Ancient Human Genomes...Present-Day Europeans - Johannes Krause

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good afternoon I'm Patrick Gary in the school of historical studies and I would like to welcome all of you to this lecture I apologize that there is standing room only we had not anticipated such an enthusiastic turnout but this is very encouraging to me and I'm sure to my colleagues from various parts of North America and Europe who are here for a more focused seminar tomorrow on topics of genomics and and history but this evening it's a particular pleasure to introduce professor Johannes clouzot of the University of Tuebingen and recently appointed founding director of the Max Planck Institute for the science of human history in llena returning to Thuringia is a triumphant homecoming for professor krauser who is a native Thuringian and who began his education biochemistry at the University of Leipzig and then University College Cork in Ireland in 2008 he completed his dissertation on the genetics of Neanderthals under the direction of Svante Paabo at the Max Planck Institute for evolutionary anthropology in Leipzig and the center for this kind of work professor Krauser was quickly recognized as a rising star in the world of ancient DNA studies he was a key member of the team that successfully reconstructed the mitochondrial DNA of a Denisovan demonstrating the Denisovans form an independent branch of the genus Homo along with Neanderthals and with Homo sapiens many of whom are present today he likewise contributed to the study that demonstrated that Neanderthals and modern humans share the same gene that makes possible human language he was a head of the research team that reconstructed bacterium from a 14th century plague Cemetery in London establishing definitive proof that the medieval black death was indeed caused by Yersinia pestis his team has also compared medieval and modern leprosy bacteria the results of Professor Crowder's work appear regularly in nature science current biology cell and the Proceedings of the National Academy of Sciences a men among many other journals in 2014 he was named along with Russell grey co-director of the new Max Planck Institute for the science of human history where the goals of his division of Archaea genetics are threefold to generate genetic data of past populations spanning the last ten to twenty thousand years of Eurasian history as a precondition for data based understanding of connections between historical events cultural changes an actual population movement second to investigate host-pathogen interactions throughout history providing evidence for the origin causative agents dissemination and evolution of major human infectious disease and finally to study human mediated transformations of biological resources such as plants and animals through the last 12,000 years professor Krauss and most recently led the international team of scholars that produced a much discussed nature article demonstrating that present-day European population derives from three distinct population groups this is the topic that he will address this evening please join me in welcoming you his krauser to the Institute so first of all Patrick thank you very much for inviting me today and for this wonderful welcome speech that was that was very wonderful and thanks for you all coming here this is this is also very cozy but very nice and thanks for spending your time with me this afternoon instead of outside with such a wonderful data as I worked okay so like Patrick mentioned I want to talk today about a topic a research project that we have been working on over the last few years mostly together was David Wright's team in Harvard but also with an entire international consortium of researchers where we addressed the question about the ancestry of modern Europeans by actually looking at the DNA that we can extract from skeletons from the past and see how basically the genetic makeup of Europeans have been changing over time our main finding as as presented you also the title was that modern Europeans are best modelled who can best be seen as a mixture of three ancestral populations that are present today in all European populations but before I go into detail about some of our findings I just want to give you a bit of a background because I know we have a very diverse group of people as I work is that okay so just just a few words of background and I know that most of that is very obvious to most of you but it's sometimes good to get a bit of a background slides so um as you all know our blueprint the DNA that basically gives the body the information about households are structured how cells look like how the body is actually built is something that can be found in every cell and there are two different compartments in your cells that have DNA first of all is the cell nucleus that has the nuclear DNA but there are also those mitochondria that produce the energy for your cells they also have DNA because at some point in the past there used to be bacteria they were taken up by the first cells and that kind of kept a little bit of their own genome which is still present in those cells now the nuclear DNA is much much bigger than the mitochondrial DNA have about 3 billion basis in our DNA so that are those letters AC T and G most of you of course have seen that before and the important thing about nuclear DNA where it is different to mitochondrial DNA is that nuclear DNA recombines in every generation so the DNA that you get from your parents gets combined into new chromosomes where we have 46 and those new chromosomes that you recombine chromosomes get passed on to the next generation so to your children and it's a very important process because it causes a very complex ancestry so if you take DNA sequences and you reconstruct phylogenetic trees it gets quite complicated for nuclear DNA because they get mixed up in every generation and this complex ancestry is also best represented if you think about the number of ancestors that each of us has for the nuclear genome that is because we have two parents four grandparents eight grand grandparents and so forth that basically over time we have a lot of ancestors so often people think and kind of ancestry as some sort of family trees that some of you might have at home if you look at those family trees they usually look like a pyramid right we go back to this night that might have been living in medieval Europe or potentially this African tribe warrior that was living at some point time in Africa in Asia or some Native American tribes but it's actually not really to that we go back to only one person we actually go back to millions and even billions of people that's nice illustration if you just think about how many ancestors you might possibly have in six hundred years just mathematical I know if you have an idea how many ancestors you might have in about six hundred years anybody 1 billion exactly two to the power of 31 billion ancestors so that's quite a large number of course this is just mathematical of course many of them is the same people probably is more millions and it's billions but it's quite a lot of people and that has also led people to actually say that within a thousand years every Western Eurasian is actually related to every Western Eurasian and in fact because Charles Grant had a lot of children we are all related to him all basically people that live in Western Eurasia or have a Western Eurasian descent so that makes it also quite complicated to study nuclear DNA for inferring relationships like you will see later mitochondrial DNA is this other part of the DNA that people study a lot especially if they look at relationships and also look at phylogenetic relationship between species or populations and that is something that that is much easier because mitochondrial DNA gets passed on from the mother to the offspring so it's maternally inherited it's much smaller only has about sixteen thousand five hundred of those positions of those bases and the wonderful thing is because it does not recombine you can easily make kind of phylogeny so you can really make basically trees they all go back to a recent common ancestor some women that lived at some point in the past if we do that for everybody here in the room and we get the most recent common ancestor for all of our mitochondria DNA's that lived about 200,000 years ago in Africa called mitochondrial Eve some of you might have heard and this term before but there's also another part of our our DNA that that's not recombine and that is a very poor chromosome that has no other chromosome to combined with that isn't about half of the people here in the room that's the Y chromosome so the Y chromosome doesn't have a partner to recombine because men only have one Y chromosome and they have one X