[Music] I'd like to welcome all of you to the 2018 lecture for the Nuremberg prize for science in the public interest were delighted to have with us dr. sponte pabo Swedish scientist a biologist and a pioneer of paleogenetics the field that looks at the DNA of ancient organisms including ancient peoples to understand its relationship to us and to evolution dr. Paiva is the director of the department of evolutionary genetics at the Max Planck Institute for evolutionary anthropology in Leipzig Germany his lab is the one that is renowned for its development of techniques that allowed them to sequence ancient DNA and and specifically the one that we all have heard of and are familiar with the DNA of Neanderthals so I'm delighted to welcome him to give to tell us about Neanderthal DNA and its relationship to evolution and to our lives today dr. Paiva well first of all let me then thank the nirenberg family and the scripts in Institute for this great great honor to receive this prize I really feel quite humbled when I see that list of awesome previous Laureus less and I sort of hope I can live up to it a little bit at least so what I then wanted to do here as an introduction first is to just remind you about something that you all are very well aware about and that is that our genome our genetic material is stored in all the cells in our body almost all cells contain the entire genome and the genome is across made up or the famous double helical DNA molecule that when a cell divides these two strands of the helix come apart and the information which encoded in a form on these four bases a sequence of them is then replicated so that two new DNA molecules emerge and a particular interest to us as geneticists is of course when this happens in the germ line when you individuals will be formed and this process is very very accurate but sometimes there are errors made so opposite to see here will normally be G but if the wrong base is built in and that's not repaired before the cell replicates again you will have a mutation that passed on to the next generation if this happens in the germ line and you will then see the results of these mutations in the form of differences in DNA sequences when you compare to Geno's today so if you compare two genomes or two individuals in this room you will have a difference somewhere around every 1214 hundred nucleotides there will be a difference and this difference is sort of rained down on the genome in each generation so if you then look at a chimpanzee instead you will have about ten times more difference it's in the order of one difference every hundred bases or so and as you also know our genome is a quite big place it's about 3 billion base pairs so there are around 3 million differences between two genomes that you compare there is quite a lot of information there to reconstruct the history of the genome and you hanley we do that by depicting it in a form of these types of trees where you see the humans here go back to shared common ancestor with the chimpanzees further back with the gorillas and further backwards orangutan but with then interest us here today is really the amount of variation that we found find among humans that lived today so if you study the variation among people across the world today what came as a big surprise when on started doing this was the finding that most variation is found in Africa although there of course much less individuals living in Africa than the entire world outside Africa all the people outside Africa less variation than the people inside Africa and not only that much of the DNA sequences you find outside Africa have close relatives inside Africa but there is an a component of the variation in Africa that have no close relatives outside Africa so interpretation of this is that modern humans the direct ancestors of people who live today emerge first in Africa accumulate genetic variation there and a part of that variation goes out and colonizes the rest of the world and with some genetic tricks you can estimate approximately when this happened and it's less than a hundred thousand years ago or so so this is the genetic basis for recent African origin model of modern humans but there is if you'd like a problem with this idea and that is that when modern humans and leave Africa and colonized the rest of the world there were other forms of humans there that had been there for a long time there had been human forms outside Africa since around 2 million years and most famously then were Neanderthals in Western Eurasia and other forms of now extinct hominins or human forms in Eastern Europe and these Neanderthals then here is a reconstructed Neanderthal skeleton on the Left compared to a modern human skeleton with this robust forms of humans that appear in a fossil record in Europe and Western Asia around 400,000 years ago or so and exist in that part of the world until they become extinct in the order of 40,000 years ago generally in connection with that modern humans appear in an area and in paleontology one had discussed over decades what then happens when modern humans came out of Africa County Europe and Asia if one mixed with these resident Neanderthals and other forms or if there was a total replacement or some contribution and from Neanderthals the present-day Europeans and from these other forms two presentations but to then address that in a direct way you will need to study the genomes DNA from these extinct forms and there are technical problems with that of course some of them are sort of illustrated here that if you compare the DNA you would extract from a present a person you get long nice fragments 10,000 20,000 bases long the ancient DNA you