well I think we'll get started on time so that we can give our speaker his whole story my name is rick coney i just like to give you a few opening remarks about the personal genomic medicine Sidora series that were concluding with this lecture today as you know the Sidora series is a wonderful opportunity for the university to bring in in on different thematic topics very interesting topics for us to consider over the course of the year and I'm not going to read that slide but it's really a really exciting opportunity to bring the entire university community together some of the previous sidor topics include the following up here and you can see that the personal genomic medicine that we're offering this year is a distinct departure from many of the more liberal arts oriented ones it's been a very exciting series that we've had and just to summarize what came before for those of you man this one or more of the topics that were presented before we started off the series with Jane Foster giving the first lecture with a compelling description of how the microbial communities that live inside us so it's not just digestion but other aspects of behavior the immune system endocrine function etc we followed that with Michael Snyder who came and talked to us about insights into how various omec technologies not just genomics but other kinds of high data big data type of approaches can generate an integrated personal AMEX profile to assess disease risk monitor of disease states enhanced therapeutic treatments we follow that one with Barbara Koenig who addressed the ethical social and legal implications and responsibilities that accompany acquiring interpreting and sharing these vast genomic data sets and finally the talk that precedes this one Elaine Ostrander is taught provided insight into human health and disease that can be obtained by studying the genomics of naturally-occurring dog populations as well as appealing to dog lovers and breeders I wanted to mention that the aside from the first one we have videotaped these and we are videotaping today's as well and they're available on the Sidor website so without further ado Lemony introduce Dan Kosh etske to say a few remarks about today's speaker thank you for coming so yeah so we're really excited to have John Hawkes here to close out the Sidora lecture series this whole series has been sort of introspective how does these modern genomics approaches inform us about our own existence and I guess we come to the most profound question of them all regarding our own existence with the story of our own evolution and so John is a real leader in this area we're really glad to have him he's a full professor at University of Wisconsin prior to that he did his PhD at University of Michigan with a postdoc at Utah I believe correct and so John again is a leader in the area of health paleoanthropology and also paleo genomics and today he'll talk about some of that stuff so thanks again John all righty I'm going to see if I can't get everything rigged here and we'll hit present and this may rattle around a bit okay so this is an incredibly rapidly moving field ancient genomics and the field that I'm going to describe to you literally did not exist in this way five years ago so it is now you know just really changing so fast that it's very difficult even to summarize what what we're working on my work is really in a very small part of this area I work on how to integrate these findings from ancient DNA into our traditional models of human evolution and what parts of this are really new what parts are reflecting new information that we have never really thought about before versus solving old problems many of which we've been thinking about for 150 years so I'm going to focus on some of that historical background in the course of that I'll be describing a little bit of DNA and analysis that's been conducted by my own research group but a lot of DNA and analysis has been contributed by research groups from around the world and I want to point out you know every time I give a talk about this I just have to indicate the amount of effort and expertise that has gone into developing first of all the technology to do ancient DNA sequencing which was developed in large parts specifically for these early hominin contexts and now is being engaged even more broadly to look at the evolution of other species and Ecology's so this was really developed first for humans it was developed you know leaders in this area are Svante Paabo at the Max Planck Institute for evolutionary anthropology his postdocs Matthias Meyer ed green johannes krauser who's now has got his own research group at the Max Planck in in Tuebingen there's an incredible group in Denmark s cavilleri F in his group that have been engaged in finding information about more recent hominin populations all of this stuff goes in and it's the work really of an entire community of people a community of people that did not exist in this way 10 years ago certainly and so this is I'll tell you guys I give a lecture at our annual physical anthropology meetings last week and I was there in a session with people who were specialists in ancient genomics and they all gave their talks and I got up at the end and I said I don't know really how to feel about this because it's never happened to me before I am the oldest person presenting in this right and I'm not that old right so so it's it's a field that has really undergone a very rapid transition this is Mount Carmel it's on the eastern end of the Mediterranean the Levant side where the Sun is rising Levant it's a very famous site historically biblically it's also a famous site in terms of anthropology the caves in Mount Carmel contain some of the earliest evidence of modern humans anywhere in the world and in particular the earliest evidence of modern humans outside of Africa this is the Rock of Gibraltar Gibraltar is a place it's beautiful I've been privileged to spend a good deal of time there because not because of the sunshine although that's very nice but because of these caves which are full of archaeological remains left by Neanderthals more than 30,000 years ago Gibraltar is the place that we now presently think the last Neanderthals that we've ever discovered lived they lived just over thirty thousand years ago and left their traces in these caves for us to find archaeologically so one end of the mediterranean the east end to the other end Gibraltar you've got this incredible range of populations that is a very tiny fraction of the world but it's only about half the total extent of range of Neanderthals during their existence so show you here the Levant has Neanderthal remains along with those earliest modern humans we've got Neanderthals here in the Caucasus we've gotten the under tolls across southern and northern Europe into Spain so Neanderthal existence was across this area but the age of genomics has shown us that bone fragments from sites well into Central Asia contain a similar signature as the genetics of these Western European sites and so Neanderthals as a population we now appreciate as a population is stretched literally from the