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Evidence for Natural Selection in Humans: East Asians Have Higher Frequency of CASC5 Brain Size Regulating Gene

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Charles Darwin

Denis Noble

JP Rushton

Richard Lynn

L:inda Gottfredson

Goodreads

1500 words

Brain size is one physical difference that the races differ on. East Asians have bigger brains than Europeans who have bigger brains than Africans (Beals et al, 1984; Rushton, 1997). What caused these average differences and the ultimate causes for them have been subject to huge debate. Is it drift? Natural/sexual selection? Mutation? Gene flow? Epigenetic? One reason why brains would need to be large in colder climates is due to heat retention, while in tropical climates heads need to be smaller to dissipate heat. One of the biggest criticisms of HBD is that there is no/little evidence of recent natural selection between human races. Well, that has changed.

CASC5 “performs two crucial functions during mitosis, being required for correct attachment of chromosome centromeres to the microtubule apparatus, and also essential for spindle-assembly checkpoint (SAC) signaling” (Shi et al, 2016). The gene has been found to be important in recent human evolution along with neurogenesis.

Shi et al (2016) genotyped 278 Han Chinese (174 females and 104 males with a mean age of 36) who were free of maladies or genetic defects. They had the coding sequences of CASC5 for humans, chimpanzees, gorillas, baboons, gibbons, orangutans, tarsiers, Denisovans, and Neanderthals. They downloaded genotypes from the Human Genome Project for their analysis.

They compared CASC5 among three human species: humans, Neanderthals, and Denisovans. Using chimpanzees as an outgroup, they discovered 45 human-specific mutations, 48 Neanderthal-specific mutations, and 41 Neanderthal-specific mutations. Further, when one exon region was aligned among modern humans, non-human primates and other mammalian species, 12 amino acid sites showed divergence between modern humans, Neanderthals, and Denisovans with 8 occurring in modern humans. Of the 8 sites in humans, 6 are preserved which implies that they were important in our evolutionary history.

Shi et al (2016) write:

At the population level, among the 8 modern human amino acid changes, two (H159R and G1086S) are fixed in current human populations, and the other six are polymorphic Fig. 1). Surprisingly, 5 of the 6 amino acid polymorphic sites showed deep between-population divergence in allele frequencies. East Asians possess much higher frequencies of the derived alleles at four sites (T43R-rs7177192, A113T-rs12911738, S486A-rs2412541 and G936R-rs8040502) as compared to either Europeans or Africans (Fig. 1), while E1285K-rs17747633 is relatively enriched in Europeans (46%), and rare in East Asians (10%) and Africans (3%). No between-population divergence was observed for T598 M-rs11858113 (Fig. 1).

x3x5hex

So East Asians have a much higher frequency of this derived trait. This is direct evidence for natural selection in recent human evolution in regards to the physical structure of the brain.

Since most of the amino acid polymorphic sites showed between-population divergence, they decided to analyze the three classical races using 1000 genomes. The variation between the races could be due to either genetic drift or natural selection. When they analyzed certain gene regions, they observed a signal of positive selection for East Asians but not Europeans or Africans. They further tested this selection signal using “the standardized integrated haplotype score (iHS) which is used for detecting recent positive selection with incomplete sweep (i.e. the selected allele is not yet fixed)” (Shi et al, 2016). Using this method, they discovered a few SNPs with large iHS values in Europeans (7 SNPs at 4.2 percent) and none in Africans.

They also conducted a genome-wide scan of Fst, iHS, and “XPCLR (searching for highly differentiated genomimc regions as targets of selective sweeps)” (Shi et al, 2016). Several SNPs had high Fst, iHS and XPCLR scores, which indicate that these alleles have been under positive selection in East Asians. Among the fixed amino acid sites in human populations, East Asians showed 5, Europeans showed 1, and Africans showed 0 which, the authors write, “[imply] that these amino acid changes may have functional effects” (Shi et al, 2016). Furthermore, using the HDGP, they obtained the frequency of the 6 amino acid sites in 53 populations. This analysis showed that 4 of the 6 amino acid sites are “regionally enriched in East Asia .. in line with the suggested signal of population-specific selection in this area” (Shi et al, 2016).