would find in a bone on the Neanderthal er a short little fragments 3040 bases long it's chemically modified and it's very little of it there often 100,000 a million fold less per amount of say bone tissue than you would have in fresh tissue and these tiny amounts of degraded DNA isn't present in a large excess of microbial DNA from microbes who colonized the bone when it was in the ground and the result of this and a tiny amount of present-day human DNA that might extend exist on a speck of dust in the air in the laboratory that would not play any role at all when you started its modern DNA in the large amounts my totally over violent your experiments here so you might stand in your own DNA rather than a DNA from the Neanderthal and so it read worked actually over 30 years now so the overcoming some of these problems some of it involves like a mania for cleanliness where you're sort of dressed up in funny clothing because UV light to destroy DNA filter the air do not have dust present and so on and with these techniques then in the early 90s we were very lucky after lots of negotiations to get access to the first Neanderthal and this was not just any Neanderthal it was Neanderthal that was found in 1856 in the under tall in Germany that gave his name to this group of hominids and it was the first time one realized that there had been other forms of humans around here before modern humans came so at that time one focused on a particular little part of the genome that existed many copies per cell is this mitochondrial genome that inherited from mothers to offspring particular variable part of that genome cameras and at the time amplified and cloned many many fragments believed substitutions are continuously there and if you then estimate the relationship of the Neanderthal mitochondrial DNA without the present and humans you find that they go back to common ancestor for this part of the genome and that's about half a million years back whereas all humans today no matter where you live for the mitochondrial DNA go back to an ancestor somewhere hundred two hundred thousand years ago so in a sort of model we're going to say total replacement when modern humans come see represent contribution from Neanderthals depressor tell Europeans to the other extreme would be total continue with in younger toes are the ancestors of present-day Europeans for the mitochondrial DNA it's very clear there's no one running around with a mitochondrial DNA over Neanderthals today this total replacement but it was also clear already back in 97 that this could just might just be a part of the story this is a very tiny part of our genome the whole big picture is in the nuclear genome where we have 3 billion base pairs from our mothers 3 billion base pairs from our fathers and the complete genetic picture but I think I'm quoted in the press somewhere in 99 saying we will never have a nuclear genome from a Neanderthal it's to degrade this to modified it can't be done and I guess it just goes to say that you should never make predictions in science particularly not negative predictions because it was gently overtaking and what overtakes you is only technology so what I hadn't anticipated that came around at the beginning of the millennium were technologies to sequence millions and billions of DNA fragments rapidly and inexpensively so you could sort of just look at all the DNA you could extract from such a fossil sequence all the DNA in it make your own little database of what's in this bowl and start comparing it to the human genome that then became available and other years and we were very lucky to be able to apply for and get funding for five a project to then improve the techniques with which extract short little fragments from the bones and convert an efficiently to form you could feed into such sequencing machines if we got a lot better in that process and we then looked a lot round Europe for four places to find good bones and ended up at this site in southern Europe in Croatia Vindhya cave will be focused on three different bones from three different Neanderthals and went and sequenced around a billion DNA molecules from those bones most of these molecules and come from bacterial DNA and fungal DNA in the bone but we could then map some of these molecules to the human genome taking these modifications that exist there into account so in 2010 we had sequence so much to each position in the genome had statistically been seen once but that means some places are seen one summer's in two times and many others are not seen at all so we had then a little over half the Neanderthal genome that we'd seen once or more but it could begin to ask questions and the one of the first questions we were really interested in was this question what have happened when modern humans met Neanderthals did one mix with each other or not so what you would expect if modern humans mix with Neanderthals in Europe would of course be that Europeans today should share more genetic variants with Neanderthals than people in Africa or in the under thought that never existed so there's no reason to think African ancestors would ever have seen the under culture mixed with them so we could ask that them in some very simple ways we had the Neanderthal genome here from Croatia comparing European individual at the time we thought we sequenced one individual from Europe to high quality cause a French person is what we thought was the most typical European did that and an african individual and then just look for any places these two individuals differ from each other European person African individual and see how often does a Neanderthal match European and African if there'd be no contribution