7. Behavioral Genetics II

[Music] Stanford University something incredibly cool I just found out about yesterday which oh I wish I had known about like two days ago but still it's useful you remember those Siberian foxes and that amazing thing you breed them for tameness purely on a behavioral trait and come back like 30 Generations later and they look like puppies they have the short muzzles and The big Roundy eyes and the cute ears and they wag their tails and all of that punchline there being number one Evolution can move really fast number two in some interesting mysterious way if

you are selecting for certain behavioral traits in this case one where you like being around humans and are all cuddly with them what you're also going to select for a whole bunch of traits that are associated with baby wolves in terms of physical appearance turns out There's a flip side of this going on right now with what are known as Metro dogs which are dogs that live in the subway system in Moscow and I don't know but they live in there and a whole deal is made out of the number of them which get on

subways and know which stops they're going to and there's an entire website devoted to Metro dogs which are in Russian but it has lots of nice pictures but what they're seeing there is that These are dogs who essentially have been feral and in feral packs for decades and decades and what have they been being selected for being able to scr being in fact quite scared of humans a lot of the time staying far from them whenever possible because they are raiding garbage cans who knows what and what they're seeing in the Metro dogs is about

30 Generations into it now their tails are looking more like the tails you see on wolves their muzzles are Getting longer their coat patterns are beginning to get less fancy and distinctive from all the different strains of dogs these guys are being selected for the exact same traits that went into being wolves so really interesting demonstration again these guys are not surviving because they've got a different shaped tail it's just part of the package if you were going to have this canine like thing and be selected for being scared of humans fun In and packed

having a fairly aggressive temperament you're going to wind up looking like a wolf after a while same deal again very rapidly so unexpectedly Russia turns out to be the motherland of all sorts of interesting things with puppies and puppies in the past and puppies in the future and all of that so that's wonderful okay however I don't have any pictures of them that I've brought today but go to www.metro doog do edu and see what they Have to say Okay so picking up on Monday's lecture I recognized Monday's lecture was probably the first one officially

to be able to blow half of you guys out of the water because it was really tough material Not only was it as promised yet another disciplinary jump but it was a first wave at a lot of material that went by fairly fast and a lot of it quite subtle what are the things that focus on in there what did we cover Monday that's critical Behavior Genetics as an overall approach is not doing the constructing an evolutionary story who's got the best story we win it's not molecular genetics looking at evolutionary change driven by actual

mutations down at the molecular level instead it's looking for patterns of behavior that go along with relatedness what we saw was the most completely useful use less version was well here's a trait that runs in a family and it runs in a family more the more related The individuals are completely use useless bringing in the first of the problems that we're going to have non-stop in the subject ruling out different environments we saw a number of the classic approaches they have which is studying monozygotic versus dizygotic twins studying adopted individuals or studying the gold standard

of identical twins separated at Birth adopted and then brought back together again and in each one of those Cases that's explaining some degree of the confusion eliminating some of the environment but over and over and over again this problem of environments are sneaking in all sorts of interesting ways adoption is non-random in terms of where placement occurs all sorts of stuff like that making it harder to tell what we then transitioned to was dealing with the most interestes realm of environment having influences which is this whole world of prenatal environment And environmental effects there one

version of it being this whole new field fetal origins of adult disease the fact that early events fetal environmental events can have lifelong consequences even multigenerational as we saw and people are understanding the nuts and bolts of how that might work that epigenetic stuff so we saw that as one a very subtle realm of environment slipping in and we also saw examples where environment could be occurring Within an hour of birth and where environment is occurring despite seemingly like similar things like the number of math classes you take environment being very critical what we also

saw just to make life a whole lot Messier and more complicated was violating the rule we have all known since infancy which is you get equal genetic input from each parent the business about mod mondria coming from your mother the business about as we saw A more subtle version of it the same equal input of genes perhaps but the regulatory control is much more coming from the mother by way of the transcription factors all of that and the cytool of the egg sperm having nothing interesting going on from a cell biology level the egg having

all of this and where you can even get something as nutty as inheritance of an acquired trait Marian Evolution okay so that was plowing through all of that and I'm Fairly certain that reviewing the last two hours in these last 3 minutes has not put anybody back in the water who was blown out of the water but so go to sections this is difficult material and it's going to get worse today okay this is hard material and make sure you read the extended notes because there's a fighting chance that will be more coherent in the

lecture okay so we got to the point last time around of seeing that okay prenatal effects the last Thing we focused on was actual nuts and bolts of it epigenetics all of that now we transition to what became the much more modern exciting version of behavior genetics unless you happen to have yourself hundreds of pairs of identical twins separated birth which is to go and actually find the gene finally beginning to bring together to marry the classical Behavior genetics approaches with molecular biology and it was starting around the ' 80s or so that people began

To be able to work in actual molecular techniques into this whole field and it started off in a very primitive way and has gotten much better since then the version that you can start off with is you know something about the trait or as we're really saying here you know something about that there are differences in the trade among different individuals and now you go looking for the gene how do you do that the first classical way of doing that is that you Actually have an observable difference in two individuals and two populations and two

branches of the same family a difference in an external manifestation of what's going on with genes a difference in phenotype appearance Behavior some such thing and what you then do is you use that approach to try to then find genetic differences you get a whole bunch of examples of folks with one version a whole bunch of folks with another version and you start looking For where the differences are slightly more constrained version you don't actually have the phenotype you are not looking at ey color you are not looking at how wrinkly somebody's face is you

are not looking at behavioral traits you're not looking at anything external the next sort of more focused step is now you're looking at Pro proteins what some proteins do here's some enzyme that turns this into that and there's two different ways the enzyme could do it or Two different variants on it and now we got this bunch of people where we take their blood and look and they've got this variant these guys have this version of how the protein goes about its business can we find the genetic difference next step down next step more frustrating

when you can't see external differences that you're tracking there's no phenotypic difference that you've got to work with where you don't know what the protein does what its function is Next lower rent version is to look at the same protein that comes in slightly different sizes because that's usually a hint that there are different functions the way the protein works is going to differ and somewhere along the way there you came up with one version by having some insertion mutation or deletion or some such thing you don't know what the protein does and you certainly

don't know what that does in terms of the individual's appearance Behavior Phenotype but at least you got something to work with there so what it is you're using as your starting point easiest external signs next is what would be called intermediate physiological end points intermediate it's something functional but it's not functional like how the person functions it's functional like how an individual protein functions and then if you're up the creek with that at least hopefully going for differences in the size of the protein The electrical charge of the protein for non-chemistry types how this version

of the protein interacts with a water environment versus how that version you don't know what the protein does but at least you got something to work with you got a difference and in all of these cases the strategy is to then see what are the gene differen that go along with it primitive initial version would be as follows you've got for example in this case you were trying to find the gene For some disease and this is where the whole field started because it was a lot easier to go after a disease either you have