Then, since CASC5 is a brain size regulating gene, they looked for phenotypic effects. They recruited 167 Han Chinese (89 men, 178 women) who were free of maladies. They genotyped 11 SNPs and all of the frequencies followed Harvey-Weinberg Equilibrium (which states that allele and genotype frequencies will remain constant in a population from generation to generation in the absence of evolutionary pressures; Andrews, 2010). In the female sample, 5 regions were related to gray matter volume and four were on the amino acid polymorphic sites. Interestingly, the four alleles which showed such a stark difference between East Asians and Europeans and Africans showed more significant associations in Han Chinese females than males. Those carrying the derived alleles had larger brain volumes in comparison with those who had the ancestral alleles, implying recent natural selection in East Asia for brain size.

Shi et al (2015) also attempted two replications on this allele writing:

We further conducted a replication analysis of the five significant CAC5 SNPs in two other independent Han Chinese samples (Li et al. 2015; Xu et al. 2015). The results showed that three SNPs (rs 7177192, rs11858113 and rs8040502) remained significant in Replication-1 for total brain volume and gray matter volume (Xu et al. 2015), but no association was detected in Replication-2 (Li et al. 2015) (Table S4).

It is very plausible that the genes that have regulated brain growth in our species further aid differences in brain morphology within and between races. This effect is seen mostly in Han Chinese girls. Shi et al (2016) write in the Discussion:

If this finding is accurate and can be further verified, it suggests that that [sic] after modern humans migrated out of Africa less than 100,000 years ago, the brain size may still be subject to selection.

I do believe it is accurate. Of course, the brain size could still be subject to selection; there is no magic field shielding the brain against selection pressure. Evolution does not stop at the neck.

So Shi et al (2016) showed that there were brain genes under recent selection in East Asians. What could the cause be? There are a few:

  1. Climate: In colder climates you need a smaller body size and big brain to survive the cold to better thermoregulate. A smaller body means there is less surface area to cover, while a larger head retains heat. It, obviously, would have been advantageous for these populations to have large brains and thus get selected for them—whether by natural or sexual selection. This could also have to do with the fact that one needs bigger eyes in colder environments, which would cause an increase in the size of the brain for the larger eyes, as well as being sharper visio-spatially.
  2. Intelligence: East Asians in this study showed that they had high levels of gray matter in the skull. Further, large brains are favored by an intermediately challenging environment (Gonzalez-Forero, Faulwasser, and Lehmann, 2017).
  3. Expertise: I used Skoyle’s (1999) theory on expertise and human evolution and applied it to racial differences in brain size and relating it to the number of tools they had to use which differed based on climate. Now, of course, if one group uses more tools then, by effect, they would need more expertise with which to learn how to make those tools so large brains would be selected for expertise—especially in novel areas.
  4. Vision: Large brains mean large eyes, and people from cold climates have large eyes and large brains (Pearce and Dunbar, 2011). Decreasing light levels select for larger eye size and visual cortex size in order to “increase sensitivity and maintain acuity“. Large eyeballs mean enlarged visual cortices. Therefore, in low light, large brains and eyes get selected for so one can see better in a low light environment.

Of course, all four of the examples below could (and probably do) work in tandem. However, before jumping to conclusions I want to see more data on this and how the whole of the system interacts with these alleles and these amino acid polymorphic sites.

In sum, there is now evidence for natural selection on East Asians (and not Africans or Europeans) that favored large brains, particularly gray matter, in East Asians with considerable sexual dimorphism favoring women. Four of the genes tested (MCPH1, ASPM, CDK5RAP2, and WDR62) are regulated by estradiol and contribute to sexual dimorphism in human and non-human primates (Shi et al, 2016). Though it still needs to be tested if this holds true for CASC5.

