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(lively music)
- Good afternoon and welcome.
It's delightful to see
such a gigantic crowd.
We are pleased, along
with the Graduate Council,
to present Svante Paabo,
this year's speaker in the
Foerster Lecture series.
Which I should tell you,
according to the terms of the agreement,
is dedicated to an exploration
of the immortality of the soul
or other kindred subjects.
(attendees laughing)
I'll get back to the kindred subject part
at the end of my introduction.
Now I know there are a
lot of scientists in here
so you'll forgive me, because I'm not one.
I have never forgotten the
excitement that I experienced
when I read the opening pages
of Donald Johanson's Lucy
about 30-odd years ago.
In fact when I left Australia,
I took a handful of books with me,
and one of them was was Lucy.
On the morning of
November 30th, he writes,
1974, I woke as I usually
do on a field expedition
at daybreak.
Johanson and his team as we
all know were in Ethiopia
in a place called Hadar.
An ancient lake bed in the Afar Desert.
They were looking for fossils
at a place called Location 162.
Having found nothing that
day, they headed back to camp
but stopped on the way
to survey a little gully.
There was nothing to be found
until Johanson called out,
"That's a bit of hominid arm."
"Jesus Christ!" exclaimed Tom Gray,
the graduate student with
Johanson at the time.
One piece led to another and another
until a pretty intact skeleton
of a young female was found,
who became known to the world as Lucy.
Reading Svante Paabo's recently published
Neanderthal Man: In
Search of Lost Genomes,
I experienced that same
sense of exhilaration again.
He begins.
Late one night in 1996,
I just dozed off in bed
when my phone rang.
The caller was Matthias
Krings, a graduate student
in my laboratory at the
Zoological Institute
at the University of Munich.
All he said was, "It's not human."
I'm coming, I mumbled,
threw on some clothes,
and drove across town to the lab.
That afternoon, Mattias had started
our DNA sequencing machines,
feeding them fragments
of DNA he had extracted
and amplified from a small
piece of a Neanderthal arm bone
held at the Rheinisches
Landesmuseum in Bonn.
It had been discovered
about 140 years ago.
Here it was, another hominid
arm was about to reveal
another piece of the grand
story of human evolution.
Just as the dry earth at Hadar,
disgorged one bone after
another belonging to Lucy,
Professor Paabo writes
that when he got to the lab
Mattias and a young
archeologist, Ralf Schmitz,
Could hardly control their delight
as they showed me the string of As, Cs,
Gs and Ts coming out of the sequences.
And just as had been true
for Johanson and Gray,
Paabo writes of his coworkers,
"Neither they nor I had ever
seen anything like it before."
Aside from the fact that
paleoanthropologists
and paleogeneticists seem to
have some of their best moments
when either just getting out
of bed or slipping into it,
what the best of them are able to do
is convey to those of
us not in those fields
but deeply interested in them
is their giddy excitement at discovery
and the high-minded
purpose of their research,
the quest for human origins.
And it is indeed as
important as it sounds.
Svante Paabo is a Swedish,
as you know, biologist
and evolutionary anthropologist,
best known as one of the
founders of paleogenetics.
Since developing a method
of isolating and sequencing
the DNA of long-extinct species,
Professor Paabo and his
lab have worked extensively
on Neanderthal DNA.
In 2010, they succeeded in
mapping the Neanderthal genome.
Professor Paabo's work has demonstrated
that Neanderthals interbred
with Eurasian humans,
resulting in traces of Neanderthal DNA
that remain in the genomes
of many humans alive today.
He was born in Stockholm,
earned his PhD in 1986
from the Department of Cell Biology
at the University of Uppsala.
And from 1987 to 1990 he
was a postdoctoral fellow
in UC Berkeley's
Department of Biochemistry.
And I'm sure there may
be still some people here
from that time.
He became a full professor
of general biology
at the University of Munich in 1990
and remained there until 1998.
But since 1997, he has
actually served as director
of the Max Planck Institute
for Evolutionary Anthropology
in Leipzig.
He's received many honors
and awards for his work,
including the Gruber
Genetics Prize in 2013,
the Theodor Bucher Medal from
the Federation of European
Biomedical Societies in 2010.
And the Kistler Prize in 2009.
In 2007, Time magazine
named Professor Paabo
one of the hundred most
influential people in the world.
Since their founding in
1928, the Foerster Lectures
have been delivered by such
distinguished individuals
as Oliver Sacks, Thomas
Kuhn, and Aldous Huxley.
This evening, Svante
Paabo will join that list
with a lecture that is
certainly a kindred subject
to the immortality of the soul
in that it might be said to be
on the immortality of Neanderthal DNA.
It is entitled a Neanderthal
Perspective on Human Origins.
Please join me in welcoming
Svante Paabo to Berkeley.
(attendees applauding)
- Well thank you very, very much
for that very kind introduction.
And it's really a wonderful pleasure
to be back in Berkeley,
that still feels a little
bit like home to me.
And it's of course also a great honor
to be allowed to deliver
the Foerster Lecture here.
But I must say also that
I'm a little bit intimidated
by the subject matter,
when I got this letter,
about the immortality of the soul.
And I think I sort of have to
announce right at the start
that I will not talk about
the soul at all, really.
So what I will then discuss is our attempt
to study the genome,
the DNA of Neanderthals.
And as you will know these are
the closest extinct relatives
of present day humans, they
are the closest relatives
that are extinct to all humans
that are around on the planet today.
This is a Neanderthal skeleton on the left
compared to a modern human skeleton.
There are this sort of
robust forms of humans
that appear in the fossil record
around three or 400,000
years ago in Europe
and Western Asia where they then lived
till they disappeared around
40,000 years ago or so.
And what I will focus
on are the comparisons
between the genomes of Neanderthals
and present day humans.
Particularly with a view to
then seeing what is unique
to fully modern humans compared
to our closest relatives.
But also then on what DNA
Neanderthals have contributed
to present day humans.
So as was said in the
introduction, I will then perhaps,
if you like not talk about
the immortality of the soul
but a little bit about the
immortality of Neanderthals,
if you like, in the sense of
how they live on a little bit
in some people today.
But before I then start, I
thought I should just remind you
about what you all know,
that our genome, the DNA,
is stored in almost all cells in our body
in the form of DNA.
Which is replicated every
time new germ cells are formed
and a new individual is formed.
And this DNA is made out of
about three billion letters
in the genetic code that are
then replicated very faithfully
but sometimes errors are made.
So when a new germ cell is formed,
sometimes, the wrong base is built in
in the daughter molecule.
So every baby that's formed,
born, carries something like
50 or a hundred new mutations
that's neither there in
the mother nor the father.
So when we, and these mutations then,
we can observe as sequence differences
between individuals in the population.
So if you compare two genomes
between two people in this room,
we will have something like
three million differences
between two random genomes we choose.
And if you then want to
reconstruct the history
of a piece of DNA or the genome
you can use these differences
that you will see between two humans.
You can add in a chimpanzee.
You will find more differences,
about 10 times more
differences to a chimpanzee.
And you can reconstruct the
history of that piece of DNA
with the help of these
differences you observe.