it or you don't if you pick the right kind of awful disease rather than going on a phenotype like television taste that one's going to be a lot harder to find the gene for the whole field started instead looking at extremes of really Major League you got it or you don't have it diseases so you've got this family that has this Disease running in the family PKU fenal ketura for example or Huntington's disease or cystic fibrosis these were some of the first ones to go and what you now do is you got the big family

and what you want ideally is a big huge family where about half the people have the disease and half don't and the initial way the whole approach would be done was you get blood samples from everybody there and you start sifting through everybody's DNA and you're Looking for a stretch of DNA that everybody with a disease hasn't common and that none of the relatives without the disease have and what you've got at that point is what would be called a gentic marker because doing it this way you're just sifting through a hay stack you're just

trying to pick up big crude patterns the difference that you wind up seeing between these two populations of relatives almost certainly in fact as far as I know never once with this Approach had you just found the individual Gene you found a stretch of DNA that's got 10 20 30 genes in there but somewhere in that stretch is the interesting one so at least you have a genetic marker here you know the genetic neighborhood where the difference occurs so this was at one point Cutting Edge a technique called rflps restriction fragment link polymorphisms do not

write that down and this technique was incredibly slick at some point early on And it is not easily done because you are dumping 20,000 puzzle pieces over here and 20,000 there and you're looking for the one difference between the two that's otherwise identical it's that sort of task nonetheless using the that approach people began to get disease markers where they got the stretch of DNA that contained a whole bunch of genes and who knows what else but at least the candidate Gene the gene that Was floating around that was responsible for this disease was somewhere

in the stretch of DNA at that point what would be done is a number of things first is people would obsessively obsessively check their statistics to see just how certain they are that this is the genetic marker for this disease because you are soon going to be advising people whether to terminate pregnancies based on genetic tests like those this is an area where More stringent rules were imposed before you announc you think you know how the universe works with respect to this disease really really major room for things going wrong in terms of it being

then applied clinically so first big demand would be you really have to be much more certain a much more demanding field than lots of others in biology Next Issue would be this uh bioethics problem which is you got somebody from one of these families who may or may not Have the disease this is a disease that doesn't get you until age whatever and you're younger than that and this immediately exploded this whole issue for the first time should people get tested if they have the genetic marker for that disease if they are a candidate for

it and this opened up a whole world of confusion about this where a key feature of these debates was the fact that you haven't gotten the gene you've just gotten a candidate stretch of DNA And there remains a very small statistical chance that you've got the wrong one for a bunch of reasons there's that possibility so do you let somebody take a test can people tell the difference between a yes and no and a statistical probability what do you do if it's a disease where the person has just spent their last 10 years watching their

parents slowly die from it and there's no cure for it and it's absolutely horrible do you give them a Test that is if the bad outcome is going to throw them off the top of a building with a high likelihood enormously complex bioethics issue the third challenge though was to step up the science from just having the stretch of DNA with a bunch of genes in there to actually find the gene and in the years since the molecular biology has gotten much much better at moving past finding a genetic marker we are 99.9% certain that

the gene that's relevant is Somewhere in the stretch to finding the actual Gene and then being able to see what's the difference in it between them and them what's the difference down to base pairs where is the mutation where's the difference coming from that's the world of sequencing genomes now that's where the field is at so that has been enormously powerful in terms of potentially finding one single Gene but everything that came through in the molecular lectures last week should be Pointing out there's not a whole lot going on in there that revolves around one

single Gene at a time so a whole bunch of really horrible diseases yeah one gene single mutation but most of what goes wrong if you want to start understanding the genetics of psychiatric disorders of diabetes of early of late onset dementias things of that sort it's not going to be just one gene so the next huge advance in the field was being able to do searches like These for multiple genes one thing that has been used is a technique called microarrays Gene microarrays and they were basically invented here on campus by a guy over in

the mid School named Pat Brown who is already very famous for having done this and I suspect has all sorts of interesting Awards coming for him down the line This spectacular technique you take what is now called a gene chip and through techniques that are absolutely boggling and make me feel Queasy what you somehow manage to do is you get all the copies of RNA that could be made in a Cell from this individual if you are completely new to this and you've managed to get in this far without having to think about what RNA

is ignore it this is just sort of a subtle detail for people who are interested in this what you do is you get a copy of each type of RNA made in a Cell you force the cell basically to transcribe all of the pro all of the Genes that has and then you get this little chip and you basically glue the end of each one of these rnas to it and you will have a chip with 20,000 of these little things and then you use probes which will allow you to see which versions of 20,00

thousands of those genes are different than this individual from that individual totally boggling has forced an entire new world of trying to analyze data this new field of bioinformatics because you're not Looking at one gene at a time you're looking at patterns and that becomes a lot harder that becomes incredibly important because again it's all sorts of the interesting stuff where it's not going to be one gene it's a dozen it's a hundred so that has been one challenging approach another is a technique called qtl's quantitative trait Losi what that basically is built around that

if you have subtle enough of tests you could Figure out this is a complex trait that is modulated by two genes or by three or by 17 you could see all of this going in the direction from techniques that would let you know your kind of in the neighborhood of a gene to actually identifying a gene that differs between the two populations to the much more useful realistic world of whole bunches of gen networks going on at a time so using these approaches people have made lots of progress sort of the most recent Version of

that and mentioned the other day there are one type of mutation of macr mutation is this business about variant of major stretches of DNA copy length variants where a whole stretch of DNA is duplicated twice or 110 different times can you identify traits that are occurring because of differences in the number of copies yet another version of dealing with this whole hierarchical multi-level business about Gene regulation okay take-home message from This is 20 30 years ago when all of this started you can start with a trait and through increasingly fancier techniques you could find the

neighborhood of where the gene is that the different versions of the gene correspond to the different versions of the trait moving from patterns of that to the neighborhood of the gene to the actual Gene to whole bunches of genes to macro differences there that's one approach the other approach of the field has been starting The other way you got a gene you've got a gene and thanks to researching it in flies and worms and rats and all of that you kind of have a sense of what the gene does and you have a reasonable guess

of what sort of traits might be relevant in a human and now you run it the other way you have two different versions of the Gene and you look for differences in Behavior or differences in protein function or differences in the size of the protein you start with a Genetic knowledge and for our purposes where people are mostly looking is at behavioral endpoints so what do you see with that lots of findings in recent years and my feeling is this is one of the more interesting ways of doing this Behavior genetics starting with basic research

with animals you got some sense of what the gene does how about it and people because there's variability first example and this has to do with a really interesting hormone that we will hear Plenty about down the line a hormone called vasopressin and vasopressin in rodents I think I already discussed Vaso pressent and rodents has a receptor the Vaso pressent receptor and while we talked about the other week is depending on which version of this you have if you happen to be a vo male it will determin whether or not you are monogamous or polygamous

that's interesting what was also interesting was that difference the Two variants were not in the gene itself but in the promoter and that winds up meaning that the promoter caused in one strain the gene to be expressed in different parts of the brain than in the other version of it okay so what we saw there was all sorts of hints from the animal world that vas oppress has stuff to do with social affiliation things of that sort so what do you now do if you want to apply this knowledge to humans the first thing you