This is some of the first evidence that I have come across for natural selection on genes that are implicated in brain evolution/structural development between and within populations. It does show the old “Rushton’s Rule of Three“, that is, Mongoloids on top, Caucasians in the middle, and Negroids on bottom, though Caucasians were significantly closer to Africans than Mongoloids in the frequency of these derived alleles. I can see a HBDer going “They must be related to IQ”, I doubt it. They don’t ‘have’ to be related to IQ. It just infers a survival advantage in low light, cold environments and therefore it gets selected for until it reaches a high frequency in that population due to its adaptive value—whether spreading by natural or sexual selection.

 

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48 Comments

  1. Fjow says:

    What do you think of this article Afrosapiens?

    Does it support the hereditarians case?

    Can this be tied to epigenetic? (it may be a stupid question from me indeed but just asking)

    Can this be also tied to your Nigerians samples quoted in your article about the Harmattan season?

    Like

    • Afrosapiens 🇫🇷🇪🇺 says:

      I think the article is interesting. I doubt it supports the hereditarian case because these polymorphisms have sex-specific expression and the SNPs didn’t show up in cognitive ability GWAS to my knowledge.

      It’s just one locus, Africans and Europeans could have the same phenotypes controlled by other genes, in the way Asians and Europeans evolved light skin from different genes. It could be interesting to test the effect of these alleles on European and African populations. The Wikipedia page says:

      CASC5 has been shown to interact with MIS12,[10][11] BUB1, BUBR1 and ZWINT-1.[9]

      So maybe the difference in Asian polymorphisms compensates for differences in these genes CASC5 interacts with.

      Nevertheless, genetic differences like that , if actually tied to cognitive ability are what HBDers need to prove their point.

      Can this be tied to epigenetic? (it may be a stupid question from me indeed but just asking)

      I doubt it, it really looks like traditional Darwinian selection, more probably than genetic drift or epigenetics.

      Can this be also tied to your Nigerians samples quoted in your article about the Harmattan season?

      I think yes. Especially if the extra gray matter is in vision-related areas. The study does not provide info on which brain areas benefit from these differences, but I know East Asia has high rates of myopia and low annual sunlight so it would fit in the low light hypothesis similarly to the West African samples.

      Like

  2. ian smith says:

    it’s interesting that afro’s sources on black cranial capacity are all authored by black africans. he has to come up with a trustworthy source. this means a paper by a white male gentile or chinaman.

    Like

    • veydunel says:

      Is that a joke ? All these data were published and accepted in foreign peer-reviewed scientific journals.
      By using the same argument, does that mean that every data published on european anthropometric characteristics should be done by non-Whites in order to be thrustworthy ?
      In fact you’re using the very same tactics than the ones who said than the old published data shouldn’t be trusted because they were done by people who were following a racial agenda.Lol

      Liked by 1 person

    • Afrosapiens 🇫🇷🇪🇺 says:

      Exactly. Don’t mind him. He’s a troll.

      Like

    • ian smith says:

      do you mean is afro a joke? yes he is. what i said was not a joke. but i agree it is hilarious that international journals would accept papers by nigerians.

      afro wouldn’t know a troll if it bit him. in france people have gone to jail for insulting jerry lewis. afro’s defense of his client is what in america is called “the OJ defense”. his experts are paid to testify, like dr henry lee.

      all of the authors are black africans. their findings are inconsistent with previous findings. they have more interest in exaggerating and less competence. their findings are done on living persons. it’s obvious to anyone with eyes that there is no big headed black tribe. and the weather phenomenon afro adduces as explanation explains nothing if it hasn’t been the same for 10,000 years or longer.

      Like

    • RaceRealist says:

      How do you know that they’re less competent? You can show that by pointing out methodological flaws in the papers. Do it.

      Like

    • ian smith says:

      oh i understand now. does that mean that every data published on european anthropometric characteristics should be done by non-Whites in order to be thrustworthy ? no. afro’s girlfriend is not thrustworthy. and no. only those data which demonstrate white supremacy are trustworthy.

      Like

    • Chinedu says:

      all of the authors are black africans. their findings are inconsistent with previous findings.

