The architecture of skin color variation in Africa

Baby of hunter-gatherers in Southern Africa

Very interesting abstract at the ASHG meeting of a plenary presentation,Novel loci associated with skin pigmentation identified in African populations. This is clearly the work that one of the comments on this weblog alluded to last summer during SMBE. There I was talking about the likely introduction of the derived SLC24A5 variant to the Khoisan peoples and its positive selection in peoples in southern Africa.

Below is the abstract in full. Those who follow the literature on this see the usual suspects in relation to genes, but also new ones:

Despite the wide range of variation in skin pigmentation in Africans, little is known about its genetic basis. To investigate this question we performed a GWAS on pigmentation in 1,593 Africans from populations in Ethiopia, Tanzania, and Botswana. We identify significantly associated loci in or near SLC24A5MFSD12TMEM138…OCA2 and HERC2. Allele frequencies at these loci in global populations are strongly correlated with UV exposure. At SLC24A5 we find that a non-synonymous mutation associated with depigmentation in non-Africans was introduced into East Africa by gene flow, and subsequently rose to high frequency. At MFSD12, we identify novel variants that are strongly correlated with dark pigmentation in populations with Nilo-Saharan ancestry. Functional assays reveal that MFSD12 codes for a lysosomal protein that influences pigmentation in cultured melanocytes, zebrafish and mice. CRISPR knockouts of murine Mfsd12 display reduced pheomelanin pigmentation similar to the grizzled mouse mutant (gr/gr). Exome sequencing of gr/gr mice identified a 9 bp in-frame deletion in exon two of Mfsd12. Thus, using human GWAS data we were able to map a classic mouse pigmentation mutant. At TMEM138…we identify mutations in melanocyte-specific regulatory regions associated with expression of UV response genes. Variants associated with light pigmentation at this locus show evidence of a selective sweep in Eurasians. At OCA2 and HERC2 we identify novel variants associated with pigmentation and at OCA2, the oculocutaneous albinism II gene, we find evidence for balancing selection maintaining alleles associated with both light and dark skin pigmentation. We observe at all loci that variants associated with dark pigmentation in African populations are identical by descent in southern Asian and Australo-Melanesian populations and did not arise due to convergent evolution. Further, the alleles associated with skin pigmentation at all loci but SLC24A5 are ancient, predating the origin of modern humans. The ancestral alleles at the majority of predicted causal SNPs are associated with light skin, raising the possibility that the ancestors of modern humans could have had relatively light skin color, as is observed in the San population today. This study sheds new light on the evolutionary history of pigmentation in humans.

Much of this is not surprising. Looking at patterns of variation around pigmentation loci researchers suggested years ago that Melanesians and Africans exhibited evidence of similarity and functional constraint. That is, the dark skin alleles date back to Africa and did not deviate from their state due to selection pressures. In contrast, light skin alleles in places like eastern and western Eurasia are quite different.

Nyakim Gatwech

This abstract also confirms something I said in a comment on the same thread, that Nilotic peoples are the ones likely to have been subject to selection for dark skin in the last 10,000 years. You see above that variants on MFSD12 are correlated with dark complexion. In particular, in Nilo-Saharan groups. The model Nyakim Gatwech is of South Sudanese nationality and has a social media account famous for spotlighting her dark skin. In comparison to the Gatwech and the San Bushman child above are so different in color that I think it would be clear these two individuals come from very distinct populations.

The fascinating element of this abstract is the finding that most of the alleles which are correlated with lighter skin are very ancient and that they are the ancestral alleles more often than the derived! We’ll have to wait until the paper comes out. My assumption is that after the presentation Science will put it on their website. But until then here are some comments:

  • There is obviously a bias in the studies of pigmentation toward those which highlight European variability.
  • The theory of balancing selection makes sense to me because ancient DNA is showing OCA2 “blue eye” alleles which are not ancestral in places outside of Western Europe. And in East Asia there their own variants.
  • Lots of variance in pigmentation not accounted for in mixed populations (again, lots of the early genomic studies focused on populations which were highly diverged and had nearly fixed differences). Presumably, African research will pick a lot of this up.
  • This also should make us skeptical of the idea that Western Europeans were necessarily very dark skinned, as now we know that human pigmentation architecture is complex enough that sampling modern populations expand our understanding a great deal.
  • Finally, it’s long been assumed that at some stage early on humans were light skinned on most of their body because we had fur. When we lost our fur is when we would need to have developed dark skin. This abstract is not clear at how far long ago light and dark alleles coalesce to common ancestors.