And you can depict this in
the forms of these trees.
Very simply here the two human sequences
go back to a common
ancestor quite recently.
Quite much further back
is a common ancestor
shared with a chimp too.
And if you now go and
study on a worldwide scale
human genetic variation.
The surprising finding
that actually much came out
of Berkeley and Allan Wilson's lab here
is that most of the genetic
variation you find in the world
is found in Africa.
Although there are cost a lot less people
living in Africa today
than living outside Africa.
Those people outside Africa
have less genetic variation.
And for most of the genome it is true
that the variants you find outside Africa
have close relatives inside Africa.
But there is a component of
the genetic variation in Africa
that's found only there.
And the interpretation of
that is that modern humans
evolved in Africa, accumulated
genetic variation there,
and a part of that variation so to say
went out and colonized
the rest of the world.
And with some genetic
tricks you can also estimate
approximately when this exodus happened.
And it's less than a
hundred thousand years ago,
probably more 50, 60,000 years ago.
So this is the recent African
origin model of modern humans.
Much designed, as I said,
here, by Allan Wilson
and people in his lab.
But there is if you like then
a problem with this model.
And that is that when modern humans
then come out of Africa,
they were not at all alone on the planet.
There were other forms of humans
also living outside Africa
since almost two million years.
Most famously, the Neanderthals in Europe
and other forms that are
less well described in Asia.
So a big debate in paleontology
since many many years
was then what happened when
modern humans met Neanderthals?
Did one mix with each other or not?
And many years ago there were people
that even believed in total continuity,
that Neanderthals would
be the direct ancestors
of Europeans today.
I think no one believed
that for a long time.
There were many people,
particularly based on genetic data,
that thought there was
a total replacement,
0% contribution from Neanderthals.
And you can imagine anything
in between here of course.
So our first chance then
to test this came in '97,
as you heard in the introduction,
when we were able to determine
the first DNA sequences
from a Neanderthal specimen,
And not just any Neanderthal,
actually the Neanderthal
from Neanderthal, so to say.
That was found in 1856 and gave its name
to this group of hominids.
And I can also perhaps say
that we're very lucky I think
that our first Neanderthal we studied
was the type specimen that gave its name
to this group of hominids.
Because almost invariably
what other Neanderthals
we ever have started since then,
there's always some paleontologists
that come to us and say,
oh it's a bit too robust,
it's a little too gracile,
there's something wrong with it,
it's not quite a typical Neanderthal.
But if this is not a Neanderthal
then they don't exist,
so to say.
(attendees laughing)
So at the time, we took a
sample from the humerus up here.
At the time quite a big
sample, not this big,
this was both for carbon
dating and for the DNA.
Nowadays we take much
smaller samples than this.
You work under clean room conditions
to avoid contaminating your samples
that contain only traces of degraded
and chemically modified DNA.
Much less DNA often in
your sample then in say
a skin fragment that may
be like a dust particle
in the air in a normal room.
And we focused on a
tiny part of the genome,
the mitochondrial genome that's
inherited only from mothers
to offspring, a particular
variable part of that.
Reconstructed it cumbersomely at that time
with a technique of the time,
amplifying short pieces,
seeing those differences
that are consistently there,
and then estimating such
a tree of relationships
for this part of the genome,
for the mitochondrial genome.
And what we found was then
that the mitochondrial genomes
all present in humans go
back to a common ancestor
between a hundred and 200,000 years ago,
as had been found by Allan
Wilson here at Berkeley.
But the mitochondrial
genome of this Neanderthal
went much much further
back to common ancestor
shared with present day humans,
about half a million years ago or so.
And since then others,
we have looked at many
more mitochondrial genomes
from Neanderthals, they all fall together
outside the variation of present humans.
So it's quite clear
there is no people today
that walk around with
Neanderthal mitochondria
in their bodies.
So in this sense it is
total replacement here,
0% contribution.
But of course this is this
tiny part of the genome.
The vast majority of our
DNA is in the nucleus.
And it's inherited from the mothers
as well as from fathers to the offspring.
And the chance to begin to look at that
came in the mid, around 2005 or so,
with new technology.
High throughput DNA
sequencing technologies
that allows you to sequence
millions and even billions
of DNA molecules rapidly
and inexpensively.
So you can then just extract
all the DNA from such a fossil,
sequence randomly all
the DNA molecules in it,
make yourself a little DNA database,
and compare it to say, the human genome,
to bacterial genomes,
chimpanzee genomes, and so on.
The first place where this worked
was in southern Europe in Croatia.
Vindijua Cave, here.
From this bone here, it's
very late Neanderthal,
around 40,000 years old.
And the first thing that
you will notice then
in this DNA fragment is that
they are very, very short,
50, 60 bases long.
Whereas from a blood sample from me,
you could easily get 10,000
base pair long fragments.
You will also notice that
only a tiny proportion
of all the DNA in the bone
come from the Neanderthal.
Our very best bones,
something like three or 4%.
All the rest are from bacteria and fungi
that colonized the bone after
the death of this individual
40,000 years ago.
So we were very lucky than to get funding
for a five year project
to try to reconstruct a complete
genome of a Neanderthal.
So we worked very hard
on methods to improve
how we extract DNA from the bone
and make it into a form
that we can feed into
the sequencing machines.
And they also got more efficient
in how many molecules they
could sequence over this time.
We looked through many archeological sites
and many bones and focused on three bones
from that cave in Croatia
from three different
Neanderthal individuals.
We sequenced a bit over
a billion DNA fragments
from those bones, most of
them from microorganisms.
And then matched these
fragments to the human genome,
taking into account that some of these
had chemical modifications
that may give errors in the sequences.
And at the time,
we then had about three
billion base pair sequenced.
So we had random fragments
from all over the genome.
Sometimes we had one fragment
covering a piece in the
human genome for comparison.
Sometimes two, sometimes even three,
but we also missed big parts.
So at that time, we then had
a little over half the genome.
But it allowed us to get an overview
and begin to ask these
questions one was interested in.
So the first question was this thing,
what happened when modern
humans came out of Africa
and met Neanderthals?
Did one mix or not?
And we put together a big
consortium of different groups,
sort of theoretical groups
that helped us study this.
Particularly Monty Slatkin and
his group here at Berkeley,
Rasmus Nielsen here at Berkeley,
David Reich and his group at Harvard.
And addressed this question
in actually three
different, independent ways
because we knew this was a
very controversial question
so we wanted to get it right.
I will just present one of
them, the most direct one here,
saying that an expectation if Neanderthals
mixed with ancestors to Europeans would be
that Europeans should share
more genetic variants today
with Neanderthals than Africans today
would share with Neanderthals.
Because Neanderthals
had never been in Africa
so there's no reason to assume
they would have contributed
anything to Africans.
So it's this idea here.
If there was a contribution
from Neanderthals to Europeans,
Europeans would on average
be closer to Neanderthals
than Africans here, let me go back here.
There's no contribution,
the Neanderthal is equally
far from people in Africa
as people in Europe.
