky of a human.

人类小手指的趾骨

And it was well enough preserved

它的保存状态很好

so we could determine the DNA from this individual,

让我们能够从中鉴别出这个人的DNA

even to a greater extent

其序列长度比先前

than for the Neanderthals actually,

尼安德特人的DNA还要长

and start relating it to the Neanderthal genome

并将它与尼安德特人的基因组

and to people today.

和现代人的基因组相联系

And we found that this individual

我们发现

shared a common origin for his DNA sequences

这个人的DNA序列

with Neanderthals around 640,000 years ago.

源自64万年前的尼安德特人

And further back, 800,000 years ago

进一步追溯下去 到了80万年前

is there a common origin

这个人和现代人

with present day humans.

有共同的祖先

So this individual comes from a population

这个人来自一个

that shares an origin with Neanderthals,

与尼安德特人拥有共同祖先的种群

but far back and then have a long independent history.

而在更久以前 他们有很长的独立历史

We call this group of humans,

从这小小一片的骨头

that we then described for the first time

通过这小小一片骨头

from this tiny, tiny little piece of bone,

我们首次发现这个人种

the Denisovans,

于是我们用发现地点的名字

after this place where they were first described.

将他们命名为德尼柔娃人

So we can then ask for Denisovans

对于德尼柔娃人

the same things as for the Neanderthals:

我们也问了同样的问题

Did they mix with ancestors of present day people?

他们与现代人的祖先何时进行交汇的？

If we ask that question,

如果我们问这个问题

and compare the Denisovan genome

并把德尼柔娃人的基因组

to people around the world,

如世界各地人们的基因组相比

we surprisingly find

我们惊奇地发现

no evidence of Denisovan DNA

没有证据证明德尼柔娃人的DNA

in any people living even close to Siberia today.

与现在生活在西伯利亚的人有关系

But we do find it in Papua New Guinea

但是 我们在巴布亚新几内亚

and in other islands in Melanesia and the Pacific.

和一些美拉尼西亚和太平洋岛屿上找到了证据

So this presumably means

由于我们认定

that these Denisovans had been more widespread in the past,

美拉尼西亚人的祖先从未到过西伯利亚

since we don't think that the ancestors of Melanesians

所以我们推测

were ever in Siberia.

德尼柔娃人在过去分布的地区更广

So from studying

通过研究

these genomes of extinct humans,

这些消亡了的人类种群的基因组

we're beginning to arrive at a picture of what the world looked like

我们对现代人祖先走出非洲时的世界

when modern humans started coming out of Africa.

有了逐步的认识

In the West, there were Neanderthals;

西有尼安德特人

in the East, there were Denisovans --

东有德尼柔娃人

maybe other forms of humans too

也许还有其他

that we've not yet described.

我们尚未发现的人种

We don't know quite where the borders between these people were,

我们并不确定这些人种的分界在哪里

but we know that in Southern Siberia,

但我们知道尼安德特人

there were both Neanderthals and Denisovans

和德尼柔娃人都曾在南西伯利亚生活过

at least at some time in the past.

他们至少曾经一度共同生活在那里

Then modern humans emerged somewhere in Africa,

现代人随后在非洲出现

came out of Africa, presumably in the Middle East.

走出了非洲 我们认为他们去到了中东

They meet Neanderthals, mix with them,

他们和尼安德特人交汇

continue to spread over the world,

接着继续分散到世界各地

and somewhere in Southeast Asia,

到了东南亚

they meet Denisovans and mix with them

他们又和德尼柔娃人尼安德特人交汇

and continue on out into the Pacific.

接着去到太平洋岛屿

And then these earlier forms of humans disappear,

后来 这些早期人类都消亡了

but they live on a little bit today

但是今天

in some of us --

在我们某些人

in that people outside of Africa have two and a half percent of their DNA

也就是那些后来走出非洲的人仍然有2.5%的DNA

from Neanderthals,

来自尼安德特人

and people in Melanesia

而生活在美拉尼西亚的人们

actually have an additional five percent approximately

另有5%的DNA

from the Denisovans.

来自德尼柔娃人

Does this then mean that there is after all

这是否意味着

some absolute difference

非洲以外的人

between people outside Africa and inside Africa

与非洲人之间存在绝对的差异

in that people outside Africa

非洲以外的人们

have this old component in their genome

拥有已消亡

from these extinct forms of humans,

古人类的基因

whereas Africans do not?

而非洲人却没有

Well I don't think that is the case.

我不这么认为

Presumably, modern humans

现代人被认为

emerged somewhere in Africa.

最早出现在非洲

They spread across Africa also, of course,

他们当然也遍布整个非洲

and there were older, earlier forms of humans there.

那里有更古老的人类种群

And since we mixed elsewhere,

既然我们曾经与其他种群杂居

I'm pretty sure that one day,

我敢肯定

when we will perhaps have a genome

当我们找到一个

of also these earlier forms in Africa,

更早期人类的基因组

we will find that they have also mixed

我们可能会发现

with early modern humans in Africa.

他们曾与早期现代人在非洲交汇

So to sum up,

总结一下

what have we learned from studying genomes

从比对现今人类

of present day humans

与已消亡的古人类的基因组研究

and extinct humans?

我们学到了什么

We learn perhaps many things,

我们也许学到了很多东西

but one thing that I find sort of important to mention

我认为最重要的是

is that I think the lesson is that we have always mixed.

我们的基因交汇在了一起

We mixed with these earlier forms of humans,

我们拥有这些古人类的基因

wherever we met them,

不管现代人曾在哪里与他们相遇

and we mixed with each other ever since.

从那以后 我们的基因就交汇在了一起

Thank you for your attention.

非常感谢

(Applause)

（众人鼓掌）