Altai from Central Asia all the way through Western Eurasia that being said I'm describing to you a population that we now know from genetics and that we previously thought from their lightness on the landscape was extraordinarily thin on the ground that's my friend Steve Churchill's book thin on the ground it's a great description across this entire range at any given time from the now we understand more than 400,000 years ago that Neanderthals originated up to 30,000 years ago when the last Neanderthals lived there were probably never enough Neanderthals to fill a good college football stadium in the u.s. they were a very very sparse population the world was a very different place when they lived in it every one of these sites that I've highlighted here is a site that's given us some genetic evidence from Neanderthals most of this genetic evidence is in the form of mitochondrial DNA sequences I know a lot of you know something about genetics and know about mitochondrial DNA just briefly it's a very small loop of about 16,000 base pairs of DNA that exists outside of the cell's nucleus and is inherited along with the cytoplasm through the maternal line so the the mitochondria in the egg remain along with you the mitochondria in the sperm are actually ejected at the time that eggs are fertilized and so it's inherited along the maternal line that gives us only one piece of the evolutionary trajectory in 1996 when the first mitochondrial DNA sequence was published from Neanderthals it was clearly quite different from the mitochondrial DNA s that that had been found for all humans living in the world today and that data only continued to accumulate right we have now looked at hundreds and hundreds of thousands of people's mitochondrial DNA s we've never found one like the Neanderthal sequences that that we have here and so in 2010 when the first nuclear genetic evidence of Neanderthals was published it came as a surprise to many people that actually humans around the world have a leg see of this Neanderthal nuclear genetic contribution one that marks up to around two to three percent of the genomes of everyone living outside of Africa now and that's an incredible finding that this ancient population that once existed is now gone actually still persists within our genomes today if you consider that for many of you in the room around two to three percent of your genetics comes from Neanderthals this is true of more than six billion people in the world today now everyone outside of sub-saharan Africa sub-saharan African peoples have a trace of Neanderthal DNA but not very much of it outside of sub-saharan Africa is more than six billion people are more than 2 percent Neanderthal that's like having two hundred million Neanderthals walking around the world that is a lot of Neanderthal right Neanderthals today an extinction are more successful than they ever were when they lived and that's the course of our evolutionary history becoming part of the modern human expansion was actually the way that we have preserved the DNA of many ancient populations of people most of which except for the Neanderthals we did not know existed before five years ago so let me give you some perspective on this stuff a because I'm a neanderthal nerd I really love these guys and be because it's helpful to go through a bit of history to help people understand that the sort of questions that we're asking today about Neanderthals and their genetics and their biology are questions that were not possible to conceive of before ten years ago really we were not thinking about things like Neanderthal immune systems Neanderthal digestion you know those sorts of things that are incredibly important in evolutionary terms all that we had were these bones and we've got a lot in the and earth all bones I got to tell you right this is the one of the first to be identified this is the Gibraltar Neanderthal skull from Forbes quarry for Cory was an active Cory that no longer exists it's now the site's gone it was quarried out that's true of a lot of Neanderthal sites this skull found in 1848 was seen by this man Charles Darwin at downe house in Darwin study you can sort of imagine him sort of in his looking-glass here putting the skull underneath of it and looking at it Darwin's been closer to this one than I have as it turns out I've seen lots of Neanderthals but I haven't been to the British Museum where this one is to study it this is the original Neanderthal from felt over cave in Germany it's from a place very near Dusseldorf called the Neander tal which means the Neander Valley and Neander was the Greek afaid name of a guy named Newman who lived in this valley the valley became named for him and so it's the Neander Valley the new man valley and in english this came in before germans changed their spelling and so in german today this is spelled Neanderthal without an H but in the 19th century 1856 when this was found it was Neanderthal with an H pronounced the same way it comes into English and it becomes Neanderthal and so Neanderthal is how its come to us it's part of a partial skeleton from this beautiful place people used to picnic there here's the cave the felt ofer cave which became an industrial quarry to build Dusseldorf and all of this is no longer there in fact if you go to the site now they have rehabilitated this the first time I visited this site there was a chain-link fence around it and a gravel sort of parking lot surrounded by junkyard cars and actual junkyard dogs barking at you it was like an old industrial site you couldn't go anywhere near it there was a beautiful museum across the road some commemorate it but the site was just totally junk they cleaned that up they rehabilitated it the course of doing that they did some minor excavation in the gravel parking lot and found additional pieces of the original skeleton along with pieces of a second individual which was identified as another individual from its mitochondrial sequence in this park you see these little crosses I love these because on one of them in a typical sort of German monumental way you've got the original 300 base pair hypervariable sequence from the mitochondrial DNA that was this this individual which was the first mitochondrial DNA sequence from the anne turtles they've got it there a CTC GE T etc on this concrete thing the data that we have now from one high coverage Neanderthal genome not from this site from the Altai the data that we have now would require a monument ten kilometres across the kind of data that we're working with with ancient DNA now is in some instances as high quality as we can get from living people we know more about Neanderthals genetics than we know about many human populations genetics which is on the one hand a sad statement about our priorities in sequencing human diversity today but on the other hand is an incredible testament to our ability to see into this prehistoric record that did not exist for us it is totally new ok so that's the history of Neanderthals but you guys know Neanderthals from another context and that is the Neanderthal context right when you say man Fred representative Fred from