Can we make Tolkien “woke”?

The Pacific Standard has a piece, How can we untangle white supremacy from medieval studies, which is an equal part nuggets of fact and equal part tripe.

Setting aside much which I found disagreeable in the piece, I was intrigued by the references to J. R. R. Tolkien’s work and their relationship to the race-theories prevalent at the time he was constructing his cosmos. It always struck me as rather obvious that Tolkien was a man of his time, and as a conservative British Roman Catholic, he would bring some fashionable Occidental sensibility to his world-building. Tolkien’s life spanned the late period of the British Empire, and his passion and legacy were to create a mythology for the English peoples. It would be reasonable his views on race, ethnicity, and religion would be in keeping within the mainstream for the first half of the 20th century.

If you read The Silmarillion it’s clear that the cosmogony of Middle Earth, Arda more broadly, was monotheistic. Though Tolkien asserted at some point that his work was fundamentally Catholic, that seems too specific (though Eru Ilúvatar does seem particularly Christian as opposed to more generally monotheistic).

It is notable that paganism is not explored in detail in the works, though there are allusions to pagan practice and beliefs. In Fellowship of the Ring Denethor, the crazed Steward of Gondor, declares “No long, slow sleep of death embalmed. We shall burn like the heathen kings of old!” Though Tolkien’s work is not explicitly as allegorical of Christianity as C. S. Lewis’, there was still a Christian sensibility about his universe and the outlooks of his protagonists. The Hobbits were modeled on English gentry and carried themselves with the propriety one expected of doughty burghers.

The pagan beliefs of men not exposed to the civilizing influences of the elves were attributable to worshipping the demonic powers of the dark lord Morgoth and his servant Sauron. This reflects the views of pre-modern Christians, where pagans did not worship fictions, but real demons who presented themselves as false gods.

The racial aspect is more what raises the hackles of the commentator in the piece above, and seems out of place today. Though I was never offended personally, it is impossible to not notice it if you dive deep into Tolkien’s legendarium. The three tribes of the Edain, “elf friends” of the First Age, seem to be modeled on Northern Europeans. The only exception may be the House of Haleth, though I suspect here as he was British Tolkien drew upon the folklore of the dark Welsh. These three Edain peoples were loyal to the elves and turned away from Morgoth and his servant Sauron. In contrast, the hearts of men who were not Edain were weak and susceptible to the allure of the dark lord and his minion.

Two broad classes of these people, the Easterlings, and the men of Harad, seem to represent all of the peoples of Asia, the Near East, and Africa. Described in turns as sallow, swarthy, brown and black, their racial identity is clear. It is not white. It also seems Tolkien’s British background comes to the fore again insofar as from what I can tell the only nation outside of the circle of the West in Middle Earth with an attention to linguistic detail, Khand, seems to be modeled on Northern India.* India, after all, would loom large in the imagination of British people of that period, in myth if not reality.

To term J. R. R. Tolkien a “white supremacist” or promoting an ideology of that sort seems to me in the class of true, but trivial. Almost everyone during the period that Tolkien was a mature man was a white supremacist as we’d understand it (including American presidents such as Franklin Delano Roosevelt). More interesting to me is the idea that Tolkien has cast an aura over high fantasy literature, and straight-jacked it into a Northern framework, which is implicitly or explicitly white supremacist.

It is hard to deny the influence in the general sense. The authors Brandon Sanderson and Patrick Rothfuss have both talked about the distorting influence of Tolkien and his legendarium on the fantasy genre. The “Tolkien copy-cat” phenomenon to some extent defines high fantasy, or at least it did until the past decade or so when many authors have tried to imitate George R. R. Martin’s style (Terry Brooks’ success was in large part due to his conscious imitation and remixing of Tolkien).