in Europe it should be 50/50 and to my surprise we found that it was statistically significantly more matching to the European person than African person suggesting they could have been a contribution there from Neanderthals even more surprising was that when we did this with a Chinese person and an African person we again saw or matching although most people who say there never been Neanderthals in China some people would debate that but when we then went to Papua New Guinea were for sure and never been down the Falls we again see this so no matter where we looked outside sub-saharan Africa in North Africa and all the rest of the world we find this additional match linked to the knee on the top and that then led to this suggestion which are largely sort of hold up to the test of time suggesting that when modern humans spread in African and started spreading out of Africa they presumably came through the Middle East and we know there were Neanderthals in the Middle East and if these early modern humans outside Africa then mixed with Neanderthals it could then carry this Neanderthal component with them so to say to the rest of the world also to parts of the world where there had never been the under thoughts to the extent that no matter where you come from if your ancestors outside Africa one to two percent of the gene or count from the undertoads suit was very sort of satisfying there were lot of follow up of that in a scientific literature quite rapidly after we published this but we also found out indeed that lots of the general public turned out to be very interested in this and I can never stop myself from pointing out that we started getting lots of emails and letters from people who self-identified as Neanderthals and after a viola started seeing a pattern in this communication Soto mainly men who say they're only under calls and very few women would claim they only under cost and want to contribute to us so you know I presented this to my group as my research I count the emails and there are cost hypercritical of anything I do so they say this is just ascertain whant men are more interested in molecular genetics that they would write to you fewer women right but I went back to all these letters and found that that's not at all true because there are plenty of women who write to us and say they're married to me under God but do we do other things too of course then just count emails so one thing that we have done since that time is arrive at very high quality neanderthal Geno's and that's really thanks to collaborations with colleagues in Russia archaeologists in Russia particularly Anatoly derevyanko in Novosibirsk excavated many sites inside the area but particularly this site in southern Siberia on the border to Mongolia and Kazakhstan the needs of a cave it's a beautiful place it is like the Alps but with no people and in 2010 we found this little toe bone there that turned out to come from the Neanderthal and by that time we had worked out more efficient ways to make libraries of molecules that you can sequence in oh sequencing machines and these methods actually build on at this double-stranded molecule and instead of using the double-stranded molecule you start out by separating the two strands from each other and each strand is then made into double-stranded molecule that is sequence to each double-stranded molecule have two chances to the sequence one from each strand that turns out to be one of the tricks is really important to get from them if look at one part of the chromosome work we had within this one full coverage with a Miss still almost half of the he node to something where we really cover every position on average 50 times over we will have a live of the part of the genome to which we can map these short fragments or quality of the genome that is just killed us in the genome double sequence today so with that we can then very accurately see which fragments in present-day people come from Neanderthals so in Europeans and on average 23 million base pairs in the genome come from the Neanderthal and that's distributed in fragment of almost 50 thousand base pairs sort of thrown around the genome so if you just look at one chromosome here each line would be one individual today and he read our fragments that come from Neanderthals so you will see that people often tend to carry different fragments that come from the Neanderthal when you compare to people but an average per person it adds up to one to two percent so you can then say if I jump from person to person across a few hundred or thousand individuals how much of the Neanderthal genome can have puzzle together from people who live today as illustrated in blue here and it adds up to something like 40 maybe 50 percent of the Neanderthal genome is still walking around on two legs today so to say so the lambda toes are not totally extinct sad lyrics on to some extent in people today but this place and the nests of a cave is an amazing place because they find them well before that I should say we have this high quality genome from here what doesn't happen is that we have also from this other caves idea been able to do high-quality genome of a Neanderthal from Europe from this bone here so we can now ask for people who live in Europe today their Neanderthal component in the genome are they more closely related to this idea in the under tall or the creation Neanderthal from Europe and not so surprisingly they are more related to you routinely undertone but we can then ask for people who today live much closer to where this Neanderthal nail are they more closely related to this Neanderthal did you repeat Neanderthal and a bit surprisingly then they are all