So we then sequenced not
only the Neanderthal genome
but five people from
different parts of the world
to be sure we had exactly the
same types and frequencies
of errors in the sequences.
A European, two Africans,
a Chinese person,
and one from Papua New Guinea
and did a very simple analysis.
So just to test this first
if you take two Africans.
We just compare those two African genomes
and find all places where
they have differences.
Then we take the Neanderthal
and see how often
does the Neanderthal match one
African or the other African.
Since Neanderthals had never
been here, there's no reason
to assume the Neanderthal
would have contributed more
to one African than the other.
So this should be 50-50 matching.
And indeed statistically
speaking that's 50-50,
it's no difference between these two.
But it was then different
when we looked at a
European and an African.
Now we found statistically
significantly more matching
to the European individual
than the African individual.
Which surprised me at the time.
I was really biased toward thinking
there had been no contribution.
But I was even more surprised then
when we compared the Chinese individual
to an African individual.
We again found more matching
to the Chinese person.
Although most people would say
there had never been
Neanderthals in China.
And even more surprising
then Papua New Guinea,
where for sure there had
never been Neanderthal,
we again see more matching to Papuans
than to Africans.
So the hypothesis that came out of this
was to say that if modern
humans come out of Africa
they presumably passed by the Middle East.
And we know there has been,
so this was the question,
how could this be?
And the model was we knew
there had been Neanderthals
in the Middle East.
So if this early modern
humans that came out
mixed with Neanderthals and
then became the ancestors
of everybody outside Africa.
These modern humans could
have carried with them
this Neanderthal contribution so to say
out to the rest of the world.
Even to areas where they
hadn't been Neanderthals.
To the extent that somewhere
between one and 2% of the genomes
of everyone outside Africa
today come from Neanderthals.
So what you can see that there is
this sort of part of the
variation in Europe, for example,
that matched Neanderthals.
This isn't so easy to see,
this is a schematic picture
of variation among a couple
of hundred Europeans.
Any sequence difference
is indicated in the genome
by yellow here.
On the bottom is the Neanderthal genome.
And you will see there
are a few European here,
for this region that's almost
identical to Neanderthal
and quite different from everyone else.
So these types of fragments,
they sort of make up
the evidence for this.
But this was not the only
possible model to explain this.
There was also the possibility
that that could go back
much further to substructure
populations in Africa.
If we imagine that Neanderthals,
maybe half a million years ago or so,
have an origin in Africa, leave Africa,
and become Neanderthals in Europe here.
And that this substructure
survives in Africa,
and that then modern humans evolved
in the same corner of Africa
where the Neanderthals did,
leave Africa and meet the Neanderthals.
And these modern humans also
spread around rest of Africa
and absorb this variation we
could arrive at a situation
where Neanderthals are
closer to Europeans today
then Africans are.
This is a more complicated explanation
but it's a possible explanation.
But the difference here is then
the similarities between the
Neanderthals and non-Africans
would be quite old, several
hundred thousand years old.
Here it would be quite recent,
Less than a hundred thousand.
So a very big question early on became
when did this admixture happen?
And David Reich and Nick Patterson
and their Pulsetrons,
Sriram Sankararaman came up
with a way to address this.
And that is to say that if Neanderthals
and modern humans mixed,
the first generation,
the hybrids so to say,
would of course have one chromosome
that come from Neanderthals
and one from modern humans.
If these individuals then
continue to have babies
with the modern humans,
there will be recombination
in each generation so that
information is crossed over
between these two chromosomes.
So there will then be mosaic chromosomes
with part Neanderthal, part
modern human parts here.
And as the generations go on,
there is more and more
crossing over happen,
so these pieces get smaller
and smaller with time.
So you can actually look
at the size distribution
of Neanderthal fragments and estimate
how many generations
back were they introduced
into the modern human gene pool.
So look at the sizes of these things.
So you have to make a
number of assumptions here
about generation time,
recombination landscapes and so on.
And making those assumptions
they came up with a date
somewhere between 40 and 90,000 years ago,
so quite recently.
Only compatible with this recent
admixture to modern humans
when they come out of Africa.
But I'm a sort of a
really practical person.
These are of course,
theoretical considerations
that rely on a number of assumptions.
And maybe some of those
assumptions are wrong.
So I really like to go back in time
and try to find actual evidence
for when this happened.
And that is beginning to be possible now.
Because there was a bone
found just two years ago
in a river in Western Siberia here,
at the place called Ust'-Ishim
at the Irtysh River.
And there was a bone washed
up on the shore there.
A femur like this.
That looks very much like
a modern human femur.
And we were very lucky to
get this femur to our lab
in Leipzig and we were shocked
when we radiocarbon dated it.
Because it turned out
to be 45,000 years old.
So it's actually older than
any other directly dated
modern humans outside the
Middle East and Africa.
So this is a very early modern
human, 45,000 years old.
So it falls actually in this
range, 40 to 90,000 years ago
when this mixture with
Neanderthals could have happened.
And certainly this
individual lived at a time
when there was also Neanderthals around.
So now we can, and this is
a sort of unpublished part
of what I'm telling you,
look for the first time
in an early modern human that
lived at this time and say,
have this individual met and
bred with Neanderthals or not?
So if you first look here
on just one chromosome,
a number of European
and Asian people today,
Neanderthal fragments
are indicated by red,
when they're homozygous
they are green here.
You can actually see a difference here
between Europeans and Asians.
If you squint a bit, you can almost see
that Asians have slightly
more Neanderthal fragments
and that's actually true.
There's evidence from
Monty Slatkin's lab here
that Asians and others also have shown
that Asians seem to have an
additional Neanderthal component
that you don't see in Europe.
But the big question for us now
is this Ust'-Ishim individual
here, 45,000 years,
does that have any Neanderthal
contribution or not?
And the answer to that is yes, it does.
And actually a lot, if you like.
Overall, not more than this individual,
but it's distributed
in much bigger chunks.
As you would expect right,
when you go back in time,
there should not have been
so much recombination having happened.
It's this thing again, so we
can go back to this scheme
and look at the length, if you like, here.
The genetic lengths on the chromosomes
of Neanderthal fragments.
And how well the Neanderthal
variants correlate
over lengths in the chromosomes.
If you look at these, these
are present day humans here
that arrived at 40 to 90,000.
This is a 45,000 year old human
that allows us to estimate
that somewhere in the order
of 300 or 400 generations
before this individual lived,
Neanderthals contributed here.
So that would then allow
us to estimate this
to somewhere 50 to 60,000 years ago.
So we're narrowing in
on when this happened.
But very clearly, it's this
model that is right then,
there's genes from
Neanderthals to modern humans
after one comes out of Africa.
So there are a number of questions
you'll often get about this.
Some people ask, is this a lot
of Neanderthal ancestry I have or a little
when we say one or 2% of our genome?
And one way to think about
that in very simple terms
is perhaps to think about
your own family tree.
If this is you, you of
course share 50% of your DNA
with your mom and your dad,
25 with your great-great-great
grandparents,
12% approximate with
your great-grandparents,
with your great-great-grandparents 6%,
3%, and if we now go back six generations,
you then on average 1.5% or so.