Congress he is such a Neanderthal that means something right it means progressive it means that you're always looking out for the rights of women it means that you're going to spend a lot on health care no it means the opposite of this right Neanderthal means stupid and backwards and of course during the course of our history of looking at them hundred and fifty years of Neanderthals we've been looking at them through a lens of them being the primitive extinct obsolete humans halfway to ape was the way that the first anthropologists encountered them now today we look at this and we say wow you know Neanderthals are a population that is as close to living people as it's possible to be and not be sort of counted among our number right there human and brain size or human and most of their Anatomy they have just a few traits that are distinctive in them they are not halfway to chimpanzee they are really among the human family in most ways but it has been a long course to rehabilitate them from this image of incredibly primitive or comical get fast relief with Evo lotion available in Stone jar of course from the Geico commercials right where it's the joke right of course so stupid a caveman could do it and that image sticks with them it has been my you know sort of privileged in the course of my career to be in places where the Neanderthals walked and where other ancient peoples walked and to think about how they lived and in a way you know to speak for them because they can't speak for themselves and you know until we discovered that actually they're not gone they're still sort of inside of us this was sort of like being the defense attorney for the guilty client you know it's like you've you know you want to say nice things about people but in reality Neanderthals were not grossly mentally incompetent they were incredibly insightful in their way they lived a challenging life with means that most living people probably could not manage and they exhibited sophistication that is under-recognized relative to other primitive peoples who lived at the same time I love this chart because this is Ernst Haeckel who famously drew phylogeny after phylogeny after phylogeny and this one is a great one because here you have Homo sapiens at the top as it usually is and all the other anthropoid ape scumming off the side of this but the direct line that comes up to Homo sapiens this is before any of these fossils had been discovered except for Neanderthals and so he had a place for the missing link he called a Pithecanthropus ape-man allow us because Pithecanthropus was not going to be able to talk he was just going to a lalalala this sort of that was really what Haeckel thought but Neanderthals also were mute in heckles point of view he calls them Homo stupidest and really that is sort of the the template that the 19th century sets for understanding Neanderthals in the 1980s this skeleton was found from Kabara in Israel it is Neanderthal in its affinities you can see there's no skull there but what it does have is a hyoid bone and that hyoid bone like the hyoid from this very early Neanderthal site the Sima de los huesos in Spain is identical in morphology to human hyoid bones so the vocal channel of Neanderthals was like ours different from chimpanzees I'll mention that the Neanderthal Fox to Fox p2 sequence one of these gene sequences that's been implicated as being important for language and development related to language the gene sequence of fox p2 of Neanderthals same as ours but there's some interesting stuff with fox p2 I'll get to it in a little bit this is a manganese dioxide a nodule that is rubbed on because it was used as a crayon by Neanderthals to color things this is a shell this is the one side of the shell and the flip side the opposite side of the shell you can see on one side this shell has natural band of color on the other side it has red ochre pigmentation covering it in the same pattern and these are shells that Neanderthals gathered and strung up bone tools that Neanderthals made cut marks on the distal wing bones of vulture and these are quite common now Neanderthals had a taste for wearing black feathers we find birds that have their feathers systematically removed in multiple Neanderthal sites we also find Eagle talons that Neanderthals have strung and worn and we know from statistical analysis compared to the overall avian fauna including large Raptors the Neanderthals seem to have been biased toward dark-colored ones it's sort of like they were Gogh we don't know really what that means but we know that it's something stylistic we know that Neanderthals were twisting string and making it this is something that we thought was limited to modern humans until very recently we know that Neanderthals were using space in caves in sophisticated ways using specific areas for processing foods for bedding down we find their bedding material in some caves that has been buried over the years but those you know sort of straw and things that are used for bedding leave opal phytoliths in the in the cave sediments so you can tell that that was there we find them transporting raw materials to make stone from to make stone tools from sometimes over hundreds and hundreds of kilometers so they age in rather extensive trading networks so they weren't dumb right and I'll mention that in Gibraltar in the base of Gorham's cave the cave I showed you earlier we have found the first engraving made by Neanderthals this one dating to sometime in MU Starion times before 40,000 years ago and you can see that we've come to call it the hashtag it is what it is right but each of these incisions took a long time deliberately sort of incising at to make we don't know what this represents it's that sort of a crossroads place in the cave and some people think well maybe this is sort of like a diagram a schematic of the cave because it does sort of go this direction or maybe it's something else we don't know what it is we can't reach into their minds and see what they were thinking but what we find is that the more that we look the more that we notice this long tail of behaviors that were rare in the under Tull time so we don't find a lot of but we've found multiple instances of it's from comparing notes with each other that archeologists started to notice the Eagle Talon thing wait you found an Eagle Talon let me look at my Eagle talons wait a minute they're all wrapped around they've all been clearly altered at the bases to be strung up together and we started to notice these things it's by sifting through sediments that you see these traces of the fibers that were twined together to make string we would never found them otherwise it's by finding new ways to analyze sediments that we find the opal phytolith traces of the Neanderthal bedding areas and you start to get at a microscopic level a picture of behavioral complexity that was invisible to us looking otherwise and of course genetics is in one sense the ultimate manifestation of that looking at microscopic evidence no nanoscopic you know invisible evidence from within bones that tell you reams of information so this is my sort of home this