more closely related to the European guitar so the fitting with this model that this major part of this contribution at least comes early on in western Eurasia into the ancestors of modern Europeans but as I said this the diffs of a cave is an amazing place they find other things there and I don't know if there are archaeologists in the audience perhaps not so many as I can speak freely and I think Western archaeologists have a sort of tendency to talk down on Russian archaeology and say oh they excavate like we did 50 years ago they just look for the big finds it's not scientific archaeology but I think you must agree with me that realizing that this could be a human bone a fragment of the last phalanx of a pinky of a child is quite skilled so we got this bone to life it's again with these new techniques we were able to sequence a high quality genome from this tiny little bone and we were very surprised to find it was not in the undertow not a northern human but something else that went far back here to common ancestor shared with Neanderthals so in years it always hard to estimate this but assuming certain mutation rates and other things if we say the deepest divergence between two African populations today in order of hundred thousand then the divergence between this individuals population and the under course is like four times deeper just a quite distant relative of Neanderthals we discussed a lot with our Russian colleagues about all to coalesce and ended up calling it the Netherlands - they're named after the niece of a cave where they were first found just as Neanderthals are named after Neanderthal when they were first found them and still today then eight years later they are only known from this little finger ball and three teeth that has been found in this cave but we think that they have been quite widespread in the past actually because if we look in present-day people we find no genetic contribution from these Denisovans in Europe and Western Asia but we find it in all of eastern Eurasia a small component less than 1% but in Oceania is a Papua New Guinea Aboriginal Australians and so on is up to five percent of the genome six percent that come from these tennis events and not only that there is a group at Princeton your Shakey's group have realised that there is interesting structure most interesting structure in the Denisovan population so when then look at genomes from Papua New Guinea here and plot fragments in the genome on this side here their identity - Neanderthals they find this in the under-told component that's quite close to the neanderthal genome that would be at one and they find this other component similar to the Denisovan genome but quite a bit further from the Denisovan genome and the Neanderthals is to the Neanderthal genome so this is in Papua New Guinea but when they look in genomes in Japan they then find this Neanderthal component they find this component that exists also here quite far from the Denisovan genome and then they find in addition a component that's very close to the genome and then incidents were sequenced so this answered yes that there were two distinct populations of the michelin's that both contributed to present-day people in Japan the sutras shows that one was just one population of the Nationals a lot more of them so you then find in you find you this not in Indian pistone or Papa New Guinea as we said but if you look in Chinese individuals or in Japanese individuals you find this other component so if we should summarize and what we think we know about origins of Neanderthals and Denisovans and their interactions with modern humans from genomes the Neanderthals and Denisovans have some common ancestors in Africa more than half a million years ago they come out of Africa and evolved then into what we call Neanderthals in western Eurasia and into what we call the Netherlands in eastern Asia we don't know what the border between these groups have been as which x but at some time there have been down the tall's here in Tennessee ok but some other times then I suppose then modern you must appear in Africa spread to the Middle East quite early on but then start spreading seriously wrong rest of the range 6070 thousand years ago and then mix probably early on with Neanderthals continue to spread there's good evidence that we'll talk about in a minute that there were other mixtures here mixed with the nestlings quite early on and mix and with another the National population here most likely additional mixture in ancestors people in Oceania and then these groups disappear but then lives on a bit today than in this components in the genomes of people today so what about Africa because modern you must appear in Africa to spread there if the mix to this earlier forms outside Africa I think there is such a good reason to think one mixed with other forms also in Africa there are some indications of that in the genomes of present-day Africans but we have no archaic genomes no genomes of extinct forms of humans from Africa yet but I wouldn't be surprised different finds that this have gone on also in in Asia in Africa so this theme of the thing now with the nuclear he knows who clearly rejected this total replacement idea there is this contribution from these other forms but the vast majority of the variation impressively people still come out of Africa this is sort of maximally seven eight percent in Papua New Guinea say from other forms and we begin to learn more about this mixture now directly more and the first hint of that came from this site in Romania where cavers found just about ten years ago this human mandible that is carbon dated to around 40,000 years ago it's one of the