A Neanderthal Perspective on Human Origins – 2014

A Neanderthal Perspective on Human Origins – 2014

October 26, 2019 100 By Stanley Isaacs


– [Announcer] This program is presented by University of California Television. Like what you learn? Visit our website or follow
us on Facebook and Twitter to keep up with the latest UCTV programs. (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)