chromosome they can recombine at the corners of of those chromosomes most of the Y chromosome actually does not recombine so therefore the Y chromosome behaves very similar to the mitochondrial DNA not recombining and you can actually also make nice phylogenies nice trees that go back to a common answer so some men that lift at some point in the past again it would probably be some in Africa if we would do it for all men here in the room probably about 200 to 300 thousand years ago could we maybe turn off the microphone and sorry sorry yeah because I have this this echo here so sorry for that so what people have been doing in the past they have then try to use this genetic information to not only tell relationships between what species like what's the relationship of humans and chimpanzees or what's the relationship between different wild birds or different wild animals but people have also studied DNA to actually show relationships between different populations and people have first started to do that on different types of molecular markers but mitochondrial DNA was a very popular type of DNA where you often see representations like that so you see pie charts with different colors you know those colors present different types of mitochondrial DNA so remember mitochondrial DNA you can make those those trees with those branches and every color represents one branch and you can then look at different populations in Europe and you can see what type of mitochondrial DNA are present in those different places in different European populations and what you see for mitochondrial DNA is actually something that when people first started that to study that in the 90s and early 2000s is slightly boring because it actually looks incredibly similar if you look at those pie charts it's very hard to see whether certain populations are closer to our population because most Europeans actually look almost identical so let's take Icelanders here and I know we have a keen eye here like a true eye slender it has been actually studying a lot of mitochondrial DNA in the past if you look at the representation that you the different types of mitochondrial DNA you see in Iceland you could think okay where did Icelanders come from we know Iceland was settled about a thousand years ago but from where did the Icelanders come from now we might think because of the language is probably Denmark indeed it looks very similar to Denmark but then you could also say we're in Europe do people like to eat certain type of fish like turd FISC for example the solute this kind of dried fish that would be in Italy here for example those Italians indeed that look very similar to those people but also the people here in Britain you look very similar and even the people here in Russia would look almost kind of similar the types of mitochondrial DNA that are presented so you can see that it's not enough information and this mitochondrial DNA to really tell us where populations might have come from and how populations might have moved around and Europe for example and this is why people then started to study in the last especially 10-15 years to not just look at this mitochondrial DNA this tiny piece of information which gets inherited on the maternal lineage with it easy to study however doesn't have a lot of information so people started to study whole genomes so this basically all the genetic information you can find in the cell the entire nuclear genome or at least the variable parts the things that are actually different between us you in the room because you don't have to look at everything but only the things that might be different between you and your neighbor that sits here so when then people do that there was one very influential study and was published in the year 2008 where some of our colleagues went out to the city of Lausanne in Switzerland and London they asked people on the street where they're from and whether their grandparents come more or less from the same region in Europe and if that was the case they collected saliva from that people so they got the DNA of that people they studied the DNA they looked at the variable parts of their DNA so we are basically one person has a one person as a see some person as a tease person is a G and they then compared 2500 Europeans from different parts of Europe for 600,000 such positions which is a lot of data you can imagine it's very big data set and that is so much data that is really hard for you to look at that kind of data so what people use to kind of reduce the complexity of such a data set or something that we they call principal component analysis so basically reduce the diversity of the data you kind of look at the main components that actually drive the differences between between the data and if you do that for Europeans we get a plot a principal component that looks like that so if you look at that you missing okay this is colorful clouds which is very inspirational maybe for some artists but you don't really see a pattern at first however if you stay a bit longer I didn't specially look at the colors the colors actually present what the people and design in London said the nationalities are and you can see this is Portugal here this is Spain France Switzerland Italy Great Britain Ireland Scotland Netherlands Denmark Germany Austria Slavic countries and here Eastern European countries so what you actually have here is the map of Europe so you can actually see this is this is pretty amazing it was really a really influential study because it showed the people that we all carry the genetic make-up where we basically come from at least if our ancestors come from the same region somewhere in Europe so this is really amazing and it has really cost a lot of lot of discussion a lot of interest but then again that's the question can that tell us something about human history can they tell us something about how certain populations migrated for example in the past you don't really see large patterns like Patrick for example he is very interested in the period in the sixth century when there was a lot of movement in Europe my creation period people who might have moved from A to B because there was some from from the east the Huns and maybe other populations who are pressing into Europe there was a lot of movement but we don't really see a lot of moving here it actually looks pretty much like the topography of Europe so we will then ask the question how fast does this pattern actually arise how old is this pattern is this pattern 50 thousand years old since the first people came to Europe is that pattern 500 years old in Lousiville time because people were more or less stable from that time period there was not so much large migrations or how did this pattern actually arise in the first place and that is exactly the type of questions that we are asking currently in our new Institute in llena but also in our research team together with David Wright and other people and what we would like to reconstruct this type of population structure not only from today but actually going back through time so see what we have today comparing that to the population structures of different time periods and then seeing how this structure actually changed because if we see changes those changes might actually indicate that there was migrations that there was things that might have been linked to historical events so if we then work together as historians I'd say okay we see in the sixth century there is a major shift and this part of Europe or in another part of Europe that could be linked to a historical or if you go even back in time potentially a pre historical event so in summary we basically all carry this genetic signature where we come from which a graphic origin our DNA what we would like to do is reconstruct it over time to actually see how things have changed which might then indicate a certain prehistorical or historical and large population shifts and movements but then of course the question is how do you do that you cannot really go out back in time and ask people to give saliva to you and so what we have to do is we have to work with some other source of DNA and that sources usually bones and it might be hard to see here but that's me and I have a Neanderthal bone in my hand which is actually the type specimen the first Neanderthal that was discovered hundred fifty years ago by fellow man from my village that actually discovered this it was destiny for me to work on this I just have to emphasize that and and from those bones surprisingly we can actually get DNA there was something that's fun to pay with my mentor discovered in 1980s and some other people have been working on that as well you can actually go take those bones they can be up to a million years old and you still get DNA you still get the blueprint of this organism from