      But their findings are not inconsistent with observable reality. As a Nigerian, I’ve always found the notion that blacks have smaller heads to be sort of a joke. Indeed, while traveling through North Dakota I went into a hat shop in an all-white town, wanting a souvenir of my trip. Guess what, I couldn’t find a hat large enough to fit my head. They searched everywhere, including the stock room, with no luck. Obviously, heads the size of mine are an anomaly in that all-white town. These people were descendants of Scandinavians, who supposedly have the largest heads among Europeans.

      Like

    • John Connor says:

      I too am quite skeptical of the notion of sub-Saharan Africans having comparatively smaller heads then say, Causcasions or East Asians. Although of course, your “observation” (i.e. anecdote) is neither proof nor evidence in that regard, as you could simply be an outlier.

      Though, as I’ve mentioned previously, I do find it dubious that significant disparities in head size between races exist (and if they do, are meaningful in terms of IQ, expertise, etc.), though I wouldn’t rule out the possibility entirely. That is, unless you, RR, or Afrosapiens have any links to provide with data on the matter. Admittedly, I haven’t had much time to look into it myself (I’ve been busy with more mundane concerns, unfortunately).

      Like

    • Afrosapiens 🇫🇷🇪🇺 says:

      I believe it’s possible that populations vary in head size, it could merely be a byproduct of differences in whole body size. However, I doubt variation fits the racial categories. It’s probably more like height, with subgroups of the same “race” showing a high degree of variation. As for the data, yes we can always bring up samples, but it’s impossible to extrapolate their results to whole races. My previous post is on Nigerian samples, that’s possibly fairly representative of West Africa, but I would not make inferences about Mozambique or Ethiopia based on these samples. Like I would not consider the height of Dutch samples as representative of France, in spite of a much shorter geographic distance between the two.

      Like

    • John Connor says:

      Makes sense, thank you for clarifying your views on the matter.

      Like

    • Chinedu says:

      Although of course, your “observation” (i.e. anecdote) is neither proof nor evidence in that regard, as you could simply be an outlier.

      I was an outlier among the white people in that North Dakota town. Among my own people my head size is perfectly normal.

      Though, as I’ve mentioned previously, I do find it dubious that significant disparities in head size between races exist (and if they do, are meaningful in terms of IQ, expertise, etc.), though I wouldn’t rule out the possibility entirely.

      I’m highly dubious of the correlation also. Although, given the tremendous inter-racial and intra-racial overlap in cranial capacity it’s a ridiculous line of inquiry.

      Like

  3. ian smith says:

    it can’t be selection for cold because contra peepee, europe was much colder than china. at the last glacial maximum half of europe was under 10,000 feet of ice. none of china was under ice. none of siberia was under ice. the cold winters theory should mean whites have larger crania and higher IQs. the world records for brain weight are held by european. but perhaps there is no data for chinapeople. turgenev had a massive brain.

    Like

    • ian smith says:

      it’s also quite sad that the first chinapeople to industrialize were the japs, and they have smaller heads than other chinapeople. and japanese women do have a fetish for large headed men. this why soul brothers always strike out with sushi.

      Like

  4. John Connor says:

    Hey Race Realist, what do you think of this study that claims to “disprove once and for all the idea that a single measure of intelligence, such as IQ, is enough to capture all of the differences in cognitive ability we see between people”?

    http://www.cell.com/neuron/fulltext/S0896-6273(12)00584-3

    Like

    • Afrosapiens 🇫🇷🇪🇺 says:

      This is very interesting. And it makes more sense than “g” in my opinion. I’ll elaborate when I fully absorb the paper.

      Like

    • John Connor says:

      Afrosapiens,

      Since leaving this comment for Race Realist, I have further pursued more of his articles and I’ve found that he has, in fact, addressed the paper I linked to, albeit briefly, in an article entitled, “More g Denialism & More Gould Refuting”. I rather unconvinced that the contents of the paper even come close to undermining the validity of the “g” factor (and by extension, IQ), particularly given the very small sample used for the fMRI scans. Also, I’m hesitant, to say the least, that one (at best, questionable) study even begins to refute the myriad of studies carried out throughout the last 100+ years demonstrating the reality of the “g” factor.

