Lewontin argued that there is more genetic variation within human populations than between them, so they can’t really be very different. Of course that’s bullshit: humans have the second-largest morphological variation of any mammal, behind only dogs. How do you get significant phenotypic differences between populations when there isn’t much Fst between them?
One way (at the extreme) is to have a single allele, one that does a lot, vary strongly between populations: at the limit, be fixed in one and nonexistent in the other. There are not a lot of alleles like this in humans, but it happens. EDAR 370A is almost fixed in Northeast Asia, almost nonexistent in Europe and Africa: it results in thicker scalp hair, more numerous sweat glands, smaller breasts, funny teeth, and changes in the shape of the ears and chin. Just one allele: it would not show up noticeably in Fst.
The way at the other extreme consists of small, systematic differences in the frequencies of many alleles that affect a particular trait. Suppose that 100 alleles influence height – there are plus and minus versions of those alleles, with the plus versions slightly increasing height while the minus versions slightly decreasing height. A systematic, smallish increase in the fraction of plus variants would make a population average taller: quite possibly a lot taller. But this only involves differences in a tiny fraction of the entire genome – the GWAS hits for height – so again, no noticeable change in Fst. You get these correlated changes from natural selection. For that matter, sweeps like EDAR 370A are also products of natural selection.
According to Lewontin’s argument, Pygmies couldn’t really be hugely shorter than most other human populations. Yet they are short (five or six stds shorter), while Lewontin’s Fst argument is simply wrong. In fact the existence of Pygmies automatically disproved Lewontin’s argument, whether we understood the exact genetic basis or not. Counterexamples do that.
Understanding the genetic basis of the phenotypic differences between populations can often tell us something about the causes of those differences – for example the time frame.. You’d expect that the main lactose-tolerance alleles aren’t terribly old, since domestication of milk-giving animals happened relatively recently (within the last 10,000 years or so) . And they’re not terribly old. On the other hand, adaptations to cold and high altitude might be very old, even going back to archaic humans – and some are. Of course the phenotypic differences exist (and sometimes matter) even if we don’t understand the past selective pressures that created them.
West Hunter 
There’s also more variation within families than between, so it’s totally okay to knock boots with family members!
Jokes aside, how much interest is there in studying the biochemistry of the transcriptional/translational products of these introgressed genes? I’m applying to University of Alaska Fairbanks to do Biochem & Neuroscience. Trying to figure out how, say, the Inuits’ weird lipid catabolism enzymes differ in function from the more common versions, would be right up their alley, I’d hope.
Like the Arctic Variant of carnitine palmitoyltransferase. Certainly some people are interested. Fairbanks ought to be, but I don’t know what’s going on there. Put on your thinking cap and you ought to be able to predict other plausible metabolic responses to Arctic climate and diet.
Off the top of my head: changing regulation of the “investment phase” in reversible catabolic pathways like glycolysis could hike up nonshivering thermogenesis. (The net equation just hydrolyzes ATP; energy released as heat.) I’ve wondered if tiny mammals have to do this a lot to avoid freezing to death- pound for pound, some of them eat way more food than larger mammals.
Changes in any enzyme that helps convert amino acids to pyruvate: that is, the protein catabolism analogue of carnitine palmitoyltransferase. Best candidate would be the catalyst of a rate determining step, or any step that all metabolites must go through if they’re going from protein to pyruvate.
Changes in membrane lipid composition, probably favoring unsaturated fats.
This is all coming from 1st semester Biochem. We’ll see if next semester gives me more diabolic plots.
God, I can’t wait to be doing all of this. As for UAF, a little digging brings up this guy https://cehs.unl.edu/npod/bert-boyer/
Maybe I should be cluttering up his inbox?
Noting that “plots” can be novels or graphs. It sounds like some graphs about natives could be regarded as diabolical. Listen carefully to the proper lingo when you get there, as “Inuit” is considered just fine with some, and problematic to others. In Fairbanks it will be mostly Yupik, but halfway up the state the population switches to Inupiat. It will not usually be a problem, but some people are always looking for trouble.