a million years ago so the oldest genome we have current is from a horse from the Yukon region so from Alaska and which is about a million years old so what we then do is we take those inch bones we drew a little holes in them so we partially destroy them it's distractive what we do but it's usually small little holes with a dentist drill here from that powder we get we get basically extract DNA then we have some fancy technology to prepare the DNA for what we then call DNA sequencing and this DNA is DNA sequencing this is really the key to everything that we do and this is also the key to what I will be talking today about and the big boom that some of you might have recognized in this field over the last let's say 10 years when we really see in almost every man's a new paper and HR science which is related to ancient DNA because there's new technologies that came on the market allows you to sequence DNA in very very short time for very very little money ten years ago or 12 years ago it took the first genome project about years to generate the first human genome it cost about two billion dollars to produce the first human genome today this machine is doing it in a couple of hours for less than 500 euro so things have changed a lot so this massive throughput in fact my parents and also my girlfriend got a genome sequence for Christmas last year not the whole genome but the variable parts but there's companies now you can send your DNA and they sequence it so act now for example works for such a company in Iceland but there's also a company that is in California which belongs to one of those search machines and in the internet you might know which one that might be and and you can actually send your DNA there for $70 you get your whole genome analyzed so it's really amazing so also very interesting information that you get out of it which is related to ancestry where you're from but also medically relevant kind of positions that might be related to certain disease for example so this is great and this has really allowed them some major throughput so we have seen especially for the archaic humans and some really high high profile also publications and where's Fanta and his team and I was part of that team at the time were able to reconstruct even genomes from Neanderthals so from archaic humans that were living ten thousands of years ago so we started with mitochondrial DNA and from early modern humans and Neanderthals but then even produce the first sequence of the Neanderthal genome about five years ago in the Neanderthal genome project and then like patrick already mentioned eventually we even found two completely new form of human which was the first time that it wasn't found by anthropologists that were digging somewhere in Africa who was actually found in the lab so by by a student of mine and myself we were looking at DNA sequences and said he noticed that DNA is not human that DNA is not the under tile that's something new it's a new form of human which we then called in this ovum because it was found in a cave called the new silver cave which is here in Siberia southern Siberia in the Altai mountains this is the cave here was a tooth as well as a little finger bone where we get a little bit of DNA from enough though to reconstruct the genome and also look at the mitochondrial DNA what we actually found was that this didn't so some sort of sister group to Neanderthals quite distinct though has um diverged here in the tree about two hundred thousand years ago and we could even find that this Denisovan carries some DNA of some Homo erectus so it has a very complex ancestry it's not just in the undertale' sister group but it also carries something from our like deep past in its DNA so it's a very very interesting finding so archaic humans have been very much in the focus of my research when I was doing my PhD but in the last years I've also started to work on more recent time periods and it's a general movement there's a lot of people now in our field and paleogenetics that are working on more recent time periods on Holocene populations and also I'm increasingly on late prehistory or even historical populations and one of the major questions that people have been trying to address with genetics is a question about the Neolithic transition so the Neolithic transition has been a very interesting topic in archaeological research and very fascinating for many years which is basically the transition from hunter-gatherer lifestyle of people to a more sedentary lifestyle where people have aquaculture and domesticated animals this process which is also called the Neolithic Revolution this change in basically subsistence strategy happened in Central Europe about 7,000 years ago and it has been offer for a long time argued whether this change was due to new people coming to Europe and bringing domesticated animals and wheat agricultural products or whether this was just culture that was just innovation which was transmitted from village to village but it wasn't really people moving but in fact it was culture moving so there were those two models that people had suggested one is the cultural diffusion model which would suggest that it was actually culture that was passed on from maybe neighboring populations which would then say we have the Paleolithic people they later on give rise to the Mesolithic people which is basically the people just before agriculture and they then give rise to the people that have have today and from the neighboring populations they actually received this culture but it wasn't really change in the people themselves and then there's the other model which we call the damaged diffusion model which argues that their words the early people that we're living like hunter-gatherers in Europe and later on there were new people coming to Europe those new people actually brought this and technology they brought basically domesticated animals and agriculture and the people that we see in Europe today are actually more or less those newcomers that came to Europe about seven thousand years ago and as we much debate about that I'm in archaeology it was very difficult to solve this question and only genetics could really help to address him and get give us some almost to have definite final answer on that and that was that there seems to have been a large my creation into Europe and major evidence from that first came from the mitochondrial DNA so showed in the mitochondrial DNA before that has those different types so mitochondrial DNA those different types of the different colors that we saw in those pie charts in Europe and here you have a time beam here starting at 6,000 before Christ - about basically today um and here we have those different types that you see in Europe different frequencies you have and dark here you have a certain type then you have those orange types yellow types and those other types here what you can see that before 7000 years before present about five thousand years six thousand years before Christ you had in Europe only one type of mitochondrial DNA which is so-called you type that's a type that we see in all hunter-gatherer so all hunter-gatherers that we have sequence which is more than hundred by now they all have this you type even from the start of the Pleistocene to the time when the added house was still in Europe but then as soon as the first farmers come to Europe with the so-called linear band cramming the frequency of this type of mitochondria drops basically to zero so this type disappears we don't see that in the people anymore so this type of DNA disappears and the new type appears which we then see for the next few thousand years to be very high frequency in europeans whereas this you type is really really really far down however you see that this is not the only event that happened because it's not that this is how we look today that we don't have you anymore we only have this early farmer type but you can actually see that over the Neolithic there's like some other more changes actually some really interesting change happens about here but four thousand five hundred years ago but the frequency of the early farmers goes down and this and together types come up and there's this new yellow types here that are also coming up so the frequency changes again about 4,500 years ago Keith in the mind that will become important later again but then of course people again said okay this is mitochondrial DNA this is the story of the females which is of course a very important part of our population but is that really representing the entire story so people and would argue again we actually need the nuclear genome at the nuclear DNA which was quite difficult at the time but still some first people try it why is it so difficult we have done the Anna Todd's why can't we do early farmers it is difficult