      That being said, I’d be very interested in your opinion on it, not mention seeing Race Realist go further in depth on the contents of the paper.

      Like

    • RaceRealist says:

      Yea I’m questioning the g factor now. I don’t think it’s physiological as claimed. They used an online IQ test and I asked James Thompson if that invalidated the results and he said no because it was used on a large enough sample. He commented on that paper when it was released, I’ll link it later.

      In regards to this study disproving g, I think there are other ways to disprove it and you can do it with verbal argumentation. Read my article on g and physiology. Do Physiologists Study General Intelligence? I’m going to go more in depth on g, physiology and individual variation in physiological factors and why, if g were physiological, it wouldn’t be put into a rank order.

      I’ll comment on the paper more in depth soon.

      Like

    • John Connor says:

      A minor correction: I meant to say “perused”, not “pursued”.

      Like

    • Drake says:

      That was RR’s old article, he changed his mind on race and IQ now, check his recent articles.

      Now, he too question “g”

      Like

    • RaceRealist says:

      Drake, I didn’t change my mind. I’m skeptical and I like being contrarian. I am questioning g though.

      Like

    • Drake says:

      Oh yeah, I know that you still believe in race difference in IQ, just that now, you don’t take it anymore as a fact, just as a possibility.

      Honestly, do you still think that race difference in IQ should be as vast as hereditarians claim?

      Like

    • Drake says:

      Without believing in equality on intelligence between races (honestly, I don’t believe it too, just that the gap between races is not as vast and defined forever as hereditarians like to claim to me), you do truly agree with your own recent articles right?

      You don’t have to respond to me now if you don’t want to repeat yourself since that you will apparently write an article explaining your actual position.

      Like

    • John Connor says:

      RR,

      Excellent, I look forward to it!

      Like

    • John Connor says:

      Also, since you’re questioning the validity of the “g” factor, are you also still questioning the purported sex differences in IQ (I.e. in terms of both mean IQ and standard deviation) as you’ve mentioned previously, though I believe that a few months ago.

      I know Scott made a post about it back in July, but I don’t necessarily assume that his position reflects yours.

      Like

    • RaceRealist says:

      I don’t question the existence of something empirically measured, I question their explanations for their observations.

      Like

  5. meLo says:

    RR,

    Update on the evidence for humans in America 130,000 years ago

    http://www.evoanth.net/2017/10/19/130000-first-americans-disproven/

    Liked by 1 person

  6. ian smith says:

    i feel sorry for rr, and rr’s is the ONLY serious hbd blog. but…

    i’m starting to think RR is actually a puerto rican.

    the truth doesn’t matter to him.

    he boosts IQ yet he deletes my comments.

    Sincerely,
    BGI Cognitive Genomics Lab
    Building No.11│Beishan Industrial Zone│Yantian District│Shenzhen 518083│China  
    认知基因组学 │ http://www.cog-genomics.org │contact@cog-genomics.org 
    ST-RM, BGI

    every syllable of every comment of mine…

    is gold…

    or rr must admit that IQ is meaningless.

    just try harder.

    you’ll get it.

    even if you are a puerto rican.

    btw, i was interested to learn that deniro is only 1/4 italian. sad!

    of course brando was 0/4 italian. sad-der!

    Like

  7. ian smith says:

    where’re all my comments under “holocaust 2.0”?

    they are very instructive regarding the supposed superiority of chinapeople.

    ancient chiner was NOT as cold as ancient europe.

    post the comments paizano.

    and the world will know.

    and by “the world” i mean afro and his pink fleshlight.

    sad!

    Like

  8. ian smith says:

    i guess i have to post the proof again, because i’m dealing with someone who thinks pro-wrestling is real.

    the proof that europeans are superior to chinapeople (except for southern europeans. they’re inferior.)

    sad!

    Like

    • ian smith says:

      europe was WAY worse than china.

      except southern italy was like jamaica.

      so the cold winter theory is true.

      fugetaboutit!

      gabagool!