is the sample of Neanderthals from crop 'inna which is the largest single assemblage of them and I love this stuff this is what I do some of you guys know I'm working in South Africa now in another sample which is very much like this lots and lots of broken pieces of things and getting information out of them has you know often been incredibly exciting for us it's from samples like this that you see variability even though they're totally broken up it's not like a sample of complete skeletons nonetheless you're finding traces of what this population was like but this bone which is a little fragment of tibia from Vindhya I think I've got Vindhya here yes Vindhya in Croatia it's very near crap you know these two sites less than ten kilometers apart yielded the first nuclear genetic evidence of Neanderthals and together with that bone these two today each of them has given rise to about a 1.2 x coverage Neanderthal genome sequence these were the sequences first published in 2010 when these sequences came out and it became clear that Wow the Neanderthal genome is quite different from ours in lots of ways but it's less different from some people than others this started to send us a message about what we were going to be able to find oh do I want to say anything about this stuff a lot of people talked about red-headed Neanderthals right and maybe the redheads today are they've got that from Neanderthals I know a lot of you have heard this it's probably not usually true today's redheads derive from many different initial founder mutations each of them has been selected in one mostly European but in a couple Central Asian populations and most of them are very recent in fact most of our pigmentation stuff today light pigmentation genes mostly less than 20,000 years old these do not date back to the and at all times but we have a couple that do and it seems that Neanderthals had their own version of red headedness that a couple of people today have so we do have some heritage and pigmentation from Neanderthals I used to give a similar talk and say no it's actually totally different what you think is the same is not the same it's mostly true what you think is the same is not the same when I talk to people about Neanderthal genetics they ask me you be surprised I want to talk to you about my husband you see he has sort of a brow and he's got hair on his back and I think this is Neanderthal I've always very carefully explained to people that's not actually the same morphology we see in Neanderthals right the brow for instance pretty much humans today if you see them having some sort of brow that looks prominent maybe their forehead slopes backwards a bit pretty much that's because of the development of superciliary arches in the centre of your head mostly this is not the case that you have a big knob on the side of your brow that sticks out like this and is continuous across your brow and in the adder tall way mostly this is different morphology and for those of us who are anthropologists who have thought about morphological evolution and how humans today might or might not have been connected to Neanderthals we have these long arguments about whether this is really the same morphology or not are we looking at the same thing or different things I can tell you that mostly the things that you're going to look at at people today that you think are Neanderthal derived or not you look at somebody and says wow that dude looks like a caveman he's not if you look at somebody and say that woman looks like a caveman I would look twice right because because that's non stereotypical you know and and Neanderthal women did indeed have Neanderthal traits and so you know I looked twice but in fact usually it's the case that this is not it's not actually the same but we now know that there are stuff that are the same and it's mostly the stuff you don't expect okay so this is David Reich and David Reich is super super smart and one of the things I like most about him is he doesn't turn to super super sophisticated things until unless it's necessary David has done a lot of analysis of Neanderthal genetics and this is us together in the Altai and David came up with what is really really a very very simple idea the simple idea is if we want to know whether a genome from the past has descendants in the present the way to look at that is to compare different people in the present and ask a very simple question does one of them have more Neanderthal than the other because there are multiple ways that you and me could be like Neanderthals it could be like the redheaded thing right where I think that Neanderthals have this phenotype I know that some people today have this phenotype you have that phenotype maybe your Neanderthal descendant blood type is this way today a lot of you how many guys know that your Oh blood blood type oh right some Neanderthals are blood type oh how many of you guys know that your blood type a alright some Neanderthals are blood type a that polymorphism existed we haven't found in the Anatol yet would be but a you know at least are still are there right does that tell you that if your blood type oh you got that from an O blooded Neanderthal the answer to this is no because in fact when we look at oh and it's phylogeny in human populations oh is heterogeneous there's lots of different types of o because o is a knockout mutation it's a mutation that deactivates the ABO gene and as a consequence of that people who are blood type O actually have many different alleles the most common of these alleles which is which accounts for I think more than 90% of O blood people today the most common of them 0:01 originated we know two and a half million years ago two and a half million years ago there were blood type o things right if you're a blood type O today it could be because you got it from Australopithecus it's not necessarily that you got it from a Neanderthal Neanderthals are your relatives but it may be because you have some distant common ancestor and both of you inherited Oh from that and likewise for a so a particular gene doesn't necessarily tell you much about whether you have some Neanderthal ancestry David's insight was to say across the whole genome actually these things averaged out and if we only have genes in common from our distant common ancestors then these two scenarios should be equally likely it should be equally likely that you are like a Neanderthal for blood type and I'm like a Neanderthal for hair color or you know any other set of things over the whole genome these should average out what we in fact find is that when we compare people outside of sub-saharan Africa with people in sub-saharan Africa and Neanderthals the ones outside of sub-saharan Africa systematically look more Neanderthal like across the whole genome there's this bias the skew and that skew is a signature of mixture populations outside of Africa have mixed with a Neanderthal like population at some time in their evolution a population that was already differentiated from the other ancestors of modern humans this is a big data sort of approach these are from the thousand genomes samples and