Arguably part of the legacy then is the implicit racial order that is outlined in The Lord of the Rings. But let’s be clear here: the audience for fantasy literature in the United States and England is going to be mostly white, and white people seem to identify with other white people in fiction whether literary or visual. I’m not justifying, as a non-white person who has read fiction and watched film and television where the protagonists were mostly white for most of my life, I can tell you it’s not that hard to identify with a character of a different race. After all, everyone is a human.

But sometimes you want something different. A few years ago I read Saladin Ahmed’s Throne of the Crescent Moon. The author is a moderately prominent political commentator on Twitter, and his views are standard postcolonial Leftist from what I can tell. This is a guy who’s against hegemony. So one of my criticisms of Throne of the Crescent Moon is that it substitutes a Eurocentric white hegemony for a Near Eastern quasi-Islamic hegemony. That is, the world of Throne of the Crescent Moon seems highly derivate of the Abbasid Caliphate of Harun al-Rashid, and reflects the cultural self-confidence of the period for Muslims. It’s certainly not one where oppression is in scarcity.

This isn’t necessarily a bug, but Ahmed basically traded swords for scimitars, and deracinated Christianity for quasi-Islam, and called it good. And perhaps it was good. I didn’t have a problem with it fundamentally. And if your problem with “white supremacy” is the “white” part then that is solved. The only issue though is that there was clearly a supremacy left within the story.

There are other ways to go a different direction from Tolkien. Consider Ricardo Pinto’s The Chosen, the first of a series. This is actually a very original piece of work in relation to the world-building, without clear analogs to the universe we live in. For lack of a better descriptor, Pinto has created a world of bronze age brutality. But The Chosen also has a strong romantic element, and it is distinctive in that it culminated in a gay relationship. In interviews, Pinto has been explicit that his vision was to create a fantasy which reflected gay themes, and he certainly achieved that.

But going back to the issue I highlighted above, the world of The Chosen is also explicitly racially hierarchical, with the herrenvolk being tall, lean and very pale skinned, and ruling tyrannically and brutally over the dark races. Additionally, there is also an aspect of “mighty whitey” as the series progresses. I wouldn’t reduce Pinto’s novels to this caricature, but there is certainly something in them that Ernst Rohm would find appealing.

Less famously, but more explicitly, than Ursula K Le Guin in Tombs of Atuan, Judith Tarr engaged in racial inversion (at least from a white perspective) in her series of Avaryan novels. The protagonists were dark of complexion. The lands of the great enemy were inhabited by a paler people, with genuinely white-skinned people being very exotic creatures on the very margins of the known world. In Tarr’s human geography the cold northern areas are occupied by the darkest skinned peoples, while to the south there were nations whose appearance was of a paler brown. This shakes us from comprehending this universe as similar to ours because this goes against what we see in our world. And like Pinto’s work, there is a strong homoerotic element throughout the whole series, and unabashed depictions of homosexual sex (though the characters are not necessarily gay in this case).

And yet in the overall skeins, the same quasi-medieval superstructure still exists as a distinct scaffold. The author scrambles our expectations and rearranges and reorders the normative frameworks in Tolkien’s high fantasy, but the broad themes of self-discovery of the aristocratic young prince whose inheritance awaits, or the conflicts between empires and civilizations ebbing away through a marital alliance, reemerges from the fog of novel landscapes. After all the modification and inversion we find something distinctly feudal that remains before us.

My point is that the regressive and reactionary nature of high fantasy is literally baked into the nature of the genre. Unlike science fiction fantasy does not explore an unlimited space of the possible. The marginally science fictional aspects of R. Scott Bakker’s Prince of Nothing series are attenuated, and you have to look closely to see them for what they are. If Bakker’s work had been suffused by spaceships then they’d transform into something different fundamentally, and the possibilities would open up. Science fiction plays with physics, biology, chemistry, as well as anthropology, economics, and history. In contrast, high fantasy as we understand it is delimited by a vision of anthropology, history, and linguistics. As such the canvas of the stories is necessarily narrower. High fantasy is by definition a genre which looks before the industrial revolution, and so takes as a starting point the norms and expectations of agrarian societies.

For the vast majority of human history, our existence has been defined by agrarian societies. I say here history, because the vast majority of our species’ existence is nevertheless pre-agrarian. The mythologies of San Bushmen, Mbuti Pygmies, and Australian Aboriginals, are all very different from the polytheisms of antiquity, with their kings in heaven and conquered gods in trapped in Tartarus. Hunter-gatherer society is and was more egalitarian. There were likely no great autocratic lords, even if there were greatest hunters or the eldest and most powerful wise women.

