Svante Pääbo: DNA clues to our inner neanderthal

譯者: Joan Liu 審譯者: Resa CC

What I want to talk to you about

我想要談的是

is what we can learn from studying the genomes

我們從研究

of living people

活著的人

and extinct humans.

和滅絕人種的基因組中可以學到什麼。

But before doing that,

但在那之前，

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

我要提醒你們一些你們已經知道的事：

that our genomes, our genetic material,

我們的基因組，我們的基因物質，

are stored in almost all cells in our bodies in chromosomes

存在於我們身上幾乎所有細胞內的染色體中，

in the form of DNA,

以DNA的形式存在，

which is this famous double-helical molecule.

即著名的雙重螺旋分子結構。

And the genetic information

而且這些基因資料

is contained in the form of a sequence

是以四種簡稱為

of four bases

Ａ、Ｔ、Ｃ、Ｇ的鹼基

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

組成的序列。

And the information is there twice --

基因資料有兩組──

one on each strand --

一股(線)上一組──

which is important,

這點很重要，

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

因為當新細胞形成時，DNA的雙股會分開，

new strands are synthesized with the old ones as templates

單股各自為模板，與(複製出的)新股合成為兩條雙股DNA

in an almost perfect process.

這是一個近乎完美的複製過程。

But nothing, of course, in nature

當然!自然界沒有任何東西

is totally perfect,

是完美無瑕的。

so sometimes an error is made

因此有時會出錯而

and a wrong letter is built in.

置入錯誤的字母(鹼基)。

And we can then see the result

舉例來說，當我們比較

of such mutations

演說廳內所有人的DNA序列，

when we compare DNA sequences

我們就會看到

among us here in the room, for example.

這類突變的結果。

If we compare my genome to the genome of you,

拿我的基因組跟你們的比較，

approximately every 1,200, 1,300 letters

在我們之中，大約每1,200或1,300個鹼基

will differ between us.

就會出現不同之處。

And these mutations accumulate

而且這些突變

approximately as a function of time.

有大概的週期，隨歲月不斷積累。

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

所以若加入黑猩猩來比對，差異又更大了。

Approximately one letter in a hundred

大約每一百個字母(鹼基)就有一個

will differ from a chimpanzee.

跟大猩猩不同。

And if you're then interested in the history

而且若你對一段DNA

of a piece of DNA, or the whole genome,

或是整個基因組的進化史有興趣的話，

you can reconstruct the history of the DNA

可以利用這些觀測到的差異

with those differences you observe.

來重現DNA的進化史。

And generally we depict our ideas about this history

一般我們以這樣的樹狀圖

in the form of trees like this.

來繪製我們對進化史的概念。

In this case, it's very simple.

以這個例子來說，就是個簡單的例子。

The two human DNA sequences

這兩個人類DNA序列

go back to a common ancestor quite recently.

可追溯到最近的同源祖先。

Farther back is there one shared with chimpanzees.

時間再往回推，就可推出和黑猩猩有同源祖先。

And because these mutations

而且因為這些突變的發生

happen approximately as a function of time,

可依時間作大概推算，

you can transform these differences

你們可以把這些差異

to estimates of time,

轉換成估算的時間，

where the two humans, typically,

一般而論，這兩個人類

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

可被推算出在大約五十萬年前有同源祖先，

and with the chimpanzees,

跟黑猩猩的話，

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

推算出的時間是在五百萬年前左右。

So what has now happened in the last few years

這麼說吧，這些年來發生的事──

is that there are account technologies around

精密科技的問世

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

讓我們得以非常快速地檢視很多、很多的DNA。

So we can now, in a matter of hours,

所以僅僅幾個小時，我們就可以

determine a whole human genome.

檢測出全套人類基因組。

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

當然人類每個個體都有兩組基因組：

one from our mothers and one from our fathers.

一組來自母親，一組來自父親。

And they are around three billion such letters long.