this is just showing a straightforward chart that is the number of alleles in snip genotypes across the genome that are shared with this Neanderthal sequence and are derived so there's new things that aren't in chimpanzees gorillas etc they're new in humans some humans have an ancestral allele shared with chimps and gorillas etc and some people have a new a mutation a new allele derived allele and here's how many of those people share a derived allele with Neanderthals for sub-saharan African peoples in this dataset it was around six hundred and sixty seven thousand or so for Europeans around six hundred and seventy nine thousand or so and in East Asians it's around six hundred and eighty three or so this is by and large the signature of Neanderthal mixture in human populations you'll notice immediately Europeans have less than Chinese this is puzzling I had to sell it this is really puzzling right Neanderthals didn't live in China they lived in Europe and Europeans have less this tells us something important about our evolutionary history Neandertal genetics are sufficiently accurate as sort of a tracer of ancestry that you can use them to look at admixed populations and get pretty accurate views about where their ancestry came from so these are African American people in the thousand genomes sample and you can see that some of them actually are mostly European and many of them here are skewed a bit more toward the European side in terms of Neanderthal similarity then sub-saharan African people are that's a signature of their admixture during after their emigration to of the Americas likewise for Puerto Ricans Berto Ricans a mixture of European Native American and African ancestry and you can see here they have a little less than Europeans do in terms of Neanderthal ancestry so there it is it's a marker of relationships alright I'm going to skip that stuff and go to this stuff so that's all very cool then also in 2010 something totally unexpected out of left field happen the Mocs font group was working with Russian scientists from the Siberian branch of the Russian Academy of Sciences and sampling systematically bone fragments taken from archaeological sites in the Altai the reason for this is twofold one actually this is a pretty unknown situation in terms of Neanderthals maybe we're going to find populations we didn't expect to find but the other reason is that these caves are extraordinarily cold Denis of a cave that I'm going to describe to you Denis of a cave is year-round temperature five degrees Celsius in the sediments so you're talking about in the deep freeze really you go into this cave and it's like a walk-in refrigerator it's like being in the beer case at the grocery store and and so this is really an ideal preservation environment for ancient DNA and in fact from this one cave we have today the most complete high coverage Neanderthal genome the genome from a toe bone and the genome of another population another population that we didn't know to expect there and when I show you this chart with all the zeros this is because we've looked for admixture of this population with living people and across most of Asia it's only there at a bare trace really a small fraction of 1% ancestry but in Australia and Papua New Guinea it's 5% of the ancestry of the people who live there so you have this ancient population that we didn't know was there that we didn't expect to find that makes up one part in 20 of the genetics of these living people who are 6,000 miles away from the Altai that's a puzzle I've been fortunate to be a guest of the Russian scientists a number of times now at Denis Eva it is a gorgeous place it would remind you of Montana and those of you have heard of Siberia you know it's very cold in the wintertime you know that you gets to minus 40 and that sort of thing and on the Siberian plane it is in fact incredibly harsh in the mountains here this is the low Altai it's not at high altitude but in the mountains it is relatively less harsh the winter temperature is sort of average a bit under minus 20 Celsius so it's a little bit nicer during the Ice Age when the Neanderthals lived there it was actually on average warmer than today there was the warmer season trees and so on are there warmer season mammals are there so this may have been not such a bad place to live it's this bone and I've shown a human one here next to it just to show you what we're looking at we're looking at the distal phalanx of a pinky finger and just the base of it and this line around it is the metathesis this is a growing finger it's from somebody who's not yet adult and from this bone from around 400 milligrams of bone powder has come a high coverage genome of a population that we did not know existed we didn't know it existed because in terms of artifacts this is what we've got right if we look at these artifacts and say what's the difference between layer 11.2 and a layer 11.3 there are some long interesting blade-like tools but aside from that is sort of Neanderthal looking right this is an archaic human populations doing what Neanderthals do more or less and I would be honest with you right I would have expected it would be Neanderthal 's we know that there are Neanderthals in the cave because we found them later okay so let me sketch out first of all a big-picture view because every time we get an ancient genome from from anywhere in the world we start to discover that there were mixtures that we didn't anticipate so let me give you a sketch once upon a time humans who ultimately as modern humans arose in Africa and archaic humans including Neanderthals and Denisovans shared a common ancestor that time seems now to have been approximately 500,000 years ago and I'll show you why we think that in a second after that time those lineages evolved in partial isolation at least for hundreds of thousands of years until ultimately they mixed with each other Denise Evans mixed with the peoples that would ultimately give rise to East Asians and Oceanian and a second mixture from Denise Evans went into East Asians meander tall's mixed with the population that gave rise to all modern humans outside of Africa and probably mixed a second time in order to account for the excess of Neanderthal ancestry in East Asia I will add to this once we knew what to look for some very clever people working on African population genetics including including Joe les chance who is now at Georgia Tech University went looking through African genomes for the signatures of population mixture the concept here was we knew before the Denyce of a genome came out that there was something funky about the genomes of Highland Papua New Guinea people we had some genetic evidence from them looking at them there was this sort of excess of ancientness across their genome when the denisa of a population when the denise of a genome came out you look at that and said oh here's what explains that they had this mixture from a population that was in fact very divergent from modern humans and that accounts for this so once you know what to look for of course you can look at anybody's genome and ask is there some excess of