When it comes to agrarian society complex structure, hierarchy, and attention to lineage and a level of inter-group brutality were typical. These are the nostalgic worlds that high fantasy draws inspiration from, and by their nature, they will be difficult to reflect a liberal and egalitarian ethos in an all-pervasive sense. It is not difficult to identify with a protagonist who is decent and who reflects our sensibilities, but often they are swimming against the cultural tide.

Not to beat a dead horse, but I think the idea of a “minimally counter-intuitive narrative” is useful here. Fantasy is “out of this world,” but it also has to exhibit some verisimilitude. Ricardo Pinto’s The Chosen is a bit atypical because it is not heteronormative in its focal protagonists, but many of the other expectations of high fantasy, the barbaric brutality, and injustice, remain in place. Kate Elliott’s Crown of Stars series depicted an alternative quasi-Christianity where men and women had greater equality, and in the world as a whole, but aside from that and the fact that the Vikings were a separate species and elves’ existed, the whole series drew very heavily on 10th century Europe. One can modify many of the elements of a world and narrative to make it fantastical, but one also needs to not push it too far.

Imagining ourselves as a viewpoint character living in the past of our secondary world can help us to understand what is, and isn’t, plausible. Dragons? Plausible. Our pre-modern viewpoint character doesn’t think that dragons are impossible creatures. Quasi-human creatures? Again, plausible. Remove all inequality and guarantee affluence? In a Malthusian world, this is simply not conceivable. Abundance existed, but only for elites, or in the afterlife. Mitigation and amelioration of injustice and inequality were plausible, and in many religious-ethical systems preferred and meritorious, but there was no expectation or conception that injustice could be totally eliminated. Matthew 26:11.

Additionally, not only does one have to be attuned to pre-modern perspectives on verisimilitude, one needs to recall that a messy and imperfect world is actually fertile ground for narrative tension. One of the problems with Star Trek as envisioned by Gene Roddenberry was that in the liberal utopia of the future all the dramatic tension had to come from external sources.

Which gets us back to the original question: did Tolkien’s world-building virtuosity contingently rig the game for white supremacy in modern high fantasy? I don’t think so. High fantasy seems to draw upon pre-modern mythology. That mythology by its nature is from agrarian societies, which precede the modern world. These societies were hierarchical. This hierarchy is quite offensive fundamentally to modern liberal sensibilities, broadly construed.  They are supremacist, albeit along the dimension of class.

In the English speaking world, the audience is mostly white, and the protagonists in fantasy and science fiction also tend to be white. This is not realistic, and it’s not racist per se, but it’s a general trend across our society and not limited to high fantasy (the New York City of Seinfeld and Friends was overwhelmingly white). Combine white protagonists with a hierarchical world…I think it’s hard to avoid being labeled a white supremacist appealing genre in the present year.

The ultimate problem here is that the current postcolonial fixation with white supremacy elides the reality that the problem is not whiteness, but supremacy. The Baltic pagans treated like beasts of burden by their German Christian conquerors were arguably even whiter physiognomically than the German Christian. Still they were treated oppressively, to the point of genocide in the case of the Old Prussians.

Let me end by quoting Agent Smith from the Matrix:

“Did you know that the first Matrix was designed to be a perfect human world where none suffered, where everyone would be happy? It was a disaster. No one would accept the program. Entire crops were lost. Some believed that we lacked the programming language to describe your “perfect world”. But I believe that, as a species human beings define their reality through misery and suffering. So the perfect world was a dream that your primitive cerebrum kept trying to wake up from.”

* If you don’t believe me take a look at the map of Khand, the names of the cities are a melange of Indian and Iranian influences.

 

Guess who’s coming to dinner: the stranger


A preprint on aRxiv, The Strength of Absent Ties: Social Integration via Online Dating, purports to explain the increased rate of interracial/ethnic marriage in the United States as a consequence of online dating. They have ways to control for the fact that the proportion of non-whites in the United States has been increasing over the same time period. It diminishes the effect based on their model that online dating results in more interracial marriage, but it does not abolish the effect. They observe that interracial marriages seem to have increased around 1995, when the internet began, 2006, when services like OKCupid became very popular, and in 2014 when Tindr became a phenomenon.