而且約三十億字母(鹼基)的長度。

And we will find that the two genomes in me,

大家會在我身上找到兩組基因組，

or one genome of mine we want to use,

我們拿其中一組基因組來檢驗，

will have about three million differences

約有三百萬不同之處

in the order of that.

大概是這個數字。

And what you can then also begin to do

然後你也可以開始研究

is to say, "How are these genetic differences

這些基因的差異

distributed across the world?"

在這世界的分佈情形。

And if you do that,

而且若這麼做，

you find a certain amount of genetic variation in Africa.

你會發現在非洲有某一數量的基因變異(突變)。

And if you look outside Africa,

若你研究非洲以外的地區，

you actually find less genetic variation.

你觀察到的基因變異較少。

This is surprising, of course,

奇怪吧!

because in the order of six to eight times fewer people

因為在非洲的人比在非洲外的人

live in Africa than outside Africa.

少了約七、八倍。

Yet the people inside Africa

然而非洲內的人

have more genetic variation.

發生更多的基因變異(突變)

Moreover, almost all these genetic variants

況且，我們在非洲外發現

we see outside Africa

幾乎所有基因變異

have closely related DNA sequences

與在非洲內找到的DNA序列

that you find inside Africa.

有密切關係。

But if you look in Africa,

但若你們看看非洲內，

there is a component of the genetic variation

有處基因變異

that has no close relatives outside.

在非洲外完全沒有相近的排列。

So a model to explain this

那麼可以解釋這個的模式是

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

部分基因變異的非洲人，而非全基因變異人口，

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

移居到地球其他地方。

And together with the methods to date these genetic differences,

再加上利用基因差異斷定時間的技術，

this has led to the insight

讓我們對現代人類

that modern humans --

有這樣的了解：

humans that are essentially indistinguishable from you and me --

根本上難分你我的人類

evolved in Africa, quite recently,

是最近約十萬至二十萬年前

between 100 and 200,000 years ago.

在非洲進化而來的。

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

稍後約五萬到十萬年前

went out of Africa

離開非洲

to colonize the rest of the world.

到世界其他地方殖民。

So what I often like to say

所以我常喜歡說

is that, from a genomic perspective,

以基因組的觀點來看，

we are all Africans.

我們都是非洲人。

We either live inside Africa today,

我們不是現今住在非洲內

or in quite recent exile.

就是最近出走非洲的那群。

Another consequence

另一個現代人類的

of this recent origin of modern humans

最近起源的推論是

is that genetic variants

基因變異

are generally distributed widely in the world,

廣泛地分佈在全球

in many places,

各個地方，

and they tend to vary as gradients,

而且以全版面的角度來看

from a bird's-eye perspective at least.

往往呈梯度變化。

And since there are many genetic variants,

由於有很多基因變異，

and they have different such gradients,

就有不同的梯度變化，

this means that if we determine a DNA sequence --

這意味著若我們可以測出DNA序列──

a genome from one individual --

個體的基因組──

we can quite accurately estimate

我們可以相當準確地判斷

where that person comes from,

這個人是從哪裡來的，

provided that its parents or grandparents

若其父母或祖父母

haven't moved around too much.

沒有經常四處遷徙。

But does this then mean,

但這是不是表示

as many people tend to think,

如很多人想的那樣

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

不同族群的人，基因差異很大，

on different continents, for example?

是不是不同洲的人差異會更大?

Well we can begin to ask those questions also.

嗯，我們也可以開始問這樣的問題。

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

舉個例子，有個計畫在執行中

to sequence a thousand individuals --

要為世界不同地方的一千個人

their genomes -- from different parts of the world.

排列基因組。

They've sequenced 185 Africans

研究人員已經在非洲兩個族群中

from two populations in Africa.

完成185個人的DNA序列。

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

在歐洲和在中國已排出序列的

in Europe and in China.

人數也大概同樣多。

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

那麼我們便可開始指出找到多少基因變異，

how many letters that vary

在這些個體DNA排序中，

in at least one of those individual sequences.