Need to ask is well do we know where the gene is in humans and with modern sequencing of the human genome you've got it so you know where the gene is for the vasor pressent receptor and the next thing you have to ask is does it come in two different flavors does it come in two different flavors and do they differ in the same way as the ones that people have studied endlessly in rodents yay yes indeed the receptor Gene is exactly the same in Everyone but there's two different versions of the promoter the same

exact story so that's great if you've gotten that far now you start looking for what the differences are between people who have one variant versus the other and you got to do your home work you got to match them for age and gender and number of cavities and all sorts of stuff like that and when you've got that under control you go looking for behaviors what's the limit of this by definition You're only looking where the light is shining already you're only looking where you already have a sense that maybe you should be looking unless

you're totally crazy obsessive and want to try to measure everything possible in people and look for a difference in most of these studies you kind of know where to look look that immediately means there's all sorts of areas you're not looking nonetheless with this approach people have gone looking in humans at These different variants on the vasopress and receptor Gene and you find some really interesting differences one was a paper published a couple years ago in a very prestigious Journal which got picked up in the papers all over the universe showing if you have the

version of the promoter that you find in monogamous male VES you as a human male are likely to have more stable relationships than if you have the other version of it whoa that's pretty bizarre That's pretty cool next thing a study that just came out on that same prestigious Journal a couple of weeks ago and this is one we're showing which depending on which version you have how good are you reading facial expressions in other people subtle differences in facial expressions then there's a whole other world of approaching it evidence emerging that in families where

autism runs majorly through the families people are seeing mutations in genes related to Vasa pressent and the vasopressin receptor so this is one really cool example of starting with that approach and this is a gene whose variants have something to do with some pretty meaningful Realms of Human Social connectiveness variability stuff totally interesting another example this is a gene coding for a protein called bdnf brain derived neurotrophic Factor doesn't really matter the main point of Bdnf is it prompts neurons into growing new processes and it turns out bdnf does something that ultimately is kind of

a drag for you in one part of the brain the amydala which I think I've already mentioned the amydala has a lot to do with fear and anx anxiety and that sort of thing and we will come back to that don't panic but the main thing is bdnf plays a role in causing individuals individual rats when they Are highly stressed to make the neurons in the amydala grow new connections new processes what are you doing you are training that rat to be anxious you are training that rat to be hyper responsive to scary things bdnf

appears to play this role so now the next step in the sequence and you'll begin to see it's the same pattern over and over people then found ah there's a couple of different flavors of bdnf there are a couple of different genetic variants There's a couple of different ways in which bdnf pops up and rats or mice or whatever differing by a base pair here an amino acid there where you then do your scut work and show okay this bdnf works faster than that version of it or it works works less but it lasts longer

or who knows what you find a functional difference there's a genetic difference there's two different versions of it and it actually makes a difference for how the protein functions and this has all Been studied in animals and now you understand what it's doing in the amydala of a rat depending on which version you have and then the exact same strategy go look at the bdnf Gene and humans and ask well do you see the same difference are the same two flavors in humans popping up as en rodents yes indeed and then the exact same approach

again looking for differences and you know where to start looking what is that literature been showing the type of bdnf Variant that you have in the exact same way that it maps and rodents maps onto your likelihood of an anxiety disorder the levels of stress hormones in your bloodstream the levels of metabolic activity in your amydala the same exact sort of finding next a whole other world which we will learn much more about Down the Line This is obviously a quick survey a whole bunch of different areas all of these we will come back to

big time Later on in the course next area this neurotransmitter dopamine you will learn amazing amounts about dopamine dopamine which works through a you guessed it dopamine receptor and in fact there's a gazillion different types of dopamine receptors and dopamine receptor number four 4 D4 the dopamine receptor 4 Gene has something to do with a whole bunch of interesting traits in rodents and it comes with variability in the rodent version different flavors and humans Have variability along similar lines and dopamine what is dopamine involved in pleasure and anticipation and behavior reward seeking Behavior what do

different versions of the dopamine Type 4 the 4 receptor Gene begin to map on to in humans levels of risk-taking behavior levels of sensation seeking levels of novelty craving that's interesting another example a gene called npy protein a neurotransmitter called Neuropeptide y do not get overwhelmed by all of these it's just the same pattern over and over npy same deal again again and two different human variants have something to do with differences in levels again of anxiety of metabolic rates in the amydala all of that and in this case the npy difference is quite interesting

because it's one of those where the difference is not in the gene structure sequence it's once again a difference in the promoter okay so what Have we have in all of these this is a really powerful approach the first version that we heard you've got to be behavioral difference you got a phenotypic phenotypic difference you got a difference in how two proteins function or their size go looking for what's the genetic difference between those who have this trait and those who don't this version reverse engineering it you start off with a gene that comes in

different flavors you got a sense of What it does from animal studies do you have the same variation in humans and does it map onto Behavior so all of these are amazing all of these it has to be emphasized in a way that will come back to haunt us also big time all of these explain tiny percentages of the variab variability in the data there's nothing remotely resembling a world in which if you have flavor vanilla of the D4 receptor versus if you have flavor chocolate if you have flavor vanilla you Are going to be

hand gliding when you were in preschool you're going to be totally sensation seeking and if you have the other version you're going to spend your entire life collecting stamps or who knows what it's not that deterministic no surprise with this Gene stuff no single Gene is going to be particularly deterministic once you get outside the world of phenol ketua and cystic fibrosis and such they contribute some explanatory power so on one hand Amazingly cool seeing these genetic links to aspects of human behavior on the other hand they're not very big effects and this is something

we will come back to endlessly down the line okay so this is how the field has gone about more recently trying to find links between variation in genes or their promoters and variations and aspect of behavior running it both ways and what all of this is looking at what is intrinsic and everything we've been Talking about with this Behavior genetics is oh my God the cliche finally emerges nature and nurture and Gene environment and Gene environment interactions what is becoming increasingly clear in the field is there's a third leg to all of this there's a

third leg that could be extremely powerful and is going the ba the basis for the chaos and complexity lectures down the line which is Chance the role of random events the role of Chance in being a form that transcends what we would call environment and is certainly not genetics a whole different world where that contributes okay where will we see chance playing out an important role in all of this Brownie and motion Brownie and motion for those who don't have a techy background I will describe it in the way that I understand it which is

flailing desperately Brownian motion has to do with the fact that molecules oscillate And there's an intrinsic movement oscillation of molecules you take a whatever full of water filled with all sorts of things molecules whatever and they're all going to be vibrating to a certain extent because of this browni and motion I suspect that was the most amazingly incorrect description of what Brownie and motion is but that's the point that's the main point simply that there's this oscillation which is completely random it is just an Intrinsic feature of how the world of physics and Albert Einstein's