earliest modern humans in Europe that lived at a time when they were still Neanderthals around so we were of course very interested to say of this person already mixed with Neanderthals we just look at one chromosome here and in other present a people we indicating Candler fragments on this chromosome that come from Neanderthals and then we ask for this person in Romania have it makes women younger tall's and indeed it has and it has a lot more than the tall DNA than anyone that's around today and in fact where it's black here we have had no information because this is a very fragmentary genome so it really seems that more on half of this chromosome is solidly on the under-told ancestry suggesting of course that is in the under-told ancestry ancestor here quite close and the family history and there are seven such large chromosomal segments that are Neanderthal so you can then show that this means that this individual here of course that 50% of his ancestors from mother and father 25 from grandparents and so on and the amount of DNA we find here from Neanderthal suggested six generations back five generations back or four generations back one of those cases it had a Neanderthal ancestry so we sort of almost caught salmon in the act of mixing with Neanderthals er thought to say so all these different mixtures you can infer from the genomes we happen to stumble around one case here Neanderthals contributing to modern humans the other such case we found just last year and this is this tiny little bone the size of a bone from the needs of a cave it's so small so you can tell if it's from a human or an animal but together with a group in Oxford from Hayase group used mass spectrometer to screen over 2,000 such bone fragments from the cave and found one bone that turned out to be from some human form we sequence the mitochondrial DNA from this it's maternally inherited and was Neanderthals we said we found in the under-told bone but then we continued to look at a nuclear genome and these are each chromosome in a you know trauma so one and two and three and so on and plotted in blue or variants typical of Neanderthals and in red typical organisms and you will see that every chromosome is colored both blue and red so this really suggests that this person has one chromosome as Neanderthal and one chromosome that is Tennyson and if we then look at the amount of variation in this individual this is us looking at present a Africans and non African Sun less variation knee and the toes and initials and even less variation and on Africans today but this individual look like Africans in this respect this really suggests that this is a first generation mixture where the mother is Neanderthal and the father is the nestlings I come from these two populations and we know the mother is Neanderthal because of the mitochondrial DNA which is the undertone but this is not totally the whole story because there are some regions five regions here marketing green that's hard to see but there's a regions longer than million base-pairs that look like this that looks solidly me on the top so if you compare this to normal Neanderthal this segment in this individual looks like we was just Neanderthal so that said yes that a father the de Nesle and father had some Neanderthal ancestor back in its family history so he had some knee under toes back here in order 10,000 years before or something like that so here we really caught on in act if you like and all these different mixtures and we stumbled across this one here a first-generation makes to between Neanderthals under the miserable so what this really tells us is that these different human forms are really mixed with each other quite frequently as we find this often at least one man has met and we can of course now look a little more on the population history here is this individual the father is the nistrim and it's quite he is quite closely related to the Denisovan genome in the nests of a cave what's a surprising the mother is more interesting she is sort of closer related to Neanderthals in Europe that lived much later when to the Neanderthal in the same cave that is just a few meters away but lived a few ten thousand years earlier in the nests of a cave so this really tells us that in the future there will be interesting population history Neanderthals would be discovered there seems to be migration of Neanderthals from the west to the east at least twice replacing early Neanderthal forms and I sort of want to stress again the surprising thing to me that then from the nests of a cave have only six individuals which have genetic data and one of them turns out to be this first-generation hybrid if you like between the under toes and innocence if we look at modern humans that are old enough to lived when the under thoughts were around only three individuals today who ever have unit information one is Russia here one is this individual unmentioned in romania and one is an individual outside Beijing and one of these individuals and turned out to have disclosed Neanderthal relative who seems to be too lucky to run into this so often so the picture that I think is beginning to emerge is that the Neanderthals may not have become extinct in a sort of sense you often think about it it may be that a part of the story at least is that Neanderthal simply mixed with modern humans when they came modern humans were probably more numerous and we just absorbed into modern human populations now it might have been different stories at different places in different times but that may be part of the story how they disappeared if you just imagine there were 50 times more modern humans and Neanderthals that would end up being 2% in