is what we can learn from studying the genomes

of living people

and extinct humans.

But before doing that,

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

that our genomes, our genetic material,

are stored in almost all cells in our bodies in chromosomes

in the form of DNA,

which is this famous double-helical molecule.

And the genetic information

is contained in the form of a sequence

of four bases

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

And the information is there twice --

one on each strand --

which is important,

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

new strands are synthesized with the old ones as templates

in an almost perfect process.

But nothing, of course, in nature

is totally perfect,

so sometimes an error is made

and a wrong letter is built in.

And we can then see the result

of such mutations

when we compare DNA sequences

among us here in the room, for example.

If we compare my genome to the genome of you,

approximately every 1,200, 1,300 letters

will differ between us.

And these mutations accumulate

approximately as a function of time.

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

Approximately one letter in a hundred

will differ from a chimpanzee.

And if you're then interested in the history

of a piece of DNA, or the whole genome,

you can reconstruct the history of the DNA

with those differences you observe.

And generally we depict our ideas about this history

in the form of trees like this.

In this case, it's very simple.

The two human DNA sequences

go back to a common ancestor quite recently.

Farther back is there one shared with chimpanzees.

And because these mutations

happen approximately as a function of time,

you can transform these differences

to estimates of time,

where the two humans, typically,

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

and with the chimpanzees,

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

So what has now happened in the last few years

is that there are account technologies around

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

So we can now, in a matter of hours,

determine a whole human genome.

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

one from our mothers and one from our fathers.

And they are around three billion such letters long.

And we will find that the two genomes in me,

or one genome of mine we want to use,

will have about three million differences

in the order of that.

And what you can then also begin to do

is to say, "How are these genetic differences

distributed across the world?"

And if you do that,

you find a certain amount of genetic variation in Africa.

And if you look outside Africa,

you actually find less genetic variation.

This is surprising, of course,

because in the order of six to eight times fewer people

live in Africa than outside Africa.

Yet the people inside Africa

have more genetic variation.

Moreover, almost all these genetic variants

we see outside Africa

have closely related DNA sequences

that you find inside Africa.

But if you look in Africa,

there is a component of the genetic variation

that has no close relatives outside.

So a model to explain this

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

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

And together with the methods to date these genetic differences,

this has led to the insight

that modern humans --

humans that are essentially indistinguishable from you and me --

evolved in Africa, quite recently,

between 100 and 200,000 years ago.

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

went out of Africa

to colonize the rest of the world.

So what I often like to say

is that, from a genomic perspective,

we are all Africans.

We either live inside Africa today,

or in quite recent exile.

Another consequence

of this recent origin of modern humans

is that genetic variants

are generally distributed widely in the world,

in many places,

and they tend to vary as gradients,

from a bird's-eye perspective at least.

And since there are many genetic variants,

and they have different such gradients,

this means that if we determine a DNA sequence --

a genome from one individual --

we can quite accurately estimate

where that person comes from,

provided that its parents or grandparents

haven't moved around too much.

But does this then mean,

as many people tend to think,

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

on different continents, for example?

Well we can begin to ask those questions also.

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

to sequence a thousand individuals --

their genomes -- from different parts of the world.

They've sequenced 185 Africans

from two populations in Africa.

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

in Europe and in China.

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

how many letters that vary

in at least one of those individual sequences.

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

But we can then ask: Are there any absolute differences

between Africans and non-Africans?

Perhaps the biggest difference

most of us would imagine existed.

And with absolute difference --

and I mean a difference

where people inside Africa at a certain position,

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

and everybody outside Africa has another letter.

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

is that there is not a single such position.

This may be surprising.

Maybe a single individual is misclassified or so.

So we can relax the criterion a bit

and say: How many positions do we find

where 95 percent of people in Africa have

one variant,

95 percent another variant,

and the number of that is 12.

So this is very surprising.

It means that when we look at people

and see a person from Africa

and a person from Europe or Asia,

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

predict what the person would carry.

And only for 12 positions

can we hope to be 95 percent right.

This may be surprising,

because we can, of course, look at these people

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

So what this means now

is that those traits we then look at

and so readily see --

facial features, skin color, hair structure --

are not determined by single genes with big effects,

but are determined by many different genetic variants

that seem to vary in frequency

between different parts of the world.

There is another thing with those traits

that we so easily observe in each other

that I think is worthwhile to consider,

and that is that, in a very literal sense,

they're really on the surface of our bodies.

They are what we just said --

facial features, hair structure, skin color.

There are also a number of features

that vary between continents like that

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

or that have to do

with how our immune systems deal with microbes

that try to invade our bodies.

But so those are all parts of our bodies

where we very directly interact with our environment,

in a direct confrontation, if you like.

It's easy to imagine

how particularly those parts of our bodies

were quickly influenced by selection from the environment

and shifted frequencies of genes

that are involved in them.

But if we look on other parts of our bodies

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

our kidneys, our livers, our hearts --

there is no way to say,

by just looking at these organs,

where in the world they would come from.

So there's another interesting thing

that comes from this realization

that humans have a recent common origin in Africa,

and that is that when those humans emerged

around 100,000 years ago or so,

they were not alone on the planet.

There were other forms of humans around,

most famously perhaps, Neanderthals --

these robust forms of humans,

compared to the left here

with a modern human skeleton on the right --

that existed in Western Asia and Europe

since several hundreds of thousands of years.

So an interesting question is,

what happened when we met?

What happened to the Neanderthals?

And to begin to answer such questions,

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

works on methods to extract DNA

from remains of Neanderthals

and extinct animals

that are tens of thousands of years old.

So this involves a lot of technical issues

in how you extract the DNA,

how you convert it to a form you can sequence.

You have to work very carefully

to avoid contamination of experiments

with DNA from yourself.

And this then, in conjunction with these methods

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

allowed us last year

to present the first version of the Neanderthal genome,

so that any one of you

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

or at least on the 55 percent of it

that we've been able to reconstruct so far.

And you can begin to compare it to the genomes

of people who live today.

And one question

that you may then want to ask

is, what happened when we met?

Did we mix or not?

And the way to ask that question

is to look at the Neanderthal that comes from Southern Europe

and compare it to genomes

of people who live today.

So we then look

to do this with pairs of individuals,

starting with two Africans,

looking at the two African genomes,

finding places where they differ from each other,

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

Does it match one African or the other African?

We would expect there to be no difference,

because Neanderthals were never in Africa.

They should be equal, have no reason to be closer

to one African than another African.

And that's indeed the case.

Statistically speaking, there is no difference

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

But this is different

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