Rapid evolution: Can mutations explain historical events? (John Hawks at CASW 2009)

is on evolution we are delighted to have dr. John Hawkes assistant professor of anthropology at the University of wisconsin-madison and dr. Hawkes hi thanks everybody and I want to sincerely thank the organizers for this invitation it's a really exciting place to talk about what I do and the last talk especially the last part of it was a great introduction to my work because we're using these data that come from microarrays ultimately to talk about the evolution in my case of humans but in the broader sense the evolution of everything understanding genetically how things are connected to genes I'm working at this from sort of the opposite end I don't sequence things in my lab I don't run microarrays I use these data to try to find out what's happened in human history so I'm gonna give you some some cases case studies about what kinds of things have been changing in human evolution I'll try to give you a broad picture of the rate of recent evolution that's been really the focus of my work the last couple of years and also try to touch on some of the things that have really changed about the way that we look at human evolution from the anthropological perspective given what we know today about human genetics all right so those of you who saw the title of my talk can genetics explain historical events you might have thought of maybe the most obvious case of this who is this yeah Rasputin right hi Rasputin's effect on history is a genetic effect and most do you know the story there were these people the star-crossed lovers Alex and Nicky Alex unbeknownst to anybody was a carrier of a rare genetic disorder which just a couple weeks ago was characterized by genetic sampling of the bones of these people and their offspring as a factor 9 hemophilia the son Alexei who would have been Czar where's the Sun there he is right in front the Sun who would have been czar inherited this it's x-linked so that you only have one copy of it if you're a female you're a carrier you don't have the hemophilia but if you have one copy of it as a male you only have one X chromosome so it's not masked so people who carry one copy of it have the hemophilia of course the family consulted with Rasputin who had sort of this odd effect on people there are all these pictures of these Russian tea parties with all of these prim and proper women and then there's one person who doesn't fit I show this in my classes there are four or five of these pictures like this but he had this dispel over Russian women evidently and was a faith healer thought you know you know I could deal with the Tsarevich and of course failed this is one way that genetics have affected history it's not the way that I'm especially focusing on but I think it's a great case because it's in the news Queen Victoria was the originator of this allele it's a very rare kind of hemophilia and they've traced it through the genealogy of her family her scheme of course was to get all of the royal families of Europe to be her descendants so that peace would prevail and she succeeded in this substantially you could see the names of all these royal families of England up here including Kaiser Wilhelm and and her own son the king and the Czar of Russia they're all her descendants right peace did not happen but hemophilia did and it also affected the royal family of Spain where two of the sons we believe were affected by it and two of them died in car crashes leaving the Spanish Succession in doubt and possibly fueling the Spanish Civil War so genetics has a direct effect on history that's the way that individuals affect history I want to talk about the way that broad trends affect history and for this we have to go back in time a little farther and think about the things that we have that are good genetically lots of times when I'm talking about genetics it's always disease this disease that the genes are there to give make you sick they're not there for that they do good things for us too and one of the things they do is to make us into super mutants here's Superman he's from planet Krypton but his milk drinking ability is distinctively European this is something that's widespread in West Eurasian populations it's also widespread in sub-saharan Africa it is in the Arabian Peninsula and we now understand from genetics that there are five different versions of this gene that have been selected in the last 10,000 years within the last 10,000 years milk drinking the ability to do this as adults as opposed to as kids which are all mammals drink milk as kids but to retain this lactase digestion this lactose digestion possibility it's something that's entirely new in our species it's not shared by most people as far as I know Superman does not have any immunity to malaria but many people in sub-saharan Africa have a partial immunity - here's the IDS mosquito that transmits it here's what malaria parasites do to your blood cells it's bad it's the leading disease infectious disease cause of death in the world today it's bad it's so bad that it has two genetic responses to it the most well-known of those is the sickle-cell response it's well known it's in all of our textbooks because it's really good it's bad for you if you have two copies of it it's good for you if you have one copy of it if you live somewhere with malaria if you have one copy of it and you live high altitude it's not necessarily so good so it's a well known case because of this selective balanced but in fact there are probably about two dozen maybe more genetic responses to malaria in sub-saharan Africa and there are other genetic responses in other parts of the world that have historically been high-malaria region this is a cause of more people to which humans have developed defensive falciparum malaria the worst the kind that kills most people today it's only 5,000 years old so we have genetic responses to this disease that have appeared within the last few thousand years this is my daughter she's pretty blue eyes blue eyes are caused by a change in the regulation of a gene called oca2 oca2 ocula cutaneous albinism type 2 it is a known gene because it makes some people in sub-saharan Africa and in the southwest united states albino but it's not a disease that makes you sick it's a disease that regulates pigmentation and there are a