So in some sense, in
the quantitative sense,
it is as if one of your
ancestors back here
was a Neanderthal.
It's of course much further back
and it's distributed
differently in the genome,
but it might give you a feeling for
of how big a contribution is this.
So something else that
people often ask us is,
well were the Neanderthal the
same species as us or not?
So should we call them
separate species name,
Homo neanderthalensis or a subspecies?
And I always sort of dodge
that question and say
you can even cite Darwin about this,
and saying to discuss if two
things are rightly called
species or varieties before
they have a definition
of these terms is to vainly beat the air.
And we still don't have a
good definition of this.
So I sort of don't answer that question.
So another question then is sort of
how much of the Neanderthal
genome remains today?
Because if your roots are outside Africa,
you have one or 2% of
your genome from them
but we carry different pieces, right.
So if we walk across many people,
how much of the Neanderthal
genome can we reconstruct
from people today?
And there were two papers
that came out in January,
one from Josh Akey's lab in Seattle,
and one from David Reich's lab
that we were involved in.
Sort of doing that in
the 1000 Genomes data.
So you can go across many
people on a chromosome here
and see which fragments
came from Neanderthals
and puzzle together pieces
of the Neanderthal genome
from people living today.
And it's very, very clear
that you can get together
at least 20% of the genome.
And probably twice that, I would think,
because we have big problems
recognizing short little pieces,
we probably miss several pieces.
So perhaps approaching half their genome
or something like that
is still going around
on the planet today.
That's the immortality part of the talk.
So, I also can never refrain from saying
that there are a lot of
people in the general public
that are fascinated by
this and write to us.
Many people write to us and
self-identify as Neanderthals
and volunteer to give samples to us.
And I started very early on
to notice a pattern in
this correspondence.
And that it's mainly men who write to us
and say that they are Neanderthals.
And very few women who
claim they are Neanderthals.
(attendees laughing)
So I sort of presented this
as my research to my group,
you know, I counted emails.
But people are getting critical
particularly when I
have ideas in the group,
so they said this is just ascertainment,
men are more interested
in molecular genetics
and they write to you, and
women are less interested.
But that's actually not true.
If I go back and see, there
are actually quite a few women
who write to us and say they
are married to Neanderthals.
(attendees laughing)
And so far there is not a single man
whose has claimed he is
married to a Neanderthal woman.
So that's of course quite
fascinating for a geneticist,
the type of inheritance that
go on here we try to do.
But something else that
we're also interested
in addition to counting emails is then
other extinct forms of humans.
And particularly we are lucky
to work with people in Russia,
particularly at this
site in Southern Siberia,
Denisova Cave.
This beautiful place, close to the border
to Mongolia and China
where Anatoli Derevianko and
Michael Shunkov excavates
in several years.
And they found this
tiny little bone in 2008
in this gallery in the cave here.
I think they were actually
very skilled realizing that
that might be a human bone.
So we got this fragment
of this pinky of a child,
the last phalanx of the pinky of a child,
and analyzed its DNA.
And it was quite unique
in actually having 70%
endogenous DNA, so very
little bacterial growth
in this bone.
And we applied some new
technology we've developed
that actually starts out by
separating the two strands
of the DNA molecule and sequencing,
putting them into these libraries
for sequencing individually.
So each double-stranded
molecule have two chances
to end up in the library,
one for each strand.
And with this method, we
were then able to sequence
a very good genome from this individual.
So for the part of the genome
about 2/3 of the genome
to which you can map these short fragments
we've sequenced it many many times over,
about 30 times over, so
we've seen every position
several times.
And we were extremely
surprised them to find
that this was not closely
related to Neanderthals
and even further from present day humans.
It shared a common ancestor
here far back with Neanderthals,
but Neanderthals then have
a long independent history.
It was clearly some other form of human,
related to Neanderthals.
And we, after much sort
of discussion about this,
we ended up calling them
Denisovans after this cave site
where they were first seen.
Just as Neanderthals
are called Neanderthals
after Neanderthal where they were found.
And there are a number of
interesting things you can now do
when you start having
really high-quality genomes
from humans that lived long time ago.
As high quality as you would
sequence from a patient today.
You can, for example, start
seeing, as you would expect,
that this individual died
several tens of thousands of years back.
So compared to people today
there are certain mutations
that have not happened here.
So it lacks mutations.
So if you go back to the
common ancestor with the chimp,
a bit over 1% less substitutions
than you would expect.
So you see sort of evolution
in action, if you like, here.
So if you now just make the assumption
this is 6.5 million years ago,
we can even date the bone here
to somewhere 60 to 80,000 years.
This is with big caveats.
I don't have much faith
in this number at all.
We'll also see variation here
showing we have problems
with sequence accuracy
in the modern humans for example.
But it anyway gives an indication
of what will be possible in the future.
So this bone is far too small
to be able to do a carbon date
but when we can do a good genome from it
we can actually, in the future,
even date it with genetic means.
You can ask, for these Denisovans,
have they contributed to people today?
And indeed, they have.
Surprisingly, although the
bones are found here in Siberia,
we find very little
contribution in mainland Asia.
There's now new evidence,
just a little bit,
but the major contribution
is out in the Pacific,
Papua New Guinea, Aboriginal Australians,
have up to 5% even Denisovan DNA.
So if we just summarize
then what we believe
from studying genomes about
the origin of Neanderthals
and Denisovans first,
we believe there's an origin in Africa.
They come out of Africa
and in Western Eurasia
evolved into what we called Neanderthals.
And in Eastern Eurasia to
what we call the Denisovans.
This is not that all to say
they were this widely
distributed at any one time.
Also note that there are not
other forms of hominins here.
He have the hobbits in
Indonesia for example
that we know about.
We don't know where the
borders between these have been
but we do know that in
this part in Siberia,
there had been Neanderthals
as well as Denisovans
at some time in history.
Then modern humans evolved in Africa.
Start spreading out of Africa seriously
50, 60,000 years ago.
Mix with Neanderthals in the Middle East.
Continue to spread out and mix
again at least once it seems,
perhaps somewhere in Central Asia,
so with the ancestors
of present day Asians.
And mix in Southeast Asia
somewhere with Denisovans
and continue out in the Pacific.
And these old forms then became extinct
but live on if you like, a little bit,
in that one or 2% in
all non-Africans today
and an additional 5% or so in the Pacific.
Now we have studied two genomes
of two extinct forms of humans.
I wouldn't be at all surprised if one find
additional admixture events,
for example, in China.
And I would also not be
surprised if it was the case
that in Africa when
modern humans spread there
there was also admixture.
There is some indication of that
in present day variation in Africa.
But it's much harder to really demonstrate
when you don't have these old genomes.
But so in this sense
then we clearly disproven
total replacement.
We have something like
7.5% maximally so far.
But the big picture is still
one of replacement, right.
So to not lose track of that,
to sort of like suggest a sort of model
called leaky replacement
or so for modern humans,
spread with some gene flow
there from these other forms.
So I think it's sort of interesting,
this is a copy of this little bone
that from such a tiny little bone,
one can actually get a lot of information
about the population history,
of the population from
this individual came.