      Like

    • ian smith says:

      observe that japan was actually a more severe climate than chiner at the last glacial maximum.

      yet japs have smaller noggins.

      was japan uninhabited at that time…blah…blah…blah?

      flushton needs to be flushed.

      then when he comes out at the end of the sewer, he needs to be treated with phosghene.

      just spray flushton and the mildew in your showers with bleach and he and it will disappear.

      it’s the same thing black girls use to lighten their skin.

      sad!

      Like

  9. meLo says:

    RR what do you think of EGI/Clannishness?

    Like

    • RaceRealist says:

      Denis Noble showed how Dawkins’ selfish gene theory is wrong.

      Read these papers:

      Evolution evolves: physiology returns to centre stage

      Physiology is rocking the foundations of evolutionary biology

      Neo-Darwinism, the Modern Synthesis and selfish genes: are they of use in physiology?

      This paper shows that heritable morphologic change can occur with little/no genetic change.

      Form and function remixed: Developmental physiology in the evolution of vertebrate body plans

      This is book is a good read into this: Evolution in Four Dimensions Genetic, Epigenetic, Behavioral, and Symbolic Variation in the History of Life

      And here is the first chapter available which specifically talks about Dawkins’ selfish gene theory.

      As to how this ties into EGI, Rushton’s GST theory is heavily based off of the selfish gene assumption. The selfish gene is not empirically backed.

      As for clannishness, I don’t put those types of qualities onto genes anymore. “They’re more genetically similar due to breeding with close cousins”, etc.

      If the selfish gene theory is shown to be false (and it is), then those two things you mentioned are false as well since they are derived from a theory that has been discredited.

      Liked by 1 person

    • meLo says:

      “Denis Noble showed how Dawkins’ selfish gene theory is wrong.”

      There seems to be a very fine line between what is considered a gene centered view and what isn’t. A lot of genes affect the developmental characteristics of physical traits, not just their stasis. Plasticity itself is an adaptive trait and just because some traits can be inherited without genetic basis doesn’t mean genes were not involved.

      “then those two things you mentioned are false as well since they are derived from a theory that has been discredited.”

      Again that’s a fallacy, but besides that I think in humans EGI might be more of a cultural thing first and a phenotypic one secondarily. It’s natural for social animals to form some variation of coalitions based on intertribal discrimination. Humans and most carnivores for that matter are highly visual creatures, so while genes themselves may not actually have an ability to differentiate between individuals with more or less similar genetic algorithms, we have developed sensory systems that allow us to see visual cues of phenotypic characteristics which will usually correlate with their own respective genotype.

      Like

    • ian smith says:

      that vid is excellent, because the motivation for the two professors is NOT HBD denialism, but jealousy for the reigning position of molecular genetics. they make all the criticisms i’ve made and more, but out of professional envy rather than political correctness.

      rr is clever for a puerto rican. he reminds me of Lorenzo Albacete.

      Like

  10. rw95 says:

    A bit off topic RR, but what do you think of James Flynn’s studies of intelligence?

    Like

    • John Connor says:

      RR has covered his views on the Flynn Effect in previous articles (though I’m unsure of whether he has revised his views on it more recently). In the mean time you can simply search for any articles on his site mentioning the Flynn Effect and check them out while you’re waiting for him to respond.

      Like

    • RaceRealist says:

      IQs have been rising 3 points a decade, which Flynn and Lynn noticed (Lynn noticed it first iirc, which is why it’s called the FLynn Effect). I think it mirrors better nutrition, industrialization, and the rise of the middle class.

      As parasites are ameliorated on Africa we should watch their IQs. As they industrialize and rid their parasites and disease burden there should be a subsequent rise in IQ, but to Western levels? I doubt it.

      Like

    • John says:

      “but to Western levels? I doubt it.”

      Why?

      Do you think that the gap will still be very large or smaller than what HBder claims?

      Like

    • RaceRealist says:

      Smaller obviously, because of parasite load, disease burden, etc.

      Like

    • John says:

      What should the gap be like then in good condition?

      Like

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