mustache works and so you got this brown motion stuff going on so where might that play out in terms of chance so we got here a cell and with our four powerhouses of the cell here and on the right let's assume this is a genetically identical cell and I just got tired of drawing it completely but the same for mitochondria and what we see here first off is genetically these Mitochondria differ one of them has a blue spot one of them has a red spot wait a second every single cell in your body was built

out of the same genome when you started off life aha back to that thing the other day mitochondria have their own DNA mitochondria are going about their own business of dividing in the cell of replicating there replicating themselves now and then with a mutation within any given cell the mitochondrial sequence of DNA Is going to differ from one mitochondria to another because they've been like separate organisms that are inside a cell going about their own Evolution their own mutations their own whatever what do you then have what would be called a mosaic of different genetic

profiles of the mitochondria within a cell so that in and of itself is pretty interesting because this is a whole other world this is not the DNA back in the nucleus and this is not sort of Variability introduced by jumping genes or accessibility of transcription factors to genes all that this is meanwhile outside the nucleus there's this whole weirdo world of these mitochondria that are functioning all on their own so the different mitochondria in the same cell will have different genetic makeups so great so these two cells are absolutely identical each of them have four

mitochondria and each of them have two red kinds one blue kind And one that gets nothing so now that cell is going to go about splitting in two and what happens is it splits and in the process of splitting what the fluid the cytool the stuff inside where all the molecules including the mitochondria and the other organel are found and it's splits and there winds up being a very simple question which mitochondria wind up in which daughter cell and what we've got Here is in this case a split like that in this case a split

like that oh my God why did that happen is that because there is a gene in this one that says when you form a new pair of cells have blue and blank in one and two Reds in the other and this one has a completely different instruction manual for how you split cells no simple randomness of where the mitochondria were in the cell when they split a totally random event so what you see here is you start off With two cells that are genetically identical and within one round of cell splitting these genetically identical individuals

are already genetically different how come because of instructions or blueprint no simply because molecules organel things like mitochondria just oscillating around and along comes a split and who is stuck on which side of the Divide so you've got variability that way intrinsic in that is another Type of variability which the second I mentioned it you will be able to run with effortlessly which is floating around and here also will be transcription factors and splicing enzymes and other enzymes and Along Comes the split and there's not the remotest chance that half of every single type of

transcription factor is going to go each way and half of every type of splicing enzyme it's it's going to be who's oscillating where and where With their cell splits so you wind up not only only with different outcomes in terms of mitochondria and their genetic makeup you're going to have different distributions of different types of transcription factors all due to this random oscillatory stuff so that's one big component where chance plays a role and what the chaos complexity lectures are going to be very heavily about is just how important stuff like this is how important

it is in Explaining what goes on how important it is in explaining why no matter how much you know about what every single molecule is having for lunch next Tuesday there's still going to be a huge degree of unpredictability all of that is to come this is just beginning to establish the idea yes nature nurture nature nurture chance also is the third leg and they're playing a large role whether chance is what's going on when you get a transposable event you Remember at the point that neural stem cells are beginning to divide into neurons that's

when they juggle around their transposable genes most dramatically whether that is a completely random event as to where the copies land when they come back to earth I'm not sure if people know but I suspect there's an element of chance in there also so this is introducing that notion in there so great so now you've got all these caveats which is Environment is subtle and coming all over the place and early experience and epigenetic changes and all the different ways you could find genes linked to behavior and don't forget variability also has something to do

with chance at the end of the day though what all of the behavior genetic approach is going to come down to at the end is a single number we have studied this trait with adoption techniques with looking for genetic markers with looking for copy uh Length variant we have studied this trait and the variability of it and thanks to us studying for a Gaz years we can now conclude that 53.5% of the variability in this trait is heritable you come up with this number at the end this trait has a 53% heritability that's the number

that winds up coming out scientists report that this or that trait has variability as 80% heritability this is the number that always comes out at the end what's The heritability ranging somewhere from 0% up to 100% this is heritability and this is absolutely critical because this is a truly influential number the one that people Come Away with when they are being taught oh this trait is genetic those who want to be quantitative will have been told whoa this trait has 80% heritability there 90% heritability all of that and it's the wrong interpretation and what we're

going to spend a bunch of Time on now is looking at what heritability actually means the heritability number because it is completely different from the everyday intuition about what it means and what it's usually telling you is how unimportant genes are in the deterministic way rather than the other way around okay so what does everyone assume what is heritability telling you it is telling you how much do genes determine the average level of this Trait you have one version of a gene and there's the other flavor and they produce different average levels of some Behavior

or something at the end what heritability is teaching you if you've got this completely wrong notion it's teaching you how much do genes have to do with the average level of that behavior that trait that whatever that's not what heritability actually means what her CR ability as a number is telling you is not what genes have to do With the average level of the trait it's what genes have to do with the degree of variability around that average okay this is a point where things immediately seem panicky and start getting very very you know complicated

all of that we will see it's not that bad and it's not that bad in a very critical way okay so okay simple first sense of getting at it here's two populations where you measure something or other and these three individuals they come in at 9 10 11 and These come in at 1 10 and 19 or whatever what's going on here you average them they have the exact same average what's the difference there's a lot more variability around the average here than in this case what's the wrong idea that people have that heritability means

ooh it's telling you how much do genes determine the average here that's not what it's doing it's how much do genes determine how much variability there is initially this seems like a very subtle Point and what's the big deal because at the end of the day it's still talking about how important genes are what we'll see now is it's actually a way of seeing how less deterministic genes are in lots of cases okay so this heritability stuff talking about variance here we have an example okay we've got some plant some plant with some Gene that

comes in three different flavors and you measure something or other about the plant this is how much water it retains or the Plant's IQ or something like that you're measuring some traits and you're asking does it differ as a function of which version of this Gene you have so you do your study and this is what you see and you say whoa okay I went and looked at this plant in a rainforest and we identify the genetic versions of it and look very different the gene that you have there knowing that gives you a lot

of predictive power over what level of whatever it is that you're measuring This plant is That's great so you're going to get your doctorate out of that and you get some publication and it's great and you finally St being a student and it's terrific and meanwhile some individual who shares like none of your genes in common on the other side of the planet meanwhile there's some so who's studying the exact same plant in the middle of the GOI desert you're sitting here in the Amazon studying this and here's this individual doing the exact Same kind

of experiment saying oh here we have this unlikely plant that grows both in the Amazon and the GOI desert but here we have this and we're studying this here and what am I studying I'm studying those three variants those three variants of this Gene and I'm asking do they influence plant IQ the same thing that you were asking over here and that individual was doing their study and they see that yes indeed the gene influences what version that you Have and here you got a b and c and here's what they see when they measure

plant IQ and it looks like that and what do they conclude whoa look at that knowing what version of the gene you have gives me enormous predictive power in predicting what the plant IQ is going to be and then catastrophically tragically the two of you meet each other and discover that you're both researching the same plant and you look At your numbers and your your heart breaks at that point because you look at these and what's going on here what's going on let's translate this notion of heritability and variance and all of that let's translate