But very frustratingly,
we don't know how this individual look,
we don't have no other
part of the skeleton
except three teeth, thankfully.
We don't know what stone tools they made,
we don't know anything
about them except the genome
and much of the population history.
And I think this is an indication about
how it will be in archeology
a lot in the future.
That when you can retrieve DNA,
also from small and
diagnostic pieces like this,
you will be able to get
a lot of information.
So this cave, Denisova Cave,
had also yielded more
interesting fragments,
this is a toe bone that was
found in 2010, deeper down.
This turned out to be a Neanderthal bone.
So we now also have a
good Neanderthal genome
that we published in January this year.
We have very high quality
Neanderthal genome.
So you can look at different
aspects of this also.
You can look for example
on heterozygosity,.
So how much variation there is
between the two versions of the genome
that this individual inherited
from the father and the mother.
You will see present day
Africans here have more variation
than non-Africans
and here is a Neanderthal and
a Denisovan having even less.
And not only that,
when one looks at the chromosomes
of this Neanderthal individual,
you find something amazing.
You find long, long segments,
19 million base pairs
on this chromosome,
where the two chromosomes
are identical to each other.
And that, of course, indicates
that the parents of this
individual were closely related.
And Monty Slatkin and his
group here at Berkeley
had modeled what the
relationships must have been
between the parents of this individual.
And it has to been one of
these four scenarios here.
The parents were half
siblings or grandfather,
granddaughter or some of these
things, double first cousins,
I can't even reconstruct what it is.
But they were clearly closely related.
So I think it will be very
interesting in the future
when we get good genomes also
from other Neanderthal sites
to see if this is a
general pattern at the time
or this was something just
happening in this cave
at this one time.
So what we then have are these
good genomes from Siberia,
we have a bit of a genome from Caucasus
and this one from Croatia.
So we can now start to look at gene flow
not only from these
groups into modern humans
but also between them.
So what we find then is
what we already know,
this gene flow of non-Africans
from Neanderthals,
from Denisovans into
people in the Pacific.
We find a little bit of gene flow
from Denisovans into Mainland Asians.
The people in China, for example,
also have a little bit of Denisovan DNA.
We find gene flow, a few
percent from Neanderthals
into Denisovans.
And quite interesting, an old component
in the Denisovan genome not
seen in the Neanderthals.
There is some gene flow, someone else here
of a few percent into Denisovans.
Something that split a
million years or more
from the human lineage.
It's very tempting to say that
this unknown contributor here
is Homo erectus or so
in Asia contributing.
So the conclusion is human
groups are always mixed
at least a little bit today.
And in the end, then I wanted
to bring up four things,
sort of consequences of this gene flow.
So a question is then,
we have this Neanderthal
component in the genome
outside Africa today.
Does that have any
functional consequences?
And there are some hints,
beginning to be some hints
in the last few years
that that may be the case.
So there was paper in January
which looked across the genome
in Europeans and in Asians
finding that there were
some parts of the genome
that actually where
there are contributions
from Neanderthals that have
reached high frequency,
60, 70% people in Asia
and this thing here,
60, 70% of Europeans and
that sometimes is shared
between Asians and Europeans,
sometimes it's unique
to one group.
So, of course, one interesting thing
is to look in these
segments and see what genes
are particularly located there.
If you look for groups of genes,
the only thing that stand out
or actually structured growth
is keratins in skin and hair.
So it may well be that
something in the structure
of the skin or the hair
in Europeans and Asians
actually is a contribution
from Neanderthals.
Well, we'll then find out
in the future what that is.
Something else that Peter
Parham's group found
early on 2011 already is that
transplantation antigen genes,
some variants of genes
and involved in regulating
the immune system
came from Neanderthals
and also from Denisovans
and have sometimes reached high frequency
in certain regions of Europe.
These are the proteins
that present peptides
from bacteria and viruses
to the immune system.
So they are important in regulating
how well we respond to infections.
So it's quite tempting then to say
that this is something
to do with these Africans
coming out, meeting people that had lived
for hundreds of thousands of years
in the environment in Asia and Europe
picking up immune
regulatory genes from them
and when they are advantageous,
they rise to high frequency.
So a group in in Shanghai who have shown
that if you look at genes
involved in lipid catabolism,
so how do you degrade lipids,
they have a big tendency
to come in Europe from the Neanderthals
that you don't see in Asia
and, of course, not in Africa.
We don't know at all what
this means metabolically
but something may be going on.
There was another study
in January this year
that identified a risk
variant for type 2 diabetes.
So the type of diabetes
you get at old age.
And this risk gene encodes
a lipid transporter
that sits in the membrane
that have four amino acid differences
to the protective allele.
And quite strikingly, this
risk allele is high frequency
in Asia and also in Native Americans,
very little in Europe and not in Africa.
And if you look at the
risk alleles here in red
and the protective alleles in blue,
you find the Neanderthal
variant in the middle here.
So this is clearly a
variant that have come over
to modern humans from Neanderthals
have risen to 25, 30% frequency
in Asia and Native Americans.
Today, it's associated with
risk for type 2 diabetes
but probably in a situation
where you have periodic
starvation, for example,
such variance may be
actually advantageous.
So this may be that this is some kind
of Neanderthal adaptation to starvation.
You can, of course, also ask,
have there contribution
from Denisovans too?
And quite fascinatingly, it
has come out quite recently
that it was already known that people
on the high plateau in
Tibet are adapted to living
at low oxygen tensions.
And that one of the major
genes involved in that
is this transcription factor EPAS1.
And Rasmus Nielsen's
group here in Berkeley
have now shown that this variant of EPAS1
that exists in 70, 80% of
Tibetans come from Denisovans.
It's identical to Denisovans here.
So this variant then
carry over from Denisovans
into Tibetans.
So it's quite fascinating that even life
on the high plateau Tibet
might actually not have been
possible or so easily possible
without the synaptic
contribution from Denisovans.
So this sort of fits
into sort of a pattern
of adaptive introgression if you like
where these earlier forms of humans
who lived for a long time
in these other environments
and these newcomers from Africa
may have picked up variants
that were then positively selected
and that rose to high frequency.
So you can, of course,
also ask what is not coming
from the Neanderthals.
So you can look across the
genomes and look for things
where you statistically
see a lack of contribution
from Neanderthals,
or you would expect to see it there.
And David Reich's group had identified
a number of these regions and
when we looked where genes
in these regions are expressed
in the body and what tissues,
the only thing that
stands out are testicles.
So the male organ.
So it's very tempting then to
speculate that the hybrids,
Neanderthal-modern human hybrids
may have had some problem
for male fertility
because that's, of course,
a common pattern when closely
related populations or species
have hybrids, it's often the males
have problems with fertility if you think
about horses and donkeys, for example,
the male mules are infertile,
the females can have offspring.
And finally, the thing
that interests me very much
is what can we say about
uniqueness in modern humans now
when we compare ourselves
our closest extinct relative?
So what has changed here in modern humans
in the short time since we
separated from Neanderthals
maybe three to 400,000 years ago?