單一個人的鹼基有多少變化。

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

答案是很多：有三千八百萬個變異處。

But we can then ask: Are there any absolute differences

但我們也可以問：非洲人和非非洲人

between Africans and non-Africans?

有任何完全差異嗎?

Perhaps the biggest difference

也許我們大部份的人會想到的

most of us would imagine existed.

最大差異曾經存在過。

And with absolute difference --

而「完全差異」

and I mean a difference

我所指的差異是

where people inside Africa at a certain position,

非洲內的人在某個「特定位置」，

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

「百分之百」有「相同的字母(鹼基)」，

and everybody outside Africa has another letter.

而每個在非洲外的人則有「另一個字母(鹼基)」。

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

這個問題的答案是，數百萬的差異之中，

is that there is not a single such position.

沒有這樣一個「完全差異」的位置。

This may be surprising.

這也許出人意料。

Maybe a single individual is misclassified or so.

也許有某個人的序列被弄錯了。

So we can relax the criterion a bit

所以我們可以稍稍放寬條件來問：

and say: How many positions do we find

我們發現有多少位置是

where 95 percent of people in Africa have

95%非洲內的人

one variant,

有「相同變異」，

95 percent another variant,

而在同樣的位置，95%非洲境外人則有「另一變異」，

and the number of that is 12.

得到的數字是12。

So this is very surprising.

所以很意外吧

It means that when we look at people

這意味著當我們看著人群，

and see a person from Africa

看到某個來自非洲的人、

and a person from Europe or Asia,

看到某個來自歐洲或亞州的人，

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

我們不能百分之百說中

predict what the person would carry.

「某人」基因組之「某處」具有「何種鹼基」。

And only for 12 positions

而且只有12個位置

can we hope to be 95 percent right.

我們能期望有九成五的正確率。

This may be surprising,

這也許令人驚訝。

because we can, of course, look at these people

我們當然可以用肉眼盯著這些人

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

並相當容易地分辨他們或其祖先從哪裡來。

So what this means now

也就是說

is that those traits we then look at

我們看到的這些特徵

and so readily see --

是很容易就看得到的──

facial features, skin color, hair structure --

相貌特色、髮色質量、皮膚顏色──

are not determined by single genes with big effects,

並非由各類單一、重要的基因決定其作用，

but are determined by many different genetic variants

而是由很多不同的基因變異決定，

that seem to vary in frequency

且這些變異似乎在世界各地

between different parts of the world.

發生的頻率(次數)也不同。

There is another thing with those traits

另外一件事與我們可以很容易地

that we so easily observe in each other

在彼此身上看得到的特徵有關。

that I think is worthwhile to consider,

我認為值得想想，

and that is that, in a very literal sense,

就字義來說，

they're really on the surface of our bodies.

這些特徵的確是在我們身體表面。

They are what we just said --

如我剛剛說的

facial features, hair structure, skin color.

相貌特色、髮色質量、皮膚顏色。

There are also a number of features

然而各洲間還存有諸如此類的不同特色

that vary between continents like that

可說是不勝枚舉，

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

像是我們如何代謝我們吃進去的食物

or that have to do

或是

with how our immune systems deal with microbes

我們的免疫系統如何應付

that try to invade our bodies.

企圖侵犯我們身體的病菌。

But so those are all parts of our bodies

然而這些是我們身體的各部

where we very directly interact with our environment,

直接與周圍環境互動，

in a direct confrontation, if you like.

你也可以說是「正面對峙」。

It's easy to imagine

很容易想像

how particularly those parts of our bodies

何以身體特定的某些部份

were quickly influenced by selection from the environment

一受到「環境淘汰(選擇)」威脅

and shifted frequencies of genes

就轉換這些受環境衝擊

that are involved in them.

的基因頻率。

But if we look on other parts of our bodies

但若我們看身體其他

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

不直接與環境互動的部份，

our kidneys, our livers, our hearts --

我們的腎臟、肝臟、心臟，

there is no way to say,

就很難

by just looking at these organs,

憑這些器官

where in the world they would come from.