I don’t know about these dates and the impacts of these services on the census data. Rather, the key and more interesting findings are that many more Americans now marry people who are total strangers outside of their social networks.* Previously more people tended to marry people who they were loosely connected to. Not close friends, but perhaps acquaintances, or friends of friends. With ~30% of marriages being attributable to online dating, people who are totally unconnected are now marrying, and so binding together two very distinct networks (in theory). This is an important dynamic to observe and note.

On the whole, I’m pessimistic about the United States. These results make me optimistic.

* Though to be fair, among a certain set it has always been common to marry people you meet at university. In this case, you are likely from two different social networks entirely. This is the case for me, and most of my friends from what I can tell. So the effect must be more impactful lower down the socioeconomic index.

The four modes of atheism

I have mentioned Big Gods: How Religion Transformed Cooperation and Conflict before. It’s worth reading. I’d describe it as a cross between In Gods We Trust: The Evolutionary Landscape of Religion and Ultrasociety: How 10,000 Years of War Made Humans the Greatest Cooperators on Earth. Of course, that means I’m not sure I got the maximal utility from reading it since it leans on so much that I already internalized. But it’s a great introduction to the modern scientific study of religion.

But there was one aspect which I found rather novel, because it introduced new data to me. In particular, the author tackled the origin of atheism, and why it might vary as a function of location and time.

There are four causes of atheism that are surveyed in Big Gods:

1) Personality (low social intelligence)
2) Hyper-analytic cognitive style
3) Societal apathy toward religion
4) Lack of strong modeling of religiosity

The first two are straightforward. There has long been a hypothesis that those with lower social intelligence or weaker in ‘theory of mind’ have a more difficult time to find personal gods plausible. In short, theism depends on a relatively normal theory of mind. Looking at people on the autism spectrum who recounted their ideas of religion and god the author confirmed the intuition. Autistic individuals tended to be less religious, and, if religious, presented a model of God that was often highly impersonal and abstract.

One issue that is important to highlight here: I suspect that many great theological “truths” actually derive from individuals who engage in excessive intellectualism around the idea of god. For the average human applying formal logic to theism is probably beside the point, though these sorts of religious intellectuals loom large in the books because…they are the ones writing the books.

This relates to the second issue. The author and his colleagues did research where they primed individuals by engaging them in highly analytic thought. Correcting for background variables they found that this biased respondents toward an impersonal god or atheism appreciably. Again, I think it gets to the fact that for most humans supernatural beliefs are about the synthesis of intuitions and passions. Excessive intellectualization is more likely to engender skepticism, or, a hyper-formal model of religion (which I think has become religion qua religion for some).

The last two elements are related. In Phil Zuckerman’s Society Without God he observes that in highly secular Scandinavia many respondents found it difficult to articulate strong feelings toward religion. It was simply not a prominent social institution in the society, though it was still part of the cultural furniture. But like furniture, it didn’t stand out. Societies with strong states, robust institutions, and impartial rule of law, along with some modicum of prosperity, tend to have lower levels of religiosity, and weaker passions about the topic from respondents. Once religiosity becomes less salient in a broad sense, then it becomes less of a concern in general for individuals.

A separate dynamic is that once people stop acting in a way that indicates that religion is important and true, others who take social cues begin to internalize this as evidence that religion isn’t that important. The authors give the example that there is social science that people who are raised Christian by parents who don’t go to church are far more likely to leave Christianity as adults because their parents did not credibly signal that religion was actually important enough to sacrifice any time and effort for. Perhaps another example which works as an analogy is that the vast majority of the children of interfaith Jewish-Christian marriages who were raised as Jews end up marrying non-Jews.

I think the first two factors in the list above explain the low but consistent basal rate of atheists and heterodox thinkers across history. One thousand years ago in Syria the poet Al-Ma’arri made statements such as below:

Do not suppose the statements of the prophets to be true; they are all fabrications. Men lived comfortably till they came and spoiled life. The sacred books are only such a set of idle tales as any age could have and indeed did actually produce.