our genomes right now it was probably not 50 times more modern humans it must be more to the story than that but that can be part of the story so in the last little part of this then I wanted to say who cares so to say what does this mean to us today if anything that we have this contribution from Neanderthals for example and we begin to learn more about that almost every month so you can sort of go over the entire genome here in Europeans and plot in red the frequency of contribution from Neanderthals and you will see that in some part of the genome 60 70 80 percent of people in Europe have something from the under thoughts in Asia some of these correlate some our Asian specific some European specific and one begins to learn what is hiding in these regions I just show you two examples one is an example of something that's quite frequent in Asia and in Native Americans up to 25 percent of Asians carry a variant from Neanderthals it's quite clearly closely related the red ones here to Neanderthals and it encodes who has a gene that encodes a liquid transporter where the Neanderthal variant defer at four different amino acid positions from the modern human variant and this name the covariant correlates today with a tendency to get type 2 diabetes the type of diabetes you get in old age so it may be surprising that something that caused a problem today has frisson come from Neanderthals of recent to high frequency but I think in this case you can perhaps speculate that those genetic variants that tend to give us diabetes today when we eat too much almost our whole life may actually be variants that are advantageous in periods of starvation so it may be that this is some Neanderthal adaptation to starvation that come over rise to high frequency and today in our current environment gives us problems I just wanted one more example that just was published last month it's a variant that comes from Neanderthals and have a different distributions is primarily North Africa and Western Europe it encodes a progesterone the receptor and a hormone that important in pregnancy and here the Neanderthal variant is associated with preterm births premature babies it's very hard to think out why that would be advantageous and rise to high frequency but I think it probably just goes to say that we know very very little of the function of genetic variants someone some variants are associated with medical problems that's why we find them but they may have other advantageous effects or had them in the past that we don't know about yet so what about the nestlings and they contributed to present-day people yes they have and there are several examples of that the most famous one is in Tibet where people aren't adapted to living at high altitudes particularly than adapting to high altitudes without accumulating a lot of red blood cells in your blood that most other people do when they live at high altitude will results in problems with blood clots and things like that so it was already known that this variant is very common 80 percent frequency so in Tibet of this year and Rasmus Nielsen school at Berkeley showed that this comes over from the nest servants into the ancestors of Tibetans so it's quite fascinating that probably without this contribution from Dennis Evans we wouldn't have so large populations of people living at the high plateau in in Tibet something seems to have been so important that they've come over both on the under calls and Anissa Mel so twice the one example is cluster toll-like receptors these are receptors on the cell surface that are important for innate immunity against viruses and bacteria that can act immediately when we get infected that doesn't need to adapt to the pathogens shows this typical frequency sort of occurs outside Africa very little in African associated with gene flow from Europe back into Africa Africa this is had come over from Neanderthals and from the Netherlands to present-day people if you look at people who have two copies of the Neanderthal variant they express more of these receptors on the cell surface and those that are heterozygous one Neanderthal copy one modern copy all those that have two modern copies and if you look at how this Neanderthal and the nestling variants what they are associated with in the population today they are associated to increased resistance to Helicobacter pylori infections the type of bacteria that gives you answers so if you don't tell answers you might thank the Neanderthals for that but this also illustrates that these genetic variants have many effects so these same variants are associated with increased risk of allergies so different so to have allergies might blame the Neanderthals so this is a overview of the things that seem to have been positively selected from Neanderthals in present-day people from Josh Akos lab Princeton and many of these have to do with immunity to infectious diseases many simpler to do with skin pigmentation for some reason but most variants from now on the tall's that we know of have to do with medical problems so hyper coagulation blood clots kidney disease many skin diseases even things like depression new problems some of this is surely ascertain my bias that there is certain medical studies really find variants associated with disease and unify whoops it comes from Neanderthals but there's probably not only that it's probably that men in the undertone variants also actually functions badly in the modern background because if we look in different part of genes this is an average about two percent comes from Neanderthals across the genome but if you look in promoters so the part of the gene that determines how much of the gene is turned on