number of genes that are part of the pathway to do this OCA to the regular more regulatory mutation that looks like it makes blue eyes we estimate to be about ten thousand years old ten thousand years ago no one on earth had blue eyes okay you guys got Rasputin anybody know who this is I don't think he's grateful for being dead this is Robert the Bruce this is the skull of Robert the Bruce in anthropology I've got to tell you that I interact with people who and I'm one of these people who feel skulls to try to figure out what's going on with them and to make the transition from genetics to to traditional anthropology and back this is quite a challenge I'm gonna try to put these things together for you it to the extent that I can because these are two different ways now that we have of looking at the past the traditional way feeling the skulls leads to a lot of conclusions about what's happening in the recent past in human populations so for example this is a chart of femur length the length of your thigh bone versus time we're here and the in opposition to almost all of my slides here I've got zero at the left side and ten thousand years into the past on the right side you'll see that I make these in a most of the time so that the past starts at the left hand comes to the present at the right what do we got here we've got essentially a chart that's showing no change to the extent that we can see these are the regressions this is a chart that shows brain size in the same population this is the population of southern Africa there's a very tip this is the ancestors of today's sawn populations what's happened to brain size is that it has shrunk and this regression is males and this regressions females it's shrunk over the last few thousand years brains are shrinking southern Africa is in no way unique I could put first because I wanted to make that point to body size brains are shrinking the body is not changing in size and also to make the point that this is worldwide here's rope Europe this is endocranial volume means in males on the top and females next the only disjoint here in this distribution is I don't have a sample of roman-era females to go inside what happened early Upper Paleolithic people people who live 25,000 15 thousand years ago had bigger brains than the ander tall's a lot of you who know anthropology Neanderthals had bigger brains than us it is true Neanderthals did have bigger brains than us but they didn't have bigger brains than the people who followed them in Europe those people's brains were expanding until about 10,000 years ago when they started to shrink the shrinking that's happened since 10,000 years ago they've gone down in males and females by about 150 cubic centimeter if we went down by another 150 we would be Homo erectus size this is a big change the standard deviation in a no cranial volume this measure today the standard deviation and this is about 87 cubic centimeters so we've changed by almost two standard deviations other stuff is h2 here's the thickness of the skull this is a simple you put the yipper on the inside and the outside you measure the thickness thickness has reduced our skulls have gotten more grass I'll and if you study 10,000 or even Bronze Age era European cranium this is Europe you'll notice that they're much more robust looking Robert the Bruce was no exception in his population that was a skull that had some gross disa T to it it coincident with this change in brain size has been a change in a ratio of the length to the breadth this ratio is one that students don't study very much anymore but that used to be what people really knew about humans the cranial index you would go around with a caliper and you measure people and you tell them about themselves oh you're there's a famous part of of on the town where the museum lady is oh your Dalek Oh cranial Selleck it's exactly what this is cranial index bigger cranial indices mean that the heads broader door compared to its length smaller cranial indices mean that it's longer compared to its breadth so the head changes in shape now why do I show you this old-fashioned measure of human variation I'm showing you this to show you that it's changed a lot the heads have gotten broader why have this changed it's probably changed this way I think although I can't prove it because the heads have gotten smaller it's gotten smaller and it's affected the length disproportionately but the interesting thing about it is that in the olden days 150 100 years ago this was the logic of human race differences why did people care about the long heads because it was the invasion of the long heads that it explained the superiority of the Nordic races we don't talk about the Nordic races anymore we don't talk about the invasion this of long heads anymore this didn't happen it's a completely fictitious but the measurements are still there this is something that has changed in recent human populations this change was recognized by Franz Weiden Reich who was known as a great anti-racist in his day but also was the person who studied Peking Man that's why he was famous and this is a chart that shows Sweden and Denmark head indices in two samples Neolithic that's early farmers and modern day and what you've got is a change in the average going from or higher and in the next slide of Swiss it's more evident these are Roman era v to say--the centuries versus 19th century the cranial index changed this is evolutionary change in the skull now when we talk about genetics we can look at genes that have changed in frequency in recent times and infer something about their history when did this mutation happen how fast has it spread that's something that tells us a tremendous amount more information in a sense than this kind of information and yet these people they were buried in the ground at that time so they tell us a kind of information that a genetics can't the challenge the challenge that my lab works on is how do you connect these things oh yes endocranial volume also decreasing in China and teeth are reducing in size recent evolution is real and it's stuff we can see by looking at archaeological samples okay a lot of you know what genes are a few of you I know this is a little outside your range so I just want to give a couple words about how we study genetics today from my point of view this is not the wet lab point of view this