Diabolic plots are always preferred over parabolic ones.
Wow, I had thought that “Eskimo” was the offensive one and “Inuit” was the politically correct one. I’ll take your advice, even though it feels like there’s no winning that game. Regardless it’s cool to talk to someone who has some context there. I’ve never been north of Seattle. There’s something undeniably romantic about Alaska, although it’s on the list because I want to study two different disciplines and it has a dual program in both.
I’ve also been informed that I should never ask an Eskimo to “go clubbing” with me. Apparently that means something else up there.
Yupik would rather be called “Eskimo” than “Inuit”.
Oh, wow. I just Googled it: apparently Inuit is a type of Eskimo. Like squares and rectangles.
Relevant:
Thanks.
I always use Esquimeaux.
“There’s something undeniably romantic about Alaska” — This may well be true, but it takes rare perception to assert it at the winter solstice! Best of luck (seriously).
It would be interesting to study the genetics of alcoholism. The natives in Canada (and Alaska too, no doubt) have high rates of alcoholism. Seems that people descended directly from hunter-gatherers have high rates of alcoholism. But be careful, or they think you are literally Hitler.
It’s been looked into with Mission Indians http://dionysus.fiu.edu/pdfs/tamara%20l%20wall.pdf
Apparently they have low frequencies of alleles that seem to protect against alcoholism. Or, agricultural peoples have high frequencies of presumably-new alleles that allow for different conversion of ethanol to acetate (vinegar, basically).
I mean, let’s suppose we take this controversial line of thought as far as possible, editing our own shiny new alleles into these peoples’ embryos in hopes of a precipitous decline in alcoholism. (A needlessly generous act that would probably never be repaid.) What kind of person would call you Hitler for trying to make people’s lives better? Someone more interested in their politics regarding Natives than in making Native lives better. My opposition to that sort of person goes far beyond any fear I have of being compared to a dictator.
Tact is important, anyway. I never bring this stuff up unless I have strong reason to suspect I’m with an audience that may be ready to hear it. And at that point, the more articulate I am, the less controversial I seem.
“It would be interesting to study the genetics of alcoholism”
This has been studied in other populations. A quote of interest:
“[T]he vast variation in ADH [alcohol dehydrogenase] catalytic activity across the human race is mainly due to just a few SNPs that profoundly change the efficiency of the isoforms. ADH1B/1 is the most effective variant and is the ADH wild-type […] Part of a ‘successful’ career as an alcoholic depends possessing the ADH1B/1 isoform. The other defective isoforms are found in low frequencies in alcoholics and cirrhotics. […] in the vast majority of individuals, whatever their variant of ADH, they are able to process acetaldehyde to acetate and water, as the consequences of failing to do this are severe. With ALDH, the wild-type and gold standard is ALDH21/1, which has the highest activity of all these isoforms and is the second essential component for an alcoholic career. […] the variant ALDH21/2 has less than a quarter of the wild-type’s capacity and is found predominantly in Eastern races. The variant ALDH22/2 is completely useless and renders the individuals very sensitive to acetaldehyde poisoning, although the toxin is removed eventually by ALDH1A1 which does not seem to be affected by polymorphisms. In a survey of 1300 Japanese alcoholics, there was nobody at all with the ALDH22/2 variant.”
The quote is from the book Human Drug Metabolism: An Introduction, by Michael Coleman.
Hmm…
Apparently wordpress converts asterisks into italics. This makes the quote look weird. If you want to view the quote in a non-weird-form, see the last paragraph of this blog-post: https://econstudentlog.wordpress.com/2016/09/15/human-drug-metabolism-iii/
Cool. Those were some of the same alleles in the study with the Natives I linked. I had no idea there was a knockout variant, that’s fascinating.
Acetaldehyde is a carcinogen, right? I wonder if people with bad ALDH copies end up with cancer, especially in the upper GI tract.
I also wonder if these people have lower alcohol tolerance. Oxidation of acetaldehyde to acetate should shift the overall reaction to the right if it happens fast enough: that’d cause the alcohol to be converted to acetaldehyde faster, hiking up your alcohol tolerance, and couldn’t happen in people with bad ALDH copies. I must read about this.