because those early farmers genetically basically look like a sprite they're extremely closely related to us so the main challenge was then to say whether DNA is really ancient DNA from a skeleton or actually one of the archaeologists one of the people in the lab so this to differentiate between contamination and the ancient DNA was not so easy for archaic for Nana thought it is possible because they have different DNA they genetically so distinct that you can distinguish them based on the DNA sequence whether they're in the under top or whether they are modern human for those modern humans was more challenging so it took some time to the first paper that came out in 2012 from ideas jakob since crouppen punto scotland here as a PhD student working on that they actually sequenced um hunter-gatherers and an early farmer coming from sweden so they were found here so the anti gatherers were found on on Gotland which is here in the baltic sea and the the early farmer was found here on the western coast of sweden so what you have then here is modern populations that you have presented here by dots different parts of europe Italy Russia and this is kind of in yeast here and here you have those kind of genomic informational again of the whole nuclear genomes basically like people didn't Switzerland on London asking people on the street but in this case using skeletons from the past and extracting that nuclear DNA you can see that the early farmer is actually quite distinct from those hunter-gatherers the early farmer looks basically like us today looks more a bit like a Sardinian or like a Basque not so much like a Central European but for sure not like a modern Swedish person and that was something really interesting here because it told us ok there are definitely very different people so it's probably people that migrated it into that region bringing accurate culture however and not to a hundred percent ancestral to the modern Swedish people in fact those hunter-gatherers look more like those modern Swedish people than those early farmers too which tells us that there must have been some more to that story it's not only that the people come in and the people stay and they have the agriculturalists they are there until today and this is the swedish n' that happened in other parts of europe but there must have been some more complexity to that story then the other big paper that came out in the same year was the genome of this fellow here some of you might recognize him kind of looks from some sort of 1980s horror movie um but he's actually the Iceman right so there was this this the Tyrolean iseman that was discovered about 20 years ago and you know in a clay shear in the Alps which is has amazing preservation of I've seen him a couple of times because I'm working also on his stomach content on his oral microbiome and people kind of strange things I - um so so people have sequences genome already in 2012 because he's amazingly preserved he has been frozen for 5000 years so he's extremely well preserved he's basically like one of those people you ask on the street in Switzerland um see I mean let's say anything bad about Swiss people and he has a very very high percent DNA so it's easy to sequence him so that was was done in the early days with almost like pretty pretty good quality genome and when people found was that genetically he looked I'm comparing it to different European populations here you see this is the different properties in different parts of Europe this is actually southern Europe here this is Northern Europe Eastern Europe he actually had the highest similar I mean extremely high actually to people that live today in Corsica and Sardinia so if you would just get his DNA like on the street in Switzerland you would actually think that he is from Sardinia or Corsica which then of course again as a bit weird because certainly he didn't travel from Corsica to the Alps it's pretty unlikely because people who doesn't were not so mobile during the time it might have been possible but it's I think quite unlikely that he actually was born in Sardinia and but in fact it tells us that those those farmers he belong to the Copper Age farmer so the kind of middle to Nate late Neolithic farmers that those farmers were probably looking different to the people that live in tirol today and another very very important story then appeared em only thing was in 2013 so so two years ago now and that was a story which made the thing even more complex but people had analyzed in this paper was an ancient fossil at ancient human so that's work that was done in Copenhagen by ask Aviles laughs group with a sequence a little boy and there was I think about 12 years old when he died and that was 17,000 years ago very very long time ago close to the lake baikal they sequenced his DNA and they compared his DNA again to different populations that live in different parts of Europe Siberia as well as Native Americans so in the Americas today what you can see on this plot it might be a bit hard to see it from the back but this is basically Europe this is Native Americans and this is where this kind of multi-child falls in it doesn't fall with Siberians but it falls somewhere in between modern Europeans and Native Americans they also did some more studies and some more complex statistics what they could basically show is this is kind of populations that would have a high G genetic affinity based on the color so warmer color more affinity kind of called a color less affinity you can actually see that populations in the Americas today as well as here in the Bur Indian region as well as in Europe have a genetic affiliation or affinity to this 17,000 year old boy from Siberia so what does that tell us it's an interesting story so what it actually tells us is that there's a genetic link between Native Americans and Europeans and that's also something that Nick Patterson already proposed in 2012 that Europeans are closer related dramatically to Native Americans than they are to Eastern Asians so there has been some sort of ancestor in the past that gave us some DNA which is also find in Native Americans DNA so there's some genetic link here Nick Patterson proposed in 2012 that this link was probably the so-called mammoth step the region that was going from Europe to Siberia and Beringia we are basically the early hunters were hunting mammoths and large animals that were just roaming in this large part of Eurasia and then later on farmers came to Europe and mix this a bit up but this is basically this kind of link that linked all your Asians and with each other but like you will see later on this was not actually the complete story skip this one so with our with our study we then wanted to address a couple of open questions because this was basically the stage where we were when we started our project we wanted to study now not only genomes from certain farmers or from those really ancient people from Siberia but look more into one region in Europe about the transition of those mezzo lithic people which other handle gatherers to those Neolithic farmers and then compare those populations to contemporary Europeans to see how they're related to each other we then also wanted to see how other early farmers related to people that live in the Near East today because archaeologists have proposed that those early farmers probably arrived some from the Near East we then also wanted to see whether this indeed only two genetic components we find in Europe hunter-gatherers and the early farmers or if there was a third component or force a fifth component and then can we actually reconstruct a model that kind of represents the population history of Europe so can we actually come up with a model that explains the genetic makeup of modern Europeans so for that we of course had to we can study ancient skeletons so we got a number of skeletons one was a hunter-gatherer from Luxembourg it's about 8,000 years old from the side that's called lush poor one is this fellow here which is basically he was just around my home University and we was in the basement where we have 10,000 skeletons was found as close to the city of Stuttgart which is very close to my universe in Tuebingen I mean 7,000 years old and we also get a number of early hunter-gatherers from Matala which is a site in Sweden it's a very very strange burial crown so those hunter-gatherers have actually buried their people in the lake but it was a secondary burial so they were buried somewhere else but then they took the heads of the dead people and put them on a pole and put the poles inside the lake on the top of a rock that must have been reaching a horrible cruel picture to see this but it was basically a little rock that was covered with em heads on poles and some point in the past 8,000 years ago and we also included some