it into a very simple question you can ask translating all of this in English you're interested in what this Gene has to do with plant IQ and you're allowed to find out one piece of information you could know whether the plant has version AB or C or You could know whether the plant is growing in the Amazon or the OB desert which piece of information is going to give you more predictive power and what you wind up seeing here is if you can either know this or the environment you want to know what the environment

is the variability o plant IQ could come in at 98 100 102 8 10 and 12 the far more of the variability in those six numbers is explained by what Environ ment that's going on in rather Than the genetic difference that's what heritability is telling you and in a study like this it would tell you that the heritability number is actually quite low because the amount of variation due to this is far less explained by the gene type than whether it's the Amazon or the Gobi desert okay so that's a first pass at it why

is this really important for the following reason you're a scientist and you're trying to understand how a b and c Influence plant IQ and you come up with something nutty and stupid like saying well I would like to be able to do field seasons in both the Amazon and the Gobi desert and your adviser will say or all of your elders will say something like no you can't do that because that's just you're not controlling for environment you're not studying it in only one controlled environment that's too you can't go to there's such different ecosystems

all of that pick one and go Study it there and what you do is you go study it there and as a result of just studying it here you come away thinking that virtually all of the variability is explained by genes what have you just done you explicitly have designed your experiment so that you can't detect the environmental role in determining that trait what counts as setting up the experiment as the right way for people who think about this sort of thing standard sort of approaches to Experiments what counts as doing a good job by

definition what you're doing is biasing towards thinking the genetic input is more important than it actually is because scientists don't decide to study this trait and two different plac you don't decide to do a study where you're looking at some trait in both rats and ocelots or something you don't TR to you know whatever look pick one species maybe even pick just one gender pick one environment don't have your Rats in one room where the air conditioning is going nonstop in the other room you're barbecuing stuff control for environment and by definition if you've done

the nice careful responsible thing that a scientist is supposed to do doing this sort of thing you control for environment what have you just done you have just removed your ability to see the role of environment and you have just artificially inflated how important You think the genes are okay let's take a five-minute break we are going to look at this in a lot more detail Do Not freak out if this is not immediately intuitively obvious questions that just came up uh the first one is pointing out one of those where I probably should have

actually uh taught something clear what are you talking about with proteins being different sizes how do you figure out proteins are different sizes and the answer is you make them stand against The wall in their bedroom with a ruler and you mark it there and then you see if they differ at size or if that doesn't work what you do is you use various biochemical techniques you basically make something akin to a thick homogeneous soup of something or other and you put the two different versions of the protein in there and essentially you sit and

wait and see how far they sink down and the one that's heavier is going to sink down further anyone who Knows about gels and electris that's insanely simplified but that's basically the notion of it put them where they move through something as a function of their weight gravity and you could then pick up size differences the other good question that was asked is what did you just say in the last 10 minutes this is very difficult this is an extremely subtle point and I'm going to hammer it in over and over again here in sections

all of that why is it so important Because number one this is a number heritability that the general lay public comes away with interpreting completely wrongly and number two the vast majority of scientists when they're working in this field of behavior genetics design their experiments so that by definition they are eliminating all sorts of Realms of environmental influences okay so going back to this here so here we see once again this simple question use this one over and Over translating all this Theory and variation and stuff always translated into the same question I can find

out what type what version of this gene or I can find out which environment this is happening which one do I want to know if I want to be in a better position to guess what's going on and when it looks like this you don't want to know the genes you want to know the environment because it's far more powerful and if you only studied this in this setting You would come away saying oh this variability is entirely explained by which version of the gene oh this trait plant IQ has 100% heritability And what you

see there is when you combine it together with numbers like these it's 15% heritability so that's totally critical to hammer in okay so what are some of the responses at that point by people who will say that's ridiculous if you're saying what heritability mostly should be teaching Us is how UNP powerful genes are what would be one of the initial responses great how many plants out there are growing in both the Amazon in the GOI desert and it's so hard to study IQ and plant this is a totally artificial dichotomy between the extremes of environment

you're like inflating things now you're cheating in the other direction to get the most dramatic artificial circumstances to inflate your sense of how important environment is This is totally artificially dichotomized so think about humans and think about one single fact which is we inhabit more different environments than any other species on Earth we live in the Amazon and we live in the GOI desert and we live in Peoria and we live in all these things and we have more exposure to different sorts of environments so immediately that argument goes down the drain okay so now

instead somebody argues something different saying okay Yeah yeah sometimes plants have IQ in the Amazon and the goby desert and I get your point your stupid point here that ooh environment can make no one's going to argue that the difference between the Amazon and the GOI desert isn't important oh yeah okay well humans they live in both all of that it's not an artificial difference but you notice something isn't it interesting that in these two different environments C plants always have the Highest IQ and a plants always have the lowest that's telling us something about

that Gene that's telling us and you're then saying well yes yes it difference my environment but we've just learned something very important about these Gene versions which is in totally different environments version C gives you a higher plant IQ so that's important yeah yeah environment but we've just seen how powerful this Gene is but then you run into the person at The conference who is studying it in the GOI desert and they put their data up and it's even worse than in the last version because it looks like this and what have you just learned

you can't say a thing about this Gene you have just learned the translation of this sentence the first critical sentence we've had over and over is if you you can only know one factoid one about which she version or one environment choose the environment we've now just learned a Second sentence a second question to ask which is what does having a b or c have to do with plant IQ and if the answer is it depends you've just seen the subtlety if the answer is it depends on which environment you're looking at if you're looking

in Amazon C gets you the best plant IQ if you're looking in the GOI desert C gets you the worst plant IQ what have you just shown what is technically the definition of a gene Environment interaction and we have just seen going from well yeah yeah they're very different but C is always the best isn't that interesting to a completely different profile what does a b or c have to do with plant IQ it depends it depends on the environment that's how you have just defined that's your diagnosis for Gene environment interaction and what ultimately

one has to argue is that it is impossible to Ever say what a gene does you can only say what a gene does in the environments which to date it has been studied in okay let's see that expanding even more because you've got this okay let's Jump Ahead okay so this is showing you now just how totally nutty and counterintuitive heritability terms actually are you ask a question what's the heritability of number of fingers on your hand well you know jeans have to do with The fact that we got five fingers instead of flippers or

some such thing genes have huge amounts to do with it you're not asking about the average number of fig fingers you're asking about the variability remember that again so what are the circumstances out there which will give somebody six fingers instead of five that's incredibly rare what about four fingers instead of five oh industrial accidents three fingers instead of five lots of Industrial accidents to change jobs or whatever what are we seeing here in terms of how much do genes have to do with having fewer than five fingers it's all industrial accidents jeans have nothing

to do with it there's no doubt some weirdo disease out there but for our purposes this is how it works what have we just discovered number of fingers that trait has a 0% heritability that's totally bizarre that's completely counterintuitive genes Have everything to do with why the average human has five fingers but they have nothing to do with the variability in that case it's entirely Environmental Al the number of fingers you have has 0% heritability now let's look at another example it's 1950 in Eisenhower America actually it wasn't until 1952 but it's a very different

world than now and one of the things that you would never ever ever never never ever see in the United States would be some guy wearing an earring unless in a very cloistered part of the country he was a sensitive guy but for most of America this is not what men do they don't wear earrings and likewise in most of America if you were a good red-blooded American woman you would not go outside without your earrings are so now you got to say okay well what causes variability in ear ring wearing behavior and it's entirely