Alcohol is a pretty brutal thing to do to yourself, especially if you don’t have the right metabolic toolkit to deal with it, right?
Acetaldehyde is extremely toxic, and increased cancer in people with ‘bad copies’ should in my opinion be expected for a given level of exposure. The problem is of course that exposure patterns are not fixed, but are explained at least in part by metabolic differences. Being good at breaking down acetaldehyde makes you more likely to drink alcohol.
“Alcohol is a pretty brutal thing to do to yourself, especially if you don’t have the right metabolic toolkit to deal with it, right?”
Yes, or if you take drugs that inhibit ALDH. There are actually quite a few of those. I figured you (or others) might be interested to learn a few more things about these topics from Coleman’s book, so I added a few more quotes below from this part of his coverage:
“Around 90 per cent of ethanol is cleared by the ADH/ALDH system, with the remainder
oxidized by CYP2E1, which has a 4–6 fold lower affinity for the drug. The genes that
code for ADH are found on chromosome 21 and there are five classes, (ADH1-5) in man.
Each class has separate allelic variants: ADH1A ADH1B and ADH1C are found in the
liver, whilst ADH3, ADH4 and ADH1C are found in the gut. Nobody has any idea what
ADH5 is for, or what it does, but it is very unstable.
The acetaldehyde formed by ADH is dealt with by aldehyde dehydrogenase ALDH […] The two most relevant forms are cytosolic ALDH1A1 and mitochondrial ALDH2 […] Rather cunningly, both ALDH variants are fearsomely efficient at processing acetaldehyde […] You might say that this adaptation signals a healthy evolutionary respect for the systemic toxicity of acetaldehyde.”
“Ethanol is primarily an inducer of CYP2E1, although CYP1A1 and CYP3A are also
affected. The degree of induction will of course be dependent on the patient’s usual consumption, but CYP2E1 does not appear to contribute that much to ethanol clearance even in very heavy cirrhotic drinkers. […] although ethanol can be so destructive to the liver, this organ is not the only route of elimination; some investigators have reported more than as much as half of ethanol is cleared extrahepatically even in alcoholics. […] For those chronically dependent on ethanol their CYP2E1 levels can be ten-fold higher
than non-drinkers and they would clear CYP2E1 substrates extremely quickly if they chose to be sober for a period of time. This may lead to the accumulation of metabolites of the substrates. It is apparent that alcoholics who are sober can suffer paracetamol (acetaminophen)-induced liver toxicity at overdoses of around half that of non-drinkers,
which is due to CYP2E1 induction. […] Worryingly, liver failure has been reported in relatively moderate drinkers after a few days of the recommended dose of paracetamol (<4 g/daily), when they have stopped drinking (whilst in hospital for example) and have needed pain relief. […] The mechanisms of the alcoholic’s sensitivity to paracetamol hepatotoxicity are not fully understood. […] When alcoholics are ‘maintenance’ drinking, that is, enough ethanol to be able to feel ‘normal’, but not intoxicated, reduced clearance of CYP2E1 substrates will be seen […] This means that ethanol will probably fully occupy CYP2E1, so any other substrates clearance will be reduced.”
I think in the alcohol context that it’s important to note that not only are there important differences in what might be termed the ‘base-line metabolism’ of drinkers and non-drinkers (and ‘drinking and non-alcohol-drinking populations’); drinking alcohol also changes how you metabolize this toxin. As well as other drugs that are also metabolized by the same pathways (these metabolic changes can in the context of some drugs be clinically significant enough to kill you).