already published genomes such as the Iceman such as the multi-child and an together--as from Spain so one of the first things you could do with this genetic information out from those from those early humans again is looking at the mitochondrial DNA is something that we do quite often and also at the white chromosome if you look at the white oak Andreea DNA there was no surprise at all in fact we saw the same thing we've seen before all the hunter-gatherers have the you type our Stuttgart Palmer has the T type so we see what we've seen before and together as you type and then the T type comes up so that was just confirming what we already knew what was new was that we could also look at the Y chromosome which people hadn't been able to do before because we had a large number now also larger number now of hunter-gatherers and we could look at the y-chromosome the male's they all carry the white type that's called I or I - which is still found in Europe today small frequency about five to ten percent in different parts of Europe but it's quite rare if you look at the frequency for example and contemporary Germans we see it higher years about 15-20 percent but most of the types that we see in Germany and Central Europe today are a different type so suggesting that the eye type was the hunter-gatherer type and then later on there might have been new types of y-chromosome coming into Europe what we can of course also do with DNA is not just looking at ancestry and relationships but of course it's the blueprint right it tells the body how to produce certain proteins how you get certain phenotypes so in the DNA you have of course also the phenotype coded and that is also something that people have been doing in the past so they could for example show that an Eskimo lift 4000 years ago and Greenland had dry earwax some really exciting information and what they could also show which was done on the slab or Aniyah um or the human here Mesolithic hunter-gatherer from from about 8,000 years ago in Spain that he had dark skin and blue eyes and this is actually something that we could confirm also an our study you could see um that terms of eye color our hunter-gatherers all had blue eyes in terms of skin color our hunter-gatherer here a darker skin whereas the early farmers they had actually lighter skin but dark eyes so it's actually quite a reverse phenotype of what you usually think about European so the early Europeans we know that by now they all had blue eyes so the hunter-gatherers they all had blue eyes we haven't found a single and together yet that did not have blue eyes and they mostly especially in western and in southern Europe all had dark skin so basically looking potentially like like Africans today or kind of maybe northern Africans what you could also do is we could look at the gene that's called amylase which allows you to digest starch this gene is very important you have it in your saliva you have a new stomach or you got I basically D creates starch by itself which is one of the major components of your diet at least if you like gluten a lot of people don't anymore it's kind of like trendy fashion now - naughty - including free which I think that's made too much sense but in our ever evolution this gene got copied in our genome multiple times chimpanzees only have two copies of this gene but some human populations today have up to 20 copies of the gene especially high in Eastern Asians were suggested to be potentially on the selection there I know Mark Thomas is here you will probably have a different opinion about that but there has been has been potentially some selection on sometime in the past and many copies and some people have suggested that early farmers had many copies because they were doing farming where as hunter-gatherers if they don't do farming if they don't have meat they don't have bread they don't have starch they don't need a lot of copies of that however what we found was our our farmer had 60 copies which is pretty high but our untogether had 13 copies which isn't the average of modern people today so actually he had almost the same number so we couldn't really confirm this hypothesis we can just say basically the hunter-gatherer looked like the early farmer so if it was selected if it was important to have many copies then happened way in the past probably sometime in the place to see so the other thing then of course we wanted to do is we wanted to compare our hunter-gatherer early farmer as well as the hunter-gatherers from Scandinavia to modern populations from Europe from today and for that we have actually collected one of the largest data sets genome-wide data from modern humans we have collected data from about 190 populations worldwide but 2,300 people that we have studied on 600,000 variable positions were very very large data set that we didn't compare to this about doesn't ancient human genomes to see how are those ancient humans related to modern Europeans and also and other Eurasians and now there's various statistics you can you could do it your mom could probably talk for four hours about the population genetics that that what here which is rather complicated I don't wanna bore you too much with it but at least I want to show you some of the results that we obtained here and one of the results which looks very busy but again nice colorful and is a is it analysis and program or software that the people used it's called admixture so what this is doing is it basically takes the nuclear DNA which is very complex because of all those recombination and things getting mixed up over time and it breaks it into the major genetic components that you have in the DNA and you can set this this software in a way that it breaks your DNA into two structural components in two three and four however many numbers you want to break up your data into you see those numbers here 2 3 4 5 6 7 up to 12 which is the number case and how many things we have the the data broken into if you if you see you have different population of different parts of the world Africa Middle East Europe South Asia East Asia Siberia America if you break your data into two components you see you get Africans and non-africans that's something we have seen a lot people left Africa that was bottleneck people have evolved outside Africa they have genetically changed over time so there's basically a different genetic structure outside Africa compared to inside Africa even though we have much more diversity in Africa and which would also break up if you kind of continue to to increase this number of K and we can go through many kind of different parameters here our ancient humans are here the Africans Europeans Middle Eastern and so forth and if you kind of increase this number of K you see certain your parents arise you can for example see the Asians becoming different the Americans becoming different here some point you have the Oceania also coming up and what is interesting if you increase this number maybe to nine that your ancient humans they also get colors here they also get new components which is if you tell us that those ancient humans are linked to certain populations in certain places in the world and one of the first things you see you might actually not see in the back and I can hardly see it here but and the second row here because this is 190 populations the second row here presents our early farmer from Stuttgart and what I can tell you you might not see in the back is this is dark blue and this is light blue so the early farmer has two components one is dark blue one is light blue so if you look where the light blue is found in the world today it's found here right this is where it's most common also the dark blue is found here dark blues otherwise more like European but this light blue is the component we see high frequency in the Middle East so kind of tells us there's some affiliation of the early farmer to the Middle East the other interesting sample here that becomes quite colorful here becomes actually this already red color green color you also the green color that is actually the sample from Malta this child's have been thousand years old that gets this green component here's where do we see green on this row green is here whereas that that is kind of South Asia East Asia so there might be some component here which could be related to to Central Asia but then also we get the red component even the red component is the one that we see in the Americas today so probably this kind of linking this child to different parts of Eurasia as well as Native Americans what we can also do is this principal component analysis that I showed you before which people have done on this saliva from Luzon and from London now this is not done on the people from Luzon and from London that Virginia typed on the street but this is from all those