判斷他們來自世界的何處。

So there's another interesting thing

所以有這層了解，我們發現

that comes from this realization

另一件有趣的事

that humans have a recent common origin in Africa,

人類最近共同的起源在非洲，

and that is that when those humans emerged

而且當時這些人類出現

around 100,000 years ago or so,

距今大約十萬年前，

they were not alone on the planet.

他們並不是單獨存在地球上。

There were other forms of humans around,

那時候有其他人種存在，

most famously perhaps, Neanderthals --

最有名的大概是「尼安德塔人」──

these robust forms of humans,

在左邊

compared to the left here

較健壯的人型，

with a modern human skeleton on the right --

右邊的是現代人類骨骼──

that existed in Western Asia and Europe

在幾十萬年前

since several hundreds of thousands of years.

就生活在西亞和歐洲。

So an interesting question is,

所以有個有趣的問題，

what happened when we met?

那時我們相遇，發生了什麼事?

What happened to the Neanderthals?

尼安德塔人怎麼了?

And to begin to answer such questions,

為了回答這樣的問題，

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

我的研究團隊在過去25年來

works on methods to extract DNA

研究如何從尼安德塔人

from remains of Neanderthals

和絕種動物

and extinct animals

的幾萬年遺骸

that are tens of thousands of years old.

萃取DNA。

So this involves a lot of technical issues

所以這牽涉到許多技術性問題

in how you extract the DNA,

像是如何萃取DNA，

how you convert it to a form you can sequence.

如何把它轉化成可以排序的形式。

You have to work very carefully

操作必須非常小心謹慎

to avoid contamination of experiments

以避免自己造成的

with DNA from yourself.

實驗污染DNA。

And this then, in conjunction with these methods

結合這些可以快速

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

排列出大量DNA分子的方法

allowed us last year

讓我們在去年

to present the first version of the Neanderthal genome,

得以呈現首版尼安德塔人基因組，

so that any one of you

所以你們任何人

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

都可以在網路上找到尼安德塔人基因組，

or at least on the 55 percent of it

或至少看得到目前能重現的

that we've been able to reconstruct so far.

55%尼安德塔人基因組。

And you can begin to compare it to the genomes

你們可以開始將之

of people who live today.

與現今活著的人類基因組做比較。

And one question

接著你們也許

that you may then want to ask

想問一個問題

is, what happened when we met?

現代人類和尼安德塔人相遇時，發生什麼事?

Did we mix or not?

有沒有混種？

And the way to ask that question

提問的科學路徑是

is to look at the Neanderthal that comes from Southern Europe

去看南歐出土的尼安德塔人之基因組

and compare it to genomes

然後將其基因組

of people who live today.

與現今活著的人類作比對。

So we then look

所以我們接著

to do this with pairs of individuals,

分析一對對的個體

starting with two Africans,

以兩個非洲人開始，

looking at the two African genomes,

看這兩個非洲人的基因組，

finding places where they differ from each other,

找出他們互不相同的地方，

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

並在每個案例中提問：尼安德塔人是怎麼樣的人?

Does it match one African or the other African?

其基因組與這個非洲人吻合或是另一個?

We would expect there to be no difference,

研究人員會預期沒有任何差異，

because Neanderthals were never in Africa.

因為尼安德塔人從來沒到過非洲。

They should be equal, have no reason to be closer

機率應會均等，沒有任何理由

to one African than another African.

與兩非洲人的任何一個相近。

And that's indeed the case.

分析的結果也的確是這樣。

Statistically speaking, there is no difference

依統計數字來說，沒有任何差異

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

可供說明兩非洲人誰更類似尼安德塔人。

But this is different

但我們來看看

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

歐洲人的和非洲人的又不同了。

Then, significantly more often,

尼安德塔人

does a Neanderthal match the European

和歐洲人相似度高

rather than the African.

而不似非洲人。

The same is true if we look at a Chinese individual

這種結果同樣也出現在

versus an African,

中國人相對於非洲人，

the Neanderthal will match the Chinese individual more often.