Al-Ma’arri was a brilliant eccentric, so he was tolerated. Some of his quips prefigure H. L. Mencken’s, as when he said that “The inhabitants of the earth are of two sorts: those with brains, but no religion, and those with religion, but no brains.”

The other two forms of irreligiosity lead to standard models of secularization through increased affluence and decreased social relevance of religion as an institution. The United States was long the exception to this trend, but as recounted in books such as American Grace, it seems that secularization is starting to have its impact on the United States as well. Basically, as social norms shift to relax incentives toward being religious, more marginal believers will start expressing irreligiosity. At some point, some will start to conform to irreligiosity.

Of course, this sort of secularization is fragile. Aside from the sorts of demographic arguments made in Shall the Religious Inherit the Earth, examples such as post-Soviet Russia (and the post-Soviet nation-states more generally), as well as the progressively more religious nature of the Baathist resistance to American occupation in Iraq, illustrate that religion can bounce back rather fast, even within a generation or severl years. The social contexts for this resurgence are outlined in the book, but they illustrate that in some ways secularization is a thin culturally conditioned dusting atop a religious cognitive substrate.

Smartphones killed the fabulist

EVIL!!!

In The Wall Street Journal Nicholas Carr has a bizarre but unsurprising op-ed, How Smartphones Hijack Our Minds:
Research suggests that as the brain grows dependent on phone technology, the intellect weakens
. By the title, you can immediately pick out tells that should induce skepticism. “Research suggests” is usually indicating that the author has a hypothesis, and they went and searched the literature for research that confirmed their hypothesis. Carr actually did better than much of modern journalism. He found peer-reviewed literature, instead of quote mining, or selective elisions. Journalism, you have a story to tell, and you’ll make someone else tell it!

And to his credit, Carr cites the publications transparently, with links. Unfortunately, you see that in some cases the sample sizes are very small, and the statistical significance is marginal. In other instances, it doesn’t seem like there’s any real causality. One can’t know if there is a confound with who decides to take phones to class and who does not. It may be that those students who are very focused simply don’t take their phones. Finally, a lot of the research cited in the piece looks like it was sliced and diced to me.

This is where a little history and cognitive neuroscience would go a long way. Traditionalists have inveighed against new information technologies for the whole history of the human race. No doubt when complex syntax emerged some spoiled-sport argued that it was being abused to gossip and waste time.

Most people know that some of the ancient Greeks worried that the spread of literacy was eroding the power of memory. Less well known is that the printing press helped usher in the final decline of the art of memory.

And literacy does rewire our brains. In Reading in the Brain Stanislas Dehaene outlines just how certain regions of the brain focused on shape perception are co-opted to recognize letters effortlessly. This may not be without cost. Muhammed Ali was semi-literate, in part due to dyslexia, and a recent biographer has argued that he had better visual-spatial abilities in part because he didn’t waste his attention and focus on learning to read instinctively.

Nicholas Carr has now built a career in large part on skepticism of the internet and information technology. He knows exactly how to write viral stories which travel on the internet by criticizing the internet.

And it is certainly hard to deny the distracting effect of the internet. But that’s looking at the glass half-empty. One of the positives of the ubiquity of smartphones is that it has forced the retirement of so many bullshitters. Today people can make something up, and you can just “look it up.” Everyone is fact-checking everyone, and distracting from the fabulous bullshit stories and “facts” that a certain type of person has always specialized in.

Like free trade, it’s easy to see the downsides of the internet, and mine the social science literature to “prove” that you’re right. That’s one of the benefits of the internet, it lets you find scientific research which can confirm any assertion you make under heaven. Carr’s leveraging the literature to service his likely false arguments is one of the internet’s downsides.

The Tibeto-Burman and Austro-Asiatic ancestry of Bengalis

My father’s mtDNA lineage phylogeography

When I first got my father’s 23andMe results the Y and mtDNA were an interesting contrast. He, and therefore myself, carried Y lineage R1a1a, the lord of the paternal lineages. That was not that great a surprise. In the 1000 Genomes results for the Bangladeshi sample 20% of the men were direct paternal descendants of the R1a1a progenitor.