is maybe more of an informatics so we've got genes how do we find them what are they how do we look at them but what visual picture should we have when we think of a gene for a lot of us it's this chromosomes and they're real you look at them through an electron microscope there they are this is a genetic map this is showing you the same thing so you just saw chromosomes but here what you've got is a schematic that one two three four many of you may not know that you can see that they're in order the one is biggest and 22 is the smallest because that's how they remembered biggest one number one 2 3 and so on that's why chromosome 1 is one they have these bans on them these are the banding patterns that were originally induced by staining them but I still use them to identify the locations of things on chromosomes if something is linked to the inheritance of one of these bands we say that's the region where it is something like 2q 22.3 and here's a little more detailed genetic map this is what you can get on genome browsers today these are open access you can find them on the Internet you can search for genes I get all of my students do this nowadays here's chromosome 2 we're looking at one little part of chromosome 2 the little red bar there and this is the lactase gene lct the gene that makes lactase it's got reading frames exons and big spaces in between them this is also showing you I want to point out some stuff that we know about genetic samples of humans for one thing we've got the same sequence in chimpanzees and orangutans so this is just showing you that there are overlaps that yes this parts are covered if you wanted to compare them and then we've got single nucleotide polymorphisms those are the snips that you heard about in the last talk these are places where one copy of a gene has one allele and another copy of the gene has a different allele in human populations so single nucleotide polymorphisms most of my inferences today are based on the snips you can click on those and find out information about them - this is really cool and there's a lot of them there's a lot a lot of snips the samples that I'm using are about three and a half million snips genome-wide okay if we zoom out a little bit you can see what's next to lactase and here's lactase here still in the middle highlighted and I wanted to point out this gene next to it MC m6 has nothing to do with milk cell membrane something or other and this arrow is pointing to an intron of the gene that has a mutation in it that makes Europeans drinkable so there it is that's the spot it's an up down stream mutation but it regulates this gene okay now one of the things that we care about in terms of understanding the evolution of these genes is are they neutral or are they selected do they do something that's good that makes people reproduce more it is they increase Fitness or do they do something that evolution from the care about and it could take it or leave it I'm interested in the things that are selected because as you'll see they impact our understanding of the demographic forces in the population how it's changed over time and of course we care about these things they're cool the things that show us the opportunities for adaptation and our lineage in the past but almost everything that we study in terms of these polymorphisms almost everything is neutral that's very convenient because it means that we can use the things that don't do anything to try to understand the things that do so let me give you a schematic of how the evolutionary process works we study changes due to new mutations by linkage linkage is due to the physical connection between polymorphisms in one place and polymorphisms in other places what you discover is that things are inherited together because recombination breaks up chromosomes so that you inherit different parts of them from your mother and from your father they reconnect but every so often across a chromosome that's broken up and recombined so that you have a different new version that contains elements of your father's and elements of your mother's to pass on to your offspring that's recombination all right so what happens if we introduce a new mutation to a sample of g DS well first thing that happens is it's here if it survives and the likelihood of it surviving is not real great it may increase if it increases what happens well notice what's happening is that this copy is increasing and it carries with it the stuff that it's can acted - this is linkage this process we call hitchhiking basically you're starting out with one thing and these other polymorphisms the allele that happened to be on the same chromosome as this one they get replicated along with it they're hitchhiking along toward higher frequency when something gets up to this stage and we have a big sample of people we can notice this you say that hey look everybody who carries this also has this this this this and this whereas if they don't carry that well look some of them have this and some of them have that some of them have this and some of them have that and some if they're all mixed up we can compare the mixing among the people who don't have it to the uniformity among the people who do have it and that tells us something what it tells us is that this thing didn't used to be very common as this proceeds as the evolution continues what you'll notice is that every so often recombination happens and what's out further away than this recombination event now this is no longer exactly the same once it receives all the way to fixation more recombination events happen which you discover is that there's a region of the genome it may be a relatively short or long region depending on how long this takes that's uniform where we don't find polymorphisms very much and then this as you go out further away from it variations increase it's at this stage where we can really find things easily and it's at this stage where we can use the process of recombination to try to figure out how old things are when I say something is ten thousand years old what does that mean it means that I've discovered that there's an area of the genome where people who carry one haplotype one allele are deep operat in variation and the length of that region before recombination is shuffling up the length of that region is consistent with an age of 10,000 years so here's