ancientness in it is there this shadow of a population that once existed geneticists have started to call these ghost populations populations whose existence you only know about because of the echoes of mixture that still exists in human populations LaChance found evidence of one ancient African population contributing to Central African pygmies another research group found evidence for a second a African population contributing to southern African peoples so you have within Africa multiple ancient populations which are mixing with each other to a slight degree right with Neanderthals we're talking about three percent at most with Denis Simmons we're talking about five percent in a couple of populations but a fraction of a percent elsewhere with ancient African populations we're talking about a few percent at most and inside the genome of the Denisovans there is a ghost population trace something that's more ancient than Neanderthals are something that contributed to them we don't know what that is it's a ghost population of Asia so again and again and again you've got these different populations that establish themselves geographically widespread that existed for hundreds of thousands of years and during some part of their evolutionary history mixed together to a small fraction this is my chart the field guide to Pleistocene hookups which is another way of putting that all of these ancient people seem to have occasionally interbred with each other and when they came into contact mixed with each other and again and again it's the same story of populations expanding it's growing it's entering a new area it mixes a little bit with the inhabitants subsequent populations have some small fraction of the genomes of these ancient people still in them and then then maybe later on somebody else comes along and covers up the evidence well I want to talk about the covering up the evidence aspect because we now have DNA from Neanderthals this is a mitochondrial phylogeny of Neanderthals and lots of different Neanderthal sites here and what I've highlighted this is from a paper by love Dolan and colleagues from Uppsala and this paper shows that a lot of Neanderthal sequences fall into a fairly closely related clade and a lot of them fall into a sort of a bra under group of clades these are all the young sites in Western Europe these are all the other Neanderthals and here we're sampling across time so these are all as you see earlier sites out in Western Europe and later sites here in US age' and here you've got a lot of later sites in Western Europe so it's like something happened with Neanderthals a group of them picked up and spread across Western Europe we once would have predicted that the earlier Neanderthals in Western Europe were the ancestors of the later Neanderthals in Western Europe we would have interpreted that as a straight line now we know from genetics that it is a more complicated line probably there are lines of descent from earlier to later in Western Europe but there are also significant lines of migration nowhere is this more true than at Sima de los huesos Sima de los huesos is one of the most famous fossil hominid sites in the world it has the largest single collection of hominin fossils found anywhere I know this because now I'm working on the second largest collection found anywhere so we're we're aiming for this we're not going to get there there's at least 33 individuals here and their skeletal representation is pretty complete it's here in northern Spain and it dates to 400,000 years ago this is Juan Luis our swagga who's been working at the site since the early 1980s and is responsible for excavating most of these specimens actually here's the family of the Sima Dilys way so saman ins people debated these for years they're four hundred thousand years old which is earlier than we find evidence of real Neanderthals all the Neanderthal features Neanderthals and so there's this disagreement are these early Neanderthals who hadn't yet evolved Neanderthal features or do they represent an ancestral population that might be more primitive and shared with the ancestors of modern humans maybe these are something likes the common ancestors of modern humans sub-saharan Africans and Neanderthals well it turns out from their genetics that this model is what accounts for them these are early members of the Neanderthal lineage but I'll tell you that and and they are they post state the separation of Neanderthals here and Denis Evans these fossils are four hundred thousand years old we infer that these events must have happened earlier than that and probably for the ancestors of sub-saharan Africans today and Neanderthals and Denisovans we're looking at a date that's something like 700,000 years ago so this is the timeframe we're talking about that means that the population that contributed to Denis events must go back yet further in time than that but as we look at populations like this the Sima de las casas mitochondrial DNA is more similar to the Denis 'van mitochondrial DNA than it is to other Neanderthals these populations we can conclude are successively changing their variation because of successive migrations and mixtures that involve groups of people so these are not static populations that are establishing themselves and remaining as Vicariate populations for hundreds of thousands of years they're actually dynamic populations that are continually being replenished and are evolving their variation over time from some source populations of course in the paleontological record we're not necessarily sampling the sources we sample probably mostly sinks so let me turn to a final topic and that is these crania this is a Neanderthal the most famous Neanderthal of all LaChapelle assents the old man of la Chapelle and this is a modern human the most famous early modern human skill of all chrome and yawn you guys have heard of crow man yawns this is modern humans up until I'm maybe up until yesterday up until 10 years ago we used to think of the crow man yawns who follow the Neanderthals in Europe as the ancestors of today's Europeans right we know what happened then the a turtles were there they became extinct cro-magnon spread they took their place today's Europeans come from them and it wasn't nonsense that we thought that right if you look at this skull you can see this high nasal angle and this face with a really pronounced canine fossa there this divot it's got sort of a somewhat sloping but much more vertical forehead than the Neanderthal you look at this skull and you say wow this is a modern human and moreover a forensic anthropologist looking at this would say well it's sort of European looking it doesn't really look like an african skull it doesn't really look like an asian skull it is to European this must be where today's Europeans came from when they looked at the skulls from this site from Mount Carmel I showed you at the beginning and this site a mood a mood means pillar it's got this pillar of rock outside of it this is just north of the Sea of Galilee here's the amudha skull here's one of the Mount Carmel skulls this is school five this is this is actually