The mtDNA was a surprise. It was G1a2. This was curious to me since Bangladesh has some of the highest frequencies in the world of haplogroups M, the subhaplogroups in question being mostly restricted to South Asia. I wasn’t surprised that I was R1a1a, but I was even more confident that my maternal lineage was going to be an M, as would my father’s (my own mtDNA is U2b, not common, but not so surprising). As you can see from the map 23andMe places my father’s maternal lineage somewhere in Northeast Asia. The only information I could get about the geography was for G1a, “G1a has been found in samples from China (Daur, Hui, Kazakh, Korean, Manchu, and a sample of the general population of the city of Shenyang), Japan, Korea, Vietnam, and Siberia (Yakut).”

The biggest sample of mtDNA results from Bangladesh I could find at N = 240 does not find any G at all, let alone G1a2. So this is clearly it is a rare haplogroup in the region. But, the authors do classify 13% of the Bangladeshis as carrying an “East Eurasian” haplogroup. Haplogroup A is found among Southeast Asians and Southern China, though not among Austronesians. Haplogroup F seems to have a similar distribution, as does D, B. The other haplogroups also seem “correctly” assigned in terms of modal distribution. They are all mostly East Asian.

Looking at the Y chromosome haplogroups in the 1000 Genomes there are two of O2 and O3, and one of C3, which are clearly of Southeast Asian origin. With N =5 out of 44 samples that is ~10%. O2 is interesting because it is found at very high frequencies among the Austro-Asiatic populations in South Asia, whether it be the Khasi, or Munda groups (general O2a). O3 seems associated with Tibeto-Burman populations, and C3 with East Asia more generally.

Read More

Genetic variation and disease in Africa


Very readable review, Gene Discovery for Complex Traits: Lessons from Africa. It’s open access, so I recommend it. The summary:

The genetics of African populations reveals an otherwise “missing layer” of human variation that arose between 100,000 and 5 million years ago. Both the vast number of these ancient variants and the selective pressures they survived yield insights into genes responsible for complex traits in all populations.

The main issue I might have is I’m not sure that focusing on 5 million year time spans is particularly useful. Rather, looking at the last major bottleneck for modern humans before the “Out of Africa” event would be key, since that’s when a lot of the common variation would disappear, and very rare variants probably don’t have deep time depth in any case. With all that being said, the qualitative analysis is on point.

One of the major issues in the “SNP-chip” era has been that ascertainment of variation has been skewed toward Europeans. Though more recent techniques have tried to fix this…this review points out that if you by necessity constrain the SNPs of interest to those that vary outside of Africa (most of the world’s population), you are taking may alleles private to Africa off the table. This is relevant because the “Out of Africa” bottleneck ~50,000 years ago means that African populations harbor a lot more genetic variation than non-African populations do.

The move to high-quality whole genome sequencing obviates these concerns. As a matter of course African variation will be “picked up” since the marker set is not constrained ahead of time.

Importantly the authors focus on South Africa and the Xhosa population. This group has about ~20% Khoisan genetic ancestry, which is very diverse, and, very distinct, from that of the remaining ~80% of its ancestry. With its large African immigrant population and highly diverse native groups, some of them quite admixed, South Africa could actually provide some hard-to-substitute value in biomedical genetics.

The Loneliest Neanderthal

Neanderthals are in the news again! This is good for me personally, as my company is selling Neanderthal trait analysis. Ooga-booga!

In any case, the two papers which have triggered the current wave of Neandermania are The Contribution of Neanderthals to Phenotypic Variation in Modern Humans, and A high-coverage Neandertal genome from Vindija Cave in Croatia. They are somewhat different. The first publication looks at introgressed archaic variants within modern populations. The second gets some results out of a much higher quality European Neanderthal which lived ~50,000 years ago.

The cool thing about the first paper is that it combined UK Biobank data, 100,000+ individuals, with hundreds of thousands of markers, and Neanderthal genomic data. Note that: a paper comparing ancient genomes with over 100,000 individuals and hundreds of thousands of markers. Now that’s 2017!

To find archaic alleles they:

  1. Looked for variants fixed in Yoruba (no Neanderthal), and homozygote or heterozygote in the alternative state in the Altai Neanderthal, which also segregated (varied) in the UK Biobank population. Basically, an allele not found in Africans but found in Neanderthals, and also found in appreciable fractions in the UK Biobank data set.
  2. They then took the SNPs above, and only retained ones confidently embedded in tracts of Neanderthal ancestry. Haplotype was consistent with admixture ~50,000 years ago (the length), and exhibited lower distance to Neanderthal than African genomes.