an example of one of these this is from my colleagues Bob Moises and Eric mooing what have they done they've compared people who carry one the yellow copy of the central allele we ask people who carry the other the blue copy this central location is the one that they're studying but then they look at other snips further along the line to see whether they're identical or not this is a measure of homozygosity over space in other words and what you discovered was that people who carry the yellow one are identical there's no variation over a long region whereas people who carry the blue one are substantially mixed over this range this is unusual and it's an inference that this gene reticulan is recently selected you get different patterns for different genes with respect to linkage over distance because some of them like g6pd glucose 6 phosphate deficiency this is the major malaria defense in sub-saharan Africa it's x-linked and it's a little bit bad for you but it's very recent this has probably emerged within the last two or three thousand years versus this one drd4 this is the D for dopamine receptor the 7r allele is an allele that is interesting because it's associated with ADHD in clinical subjects so it gives you a little bit higher likelihood with of having ADHD it looks like it was selected but we'd say a lot longer ago because it extends over less it's our best guess for this is within the last 40,000 years as opposed to within the last 4,000 years so this is giving us a gross picture of the ages of mutations that have been recently selected and it's giving us some picture of what's going on in our evolution here's another way of looking at recent selection this is the geographic distribution a lot of times when we read about selection it's about why populations are different from each other if we assume something about the history of populations how big the populations were how long they've existed then we can predict things about how different they ought to be human populations on average if we compare alleles in Europeans Asians Africans Native Americans because alleles have about a point one chance of being shared within a population versus being separated between populations at point one chance is what statistic we call FST and if we see an FST that's really really really high something like point eight so that's odd this this Gina has this strange Geographic pattern it's really different between regions here's a gene that's like that this is a snip in a gene called slc24a5 here's the derived version of it is the orange here and the ancestral version of it is the blue and this is showing you a pie chart for each of many populations of the frequencies you can see that the ancestral version is a hundred percent in most of East Asia and in most of sub-saharan Africa the derived version is up close to a hundred percent in southern Europe and at high frequencies as far as Western India and Pakistan what's going on with this slc24a5 is the single biggest gene influencing skin pigmentation in europeans this is a light-skinned gene I say a light-skinned gene because there are a lot of them there's as many as a dozen in Europeans and there's a dozen in Asians and they're different for the most part this is one case North Asians have light skin they do not have light skin by the mechanism of slc24a5 they oh I wanted to put this one up here to show you that in order to identify selection this way you sort of really have to have the mutation that causes it or at least one that's very very tightly linked to it because here's a snip also in slc24a5 but just a little bit downstream and you can see that this snip doesn't have the same extreme geographic differences does have a geographic difference they're not as extreme it's the selected things that have this really odd difference in this case all right this gene I'm gonna show you this is a snip in mc1r mc1r is the redhead gene but this allele doesn't make you red-headed this is a functional mutation that probably although the the mechanism isn't known probably makes lighter skin pigmentation in East Asians I say probably because it's selected it's recent and is a very different between populations Europeans who have red hair have different functional mutations and there are three of them that are correlated with red hair in Europe so here's one gene different alleles in different places all of them probably selected from a pigmentation variation this is interesting our species is evolving like crazy in pigmentation in different ways in different populations presumably because of the same underlying selection pressures and there's sort of a more this is this is so cool and yet so old-school how would you really want to know how things changed in the recent history well the way that you really want to know is to dig up bodies and see what their alleles are and of course we're able to do that now to a substantial extent so here's a chart that's this is a map of basically Europe these green shaded areas are areas of early agriculture this is from a paper came out about a month ago not from my lab from Ramon T and colleagues and I wanted to show this to you because it's so so interesting what they've done is they've sampled the ancient mitochondrial haplotypes of people and these these bubbles show you where they sampled and the number of samples that they had they sampled early farmers people buried in early Neolithic contexts and hunter-gatherers who lived there right before the early farmers and modern people who live there now what they just covered is that the early farmers don't look like the hunter-gatherers hunter-gatherers are mainly half a group you early farmers have a very low you and high frequency of n well that's interesting it means that agriculture as it came into Europe was bringing new people into Europe with it it was not being adopted by the people were there before but the other cool thing is that these Neolithic people with their high frequency of n today and is virtually absent in Europe these Neolithic people aren't today's Europeans either so you've had two population changes now how does this happen that processes that we could be competing with each other to explain this a migration people picked up they brought their farming with them they put down and then later on some other people picked up and came in plunked down and you've