A few quotes about ALDH-inhibiting drugs:
“Patients often believe that they should not drink when given antibiotics. This is only true
for antibiotics that block ALDH […]. Inhibition of acetaldehyde clearance causes a severe flushing/vomiting/sweating and nausea effect which is exceedingly unpleasant. There is a surprising list of ALDH inhibiting drugs such as metronidazole, cefoperazone, cefamandole, griseofulvin, chloramphenicol, nitrofurantoin and sulphamethoxazole. Other agents, which can be inhibitory, include isoniazid and sulphonyl ureas. Antabuse, or disulfiram, is intended to block ALDH, so exploiting acetaldehyde toxicity to help the alcoholic stop drinking […] a single moderate drinking session is likely to change the pharmacokinetics of prescribed CYP2E1 substrates. […] even small doses of ethanol can affect warfarin metabolism, reducing first pass and leading to excessive bleeding. Warfarin patients should not drink ethanol at all”.
Alcohol also affects the metabolism of TCAs. A few more quotes related to ‘what it takes to become a successful alcoholic’:
“It is generally true that those who pride themselves on their high tolerance to ethanol are more likely to develop alcoholic liver damage than those with little or no tolerance. […] On
a practical level, the longer you can stay conscious and able to drink, the [longer the] addiction can be serviced and the more ethanol-related toxic species will damage you over your drinking lifetime. If you can detoxify the acetaldehyde rapidly and efficiently, you will recover quickly from the previous night’s excesses and you are ready to drink more. These factors facilitate dependence and eventually health destruction. In contrast, those who become hilariously incoherent after one or two drinks are less likely to develop such heavy dependence on alcohol. Indeed, those who cannot detoxify acetaldehyde and thus suffer its systemic toxicity after exposure to ethanol are virtually immune to alcoholism […] These general observations are supported by the polymorphic clearance of ethanol by both ADH and ALDH.”
“[O]ne of the major toxic pressures in alcoholic liver disease at the cellular level appears to be CYP2E1 induction. It is thought that CYP2E1 mostly converts ethanol to toxic acetaldehyde that must be detoxified by other systems such as ALDH, which are at full stretch in alcoholism. CYP2E1 can also form the toxic hydroxyethyl radical from ethanol and on the rare occasions the alcoholic is not drinking, CYP2E1 not occupied in ethanol clearance emits a constant stream of nasty reactive oxygen radicals that must be detoxified by the hepatocyte. […] It is thought that ethanol abuse and CYP2E1 induction leads to long term oxidative stress. Interestingly, if CYP2E1 does play a decisive role in the oxidative destruction of the liver in alcoholism, then its level of expression could explain why some individuals can survive decades of very heavy drinking with minimal cirrhosis. Perhaps if long-living alcoholics are associated conclusively in clinical studies with a low expression/low induction version of CYP2E1, such as RsaI; or alternatively, those who succumbed to fatal cirrhosis relatively quickly possessed versions associated with high reactive toxic species turnover, such as Dra1 […], then this might illuminate the role of CYP2E1 in cirrhosis progression.”
US you’re giving me delicious fodder for a head-first dive into the literature. I had assumed that undesirable ALDH alleles would cause worse inebriation, higher cancer risk, and even higher addiction rate since they’ve been correlated. I must look into it further.
You’re right that the cancer risk should only increase post-exposure, but if these people have higher exposure on average then the effect, to one degree or another, should hold for nearly all of them except teetotalers: even then, alcohol isn’t the only place you find acetaldehyde.
I’ll be reading into this regardless. Thank you.
“US you’re giving me delicious fodder for a head-first dive into the literature.”
I’m happy to learn that.. Have fun studying these topics in more detail!
Thanks & will do!
It’s quite an interesting field to watch from an HBD perspective. Recent research has revealed some pretty un-PC stuff about selection for resistance to alcoholic diseases: https://www.ncbi.nlm.nih.gov/pubmed/26924531
Check out that north-south cline in European populations, and the Irish in particular!
Meanwhile, sociological articles about alcohol use (I’ve read a fair number at this point) never mention these things, but talk incessantly about different drinking patterns and subcultures. Most of the researchers themselves are ethnic Northern Europeans wringing their hands about why they can’t have countries that drink more like Southern Europeans do.
I’ve thought for a while that discussing alcohol resistance can be a back door to getting people to think more about HBD, for several reasons: it shows the power of recent selection, more people are willing to admit inequalities in populations’ response to alcohol, and it’s a case where Northern Europeans do not look superior to everyone else (so you can get people to stop angsting about white supremacy).