And that may be an
interesting set of things
because I think we all
agree that our technology,
for example, we, modern humans
have changed very rapidly.
Neanderthals lived for
three 400,000 years,
the technology were not that different
in the beginning of that
time and in the end,
modern humans have existed
for perhaps 100,000 years
and I think our technology
today, we agree,
is quite different from
what it was back then.
Art that really depict things
that we recognize as art
counts with modern humans
spreading across the world,
becoming extremely numerous,
spreading across water
over long distances, countless
modern humans and so on.
So it's very interesting
now to make this catalog
of all the changes in the human genome
that have come since that time.
So now focusing on these
things that exist in all humans
no matter where we live on the planet
but where the Neanderthals
look like the apes.
And that's not a very long list of things.
These things that had
happened here became 100%.
It's in total, just a little over 30,000
single nucleotide change.
Some insertions and deletions and so on.
So it's very sort of fascinating
that you can look through
this list in an afternoon
in a computer actually.
You can, of course, for most part of it,
not make sense of it.
We don't know what
these things, of course.
But among them, I believe,
there will be some
important things hiding.
So for example, if you look at
the amino acid changes there,
only 96 amino acid
changes in this category
that affect 87 proteins
and this is a list of these proteins here.
So we are of course biased to think
that something with cognition
is particularly interesting
so the developing brain was something
we were very interested in looking at
together with the people at
the Allen Brain Institute
and originally, I was very
excited to say that 88%
of these proteins were expressed
in the developing cerebral cortex.
But we then did some controls,
for example, finding genes
with no amino acid change
but a silent change as obtained
in exactly the same way.
And 100% of them are expressed
in the cerebral cortex.
This just goes to say
that almost everything
is expressed in the developing brain.
But with appropriate controls,
only one that sort of seems to stand out
or things that are expressed
in a ventricular soul
of the developing cortex
and that have some kind of gradients
from the temporal gradients.
So in the layer of the
developing cerebral cortex
where cells divide, stem
cells divide and form neurons,
we see significantly more
of these genes expressed.
And this relies on very few genes now.
It's actually only six
genes that are responsible
for the signal, all in all
it was only 87 genes, right?
And strikingly, three of these genes,
two of them are in the kinetic
core and one in the spindle.
So this is sort of where
the spindle attaches
to the chromosomes and
pull the chromosomes apart
of cell division which
surprised me very much.
I thought cell division
would be so conserved,
that not have changed the modern humans.
But of course, there are evidence
that in the developing cortex here,
how the stem cells divide
the plane of division,
for example, determines
a number of neurons
and types of neurons that are formed.
So it may be this is all
speculation, of course,
but that these three
genes with their changes
is something we should
look particular careful at
in the future.
So we can also now begin
to look taking variation
in Neanderthals into account.
So we have then genomes
from three Neanderthals here
and the Denisovans and
we can begin to look
for groups of genes that have changed,
particularly one group of
hominids and the other.
And if we look in
Neanderthals and the others,
only one such category of
genes that seem to stand out
and these are genes
involved in hyperlordosis,
so how much your spine is curved.
And here are more things back here
and sort of morphology and in metabolism.
But this is quite interesting
because this is something we can look at
in the fossil record.
So the curvature of the spine and indeed,
Neanderthals differ from modern humans
in having less of a
curvature in the spine.
So since this sort of makes some sense,
we were quite interesting to
see what categories come here
in modern humans and they come
only two categories there.
One is sort of behavior
and one is pigmentation.
And again, it relies on very few genes.
Just five genes.
Two of them had to do with pigmentation
but they are not actually totally fixed
when we now have gone
on and looked in Africa
much more carefully.
A few percent of people in
Africa have ancestral variant
so this is not so interesting.
It probably have to do with
differences in pigmentation
but these genes involved in behavior
seemed to be really fixed in humans.
You can of course look
at what they are involved
in the processes, what
diseases they are involved
and you then arrive at
the last question here.
How will we, in the
future, study these things
that may have to do with
human specific traits?
And I've sort of gone around for 10 years,
now making jokes and talk
saying what we want to do
is of course to put Neanderthal alleles
into transgenic humans and human alleles
into transgenic chimps
and study their phenotypes
and that we have problems
with ethics committees
and things like so we'll
never be able to do that.
But this is sort of been a joke
but it's almost less of joke
now because there are people
who have sort of stood
yes, that we should now use
stem cell technology and
high throughput mutagenesis
to actually clone Neanderthals.
George Church, for example, at Harvard.
So I think we have exactly
the same issues there
for many, many reasons.
Technical and ethical,
we will never do that
but this is not just a joke.
This is of course what one
would have done in drosophila
or in some other model animals.
So what can we hope to do in the future?
I think one thing we will be able to do
is find back mutations in humans.
As we said in the very beginning,
every baby that's born has
50 or 100 new mutations.
There are seven billion
people on the planet.
The genome is just
three billion base pairs
so every mutation
compatible with human life
exists out there.
We just have to find
them and start in them.
And that I think will be
possible in the future
when we all have our genome sequence
when we go to the doctor.
But that's a little bit away.
I think we can introduce
these things into stem cells
and study cells in vitro
and I think we can also
introduce them into mice
and sometimes make sense of it
and I see that have grown over time
so I will sort of not really
show you then one such thing
which has changed is
that happened back here
and seems to have to do with
language and articulation.
Those mutations we have,
sort of, as a model
put into transgenic mouse.
So the mouse now makes a
human version of this protein
that seems to have
something to do in humans
with language and speech.
And you can then study that mouse,
the brain of it,
electrophysiologically, for example,
and find that you have
certain electrical features
of the neurons have changed.
And you can also see that these neurons
make longer connections in
certain parts of the brain
and those parts of the brain
are involved in motor learning
so these are these
cortico-basal ganglia circuits
that seems to be changed.
So you can then develop a
theory about what this caused
and there's some new data
now that's now published
by Christiane Schreiweis
together with Ann Graybiel at MIT
where they studied motor
learning in this humanized mice
that have this humanized protein in them.
So these are experiments
where the mouse have to learn
that it should go towards
a certain light signal
to get some reward there.
And if it should always go to the left,
after a while, you can
take away the visual cue
and the mouse will
automatically go to the left.
It has sort of automated this.
And if you look at how quickly
you come to this automation
of the thing, it's quite a difference
between the humanized mice
to the wild-type littermates.
They learn in seven to
eight days to do this
what takes 11 and 12 days in
their wild-type littermates
bringed by the same mother, et cetera.
So this is sort of the switch
from this sort of declarative
to the procedural.
It sort of automation on
motor learning if you like.
So if you think about learning
to bike when you're a kid,
you first think about what you
do and you're very bad at it
and after a while, you
sort of automate the thing
and then you get very good at bicycling.
And there's this switch here
to sort of automating motor movements.
And you can of course sort of speculate
and say that that's exactly what we do
when we learn to speak as children.
We learn to automate
very complex coordination
of motor movements in our vocal cords,
our lips, our tongues to
produce articulate speech.
Something that no other ape can do.
So there's an hypothesis
that these changes alters
these cortical-basal circuits
to allow for faster automation
of motor movements and
perhaps some aspects
of language and speech.