尼安德塔人和中國人的相似度高。

This may also be surprising

意外吧

because the Neanderthals were never in China.

因為尼安德塔人從未到過中國。

So the model we've proposed to explain this

因此，我們有這套構想

is that when modern humans came out of Africa

現代人類祖先大約在十萬年前

sometime after 100,000 years ago,

離開非洲，

they met Neanderthals.

他們遇見了尼安德塔人。

Presumably, they did so first in the Middle East,

可能他們在中東首度照面，

where there were Neanderthals living.

在當時是尼安得塔人的居住地。

If they then mixed with each other there,

接著他們可能在那裡混種，

then those modern humans

那麼這些現代人類

that became the ancestors

就成了

of everyone outside Africa

非洲外所有人類的祖先，

carried with them this Neanderthal component in their genome

這些帶有尼安德塔人元素的現代人類

to the rest of the world.

遷移到世界各地。

So that today, the people living outside Africa

因而今天，在非洲境外的人

have about two and a half percent of their DNA

有約2.5%的DNA

from Neanderthals.

來自尼安德塔人。

So having now a Neanderthal genome

現在有尼安德塔人的基因組在手

on hand as a reference point

作為參照，

and having the technologies

還有先進的科技技術

to look at ancient remains

可檢測古代的殘骸

and extract the DNA,

和萃取DNA，

we can begin to apply them elsewhere in the world.

我們便應用這些技術資源在世界各地的研究。

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

我們第一個造訪的地方是在南西伯利亞

in the Altai Mountains

的阿爾泰山，

at a place called Denisova,

一個叫丹尼索瓦(Denisova)的地方，

a cave site in this mountain here,

在這座山的洞穴內，

where archeologists in 2008

考古學家在2008年

found a tiny little piece of bone --

發現一塊極小的骨頭

this is a copy of it --

這個是複製品，

that they realized came from the last phalanx

他們發現這是屬於

of a little finger of a pinky of a human.

人類小指骨。

And it was well enough preserved

保存得相當好，

so we could determine the DNA from this individual,

所以我們能測出這個人的DNA，

even to a greater extent

所獲得的資料甚至比測

than for the Neanderthals actually,

尼安德塔人的DNA還來得更多，

and start relating it to the Neanderthal genome

我們將其與尼安德塔人和現今人類的

and to people today.

基因組做比對。

And we found that this individual

由這個人的DNA序列發現

shared a common origin for his DNA sequences

其與尼安德塔人約在六十四萬年前

with Neanderthals around 640,000 years ago.

有共同起源 。

And further back, 800,000 years ago

而追溯至八十萬年前

is there a common origin

才與現今人類

with present day humans.

有相同起源。

So this individual comes from a population

所以這個人來自於某個

that shares an origin with Neanderthals,

與尼安德塔人有相同來源的族群，

but far back and then have a long independent history.

但更早且有悠久而獨立的歷史。

We call this group of humans,

我們稱這個族群的人類──

that we then described for the first time

也就是我們首次

from this tiny, tiny little piece of bone,

從這塊小小骨頭研究出來的人種──

the Denisovans,

「丹尼索瓦人(Denisovans)」，

after this place where they were first described.

以發現這塊骨頭的地方命名。

So we can then ask for Denisovans

所以我們能在丹尼索瓦人(Denisovans)DNA

the same things as for the Neanderthals:

尋求同樣的東西如同對尼安德塔人的探索：

Did they mix with ancestors of present day people?

他們有跟現今人類的祖先混種嗎？

If we ask that question,

倘若我們這麼問，

and compare the Denisovan genome

並將丹尼索瓦人的基因組

to people around the world,

與世界各地的人做比較。

we surprisingly find

我們意外的發現

no evidence of Denisovan DNA

今日住在西伯利亞一帶的人身上

in any people living even close to Siberia today.

沒有任何丹尼索瓦人的DNA血緣。

But we do find it in Papua New Guinea

但在巴布亞新幾內亞(Papua New Guinea)及

and in other islands in Melanesia and the Pacific.