aren't at Harvard we do have an American early modern human it's just a short drive away guys so Neanderthals modern human we looked at these and said well these must be the proto crow man yawns this must be where the modern humans came from they emerged from Africa they're here in the Levant a hundred thousand years ago they ultimately get to Europe to replace the Neanderthals after forty thousand years ago tidy story that tidy story is screwed up by this specimen this is from a place called a wasps a wasps a is in Romania and a wast a is a cave and this is a place where in order to get to where the skull and the mandible are you have to swim underwater in the cave and come up so you have to have diving equipment go in there and work two specimens been found there two different individuals this individuals genetics are more neanderthal than any living human he's got between six and ten percent Neanderthal in his ancestry and his Neanderthal unlike yours comes in big chunks big contiguous chromosome chunks of Neanderthal Alois say - this skull had a Neanderthal great-great-great grandparent Oh wasps a walked among the Neanderthals and this skull the earliest modern European around 45,000 years old this skull marks the time that those populations are in contact now there's a problem with that if he's in a population where he could be ten percent Neanderthal why isn't anybody today ten percent Neanderthal where did it go and if he's in a population where his great-great-great grandparents in the and earth all why is it that everybody today looks like our Neanderthal ancestry came in seventy thousand years ago there's an answer to this and it's an answer that we guessed at from morphology here's a feature of the mandible this mandibular foramen Neanderthals typically have a form that's like this that's just bridged over we call it the horizontal oval and when we look at its frequency over time Neanderthals have this really commonly but the first people after Neanderthals had it a lot too and it declines continually up to the present here's another feature of Neanderthals you see it's not an instantaneous drop it's actually a decline what's going on there we now know what's going on when we look at Europe and look at the genetics of people across Europe their genetics today are a very good marker of where they live if you sample people who have four grandparents from Paris for grandparents from Sofia for grandparents from Madrid right this is what you get plot out there genetic variability and it plots on two axes principal component one principal component two and all you have to do is to overlay the map of Europe on this to realize that oh here's Spain here's Portugal here's France here's Switzerland here's Belgium here's Deutschland here's Denmark but it's exactly where you think it should be right humans variation today plots with the map which is why you can send your DNA to 23andme and they'll tell you where your ancestors came from but when we look at ancient people in Europe here's that same map stretched a bit because some West Asian populations are in it when we look at Neolithic people in Europe when we look at Pleistocene people hunter-gatherers in Europe we find that they map completely differently the ancient DNA from these people is no longer represented in today's populations when we look at the mitochondrial sequences in early farmers versus the hunter-gatherers these are the crow man yawns these are people that follow the Neanderthals you see that Wow this is a complete genetic turnover the early farmers of Europe have something like five or ten percent of the genetics of the people that live before them Europe according to ancient DNA is a totally changed continent multiple times so when we look at Europeans today we're looking at the legacy of ancient populations from sources that mix together and those ancient sequences come from populations that don't exist anymore this is what we're getting from ancient DNA and that's sort of the story that I want to end on because when we look at today's Neanderthal ancestry we're looking at something that's been filtered through 40,000 years of population mixtures and movements it's really great to send your DNA to 23andme is on the personal genomics front right it's really great to send in your DNA and they'll tell you how Neanderthal you are but what they're telling you when they do it is how much you're not like the people that came from the same place you've come from and how much genetic transitions of the past have influenced today's genetics we're looking again and again and again at massive genetic events that reflect population growth dispersal cultural changes all of those things that we could look around the world today and see happening have massively affected our populations prehistorically and that's a much more interesting history I think than we expected to have found all right thank you everybody I'm happy to take some questions but I also know that some people probably have to leave so if you have to leave don't feel bad but I'll be happy to stay and answer some questions as well yeah for Denis of it camisa de yes you had to lynnie lineages that were quite separate yeah same side different size so what's going on is that we have Denise abend DNA from one site and we have traces of a Denise event like population that inter breasts that that put in genetics in today's people those are we infer fairly different more different approximately as different as the most divergent living people are from each other so it's like the denise ovens of the past were a structured population which was maybe as diverse as today's African population and the part of it that interbred with modern humans was distinct in some ways from the part that we've sampled from ancient DNA yes given that how much change that you reported at the beginning of your presentation I'm going to guess it's going to continue to accelerate tell me a little bit about the prospects for deepening the reach of DNA to reach these ghost populations or others we are we're limited in part by preservation in the sense that there are only a very small number of sites where the preservation is ideal at most sites the preservation spore we've gotten DNA out of a large number of Neanderthals but for the most part it's not economical with today's technology to do better so we know there's DNA there but it's highly contaminated it's highly broken up into short fragments and it becomes possible to reconstruct a mitochondrial genome because there's a thousand copies of the mitochondrial DNA for every nuclear genome but but beyond that it's cost prohibitive to go further there's DNA there and with better technology we could probably do better the Sima de los huesos DNA which is 400,000 years old is predominantly broken into fragments of less than 40 base pairs and mostly clustered 20 to 30 base pairs so you're looking at really the limits of being able to differentiate a human-like fragment from you know even microbial fragments start to fall into that range so I think that's probably near the upper limit in terms of time depth and it is certainly beyond