got selection the farmers came in maybe they were bringing new genes maybe not but some new gene works in that context and then later on the new gene didn't work anymore or a different one work better and so you have a genetic replacement as a consequence of Fitness whose consequence of reproduction this is my job to try to sort these out I would say I've sorted this out yet but I'll tell you the dynamics that that underlie it for example what do you have a new mutation one of the things about it is that it if it's selected increases extraordinarily slowly for a long time our best estimate of the age of the lactase version in Europeans is about eight thousand years old five thousand years ago these early Neolithic skulls are skeletons the ones that were genetically sampled they don't have it it's not found in them so about five thousand years ago introduction of Agriculture into Europe is not there that's exactly what we expect it takes a long time for this to get to any substantial frequency and if you sample twenty five thirty maybe fifty people from that time you're not going to find it today this is about 80 percent in parts of Northern Europe which means that the number of lactase intolerant people is about a square of 20 percent or about 4 percent in northern Europe that's about right it means that 80% of today's Northern Europeans 80% of the population of Germany got this gene from one person who lived 8,000 years ago what's the population of Germany something like 60 million right so say 80 percent of the hundred and 20 million copies of lactase in Germany now came from this one person but I'll tell you something else about this and something that's very interesting is that there's 40 million copies of this gene floating around in Germany now that are descended from the people who had the non tolerant version there were not 40 million of those genes 5,000 years ago there probably weren't 10 million of those genes so both versions of this have undergone a massive increase in population one more than the other ones gone from zero up to 80 percent the other ones gone from not very many to many all right so a kind of thing we can look at is if we look genome-wide and ask how many of these things are there that look like they've increased in frequency a lot lately how many it looks like about 3000 a lot of them different populations just art is showing a blip for every one that we found that has this signature where it's it's a linkage disequilibrium signature and a couple of things these little lines these are chromosomes each block and these little lines are showing different samples Europeans Chinese Japanese and Yoruba those are the major hapmap samples and what you discover is that sometimes they're shared you see a lot of them they're shared sometimes they're not different ones in different populations that's a clue of what's going on the other thing is that the sheer number of them when I started this work in 2006 nobody thought this was unusual well 3,000 gene under selection no who knows how many should there be the 3,000 genes under selection let me tell you there are 40,000 amino acid changes between humans and chimpanzees and probably only about 12 thousands of those were selected so what we're saying is that 1/4 of the potential differences between humans and chimps are underway now in the human population that's like 3 million years of evolution packed into the last 20,000 years that's crazy so I got interested in this what's going on obvious kind of answer for what's going on is to look at what's happened to the human population the recent times and the number one thing that's happened to our population of global cities is that we've increased in numbers that increase was mainly Neolithic at post agricultural and later so looking at this Neolithic time period we might expect that there would be some really interesting stuff genetically this is a time when people are changing their environment after all they're adopting new foods they're living in cities for the first time they're expanding to new places where people never lived before but also there's just a lot more of them but population increase didn't start then started earlier we know that archaeologically we do things like this is sort of silly stuff like we measure the size of tortoises but the thing is that people eat tortoises and the more tortoises that people eat the less old the tortoises get and so what you find is that when the population grows you get a lot of little tortoises and here you can see the tortoise size declining as we go forward in time and people broaden their diet so archaeologically if we know that populations were growing before agriculture and of course this is the major explanation for why people invent agriculture population pressure they've got to find new foods so if we look at a schematic of how the populations been growing it's been growing gradually at least for a long time certainly after the expansion of modern humans the African population was always quite a lot larger than populations outside of Africa until the Neolithic when things sort of reversed for a while because agriculture is invented in primary centers in China West Asia ultimately the new world Africa gets agriculture a little later but then it does exceed him quite rapidly I wasn't the first person to think of this and how could I be but Darwin had actually written about population size and with Darwin it's always about the pigeons he's got these pigeons that have feathers on their feet and all kinds of weird things and they like those pigeons in 19th century England they compete fairs the can still find them at the State Fair now right you've got these crazy pigeons well everyone says how do you get the best animals well there's one thing I know this is Darwin you have to have a lot of them if you're waiting for these weird things you've got to have a lot of animals because these kinds of variations occur rarely Darwin didn't understand mutation they didn't know about the mechanism of inheritance but he understood that if you want to see rare things you don't have a lot of them and are a Fisher wrote about this in the 1930s Fisher this was directly about a constraint on the process of evolution Fisher was arguing with Sewell right they both together with Haldane develop population genetics they had a fundamental disagreement