They did some stuff with tag-SNPs though. Overall they found a lot of the usual suspects. Pigmentation. Chronotype. But this passage jumped out at me:

In fact, for most associations, Neanderthal variants do not seem to contribute more than non-archaic variants. However, there are four phenotypes, all behavioral, to which Neanderthal alleles contribute more phenotypic variation than non-archaic alleles: chronotype, loneliness or isolation, frequency of unenthusiasm or disinterest in the last 2 weeks, and smoking status.

What they are saying is that for a lot of traits Neanderthals don’t really change the direction of the trait in humans, they just add more variants. This seems to be the case in pigmentation. Entirely unsurprising, Neanderthals were around for hundreds of thousands of years. Of course they had a lot of variation amongst themselves.

But the behavioral traits above shifted the modern humans in the aggregate who had the archaic allele somewhat. That is, being Neanderthal derived made a difference.

There have long been speculations about the sociality (or lack thereof) of Neanderthals. It would not be surprising if small population sizes meant that Neanderthals were less gregarious than modern humans, and that their lack of gregariousness did not redound to their benefit when they encountered the last wave of moderns.

Which brings us to the second paper. The big deal here is that it gives us a very high quality ancient genome of a European Neanderthal that lived ~50,000 years ago (the Vindija sample). Before this we had a high quality ancient genome of an Asian Neanderthal that lived ~125,000 years ago (Altai sample).  ~75,000 years is a long time. It’s so long that almost all the ancestry of modern non-Africans would have converged to a common population that long ago. Additionally, all the available data indicate that most of the admixture into modern humans from Neanderthals occurred around 50,000 years ago. So this new sample is definitely welcome.

It is not surprising that the Vindijia sample seems to be closer to the Neanderthal admixture population than the Altai sample. First, it is likely geographically closer, since all non-African populations have some Neanderthal ancestry West Asia is probably the top candidate, and southeastern Europe is not that far from West Asia in comparison to Mongolia. Second, it is basically contemporaneous with the Neanderthals who contributed ancestry to modern humans who left Africa. This means that the Neanderthal admixture percentage in non-Africans goes up moderately.

To me this is the most important paragraph:

It has been suggested that Denisovans received gene flow from a human lineage that diverged prior to the common ancestor of modern humans, Neandertals and Denisovans (2). In addition, it has been suggested that the ancestors of the Altai Neandertal received gene flow from early modern humans that may not have affected the ancestors of European Neandertals (13). In agreement with these studies, we find that the Denisovan genome carries fewer derived alleles that are fixed in Africans, and thus tend to be older, than the Altai Neandertal genome while the Altai genome carries more derived alleles that are of lower frequency in Africa, and thus younger, than the Denisovan genome (20). However, the Vindija and Altai genomes do not differ significantly in the sharing of derived alleles with Africans indicating that they may not differ with respect to their putative interactions with early modern humans (Fig. 3A & B). Thus, in contrast to earlier analyses of chromosome 21 data for the European Neandertals (13), analyses of the full genomes suggest that the putative early modern human gene flow into Neandertals occurred prior to the divergence of the populations ancestral to the Vindija and Altai Neandertals ~130-145 thousand years ago (Fig. 2). Coalescent simulations show that a model with only gene flow from a deeply diverged hominin into Denisovan ancestors explains the data better than one with only gene flow from early modern humans into Neandertal ancestors, but that a model involving both gene flows explains the data even better. It is likely that gene flow occurred between many or even most hominin groups in the late Pleistocene and that more such events will be detected as more ancient genomes of high quality become available.

These results seem to support earlier work indicate that Denisovans were admixed with an ancient hominin group which diverged very early on (probably the descendents of East Asia erectus?). And, that Neanderthals received gene flow from a lineage of modern (African?) humans 150,000 or more years ago. Since the latest work suggests that modern humans in some form have existed between from 200,000 to 350,000 years ago, this is entirely plausible.

But, it brings us the take-home message that the emergence of Pleistocene humanity was to a some extent characterized by reticulate gene flow, rather than a bifurcating tree.