So I think this is very encouraging
that one can perhaps
sometimes develop models
of humanizing aspects
of brain and a mouse.
Dresen trying to do
that with these things,
for example, for modern human changes now
and for a number of other
things that may be of interest.
So to end then, I'm going to say
that if you're interested
then in modern human origins,
I hope I sort of convinced
you that is quite useful
to have the genome of
our very closest relative
'cause you then can focus
on what's really unique
to modern humans relative to them.
In the future, when we
have more Neanderthals,
we'll also be able to study
what's unique to Neanderthals
but that will not be enough.
We will have these changes
and we will have to go
after them functionally
and a way to do that would be
to modify human and ape cells
in tissue culture, I think,
but also then to modify
and humanized mice.
(attendees laughing)
And with that, I should
say that many, many people
are involved in this.
More people than I can mention.
I'll pick up one person.
Matthias Meyer who
developed the technology
to make these ultra sensitive libraries
that allowed us to get
these high quality genomes
from Denisovans and Neanderthals.
Many, many people have been
involved in analyzing the data.
I mentioned them in
the talk several times.
Monty Slatkin and his group here
and David Reich and his group here.
Janet Kelso who coordinates
all the bioinformatics
in Leipzig and Kay Prufer
who particularly then
worked on the Neanderthal genome.
And we wrap up then.
Thank you for your attention.
(attendees applauding)
- [John] Thank you very
much for a fascinating talk
and Svante will take questions.
- [Attendee] Dr. Paabo, it
really makes sense to compare
Neanderthal technology
with later human technology,
with the technology we have
now or that we had 10,000 years
after Neanderthals disappeared.
As opposed to comparing
Neanderthal technology
40,000 years ago when they went extinct
to the technology that humans,
that modern humans had at the time
which I understand that recently,
some researchers have compared Neanderthal
hunting instruments with modern
human hunting instruments
of that age and found that actually,
neither was more efficient than the other.
And I think that you'll find precious
little representational
art made by modern humans
that's that old.
- Yes.
- [Attendee] So do we?
Are we sure that Neanderthals
wouldn't be making
satellites now if they had
been the surviving species?
- No, that is a good question.
Of course, my take on it
would be that Neanderthals
had three, 400,000 years to
do this yet they didn't do it.
And humans had hundred
thousand years or even less
and actually did it.
But that's not to say, it's
not so to clear what is,
it's not clear that this, for example,
individual intelligence that differs.
Some people have the
idea that it's something
with human sociality,
that we have sort of developed
sort of, what should I say?
A sort of compulsion to
communicate and teach
that allows us to have an accumulative,
that's ratchet effect
where we sort of convey
all our technological advances
to the next generation
so they can just continue
to build on that.
And that may be the key
why technology and culture
took off in modern humans to that extent.
It may be that the
Neanderthal could learn it
but they would not have as a society,
this sort of compulsion to pass it on,
but, you know, yes, it's
also a criticism of this
can be to say yes, sure,
only Europeans had firearms
and Native Americans didn't,
that doesn't mean that there's
a difference genetically
between the groups.
But there is still some
difference in sort of having
300,000 years and not doing
it, I would say, madame.
One can have different
opinions about that.
Yeah.
- [Attendee] I've been wondering,
do Neanderthals have a myostatin gene?
A myostatin.
I don't know if you're familiar with.
If you delete a myostatin
gene from a human,
they lose almost all their body fat
and they gain 40 percent
more skeletal muscles
so they become like incredibly athletic
and there's a few people
who have this mutation
and there are super athletes.
There's one construction worker in Germany
who could pick up 320-pound
slabs of concrete by hand
and carry 'em around.
So I'm curious, you know,
they're they're known
for being much stronger than human.
- Yes, we haven't looked at that gene.
Someone should look at it.
It's all out there of
course in the public domain.
I maybe more regulation
of the gene or something.
I'm sure they have it.
It sort of popped up otherwise but yes.
- [Attendee] A couple of months ago,
I was at Atapuerca and they showed us
a pre-Neanderthal skull and
said that they had found
Denisovan mitochondrial DNA in it
and I was wondering if
you could confirm that.
- Yes, that's actually our work, yes.
So yeah, so this, Atapuerca
Sima de los Huesos,
one finds 400,000-year-old hominis.
So it's a big, 20 or I forget how many
and we have looked at,
so these are almost 10 times
older than the Neanderthals
we have looked at.
So we've been able to retrieve
from some of the bones
tiny, tiny amounts of short pieces of DNA
and only been able to look
at the mitochondrial genome
so far but we will for
sure get some nuclear DNA
this year or next year.
But the surprise was that
the mitochondrial genome
actually goes back to common ancestor
with the Denisovan mitochondrial DNA
but far back.
So I wouldn't call this
Denisovan mitochondrial DNA.
It's still a deeper divergence
between any two living humans
in the mitochondrial DNA today
but yes, it's sort of surprising
and we certainly thought
that these were if anything
the ancestors on Neanderthals
and would go back to common
ancestor with Neanderthals.
It may just be that we're so far back
so we're close to a common
ancestral population
on both Denisovans and
Neanderthal at that time
but the nuclear genome will tell.
- [Attendee] One more quick question.
I understand that there's evidence
that the Neanderthal used,
the maturation rate for
children was considerably faster
than humans and I wonder if you guys
have any insight into the
genetic basis for that.
- No, but I know people in
Philipp Khaitovich's group
in Shanghai, for example,
is looking into that.
Yes, I think it might be
something coming on that, yes.
- [Attendee] Hi, great talk.
I'm wondering, you showed
three different mutations,
it were Neanderthal in brain chemistry
and you listed, I believe autism
as one of the possible consequences
and schizophrenia is another one
and there was one in the middle,
some kind of glycolysis and
I was wondering, what that--
- We have Tourette syndrome but it's not,
the differences to Neanderthals
don't cause those diseases.
It's when those genes are not out
and they've one copy of
them, you have those diseases
but the Neanderthal difference
is that are the difference
to the Neanderthal
in modern humans is sort of a
subtle difference in the gene
but this just gives a hint that
it may have something to do
with cognition or
something like that, yes.
- [Attendee] And also
Denisovans, the ones that went,
are you saying the Neanderthals
are not the ones in China
but the Denisovans?
- Yes, I certainly think
that whatever was in China
could well have been Denisovans,
it was not Neanderthals,
I would think but yes.
But I think autism is very interesting.
I mean our Mike Tomasello, for example,
is a sort of comparative
psychologist who've suggested
that the things affected
in autism maybe something
aspect of our cognition
that may be uniquely human.
This sort of an enormous tendency for us
to put ourselves in other people's shoes
and others people's perspectives.
- [Attendees] You showed a slide where,
I'm not sure if I read it correctly
but there was some,
you're showing differences between humans,
what humans had unique versus
Neanderthals and chimps.
And then you showed,
I forget which group is unique to what
but you showed differences,
there's differences in
pigmentation and behavior.