with a significantly less contribution from Neanderthals than we would expect suggesting that many partial genome had to do with regulation that come over or actually selected against and removed from the population but finally then what we are particularly interested in in in my group is the opposite of this if you like what was not contributed from the under tools to present-day people because what you can now do is to walk over the genome their first chromosome second chromosome plot as we did before in red contributions from Neanderthals are frequently are in Europe in Asia angry and then we can say or the part of the genome which statistically we would expect to see the undertow contribution that we see now and indeed you can find such regions and in particular you can study non-africans and not only non-africans but people in Oceania because they have then to sort of contributions from Neanderthals first the 2% and the later contribution from the nestlings 4 to 6% and then you can ask other regions in Papua New Guinea here that are like this that are neither the nests of them nor Neanderthal contributions that have twice resisted so to say to take out these days the region such as this and is there something interesting that hides there and why are we interested in this that's because we could imagine that in such regions or hiding sort of the genetic background for functions that are unique to modern use the things changed in the last half million years since we separated from the under tall's and spread to everyone around the world and why are we interested in these things well I think that modern humans are very special when you're comparing the Neanderthals to the Netherlands to other forms of now extinct hominins if you look at me on the tall stone stone technology at the beginning of their history 400 thousand years ago at the end of their history 40,000 years ago to me they look the same an expert can sort of explain to me there are some differences there and then I can see it but modern humans then have existed around the world for a hundred thousand years and I needn't be an expert to say that modern human technology 100 thousand years ago today is very different so sort of what comes with modern humans is technology that after one star changing very rapidly and also become regionalised so you can see that the technology in Western Europe is different from Central Asia where as Neanderthal technology was homogeneous because it's changed so slowly art is another controversial thing there are now some evidence for our retina on the tall's mast and made so this is probably the most sophisticated neanderthal art to know over the cave site in Spain if I'm a little sissy jizz I would say it looks pretty much like modern art to me because I can't really see what it depicts we're sort of figurative art that you really see immediately what the pace comes with modern unis and of course modern humans is the first group that becomes not just a hundred thousand innovators at any one time millions of people spread over open water systematically and colonized the whole planet and end up influencing in the end much of the biosphere as you study here so an idea then is that when we now have the genome of Neanderthals and Denisovans and Geno's from all around the world we can sort of focus on these things here that changed in the human genome became present in everybody no matter where we live and make a catalogue of those things and this catalogue is not very big actually so it's in the order 30,000 changes in the genome or so I should now say for the 2/3 of the Union where we can map these things that's really single copy they're all of course differences that we don't know very well in repetitive part of this you know but so our great interest is sort of look at these things and say which ones of these might be important and I just want to in the end give you a flavor for that by focusing on the most trivial type of changes in your life we changed it to change amino acids in proteins and the molecules that really do the function in our body so these 96 changes affect only 87 proteins and stills and the question is which ones might be important and we have this bias of course we think that you modern human cognition of sociality is special so things that have to do with brain development of brain function might be particularly important and we're looking at a couple of these but one that has fascinated us or three of these proteins turn out to all bid have to do with the machine that pulls the chromosomes apart in cell division this is a spindle and high net the course where the chromosomes in the middle here are pulled apart to the two daughter cells three of these protists have a function here I was very surprised when I saw this I thought cell division would be very conserved and not have changed in modern humans relative from Neanderthals but we sort of like to speculate and say hey during brain development we know that how cells divide the cleavage planes here is very important for how many neurons you make and in the brain in the end this was only speculation until then it became possible to make stem cells from somatic cells that you could then differentiate in the laboratory into different types of neurons and into this cerebral organoids which are little so the bubbles if you like of tissues of developing brain that are just a few millimeters being that you can culture in the laboratory and this is an a model system for brain develops so what Willian others do is do this for from simple c stem cells and human stem cells compare the human see in humans and they look very very similar but there are some differences that