the upper limit in terms of economics at the moment although as technology improves the economic limit will become probably less important yeah so I wonder if you'd care to speculate on what is the underlying cause of all of these turnover some European populations of less 20,000 years it's a really interesting question and one that gets to where where my lab is really going because the question is what accounts for all is turnover particularly in Europe right partly it's got to be selection driven demographic expansion in recent human populations is you know there's culture that contributes to why some populations grow and you know are better at growth but over this kind of time it's got the cultural traits you can learn right we used to think that maybe people picked up farming technology and it's spread gradually across Europe as some sort of diffusion you know sort of we now know that actually farmers came and people should people can learn how to farm and ultimately those people did mix a bit but there seems to have been a sort of a persistence of this seems to have been true in the Bronze Age you've got these people that move through Europe and they're warriors and they probably kill a lot of people and they take over other places and the genetics of the European population is different after that what drives that well actually people showed up and killed people but also this is when some major selective changes are happening in the in the gene pool of these people you know you've got things like lactase persistence increasing in frequencies so suddenly you can grow your population faster if you're dairying then you would have been able to do otherwise so I think it's a combination of cultural phenomena which are increasingly sort of demographically harmful and an selection and coevolution you know making people better and better suited to these cultural shifts yeah so I mean how do you get selection in these two small dispersed populations I mean isn't that the ideal situation for trade for instance this is the great question right because I used to think a lot about drift and gene flow and there's a problem right in the old days you have the problem of how do we get Neandertal genetics into us if you thought that it was there right many people doubted it was there was just gone I said well you know it doesn't seem very plausible it's gone and we've got these morphological features it seemed to show some gene flow and but how does that actually happen because when you're in small dispersed populations and you're spreading genes even if the gene is driven by selection it takes a darn long time to spread to propagate you know we used to do estimates of this and we could show that if something was selected and this advantage is 1% you could move it across the old world in 800,000 years and it's like that can't work right that that's not what we're looking at I think what we're looking at is that growth happens faster than dispersal and at a certain phase once your populations gotten big enough you just have sort of this hopscotch sort of dispersal when farmers enter Europe is happening because people it's not happening because people are moving like you know next door it's because people eventually their population gets big enough and they move 40 miles down the road and and more they move four hundred miles down the road and you've got this sort of hopscotch effect it's much more like if you want to think what it's like it's not like beach mice you know where you're where you're looking at selection in a gradient it's more like tamarisk where you're looking at the sort of invasive species that hops two different river valleys and there it grows and I think that's what's going on with these populations I think the demography is driving it the advantage of that is that if you have a series of steps where the population really is growing every one of those instances of population growth increases the fixation probability of anything adaptive so it's like that's the only way adaptation can happen in a population where some parts of it are doing that because that's every advantageous thing that's there has a better chance of making it yeah can you tell us anything about changes in into topic relations over the extensive you know that they were alive I mean yeah I know either some degree biological adaptation or is there any evidence of cultural change it's clear that much of the interesting part of the Neanderthal record the cultural stuff is late it is not evident yet whether that's because our record is better late which it is or whether they really got more interesting later and this is a great question for us because of course it it comes to the issue of were those behavioral features that make later Neanderthals interesting something that came from our distant common ancestors with them eight hundred thousand years ago or something like that or is this a case of convergence or cultural transfer you know the some sort of communication the equal talents we now have for more than hundred twenty thousand years ago so that suggests maybe if we look hard enough we'll find more interesting things early so that's a possibility there were different morphological types of Neanderthals and as I look at them today you look at Levantine Neanderthals the stereotype of Neanderthals is that they're sort of short they're thick they've got relatively short limbs they're cold-adapted in Israel they never were in Israel the Neanderthals are tall and they have cranial features that connect them to to European Neanderthals but they're not profoundly European looking the earlier Neanderthals like those from crop 'inna I said early right now we have to include Sima de los huesos they have very few of the classic Neanderthal configuration it's good that that population evolved a lot cropping ax is in many ways a less extremely morphologically differentiated population compared to modern humans and it's 120 thousand years old then 45 50 thousand year old Neanderthals were the classic French Neanderthals are the most weird in that sense so yeah there's a lot of information there in the morphological record that information is not yet there for us in the genetic record I can't yet talk about gene frequencies over space except for mitochondrial frequencies over space all right uh I'll take one more yeah same places in this product in this section of our evolution very little but what has played a big role is sea level as sea level has today sea level is very high it's a high stand compared to what was true for most of our evolutionary history mostly we have sea levels that are 100 metres or more below where they are now and so there are huge areas of some parts of the world that are exposed in the past that today are underwater we actually have fossil evidence from some of those places where people dredging the bottom for gravel have found fossil hominins so there's you know evidence of habitation there they find stone tools quite a lot and we're doing now some parts of the world some underwater archaeology to investigate those past landscapes all right thank you again everyone thank you