Explained by whether you are female or male which is a genetic trait what we've just seen is whether or not you wear earrings in 1952 has 100% heritability totally counterintuitive think through this again and again and again because this makes sense when heritability is a number about this rather than this you get a world where 0% heritability for your number fingers and 100% heritability for whether you Were wearing earrings at that time because once again asking okay I've got a choice in the matter I can either know the entire Genome of this individual or I

can know whether they are in a frat where they close their eyes and work with a wooda every now and then which fact do I want to know that's the one that will tell me what about the environment going on with them or now you have a choice I can either know the entire Genome of this person or I could Know that um what sort of environment they're living in a 1952 what you want to know there is male or female if I know that I can completely predict this behavior of earring wearing so this

totally counterintuitive thing here where heritability is telling just the opposite of what people intuitively think and as soon as you deal with that and recognize that and recognize the way scientists do experiments is to try to do things as cleanly as possible study It only in one place in only one setting in only one circumstance you've just artificially guaranteed that you're going to come away more impressed with the genes and they actually deserve to be so how would this look beginning now in more detail so what we've got here are a number of different ways

in which you can see when are genes important when are environments important that sort of thing okay so we have here two different Traits no we have one trait two different flavors the Gene and flavors A and B and three different environments so here you have the Amazon the GOI desert and a roller coaster and you're measuring plant IQ and there's two different versions of the gene there and you're asking well what does Gene what do environment have to do with it your data look like this what does it tell you environment makes no difference

at all it doesn't matter if you're in The desert the rainforest whatever which version of the gene you have entirely explains the variability so this is what a heritability of like 100% would look like now you do the study and instead you get data like these you'll note which is one of the most important things about being a card carrying scientist which is data are plural which talk about counterintuitive earrings are genetic and data are plural so now you get these data and you see as Follows in this environment no difference depending on what type

of Gene you have in this environment no difference no difference in each environment very different averages ah this is what it would look like with 0% heritability there's no difference at all of the variation explained by Gene variation it's all environmental so now we have a version that forces us to put in the same phrase We heard about before this is what your Data look like now and you now ask the question well what does being an environment what does your environment have to do with your plant IQ and the answer is it depends on

which version of the gene you have and now you ask what does having a certain version of the gene have to do with your plant IQ and the answer is it depends on which environment you're in this is in a sense the verbal definition again of a gene Environment interaction what do genes have to do with this trait depends on the environment what this environment have to do with a trait it depends on the type of genes this is what the data would look like and here you have an interaction and in some fudging of

the numbers this is what 50% heritability would look like what we just saw here before hypothetical example of the messiest it could get this is the one where the people come back and say yes Yes yes environment matters but you notice version C is always associated with the highest IQ and here we have the version where depending on the setting if you have this type of Gene gets better if you have this type of Gene it gets worse this is one where there's a dramatic interaction between what the genes are doing and what the environment

is doing this is one that's going to have an even lower heritability because this is one where you are saying big Time it depends it depends on what the Gene type is it depends it depends on what the environment is this is in a sense as dramatically as it could be that case so you constantly have stuff like this going on let's look at an example where in fact you wind up seeing something like this back to our iconic mutation disease from the other day there PKU phenol kitura just remind you do not worry about

the details it's this disease where normally there's this Thing in your body which would be toxic to your brain unless it's turned into something else and this is the enzyme the protein and thus coded for a biogene this is the enzyme that turns the scaried version into the safe version and in PKU you have a mutation in this enzyme it's not doing its job the scary version builds up and wipes out your nervous system that looks bad and what we've got now is a trait where you're going to say Well let's see I uh I'm

very interested in knowing being able to predict whether or not this person has a fairly normal looking brain or whether it looks like swiss cheese do I want to know whether or not they're growing up in Idaho versus Montana or do I want to know whether or not they've got a mutation in this enzyme obviously you want to know if there's a mutation in the enzyme seemingly heritability is 100% but now you do something which people have been doing for people with PKU for a couple of decades now which is you put little labels on

bottles of food and stuff saying if this food contains the scary bad news thing and if you have PKU if you simply don't eat food that contains that if you have what's called a phenyalanine free diets or you don't get your brain looking like swiss cheese what have you got there you've just put in an environmental influence that has Reduced herit down to zero this is a case where we've got something like this looking and here we're measuring is like the Swiss cheese index or whatever of the brain and what we've got here is this

is an environment where people know what how much of the stuff there is in different types of food and don't eat it a simple envir not so simple but an environmental intervention a behavioral change in the environment and you've just reduced Heritability from 100% to zero % so that is a dramatic version now let's look at a version of a real life example of this and this would be with I think I've already put this one up um okay does this look familiar by now no okay that was a Thanksgiving okay what we've got here

is a gene that's got something to do with depression it's a gene that has something to do with the neurotransmitter serotonin details don't Matter they will come later but the gene comes in two different flavors and one version of it based on everything that's known from laboratory animals one version should be the kind that predisposes you more towards depression so in this incredibly important study that was done a number of years years ago guy named caspy Duke University and colleagues they had been studying 177,000 people basically from birth up to age 25 or so in

New Zealand and who Knows why in New Zealand but studying him there and following and asking they took blood so they know the whole genetic profiles and looking at among other things by age 25 does the person have major depression or not have they had an episode of depression and now let's go look at which version of this gen they have and what would everything predict from all the animal studies which is you have the bad version of the Gene and you're as a human going to have A higher chance of having a depression that's

not what the data looked like instead it was one of those it depends it depends on the environment what you saw was it all depended on how many major childhood stressors there were loss of a parent divorce abuse some such thing in the absence of any of those you know this was the rate of depression and the people having the good version and throw in one child to trauma two of them three of them and the Incidence is going up slightly now you've got the bad version of the Gene and it puts you more at

risk only in certain types of environments so here we have a great Gene environment interaction that's something straight out of this one you're saying well what does this Gene have to do with the risk of depression and the answer is it depends it depends on what your childhood environment was like but now one additional detail showing that this Is actually a case of this one that just gets ignored whenever people talk about this study because it's cool but it's actually not all that important okay so here's the people with a good version of the gene

but it makes this point though you got the good version and they're down here and you know what's going to happen the bad version is going to be exactly the same but you look at the data closely and and in the absence the bad version is actually a little bit Protective from depression versus the quote good version what have you just discovered there it's one of these this is a radical Gene environment interaction not only is it the case that does this put you more at risk well it depends on the environment depending on the

environment it could put you less at risk this one is not a big deal because there's a tiny difference there's no reason to pay attention to it other than sort of pointing it out pedagogically But this is an amazing example where this can go in the opposite direction this is a hugely important Gene environment interaction so what all of this begins to set you up for is we've got this heritability number and people come away constantly thinking about it's telling you about how much the average level of a trait is determined by genes it's instead

telling you how much the variability what that means thus by Definition that there's all sorts of nutty counterintuitive things going on where earrings are totally heritable a number of fingers are not what that tells you is by definition the way experiments are set up to make things nice and clean and interpretable scientists typically remove environmental variability scientists typically artificially have boosted up the seeming heritability of a trait what does that tell tell you the more Different environments you study a trait in the lower the heritability is going to be because you are going to be

giving more and more opportunities for things to be different more opportunities to be able to say it depends it depends on which environment we've just studied it in 99 different environments and it always looks like this no difference by environment and genes always make a huge difference and then you go out and before dying of fatigue you study it in The 100th environment and it now looks like this sort of thing what you've just learned is this is a it depends example the more environments you study something in the lower heritability is going to be