populations that we have gathered together this 2,900 people from all over Eurasia so this all presents different individuals from different populations here and what we see here now is not all 2400 those are only the Western Eurasians so those are populations from the Near East and from Europe so you see many different populations here those are all the Near Eastern populations that build this kind of cloud that you see here those are the modern Europeans in between you have some Mediterranean populations that was one of the first patterns that we recognized when we plotted this together we can actually see there's almost like two clients there's a client here and there's a client there and in between those two clients not have this Mediterranean populations but those Europeans actually look quite quite moved from here there right they kind of like look like moved into this direction so they were moved in this direction if you then look what is in this direction what actually is plotting here which basically those people could be mixed off from this component with something that is down here you see those are all the hunter gatherers the hunter gatherers actually quite distinct not no population we have in Europe today looks like hunter gatherers looks like the native or indigenous Europeans especially those Western Europeans the one from lush poor as well as one from Spain Lavanya one with the blue eyes and the dark skin there like down here they're quite distinct to all modern populations we have in Europe today what we have down here are early farmers our early farmers indeed again look like certain populations in Europe and no surprise we've seen that before the Iceman they look like Sardinians so people in sardinia look genetically like the first farmers that has been replicated now many times so this is even people here from Sardinia they're almost indistinguishable from people that were the early farmers that came maybe about 7,000 years ago to Europe however the rest of the Europeans they look somehow different they kind of fall kind of in between here and there so hunter-gatherers and new eastern populations but they also kind of moved towards this kind of direction in this plot right there kind of like moved towards this upper part II of the plot what do we have at the upper part of the plot we have the multi Chad so this child from Lake Baikal and this made us to actually propose a third component that we have in Europe which is the early farmers to hand the gathers but then this what we would call North Eurasian ancient North Eurasians so this link between Native Americans and Europeans that is actually kind of responsible for this kind of upward movement of this Europeans is basically found em in best represented by this multi child from Siberia so then using this data and using some more statistics that I don't want to go into you could then try to reconstruct a population model for Europeans which would best represent what modern Europeans are basically consisting of you can see this is the modern Europeans here this is Native Americans and there's different populations from the past which are basically inferred which we kind of basically hypothesize existed in the past and then comprise modern Europeans and there's those three major components represented here by those ancient humans the ones from Malta the hunter-gatherer as well as the early farmer and then those are the populations that we basically think those ancient people belong to or or represent best to what you can then see is that after the Out of Africa movement there has been some initial split into this component that we call basal Eurasian which is a very weird genetic component that we do not understand at all we need it in the model but we don't know what those people are it's a genetic component that that basically splits off from the people that first came out of Africa and it's around somewhere we don't know where it could be somewhere in the Near East we really have no idea right now what this population could be probably in the eastern population because it contributes about 50 percent to the makeup of the early farmers so it's kind of a mysterious we call it sometimes ghost population because we don't really know what it represents here we have the Western Eurasians basically the indigenous Europeans the hunter-gatherers which are best presented by lush or by this hunter-gatherer from from Belgium and here you have the ancient North Eurasians which also contributed largely to Native Americans but then also to the small touch child in this population and also contributing to modern Europeans so basically modern Europeans are best represented by genetic mixture of those three components North Eurasians West Eurasians basically those hunter-gatherers and then those early farmers so that basically then was this model that develop that we have this three-way mixture of modern Europeans with the street and genetic components and this weird component here that we don't really know yet understand and this allows us now to actually take every European population and calculate how much genetic makeup does this certain population have from those three genetic components the most Eurasians the hunter-gatherers as well as the early farmers let's say we take for example Estonians here Estonians have quite a large component of hunter-gatherer DNA a bit higher component of North Eurasian DNA and a lower component of early farmer DNA if we take a person who from Sardinia it's almost no hunter-gatherer and very very little north Eurasian DNA so we can do that for every population this is just gem that we have presented here so in summary for this model we would then suggest what kind of the recent Holocene history of European populations that about 9,000 years ago early farmers come to Europe on their way to Europe they mix with certain populations and to gather up populations potentially in East Europe because we have a little bit of hunter-gatherer DNA in the early farmers about 7,000 years ago they arrived and Central Europe in Scandinavia we have something else going on I don't want to go too much into detail but then less than 7,000 years ago a new genetic component comes from the east which is this North Eurasian component why do I say less than 7000 years ago because neither the hunter-gatherer from lush poor nor the early farmer had this component they do not have that but every European population today has this component so therefore we know it was not around 7,000 years ago in Central Europe and it must have arrived later and that was proud that was basically the end of of the story of this paper that we published in October we said ok we have those three genetic components but it kind of really bothered us to not know when this it actually arrived and this then sparked a new study which I want to talk about at the end which was a study that was just published actually two weeks ago which is the follow-up study which we called Europe - so the other one is Europe one and in this study we not only looked at ten ancient humans but now at a hundred so you see it's always kind of an increased tenfold increase for the next couple of years probably the next paper has a thousand or something like that ancient humans that we now genotyped for about four hundred thousand positions so this time we didn't sequence the entire DNA of those ancient skeletons but we only looked at the variable parts with a new technique that we have developed in the lab that allowed us now for very little money sequence many many ancient humans one hundred now and those spanned from the Mesolithic to the Iron Age so they're from different parts of Europe this animal or ancient humans not modern humans and they go from basically the Pleistocene hollows early Holocene and early Neolithic mid Neolithic Copper Age late Neolithic Broncs Age to the Iron Age from different parts of Europe Western Europe sampling group and Eastern Europe so quite an high number of of samples which was really incredible because in we can even do more fancy statistics and the first one we could do again is this wonderful clouds and the principal component analysis this time the modern humans are in gray so that they kind of don't disturb and the view and the colourful ones are all those ancient units right so you have the two clients again this is the Near East this is the modern Europeans here we have again our hunter-gatherers the same place where we've seen them before with our few hunter-gatherers now we have more but they basically all cluster together again here we have the early farmers began the same place in the plot this is Sardinians is the early farmers this is now the early Neolithic but it's also the middle Neolithic so they look the same so the first people that came 7,000 years ago and the people that