At the same time, it’s a situation where much money is spent, the consequences of the genetic differences are dire and socially important, and these differences have affected whole cultures of the populations involved (think Hamlet and the temperance movement). The differing foundations created by HBD have caused some very interesting cultural and historical edifices to be built surrounding alcohol in different regions of the world.
I was going to start a blog where I talked about all this and became the HBDchick of pop differences in alcohol tolerance, but I’m too damn lazy.
Contrasting alcohol tolerance with IQ:
It’s more obvious that it should differ globally
It’s more easily explained than, say, g, which is a mathematical construct extrapolated from an aggregation of related data
The physiology is better understood
It is more difficult to obfuscate
It is slightly less controversial, I suspect
A lot of which must stem from the fact that alcohol tolerance is just simpler than asserting that you are actually a computational machine, made with ~86 billion lipid-coated signal-shooting cells, which clearly works better or worse in comparison to others like it.
Unrelated, I find it interesting that the people who refuse to recognize the obvious biological basis of this are the same ones who (according to you) think that having a drunker society is actually desirable.
What do we know about average differences in scent/smell across populations? I mean what there scent is not their sense of smell. Can’t seem to find anything on this, but I have a suspicion it’s not just from food.
Test. (seems my prior comment is in the spam can)
(another try)
This is the way that I as a layman seem to understand the problem, so I use this explanation when talking to friends and family. Is it correct? Does the analogy between alleles and isotopes hold?
On average, Lewontin’s fallacy purports, the genetic variation between Pygmies or Dutch is larger than the variation between those two groups, which is formally correct. However, Lewontin’s keeps insinuating that this shows differences to be irrelevant, which they are not. Contrary to Lewontin a random selection of Dutch will always beat a random selection of Pygmies at eg a match of basketball or in any activity where size or strength matter,[1] because after all, even slight variations in the way genes express their small differences[2] matter, be that in single, very important genes or complex multigenic traits where we still don’t have much insight in their structure but can tell differences by outcomes that the expert can pinpoint with statistical means while they are obvious to the layman with his non-lying eyes.
1) Size and strength need not to depend on each other, but on average they do.
2) These gene variants are called alleles. They differ in minor details as do isotopes, that are identical in the number of electrons and protons but differ in the number of neutrons, procuring sometimes significant differences in their chemical or physical properties, eg some kill you while others do not.
MM: “Contrary to Lewontin a random selection of Dutch will always beat a random selection of Pygmies at eg. a match of basketball or in any activity where size or strength matter..” With training, I’d guess Pygmies would wipe the floor with the Dutch. Pound for pound, inch for inch, they are far stronger than anyone on Earth. Endurance-wise, some other groups (eg. San, trained) might be narrowly competitive though.
Greg, is the EDAR allele also determinative on dry(Asian) ear wax? Anyone happen to know if KhoiSan-Bushmen have wet or dry earwax?
” they are far stronger than anyone on Earth” I don’t believe it. They’re routinely pushed around by the Bantu farmers.
EDAR doesn’t do ear wax. Bushmen have wet ear wax.
Ants would wipe the floor with the Pygmies though.
I do not agree with you. I believed that the main assumption of Lewontin is incorrect, formally or informally; to be correct, one or very few loci should be taken into account, otherwise the more genetic traits are counted, it becomes impossible.
P. ex. if a child who has inherited the blue eyes of his mother, and his father has brown eyes, it is true that a stranger may be more similar in that one trait to that child than the father, but in absolute terms it is absurd.
…therefore they’re irrelevant. (they are not that stupid)
Best short-cut refutation of Lewontin I’ve seen, though I’d delete the colors as they are a bias that an astute bioMarxist would pick up.
That’s not a great presentation of Lewontin’s Fallacy, because under that model, the left and right tails of red and blue clusters are indeed closer to each other than they are to the other tail of their own cluster.
If that were true in reality, Lewontin’s assertion that clusters were irrelevant to relatedness would actually have some teeth. So bizarrely the image actually credits Lewontin, rather than discredits him. (Which takes some serious next level effort to achieve).