how important are random changes right thought that random changes were very important Fisher thought they were unimportant today random changes are most of what we talk about when you talk about molecular distances between species almost all random changes but Fisher wanted to focus on those things that were functional that made difference he said as you get better and better adapted to your current environment the possibility of adaptive mutations should get less and less because the chance that you're going to get closer to the optimum from some change it's less as you get closer to it so for Fisher this became a thing that would be complicated by population numbers the more individuals you had the better chance you would have to have an adaptive mutant we sort of dug this up and develop some math to describe how the number of favorable mutations should respond to population growth in humans and this is the pattern expected to see based on human population growth let me just explain what's going on here more than thirty thousand years ago the population was small so there were a few favorably mutation for that reason the other thing is that the ones that have happened if they're very good they'd have already spread through most of the population as you go up toward the Neolithic you're seeing a lot lot lot more of them until you get to some peak and why does it fall here falls here because there's a limit to our ability to see stuff we know that recently every so often we find them there are mutations that have really cool effects and we can't assess now whether they're Fitness bearing mute effects necessarily but there are things like a mutation and Limone su Garda Italy that made people relatively much less likely to get cardiovascular disease you go to this village and see the only old people buried in the cemetery and they went to discover and they said well there's this mutation they're all descended from this person that migrated to the village in say 1700s that's an example of a really recent mutation we don't know whether it made people have more kids and that's the thing is that when we get up here to more recent times we'll never know they're too recent for us to judge their evolutionary impact and our power to see their impact declines as we go up toward the product so what we've got here is a chart that predicts not what there should be but what we should be able to see it's an ascertain McCart when we plotted this chart against the data we've Bend we said let's find all the things that that we can find let's make an estimate of their age and see how many of them fall into these age intervals this is no this is simulation data don't don't give me that kind of credit we we simulated this a bunch of times to see if we got the expected answer right and this this is what it ought to sort of look like yeah wow I thought wow too but this is what the data actually look like these are binned snips that we infer to be connected links to things under recent selection in two populations the red is the Yoruba West Africans and the blue here is the CEU these are Utah people but inferred to be Northern Europe and you can see that they both have that pattern that we expect to see and that's that's encouraging but the other thing is that there's a couple of demographic details that that reflect what actually happened that it sort of lead lend to the sense that this is actually telling us what was going on one is that you can see there's a bunch more here in Africa the African population was always bigger until you get up to about 8,000 years ago where you have a later peak in Europe this is the early animalistic population spike we would interpret in Europe so it looks like this is what's going on but a natural question and and furthermore the yeah I want to explain that slide because it's easier to explain this way furthermore the thing is that if you count there's a bunch of things now if things were always happening at the same rate if there were almost three thousand things proceeding to fixation in the human population then if you compared us to chimpanzees there should be many millions of things six million things there aren't there are only maybe twelve thousand things that separate us from chimps and amino acid substitutions and if we count non-coding substitutions regulatory mutations and things that we were less able to see now maybe there's double that number maybe triple that number it's not six million so on that basis alone we'd say look this is consistent with our explanation the demographic forces have increased the number of mutations this is this leads to a nice picture if you just the number of years involved in the last forty thousand versus the humor chimp divergence was on the order of five million years ago you can see that that's a tiny fraction of the time it's a huge fraction of adaptive changes if we just measured this time and said how many adaptive changes is this how many would we expect we'd say that the number of adaptive changes that separate us from australopith eCos is probably around the number that have happened in the last 40,000 years that's huge we can sort of categorize what's going on and if there's things that you expect neuronal function for instance you say well ok the brains are changing why are the brains changing we saw that the brain size was changing we don't know how that connects genetically but evidently there's something going on with our brains protein metabolism this is primarily dietary not lactase that's sugar metabolism but other kinds of dietary things DNA metabolism this may be related to aging reproduction sperm sperm are crazy on this I don't know what's going on sperm let me give you some concrete examples this this is the distribution of the null allele at the Duffy blood group locus Duffy is one of those blood types they don't test you for because it doesn't cause a problem with transfusions but it does lead to rare incompatibilities when they found it around the time of the Korean War led to rare very rare incompatibilities and transfusions so they characterized it today we understand that like there's a three allele system and one the null allele the O equivalent is very common up to 95 percent here in West sub-saharan Africa it's very rare other parts of central this is one of the big genetic differences between populations now