Translating that into English the more environments you study a genetically influenced trait the less interesting and important the genes are going to be the less interesting and important they're going to be and answering what does this Gene have to do With whatever and what we're seeing over and over again is the only way to answer it or over and over it's going to be a it depends it depends on the environment ultimately as I said a little while ago ultimately it winds up being meaningless to ask what a gene does ultimately the only really truly

scientific way you can answer a question like that is what does this Gene do in this particular environment people make this big deal out of oh genes do something Environments do something and every now and then hooray they interact in some exciting way and teaching the gene environment interaction cliche that's what's happening every single time and that winds up being the basis of that quote from Paul Erick in this department that I put on the handout which is great summarizes this entire Point asking whether genes or environment have more to do with some trait is

akin to asking whether height or length have more to do With the volume of a rectangle they're Inseparable there's no such thing as a gene influence outside the context of an environmental interaction okay let's look more at what this looks like here this being one great example and this being this iconic one and this is a finding that is destined to be like the most important in the last quarter Century in biological Psychiatry it is the most most powerful demonstration in the realm Of abnormal human behavior of what your genotype has to do with your

behavior the most amazing logical intuitively reasonable demonstration of it depends it depends on how stressful the childhood environment was really great bringing things back to last week's sort of molecular lectures people already know who study this the two different versions of the gene certain classes of stress hormones interact with the two versions differently when stress hormone Levels aren't particularly raised that difference isn't being manifested the more of a history of stress and it's obviously more mechanic more complicated than just how much you're exposed to but the promoters the variation here is in the promoters the

promoters interact differently with those glucocorticoid stress hormones in the absence of the glucorticoid stress hormones because in the absence of something exciting the genetic difference makes no Difference so we've just translated an epidemiological answer what does this Gene have to do with depression it depends it depends on your childhood stress history we've just translated that into last week's molecular biology what does this genetic variant have to do with whether or not you have depression it depends it depends on how much childhood exposed to glucorticoids you had so we've just leaped from analyzing this in the

context of this Field to Translating that into last week and translating that into the endocrine conductors that are going to come next week beginning to show okay you're an epidemiologist the answer is what sort of environment you're an endocrinologist the answer is well the hormonal environment whether you define it it's the same punch line it depends it depends on the environment so this is the best most amazing example of this in all of Psychiatry except These guys Caspian colleagues measured something else and they got just as best as of an answer for that which is

they looked at another Gene that has variation one we will hear about down the line a gene called Mao monoamine oxidase all we need to know right now is a gazillion animal studies suggest that one version of the gene predisposes more towards aggression than the other whoa so they got 177,000 people who've just had 25 years worth of opportunity to be Aggressive or not and they got the genes and now they ask the question rather than at age 25 has this person ever had a major clinical depression now they ask at age 25 has this

person ever been in trouble with a law for some sort of antisocial Behavior antisocial behavior is the new jar for what used to be called sociopathic Behavior has this person been in trouble with a law for sociopathic Behavior antisocial and does It vary depending on which version of The Mao Gene you have and what you get is not only is the answer it depends the graph is basically identical to this one it's superimposable the magnitude of the effect what was this in that case how whether or not you had and how severe your child history

was of abuse the more childhood abuse you had the more having the wrong version of the gene increased your odds of having antisocial aggressive behavior once again a major Dramatic it depends and it's stunning you look at these two different papers both were published in science a couple of years apart Landmark studies all of that and the two graphs really are virtually superimposable the same magnitude of effects the same answer it depends on your childhood so that is a very strong example next one another one now you go back to this Gene difference with the

serotonin the depression world and now you study it in monkeys and the Variation there there's variation in brain chemistry related to depression all of that depending on how stressful the monkeyy childhood was same exact sort of finding what else now you begin to look at going back to that world of dopamine receptors and thrill seeking and all of that and what you look at there is variability in a certain type of different dopamine receptor Gene and what you find there is if you have a certain version of that Gene you have Less social attachment there's

a whole psychology of how you measure that and God knows why it's associated with less social attachment if if and only if you got brought up by a mother who was cold and withdrawn there's once again a it depends my looking at that it's nowhere near as clean as this but it's the same sort of theme again another example of it there's another Gene called fad 2 and don't even ask me what it stands for but which version of the gene you Have has some predictability over your IQ that's kind of interesting inter it's not

a big effect but nonetheless it is demonstrable which version of that Gene you have has some control but there's a it depends which version of that Gene you have has something to do with IQ if and only if something let me tell you what this fat 2 is involved in it is involved in carbohydrate metabolism carbohydrates carbs carbohydrate metabolism it codes for Some enzyme that breaks down carbohydrates and no doubt some certain kind okay what's going on here you've got two different versions of a gene that break down carbohydrates and you got one version and

on the average you'll have a higher IQ if and only if some environmental thing was happening any guesses what that environmental thing might be high carbohydrate diet high carbohydrate diet okay that makes tons Of sense yes indeed that winds up being relevant remember you're now not remember CU I didn't say it already but you're looking at IQ and kids so you're looking now at carbohydrate stuff going on early in life so frame it in that context so we got a start of an answer here so what else could be happening if and only if the

version you have of this Gene that involved in breaking down carbohydrates translating into how you're dealing with the amount of Carbohydrates in your diet gets you a different IQ with an if and only the if what would the if and only if be build on that comment there what else could it be okay I'm not even going to look somebody shout out an answer you're right okay who's the who started somebody started saying something who started saying something okay any other ideas who said that look at that they start pointing The person doesn't even fess

up who said that you're right okay you want to be that way I'm out of here okay so uh if and only if you read the damn notes as it turns out yeah yes breastfeeding okay breastfeed if and only if you are having a particular type of diet very early in life that is extremely rich in the types of carbohydrates that this enzyme works on so a very dramatic if and only if there I don't know why I write that stuff or I don't know why I show up here I should be doing one or

the other in some sort of environment interaction thing so yeah breastfeeding okay so one more example a very interesting one and this is one that has at some point or other I bet been pertinent to every single person in this room which is there's another genetic difference that has something to do with a certain cognitive aptitude and this one everybody knows about and this One is as follows if you have there's two different versions of this sort of genetic picture and they're associated with different levels of aptitude in this particular cognitive realm this is not

a world anymore of one single Gene at a time fad 2 any of these this instead is talking about a whole bunch of genes if you have a y chromosome or not if you are male or female a genetic trait and what is the thing that has been demonstrated most consistently in The literature for ever and ever and ever in terms of a gender difference in a cognitive skill in math performance that has come through endlessly we already talked about it the other week a small difference in the average median performance on Junior High School