That’s not true for genetic differentiation between human ethnic groups, because the shape of the clusters is spilled out into n dimensions of random extent, such that any given member of cluster x is never closer to a member of cluster y than another member of cluster x.
(And I mean, generally I hope Alt-Righters don’t start using this image as a meme. They’re too dumb to understand the ideas they parrot.)
Nah, it took me 9000 hours in mspaint and it’s 100% scientifically accurate. And it’s already trending on /pol/ and stormfront.
Reblogged this on Nicht-Linke Blogs.
Re Inuit vs. Eskimo. Just be aware that today’s mandatory label is tomorrow’s unforgivable slur.
The important thing about the Inuit/Eskimo thing is to mark that you are in the in-crowd. Just like knowing that the current incarnation of sexuality is LGBTTQQIAAP. What? You didnt know that? Then you are a nazi who hates gay people. Oh crap, its changed already? Arggg!
No no no, you don’t understand! Of course the Pygmies can be short. Height, like skin color, or hair form, is a superficial trait, which means that it’s on the surface, and you can actually see it. Those traits are different! What Lewontin proved is that all populations are exactly the same in all the meaningful, important, non-superficial traits, the ones that you can’t directly see with your own eyes. Like intelligence. Especially intelligence!!!!!
Not true at all. E.g. Are bones also superficial features? : https://img.4plebs.org/boards/pol/image/1503/97/1503972163517.jpg
The doublethink is strong in this one!
https://www.sciencedirect.com/science/article/pii/B9780123868824000165
I’m wondering if it is possible to push Lewontin’s argument a little further and achieve reductio ad absurdum. Similar to the families example above, pick a new pair of groups to apply it to. I’m not sure which if any of these are true, so looking for more informed opinion.
For example dog breeds: “There’s more genetic variation within dog breeds than between breeds”
Then there’s Humans vs. Chimps: “There’s more genetic variation within the human species than between humans and chimps”
If it’s true of our closest relative, how far can it be taken?
“There’s more genetic variation within the human species than between humans and pigs? rats? fish?”
There’s more variation between airplanes than between the average altitudes of airplanes and cars.
I’m thinking genetic similarity (at least in the narrow band of coding genes) may not be as important as the expression of those genes which are controlled by multiple factors which can vary by population.
The key point is that those Fst numbers are unweighted by their phenotypic effects.
Another real life example: In terms of adaptation to a tropical climate, South Asians probably have lower Fst relative to phenotype differentiation against Europeans compared to East and North Africans.
Reason being SA are going to descend from a population, the “Ancestral South Indians” (or Australoids in old school phys anth terminology) that shared the Out of Africa bottleneck, then ended up staying adapted to a tropical climate, and hence dark skin, broad nasal passages, etc.
North and East Africans instead descend from Africans who did not share the OoA bottleneck that is responsible for most Fst differentiation between Eurasians and Africans, but have the same adaptations to tropical climatic. Hence they probably get “less” obvious phenotypic per unit of Fst. A European person with 20% West African will probably be more differentiated by Fst (and particularly by shared drift measures like f3!) from a European than a European+20% ASI… but the two admixed persons would necessarily be more or less tropically adapted.
All this could be offset to some degree by looking at Fst only within genic and coding regions.
However, that said, there is evidence that the structure of genetic differentiation on selected SNPs is generally predicted by Fst – http://journals.plos.org/plosgenetics/article?id=10.1371/journal.pgen.1000500 – “We find that the average allele frequency divergence is highly predictive of the most extreme FST values across the whole genome”. That is, populations with high pairwise Fst also tend to have more of the extreme Fst variants – it doesn’t seem to be the case that there are lots of populations with low pairwise Fst and lots of the extreme Fst variants, or populations with high pairwise Fst who lack extreme Fst variants…
It is interesting how effectively this fallacy works on anthropologists. This is probably due to a combination of (1) non-quantitative folks who may not understand genetics and F_ST is and (2) a desire to believe.
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