W we know makes you almost immune to vivax malaria and when we talk about how genes affect history here's a population that has an allele we infer to be something like 30,000 years old vivax malaria her to be around 35,000 years old so it was a rapid and effective mutation the places where Duffy is high-frequency today don't have significant vivex problem vivax is the most common malaria in Thailand you know this it's it's a malaria that's major in the Mediterranean Basin it's not here it's not here because the people don't get it falciparum malaria is taking its place you can't you can run as fast as you want to genetically but you can't keep up with the pathogens but what we're seeing is that a real effect on history there are complexities involved in this and I'm gonna sort of talk about how hard this is because when I talk about what the genes do and I the last talk sort of went through categorization what the genes do you have to understand that cases like vivax or these cases like duffy are very rare that we really really know what the gene does and if we have any experimental data on how it relates to disease pathogens diet whatever people are exploring this stuff now this is a paper that came out last week and I think it's interesting because these guys are looking for genes that explain blood measurable variables like like the number of platelets you know really gross we measured this stuff what they found is one region that has two snips that are very tightly linked across eight hundred kilobases which means that they're selected this haplotype that carries these is about 30% in Europe I'll show you a map in a second it looks like it's two thousand years old give or take so it's a new haplotype it's selected it explains platelet count for some snips in this area I'm showing you this slide to show you how complicated this is because what we've got is an area it's an area that stretches over some distance there are snips in it that show up if you put them on patient with case control studies they show up as loaded on cases so you're saying that these snips in this area are candidates as causative snips for platelet count for coronary artery disease for type 1 diabetes which is autoimmune for celiac which is autoimmune so you're saying that these are things that we think are connected why all these things connected in the same area because they're late it's the linkage that makes them connect we don't know which one causes it if any or if there's some combination here that causes it furthermore look at all the genes that are in this region I want to show you the next slide that has a closed set but on genes here all the genes when I say that the the more or less have to do with these categories understand that in some cases you get something like this where the selected haplotype in here could be anything having to do with alcohol metabolism aldh2 is a good candidate for this there's brca1 associated protein over there there's other things that are involved in in cell metabolism who knows coming from the informatics end saying we found this area that has something interesting in it and that area is loaded on disease relevant traits we still don't know what happened but it helps somewhat to know where it happened here's this snip that is tightly linked to the selected haplotype here's this geographic distribution what's going on with this the hypothesis predicted in their paper and I think it's probably been is that there's something immune related some pathogen if I had to throw out a guess as to which pathogen it would be it's probably smallpox but that's just a guess how do you connect these things I've been working on trying to connect these things by focusing on well-understood metabolic processes I'll give you an example hearing we know of a lot of syndrome ik hearing loss disorders that there's a mutation it causes deafness so we know that genes that are related to building the cells of the inner ear that receive sound hair cells that's convenient because this is a well understood system we know how they're connected to each other and it's an old system these have been receiving sounds since early vertebrate days so they've functionally sort of worn in a groove we know what these things are doing here's a hair on top of one of those hair cells yeah I'd get no credit for any of these pictures but they're cool here's another thing a separate part of the hair cell system is that the hairs are embedded in this basilar membrane there's another membrane at the top of them called the tectorial membrane maybe that they receive sound is that when the hair cells are touching this it vibrates and they pick up an electrical signal so that's the way that hearing hands but there are mutations essential to building this membrane that if they rupture this is a mouse ear if they rupture they the membranes don't make contact and there's deafness for that mechanism so we know what these genes are here's a list of recently selected genes that are in this category things that involve hearing and in particular the hair cells of the inner ear in that system so this is reason why I focused on it is that when we make a list of stuff that we think is selected these things pop out as very highly loaded this is a high proportion of genes involved in this system we still know what they do we've got some hints I want to focus on PCD age 15 partly because we know pretty well what it does it makes these little links between the the cilia the the fibers that make up the stereocilia and we know a lot about his geographic distribution here's a gene that's strongly selected in East Asians in the last 10,000 years why I don't know we could throw out some hypotheses maybe this is about tone languages that's a hypothesis maybe it's about it's something that would have been adaptive 40,000 years ago but didn't happen a lot of my things are like that 40,000 years ago it would have been better to have these stereocilia different but it didn't happen because we're looking at rare adaptive changes but we're catching up so that when the population grows to a critical level with the Neolithic population sizes you happen to get these good things once in a while and they happen in some populations and not others which is why we have these pigment variants that are different in different populations happen in Europe didn't happen