were still there sell 5,000 years ago they basically all look the same however what is really interesting is this is the late Neolithic this is kind of late Neolithic to Bronx suddenly between the mid and Neolithic and the midday or lithic this population shifts here and shifts to a place where we are today this is us right this is cool as everybody is from Europe but kind of Western Europeans and you can actually see that they fall very much here in this is part of a modern populations so what has happened here why did the population steadily move from here to there and kind of move towards kind of this part where you have the North Eurasians again what do we have in this plot is one population that we also have studied which is the so-called yam nyah-nyah-nyah is actually a population that archeologists have been interested in a very very long time because it was a population that was present north of the Black Sea and the so called Pontic steppe was his large region where those pastoralists were living and there was hypothesis already in the 19th century that those people at some point came to Europe and brought potentially indo-european languages that was basically the homeland supposed to be of the indo-european languages was some hypothesis that people had been discussing already in the late 19th century and had still be then been around not in the 20th century um however this is a population that we find in the past north of the Black Sea so not in Central Europe but there's one population in between which genetically falls very very close to this young nya that is a population we called the coordinate where the coordinate where was the type of pottery in a type of culture that was present in large parts of Central Europe this was present about 4,500 years ago in Central Europe right so this was not an Eastern European population that was actually a Central European population that genetically basically looks like those people from very far Eastern Europe from the Uralic region and north of the Black Sea but is then present in Central Europe and then this population disappears new populations pop up with the Bronze Age and basically they turn to this so basically it seems that those Bronze Age populations are kind of a mixture between those early nearly people and discord we're people and this is also something we can again presented some sort of a mixture like analysis where we have with the three different colors here those three different genetic components so with the orange here we have the early Neolithic middle Neolithic so the early farmer component in blue here we have the hunter-gatherer and here you have the late Neolithic as well as the early Bronze Age as well as those gam nya populations this is our the yam nya here those are the populations in the Bronx age hunter-gatherers early farmers so what you see is the under gatherers they're all blue here that don't have this green they don't have these young nya components the early Neolithic farmers they also do not have this Mei component the yam nya have this green component very strong as well as the cord at where the quadrant where those people that were in Central Europe about 5,000 years ago or 4,500 years ago they basically genetically look almost exactly like the UM nya but what we see here in this plot is also represented here genetically an iron core that we are basically almost indistinguishable and that basically led us to the hypothesis to think that the Corot we're probably is very close related to yum nya which some archeologists have also suggested in the past they come probably in some large my creation from the Pontic steppe north of the Black Sea to Central Europe and they bring this green component that we find in people today that we find in the Bronze Age we find the late Neolithic but we don't find in the early Neolithic and we don't find it how to gather all so basically this kind of shift towards the north that's kind of shift towards the north Eurasian component happened with the quartered we're about 4,500 years ago so that basically lets us to fill this kind of number here so we can now say that this component this kind of North Eurasian component came with Yemaya with the quartet we're about 4,500 years go to Europe and in fact we could show it replaced this middle Neolithic people that were living here and actually part of Germany at the time or today Germany I'm the children you didn't exist they replace this population almost completely almost a hundred percent replacement whatever happened whatever those people the courts where culture was kind of more sophisticated more successful maybe better in warfare we know they had wheels and wagons they had horses at least in the higher percent and then the other early farmers somehow they were kind of the master my creation into this region and then over time actually mixed up with the people that were living in this region and this was a major finding because it tells us that there was my creation that we really didn't know so much about before we knew what we had at least a good idea that there was this early Neolithic people the first farmers coming to Europe 7,000 years ago but a good idea that this happened but what we didn't know is that there was another large migration happening in the late Neolithic the new people coming in and that had direct implications and also for some hypothesis traveling related to other languages especially to the indo-european languages their two main hypotheses that people have been discussing in the past about where and when indo-european languages came to Europe there's the so called Anatolian hypothesis and there's the Pontic steppe or Corrigan hypothesis and one hypothesis states that with the first farmers nine to seven thousand years ago the indo-european languages came from Anatolia came to Europe and then basically spread in Europe and later on then also spread and towards central and southern Asia and the other hypothesis is the corgin apart Azure Pontic steppe opposes which or it goes back to time apart is about Muhammad from from from symbol of German archaeologists from the 19th century I'm suggesting that it was rather from kind of the northern north of the Black Sea here the so-called Pontic steppe from this Pontic steppe and some time ago they said well 5,000 years ago 4,500 years ago and there was this movement together with a court at where those languages might have spread into Europe and then spread into different parts of Europe and also and in the other direction towards Persia as well as to Asia so those two hypotheses are basically both in some ways supported by our data because we can show that there was a large migration 7,000 years ago but there was also a large recreation 4,500 years ago so we can at least say that based on genetics both hypotheses are equally likely I think linguists as well as archaeologists and potentially also geneticists in the future have to see which of the two hypotheses will be more supported so it was early spread of indo-european languages or late spread of indo-european languages I think what we have to do is look at populations look at their genetic makeup see what languages they might have spoken some for example pre indo-european languages like me no one's potentially like Etruscans for example like Basques can we find something that can actually correlate that um genes with potential language evidence my kind of last point I would like to make is because we have so many sequences of a hundred ancient humans we can look again at the phenotypes over time and that was actually quite interesting because now we can look at some more immune terms not just the blue eyes and the skin color but we could actually also see that there were certain genes that were changing in time since hunter-gatherers towards people today then we're not just the blue eyes or we said like the hunter-gatherers they all had blue eyes over time blue eyes go actually down the kind of lowest number of blue eyes we have in the middle Neolithic so probably the farmers coming in from from the Near East they had probably not blue eyes so basically I had a lower proportion therefore but later on the kind of researchers here when the people come from the Pontic steppe they had probably a large component of blue eyes again and then it kind of drops down to what we have to take in or actually are actually more or less constant and until today what we also could find was some genes that are related to vitamin D so vitamin D is a very very important thing in our history and it is thought that the reason why the skin color changed so much over time so we have here in blue and then green so blue and in green we have skin color genes that basically cause lighter skin that were basically absent completely now hunter-gatherers but then with the early