I was just kind of
reminded this documentary
that I watched about the
domestication of dogs
and they were, just by selecting
for docility or tameness,
they see corresponding
changes in pigmentation
like coat color and you see this
in a lot of different mammals.
Is there any parallels to that
and to domestication
of mammals and humans?
- We would love to find such parallels.
I think it's a great question.
I mean this particular this
experimental domestication
that has been done in
Novosibirsk by Belyaev
and his followers, successors now,
domesticating silver
foxes and rats and mink
and they see exactly what you say.
So we work with them, actually,
and I'm looking for
example that correlates
gene expression in the
brains of the docile
and aggressive variants of these
and compare, for example,
humans and chimps
or bonobos and chimpanzees
and dogs and wolves, actually,
to try to find some common theme there
but so far, nothing really have stood out.
Yes, it's certainly something
we're working on, yeah.
- [Attendee] Hello, thank you
for the wonderful presentation
and I had a question regarding
the function of mosaicism
as we see, as it results in modern humans.
So you mentioned that,
my grandma six generations back
contribute about 1.5% of our DNA
and that's the same that
we have from Neanderthals.
So my question is talking about function,
is it all the same that
grandma was a Neanderthal
or is there some kind of difference
in how this would manifest?
- Yes, so I don't know if
that's such a good image.
It's, of course, different
with the Neanderthals
because this happened a long time ago
and these fragments are sort
of spread all over the genome
and it's now is some kind of equilibrium.
We all have it so it's
not decreasing anymore.
So the the
great-great-great-great-grandmother's
part there
will of course be in
big, big chunks, right?
- [Attendee] Yeah.
- So there is certainly a difference
but yes, I didn't quite get the,
perhaps, answered the question correctly.
- [Attendee] Is there
something you could say
about how that difference
would manifest in function
or is it just?
- Well, so the only thing we know
about the Neanderthal
contribution and function
is really what I reviewed here.
The immune response genes, the keratins,
the lipid catabolism and type 2 diabetes.
There will be more things coming
in the literature, I think
but that's the only things
that are known today.
- [Attendee] Thank you.
- [Attendee] Hi, I was just
curious how many high quality
Neanderthal samples exists?
So for example, if we wanted
to do a hundred or thousand
Neanderthal genome project,
do we buy more sequencers or more shovels?
- Yes, so we actually thought
about launching next year
to have something catchy to
say, 100K genomes projects
and they will not all
be high-quality then.
We are working on a high quality genome
from this site in Croatia.
I think there will be one.
Might get a few more but
the rest will be 1x coverage
or something like that.
Low quality things but
enough to reconstruct
population history.
- [Attendee] You mentioned
earlier in your talk
that there are no
Neanderthal mitochondrial DNA
in human populations.
Later on in your talk, you mentioned
that one of the findings
seemed to be a decrease
in the hybrid male infertility.
And my question is have
you had the opportunity
to come up with any hypotheses
about the representational
sexual selection in hybridization?
- Yes, so we were quite
convinced from David's work
that on the X chromosome,
there is less Neanderthal
contribution and less
in the rest of the genome.
That made us think always is mainly men,
Neanderthal men who contribute this
because they will of course
contribute less on X chromosome
because only half kids of a man
gets an X chromosome from him.
But then, we've seen
other parts of the genome
where there also seems to be
less Neanderthal contribution
and less regular chromosomes
so there is big selection going on.
There are some things that
are not accepted to come over
so that has made us very sort of shy away
from saying anything about that.
If I would just guess
from what we've seen,
I would say if I will guess on one,
it would be more man than females
but we haven't shown that in any sense.
- [Attendees] Thank you.
- [Attendee] Thank you
for the wonderful talk.
What can we use?
What can we infer about
socialization amongst Neanderthals
from the evidence you had?
You showed us that this one small group
was pretty much related
and you also showed us
bone fragments that were split.
- Oh, yes.
- [Attendee] And so what
do we know about the bones
that were split?
What were their genders?
How were they preserved?
- It's interesting that you
asked that question here
because Tim White, I
don't know if Tim is here.
The paleontologist here at Berkeley.
He has shown that these
bones have been treated
very much have been eaten
probably by other Neanderthals.
So it's very telling for
example that the bones
with bone marrow have been crushed
and those without bone marrow are not.
And there are cut marks, for example,
where muscles attach to the
bones and things like that
and there's a site in Spain at Sidrom
where is a social group
that have all been eaten.
Children, adolescents and adults.
So I do think one ate each other.
One can of course discuss if that's part
of some ritual burial or so.
Tim has pointed out that
that it's very similar
to how one treats deer
bones or something like that
at these signs.
But there are also other
sites where they had buried,
intentionally buried,
it seems, each other.
So yes, I think there
were eating going on.
They were clearly at ease in this site,
but were very closely related parents.
At the level of half seeds.
That's really everything, the latter
is the only thing we can really say about.
The population sizes seem
to have been very small
and isolated from each other.
So not only do they have
little genetic variation,
they also have lots of differences between
say the carcasses, Grasham and Siberia.
More so than present day humans.
That's really all we can
say from the genetic data.
So not so much.
- [Attendee] Hello, I did,
Neanderthal and Denisovan,
where did they evolve?
I guess it's number one and number two,
did they both evolve from Homo erectus
or do we have to wait for Homo erectus DNA
to figure that out?
- So we believe their
ancestors evolved in Africa
and came out of Africa then
half a million years ago or so.
Not that that is shown very well
but I think sort of, if we
say that is what paleontology
called Homo heidelbergensis is
perhaps the ancestor of this
and you find the sort of
Homo rudolfensis in Africa
so probably come out of Africa.
They probably evolved out of something
but that is really a question
for the paleontologist
if we then call that Homo erectus
that they are on out of.
I would love to get to erectus genome.
Maybe in Asia or so where there are things
as a called erectus that survived late
that it will become possible.
- [Attendees] Two short questions.
One is about the Ust'-Ishim skeleton.
I was wondering, you said
that it has clear
Neanderthal contribution,
does it also have Denisovan contribution?
And the other part is the
possible Neanderthal adaptation
to starvation.
What would that have consisted of?
Sort of indication, what that
metabolically would have been?
- So, bit hard of hearing but we see this
Neanderthal contribution to Denisovans
but we do not see it the other way.
Sort of they might have
been some small thing
we don't detect about this.
- [Attendee] Ust'-Ishim
skelton was, we think,
modern human but with a
Neanderthal contribution
but not a Denisovan one?
- To Denisovans.
So from Neanderthals into Denisovans, so.
And this yes, adaptation to starvation
is a speculation from
saying that this risk allele
for type 2 diabetes
comes from Neanderthals
but it's very curious of course if,
it's probably not because
it gives you type 2 diabetes
that is resistant to high
frequency in present day humans,
it must have had some advantage.
And I think it's reasonable to speculate
that these variants sort of
make you store energy better
and today in a situation
where with ample nutrition
all the time, that
gives us type 2 diabetes
but those individuals would
probably also do better
in a situation of starvation.
- Well, this one wonderful event
is coming to a rapid conclusion.
Thank you very much for coming
and please join me in
thanking Svante Paabo.
(attendees applauding)
(lively music)