美拉尼西亞(Melanesia)和太平洋上的其他島嶼，找到它的「足跡」。

So this presumably means

所以這可能意味著

that these Denisovans had been more widespread in the past,

丹尼索瓦人在過去所到之處範圍甚廣，

since we don't think that the ancestors of Melanesians

不過我們認為美拉尼西亞人的祖先

were ever in Siberia.

未曽到過西伯利亞

So from studying

所以研究這些

these genomes of extinct humans,

已絕種人類的基因組，

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

我們便可得到當時現代人類出走非洲的

when modern humans started coming out of Africa.

世界的概況。

In the West, there were Neanderthals;

西方有尼安德塔人，

in the East, there were Denisovans --

東方有丹尼索瓦人，

maybe other forms of humans too

也許還有其他的人種

that we've not yet described.

只是我們還未發現。

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

我們不是很確定這些不同人種(族群)的疆界在哪，

but we know that in Southern Siberia,

但我們知道在南西伯利亞

there were both Neanderthals and Denisovans

有尼安德塔人和丹尼索瓦人，

at least at some time in the past.

至少過去某時曾在那出現。

Then modern humans emerged somewhere in Africa,

然後現代人類在非洲某處出現，

came out of Africa, presumably in the Middle East.

離開非洲後，可能到中東。

They meet Neanderthals, mix with them,

他們遇到了尼安德塔人，與他們混種後，

continue to spread over the world,

行蹤遍及世界各地，

and somewhere in Southeast Asia,

並在東南亞的某個地方，

they meet Denisovans and mix with them

他們碰到丹尼索瓦人和他們混種

and continue on out into the Pacific.

接著進入到太平洋一帶。

And then these earlier forms of humans disappear,

然後這些早期的人種消失了，

but they live on a little bit today

但他們遺留的小小一部分至今

in some of us --

仍殘存在某些人體內，

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

因為非洲境外人的DNA 有2.5%

from Neanderthals,

來自尼安德塔人。

and people in Melanesia

在美拉尼西亞的人

actually have an additional five percent approximately

事實上有另外約5%的基因

from the Denisovans.

來自丹尼索瓦人。

Does this then mean that there is after all

那麼就是說

some absolute difference

畢竟還是有些完全差異

between people outside Africa and inside Africa

存在非洲境內和境外的人

in that people outside Africa

因為在非洲境外人

have this old component in their genome

有這種古代元素在他們基因組，

from these extinct forms of humans,

是來自滅絕人種的基因

whereas Africans do not?

而非州內的人則沒有，是這樣嗎?

Well I don't think that is the case.

我可不這麼認為。

Presumably, modern humans

現代人類可能

emerged somewhere in Africa.

出現在非洲某個地方

They spread across Africa also, of course,

當然他們散佈在非洲各處，

and there were older, earlier forms of humans there.

那時有更早期的人種存在那裡。

And since we mixed elsewhere,

因為我們在其他地方混種，

I'm pretty sure that one day,

我可以肯定有一天，

when we will perhaps have a genome

我們或許將有一組基因組

of also these earlier forms in Africa,

是屬於非洲內更早期人種的，

we will find that they have also mixed

我們會發現這些更早期人種

with early modern humans in Africa.

已和早期現代人在非洲混種。

So to sum up,

所以結論是

what have we learned from studying genomes

我們從研究現今人類

of present day humans

和滅絕人種的基因組

and extinct humans?

學到了什麼？

We learn perhaps many things,

我們可能學到很多事，

but one thing that I find sort of important to mention

但我認為最值得一提的是

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

我領悟到「人類一再地融合」。

We mixed with these earlier forms of humans,

我們和更早期的人種混種，

wherever we met them,

不論我們是在哪裡遇到他們，

and we mixed with each other ever since.

自那以後，我們彼此融合。

Thank you for your attention.

謝謝你們的參與。

(Applause)

（掌聲）