farmers they come up and then doing this kind of new my creation of people coming from the Pontic steppe it even those more up so that today basically almost all central Europeans have one of the two or even both genes that give light or skin color and it's thought that this was important because of vitamin D production because if you are a farmer you don't eat a lot of meat and the only way for you to get vitamin D is and by being exposed to sunlight now some of you I'm sure have been in Europe in the past it is pretty dark in the winter and sometimes depending where you are you have about three months you never see the Sun so that's that's pretty bad because you cannot produce vitamin D that gives them vitamin D deficiency which is pretty bad and it's kind of important for your health so this is why we think that those light skin colors have evolved in Europe but there's also other things which are important vitamin D production and which actually grows in frequency like we see here which basically will also and select it and then also and we see selection on on fat metabolism and not really sure yet why that would be but that's something where we can also see that the frequency of this gene increases over time and then the other thing that we always see in actually mark Thomas which also here in a room we'll talk tomorrow he has been working a lot on that and that the one thing which shows the strongest selection actually of all the genes almost we know up which has really changed in frequency tremendously is actually almost surprisingly within the last few thousand years that is a gene which is I'm basically giving you the ability to drink milk when you're an adult so you know that you're lactose tolerant so actually most people and basically all mammals cannot digest milk when they're adults because usually this lactase gene gets shut down when you get older which makes a lot of sense because the mother doesn't want to give milk for the rest of their life right I'm sure there's some empathy here in the room for that but what happened in Europe was that there was a gene which had basically zero frequency in the hunter-gatherers early farmers also didn't have it even though that I had cows they couldn't digest milk whenever adults but then around the time when the Pontic steppe people come in so this kind of migration from the east this kind of gene comes potentially in we're not really sure if it comes in during the time but then we see it the first time it rose in frequency a lot to about sixty percent and Europeans today it's like a tremendous shift from here to there within only about four thousand years right this is actually such a strong selections incredible it's like basically you have way more offspring if you can digest milk on your adult and if you don't and it has been very strong and has come up in frequency here and people have also seen that since the 1970s basically as one of the genes being under selection and coming up again and again and we can see that in this data again then it actually comes pretty late people had suggested before and that it was something that evolved about 6,000 years ago with farming but it seems to be something that actually came later on at the early Bronze Age and then mostly during the Iron Age this is all genes where you can look at single m mutations so single places in the DNA that gives you this phenotype but there's a lot of traits that we have which are complex traits and so basic it's not just one gene that gives you the ability like you to drink milk but there's like thousands of genes sometimes hundreds of genes or hundreds of variants that actually cause a certain phenotype one phenotype is actually height height is a very complex trait but people have been studying that quite extensively they have found about a hundred M genes that contribute to the height of a person so what we could now also do is because we have a hundred people and those genes of these people we could also see if we can say something about height over time how did actually selection and hydro current that had actually occurred can we see it can be detected what we could actually see was that it was indeed selection changes and frequency of those genes but surprisingly what we found was that this is the early Neolithic this is those later popular so late on the southern European late Neolithic and middle Neolithic the other kind of Central European early middle and late Neolithic you can see that there's actually a selection for decrease in height and southern Europe so for some reason it was advantageous and southern Europe to be smaller not really sure why that is some people have also suggested that for Sardinians because they are extremely small it's also selection on some of those genes and in sardinia so potentially it might be advantageous to be smaller if potentially the environment for example has less resources that could be one explanation but what we also see which is quite interesting that those gamma I actually had an increase in height they were selected for being tall so it's quite an interesting story those people had horses they had wagons they came from the east potential brought languages where really tall warriors certainly sounds like a story from the 19th century but unfortunately of somehow it's also supported by the genetic data so what can you say in terms of from conclusions here we can say first of all modern Western Eurasians are a genetic mixture of at least three larger ancestral populations which is hunter-gatherers those northern Eurasians and then the early farmers the early farmers which I didn't talk too much about have their roots in the Near East we see a very strong genetic link to Near Eastern populations today the North Eurasians or the North Eurasian component arrives with the courted we're pretty late only four thousand five hundred years ago comes this new genetic component 13 era component that links Europeans to Native Americans and which then also potentially could have been connected to indo-european languages the coded way is extremely similar to the M nya which is also very important part of information because a lot of people had discussed call it where's absolutely it's it's distinct population and there's some archaeological resemblance but it might not be and that there's really a biological close between those populations but that however seems to be the case in at least this so-called middle of Zahle region or this region in central and Germany we see that the middle Neolithic people get almost 100% replaced for whatever reason they get wiped out quadrant where takes over and brings this new genetic component we're not really sure why it happened but it's an interesting piece of information so what we can say in conclusion is that there were at least two mass migrations during the Neolithic the first early on the first farmers bringing kind of aquaculture domesticated animals to Europe about 7,000 years ago and then 4,500 years ago this quarter where people come in bring in new genes bring in this north Eurasian component that we find in all European populations today and then as I mentioned that might potentially then also and give us some information about the spread of languages so by that I would like to first thank all my collaboration partners mostly David Rice team which was really a great collaboration over the years Josef lesser leaders have been very important in my lab ELISA and also people from the Max Planck Institute in light sage then the last study I talked about which was mostly coordinated by David Wright and also by workin hard who will join us very soon in Jena and collaboration partners this project a few pictures of the new institute like patrick already mentioned wonderful new place is actually nice because was already built so we didn't have to build it it used to be the Institute for economics but they redirected it no comment here so we have three departments linguistics and cultural evolution archeology as well as our Q genetics and what we also do which I haven't talked about the package mentioned we do a lot of pathogen research there we have to be quite active from kind of looking at different pathogens we look to the black death genome leprosy the Irish potato famine causative agent from the past as well as tuberculosis from the new world which is all very exciting talk too much about that I want to thank my research team and a lot of funding bodies because this type of work cost a lot of money so thank you for your attention
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Channel: Institute for Advanced Study
Views: 398,566
Rating: 4.6961546 out of 5
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Length: 73min 13sec (4393 seconds)
Published: Wed Jan 27 2016
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