in Asia the other one happened in Asia this really comes back when I was starting in my PhD program I was taught by Frank Livingstone who was one of the people who really started to understand the malaria connection what genes are adaptive in the case of malaria the thalassemia is the sickle cell and I asked him one day Frank it looks like hemoglobin e which today is common in Thailand looks like hemoglobin E is just better than sickle cell and C and all these things they have in sub-saharan Africa it doesn't kill people when your home was I go why didn't the Africans get hemoglobin E and he said didn't happen there and that's really the message of how we're looking at this now we've got hits they happened because of changes but they're all building into a picture of recent rapid demographic changes and when we look at the lactase example these are changes that contribute to the growth of populations lactase the digestive allele grew faster than the non digestive allele that didn't happen by the lactase drink the milk drinker is killing off the other people it happened because they had more kids so the population grew faster than would have without lactase so the populations that had lactase grew faster than the populations who didn't okay I'm gonna stop there so that we have a few minutes for questions oh just shout anteye selective Oso forces how does this deal with aging today we live a long time yeah it doesn't make any difference at all this stuff that makes you immune to cardiovascular disease when you're 70 it doesn't make a bit of difference to fitness the stuff that makes you more likely to reproduce when you're 16 it might make a difference if it doesn't compromise reproduction later there's stuff that one of the things with cancers is that you get these mutations that sort of occur in pulses early in life and then later they have manifestations so maybe a cell cycle regulate regulatory gene might improve your early life in ways that affect your later life but yeah this is highly loaded on stuff that the things that we're studying with selection highly on stuff that make a difference to whether you have kids and make a difference to whether you survive pathogens and other mortality causes early in life yeah let me give you a Bic answer because my my usual answer to this would be to google and find out but the quick answer is we know a lot about one that does it in Europe of the ccr5 Delta 32 mutation which is an HIV resistance mutation but it's not there for that reason it's there because in medieval times people were able to do so when we look at new stuff we come down to this problem how do we tell if it's making a difference today in genomics I think this is a real frontier of here's some new things they were never selected before but today they make a difference how do you find them once in a while you're lucky and it's something that happened to be selected before Delta 32 is a good example that happened to be selected before today it makes a difference but the whole principle of the hapmap do why have they gone from the hapmap to this to the thousand genomes because the hapmap failed its failure was more or less preordained I mean the idea was that by sampling a few hundred people you were going to find common mutations that correlate with disease I've got to tell you any evolutionary biologist could tell you that common mutations that correlate with disease should not happen how do they get to be common if they kill you yeah once in a while they do something good at the same time right so once in a while like sickle-cell you get something that gets up to some substantial frequency and it happens to have a good effect and we find some of those it's a great credit to to the humanity I guess that we've evolved so fast and have long linkage blocks that happen to correlate with things but it shouldn't have worked so the thousand genomes has the promise of finding these new rare variants that aren't widely shared but might have happened multiple times but it's gonna take a lot more than a thousand people to find this so just take tens of thousands maybe of thousands of people to find these things that load on diseases because of shared mutations that are recent I I had a question yeah you correlated shrinkage and skull skies with shrinkage in brain size couldn't the brain just be folding more I mean oh so so yeah I didn't I didn't go into the detail that I that I might if I was teaching undergraduates right but well because they always give the best answer so I asked them why is the brain shrinking and of course the number one answer we don't need it anymore we what do we need these brains for yeah we've got iPods this is so so yeah we don't know yeah the fundamental principle is that maybe I'll give you the hopeful explanation the explanation I think on my good days I say here's what's going on with brain shrinking what's going on is we're not on our way to back to Homo erectus times we're actually getting more efficient big brains are bad because they're energetic this is like a 20 watt light bulb on your head all the time and in the context of your energy budget that's that's a lot so if you're living in a famine prone population as all early Neolithic populations were the best thing to do is to have small brains besides which small brains developed faster so if you want to reproduce when you're 16 17 18 years old the best way to do it is not still be growing your brain when you're 16 17 years old so for all those reasons say that efficiency demands that the brain should be smaller and if you could find a way to do it in a smaller space that would be highly selective so maybe we've gotten better with smaller brains but I gotta tell you that maybe we're getting dumber how do we know right I say on a good day I think we're getting more efficient on a bad day I say this idiocracy we're on our way on that very positive note thank you dr. Hawks is going to be around on campus over the next couple of days he'll be at lunch so if

Channel: The University of Texas at Austin

Views: 30,699

Rating: 4.6983604 out of 5

Keywords: bone, tooth, genetics, archeology, human, DNA, Neandertal, genome, evolution, nomad, evolve, population growth, mutations, John Hawks, CASW, NASW, UT, Longhorn, University of Texas at Austin

Id: CUo6cop4vXg

Length: 59min 7sec (3547 seconds)

Published: Tue Nov 03 2009