you can find in particularly if you then look at this epithelium where these stem cells divide these cells here in the top or in the bottom in this picture divide and make more stem cells that will eventually become euros and if you compare on this happens for humans and chimpanzees the sustaining or the cell nuclei with the chromosomes and you will see in this picture of these chromosomes form this of the plate here from the two daughter cells that are then pulled apart here they're pulled apart and it's happening in the shrimp here and here it happened in a human and you will notice as this time the lineup here metaphase is longer in humans than in chimpanzees or the mouse so here's a difference that seems to be specific actually during brain development and this of course made us think about these three genes again that are involved in forming and pulling the chromosomes apart here so these three genes so what we are now involved in doing is sort of putting these changes into the mouse making the mouse and the modern human versions and in stem cells putting in ancestral versions in the human genome in the stem cells and then look at this cell division how it happens during brain development in a mouse and in these organoids to look for that so I think that this sort of a flavor of what will be the most exciting thing in the next five or ten years to my mind is to try to find sort of biological differences that really set modern humans apart from Neanderthals I hope I sort of convinced you them that if you are interested in human evolution here it's very valuable to the genome or a closest evolutionary relative because you can time things you can see what happened back here in the genome and what happened more recently the things that we are mostly interested in now when we start getting more genomes of Neanderthals and initials in a future we'll also be able to focus on functional changes in the Neanderthal genome here and the way forward to test this I think would be to sort of model this in stem cells and also model it in animal models as humanized mice for example to end I should say many many people have been involved in this more people than I will be able to mention many paleontologists to contribute valuable specimens many people that help us analyze the Geno's over the years many people involved in the functional work in the lab is showing you the pictures of the group leaders currently in the department mentioned particular Matthias Maier developed the techniques to make these high quality high complexity libraries without his work we would not have high quality you know some Neanderthals and janna cancer or coordinates all the bioinformatics and much of the population genetic analysis and some of the people we collaborate with on the functional were actively landowners group or on Mouse development on the brain and with that I don't thank you for your attention so I took the appropriate conservative view that it could have just been a simple swapping out but then use also pointed out that there's not a single Neanderthal female lineage mitochondria in any human and then you have all these deserts and then you have the fact that most of the selection is for which evidently Kuroko have occurred is to protect from infection and adjust to the environment Heights and so on so you look at that whole picture doesn't it suggest more that it was not just a something out but a replacement by some form of success yes it's almost hard to say what what do you mean with success but yes I mean they're all parts of the genome that were positively selected these deserts surely yes I would say that female lineage may well have come over I mean you could easily buy us chance loose mitochondria actually but yes I mean I think there is sort of evidence for that some of these Neanderthal variants don't work well in a modern human background that is for sure true and that's also probably why we only have about 50% of the Neanderthal genome around today and of the whole thing the one of the comment is that you mentioned for example grizzly could mate with polar bears and so on what has happened with humans is sort of as if the grizzly bears of North America came out and bred with all the other bears across the planet incorporate a little bit of a DNA and all this left our grizzly bears that's what seems to happen to humans and I can find no example in history of the planet where that has happened so I think we use the word okay dangerously useable that humans are special no I do think I mean that's why we're so interested in these 30,000 changes that modern humans are very special there had been other hominids around for two million years and no one has spread it on the planet like this so developed technology like this we are certainly a very very special primate hi thank you um so I was curious you kind of hinted at this but I'm not sure if it's yet been resolved do you know which hominid lineages are most represented in the ancient Americas mm-hmm was so Native Americans are really a sample of East Asians so they do have the Neanderthal component like everyone else have and they have this decimal component in addition so yes from this perspective they asked your class Asians thank you very much [Applause] [Music]
Most people are part-Neanderthal, the closest extinct human relative. Svante Pääbo explores human genetic evolution by analyzing preserved genetic material from the remains of ancient organisms, including Neanderthals. What can we learn from the genomes of our closest evolutionary relatives? Pääbo is an evolutionary anthropologist and pioneer of paleogenetics and the director of the Max Plank Institute of Evolutionary Genetics.