John's Hopkins Superstar kids taking the SATs but a big difference in the tale at the end the high performance all of that this comes up in Endless endless studies this comes up with kids at fairly young Ages there is this gender difference on the average yes we're saying on the average don't forget you say on the average before you then ignore that you say on the average boys are better at math than girls men are better at math than women male plants in the GOI desert better at math than female plants there and so we

got a genetic trait here being a function of you know whether or not you got a y chromosome but then a few years ago There was an astonishingly important paper published in science and what these people did was look at math performance scores of I think it was 480,000 different high school kids and all over the world they didn't just study It in America they studied it in 40 different countries and they asked a very simple question which is are there big differences in gender quality of life issues in this country and there's a Whole

index that comes out of the World Health un something or other called a gender equality index which takes into accounts like if there is and if there is how dramatic of a gender difference in educational opportunities in Freedom of movement in Freedom to serve in an elected office and freedom to vote and freedom to choose who you're married to and obviously the enormous variability on this planet in terms of that and what they showed was the greater the Inadequacies the greater the difference in gender treatment in a society across 40 different countries the bigger the

difference there was in math scores it's not a function of gender it's which society you're growing up with with your gender what was at the most extreme let me make sure I get the countries right here who had the worst profiles of the 40 countries in terms of the biggest gender differences in these quality of life measures turkey Tunisia And South Korea where was the United States sitting somewhere around the middle with most Western European countries and which were the countries on Earth which as a block had the lowest degree of different treatment of people

in their society based on gender the everh handy wonderful utopian Scandinavians so income the Scandinavians and what you show is by the time you look at the country on Earth that has the least Gender differentiation of any which is Iceland you notice something different there still is a gender difference in Iceland girls are better at math than boys slight ly a small difference going on there but nonetheless as you go from the countries in which from day one girls transitioning into women are given the most constraints of freedom of life that's where you're going to

see the biggest math difference in scores and you look at less and less of those sort Of inequities and the gender difference in the math score by the time it's at the Scandinavian countries it's down to zero and then you get to Iceland and it actually reverses it's got nothing to do with your Y chromosome we immediately come back to the first of those questions from before that diagnostic question you got a choice you want to have a sense of in this population now even at the individual level you got a choice you're comparing two

individuals And you want to guess which one is better at math than the other you can either know their gender or you could know whether they grew up in Tunisia or Iceland which fact you want to know you want to know about environment environment is vastly more powerful there another feature of that that has been interesting so you then say okay the extremes okay so in some societies the means are exactly the same but what about that difference way out Of the highest level of performance as I mentioned the other day in the mid 1980s

looking at the highest first percentile of math performance on junior high school kids with the SATs and there was a 13 to1 ratio of males to Fe females in there when it was last studied a few years ago it's down to a 3:1 ratio oh that's obviously due to Evolution over the last 20 years because it's got to be due to genes because it's C that's like saying genes explain the fact that in 1980s people like wore pads on their shoulders and like power sneakers to work or whatever and the fact that Nobody Does it

anymore shows that the gene for wearing that on your woman executive Decor deal has evolved it's mutated that's asinine you do not go from 13 to1 to 3:1 with a trait in 20 years in a highly interbreeding mixed population in other words humans and have this as a genetic trait even function at the extreme has squat to do With the genetics of gender it's I want to know what Society the person got raised in I could care less what their chromosome is if I want to know how good they're likely to be at math compared

to the other person tell me where they grew up that's the most important thing to know interesting additional thing the second most reliable finding in all of measures of cognitive aptitude thing that has a gender difference is on the average Girls being better at verbal performance tasks than boys women than men all that sort of thing so what's going on in those 40 different countries there what you wind up seeing is it depends on which country you're in it depends on that gender equality index and what you see is in the worst countries there by

these measures Tunisia who else was it Tunisia turkey in South Korea what you see is yeah uh women get better scores on verbal tests than men and as you go To the more equal places the gender difference increases in other words you got one of these the more gender equal a society is the less of a sex difference there is in math capabilities and the bigger the advantage is for females over males and verbal performance it's got everything to do with what Society you're in this gender difference in this realm of cognitive skills means next

to nothing and if I had any technological skills I kept saying I was going to Bring the figure from this paper I'll have it posted cuz this one figure it's AOSS all these you just look at it and there's the answer it's got nothing to do with the genetics of gender difference okay so what else would one want to emphasize here okay what else would one want to emphasize here which is this is a total mess and totally complicated okay what have we gotten to so far in this field of behavior genetics there's all these

different Ancient ways of inferring something twins adoption there's the much more modern ways finding actual genes that's wonderful that's exciting nonetheless over and over and over environment gets understudied environment is far more subtle than you think environment starts earlier in life than you think and when you do it in a very formal quantitative way analyzing what genetic influences are about you discover that scientists study things under circumstances where You constantly underestimate the importance of environment blah blah etc etc but at the end of the day don't genes have something to do with something or other

going on with this and obviously obviously they have some very important roles you have genes that completely determine aspects of behavior single genes that completely determine your intelligence if you're a housefly lots of interesting studies There showing single Gene determination a lot of these behaviors and it doesn't matter sort of what the economic opportunities are for house flies in that country versus Humans what what you see there is yeah there are Realms of Behavioral biology where genes play very very strong roles and we will certainly see some of them in the lectures to come but

with two qualifiers the first one we heard the other day which is even when with all of these criticisms on board And you've got every critical tool to slice up anybody arguing that here's a high heritability important genetic component blah blah Etc you've completely cut it to pieces and there still is a gene that seems to be doing something important for trait x what we heard about the other day is nonetheless think about if there is an indirect genetic route for getting there is there a gene for extraversion or is there a gene for your

height and how people of Your height are treated is there a gene for picking at grubs or is there a gene for if you're really tall you pick at grubs and people don't make fun of you is that all that business about indirect genetic effect so even when you see a gene for something you have to begin to ask to make sure that you are not in fact looking at an indirect effect final qualifier when you look at the really interesting genes in terms of what they do when you look at some of the ones

That have the most to do say with what differentiates our genome from the chimp genome when you look at things like juggling your DNA just when you're making new neurons what you see over and over is what human genes are about most dramatically is coding for ways in which you have freedom from the effects of genetics and that is going to be a theme endlessly in the lectures to come okay for more please visit us at stanford.edu