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July 17, 2017

Castes are not just of mind

Filed under: Caste,Human Genetics,India — Razib Khan @ 8:31 pm

Before Nicholas Dirks was a controversial chancellor of UC Berkeley, he was a well regarded historian of South Asia. He wrote Castes of Mind: Colonialism and the Making of Modern India. I read it, along with other books on the topic in the middle 2000s.

Here is Amazon summary from Library Journal:

Is India’s caste system the remnant of ancient India’s social practices or the result of the historical relationship between India and British colonial rule? Dirks (history and anthropology, Columbia Univ.) elects to support the latter view. Adhering to the school of Orientalist thought promulgated by Edward Said and Bernard Cohn, Dirks argues that British colonial control of India for 200 years pivoted on its manipulation of the caste system. He hypothesizes that caste was used to organize India’s diverse social groups for the benefit of British control. His thesis embraces substantial and powerfully argued evidence. It suffers, however, from its restricted focus to mainly southern India and its near polemic and obsessive assertions. Authors with differing views on India’s ethnology suffer near-peremptory dismissal. Nevertheless, this groundbreaking work of interpretation demands a careful scholarly reading and response.

The condensation is too reductive. Dirks does not assert that caste structures (and jati) date to the British period, but the thrust of the book clearly leaves the impression that this particular identity’s formative shape on the modern landscape derives from the colonial experience. The British did not invent caste, but the modern relevance seems to date to the British period.

This is in keeping with a mode of thought flourishing today under the rubric of postcolonialism, with roots back to Edward Said’s Orientalism. As a scholar of literature Said’s historical analysis suffered from the lack of deep knowledge. A cursory reading of Orientalism picks up all sorts of errors of fact. But compared to his heirs Said was actually a paragon of analytical rigor. I say this after reading some contemporary postcolonial works, and going back and re-reading Orientalism.

To not put too fine a point on it postcolonialism is more about a rhetorical posture which aims to destroy what it perceives as Western hegemonic culture. In the process it transforms the modern West into the causal root of almost all social and cultural phenomenon, especially those that are not egalitarian. Anyone with a casual grasp of world history can see this, which basically means very few can, since so few actually care about details of fact.

Castes of Mind is an interesting book, and a denser piece of scholarship than Orientalism. Its perspective is clear, and though it is not without qualification, many people read it to mean that caste was socially constructed by the British.

This seems false. It has become quite evident that even the classical varna categories seem to correlate with genome-wide patterns of relatedness. And the Indian jatis have been endogamous for on the order of two thousand. From The New York Times, In South Asian Social Castes, a Living Lab for Genetic Disease:

The Vysya may have other medical predispositions that have yet to be characterized — as may hundreds of other subpopulations across South Asia, according to a study published in Nature Genetics on Monday. The researchers suspect that many such medical conditions are related to how these groups have stayed genetically separate while living side by side for thousands of years.

This is not really a new finding. It was clear in 2009’s Reconstructing Indian Population History. It’s more clear now in The promise of disease gene discovery in South Asia.

Unfortunately though science is not well known in any depth in the general public. The ascendency of social constructionism is such that a garbled and debased view that “caste was invented by the British” will continue to be the “smart” and fashionable view among many elites.

July 16, 2017

Open Thread, 07/16/2017

Filed under: Open Thread — Razib Khan @ 2:07 pm

I know that Game of Thrones is premiering tonight, but just wanted to remind readers that R. Scott Bakker’s The Unholy Consult will be out in a week. The author, R. Scott Bakker, has a blog, Three Pound Brain. He has some strange ideas…much of which I can’t make heads or tails of. But that’s OK, I enjoy his fiction, I don’t worship his philosophy.

I’m traveling, so not much time to comment. But let me say that I’m sad to see that Maryam Mirzakhani has died.

If you want to get a sense of the historical background of the framework within which I write much of this blog, you might find Will Provine’s The Origins of Theoretical Population Genetics of interest.

Tucker Carlson Goes to War Against the Neocons. I know that most people on the Left don’t like Tucker Carlson now because of his recent political postures, but back in the 2000s he was known as a quite heterodox (read: not partisan and boring) commentator. And I have to say that it is nice for someone to say what may of us, including former supporters of the Iraq invasion, think now and then when we recall the period before 2011.

July 14, 2017

The past was not PG

Filed under: Bible,Culture,Game of Thrones,Mythology — Razib Khan @ 9:34 am

The Week has published a screed against the low moral quality of Game of Thrones, Game of Thrones is bad — and bad for you. Obviously there is something to this insofar as one can see a coarsening of entertainment, or at least a decline in the stylized aspects of the depiction of reality.

But one of my initial reactions is that much of the narrative that we value from the past was not particularly PG. If you read The Harlot by the Side of the Road: Forbidden Tales of the Bible you see that the “Good Book”, in fact the only book many read front to back by many after the Reformation in Protestant Europe, has some quite unsavory tales. The story of Judah and Tamar in particular is hard to digest from a modern Western perspective because many of the elements are understated and workaday. Greek mythology is no better obviously. From Zeus raping Leda, Achilles throwing a fit because his sex-slave was taken away, to the tradition of Agamemnon sacrificing Iphigenia.

In some cases the shocking aspect of ancient stories is because moderns have different values. Slavery and concubinage were taken for granted during the period that the Hebrew Bible and Classical mythology crystallized into the forms which came down to us. In other cases I presume that it was unlikely that small children were going to ever read the original stories themselves, so sexual elements that might confuse were probably omitted in some oral tellings.

This is not to say that Game of Thrones is a modern masterpiece. But some of the disquieting, and frankly perverse, aspects of the narrative are only shocking if your standard is the relatively antiseptic literary fiction which one finds between the Regency and the cultural revolution of the 1960s. That is the aberration in human history, while gritty genre fiction much closer to primal human storytelling.

July 13, 2017

When white people were “ethnic”

Filed under: Religion — Razib Khan @ 3:22 pm

In the period between 2005 and 2010 I spent a fair amount of time reading about American history. And one aspect which interested me was the nature of the assimilation of white Americans of non-Protestant background, in particular Roman Catholics and Jews. This was triggered by reading The Impossibility of Religious Freedom, where the author argues that the modern American conception of church-state separation is difficult to understand in practice unless religion is defined as something similar to low church American Protestantism

Though the American founding was famously eclectic and tolerant, as befitted a republic designed by men with elite Enlightenment sensibilities, it was culturally without a doubt Protestant in heritage, if not belief. The American Revolutionary Zeitgeist was steeped in British-influenced anti-Catholicism. In keeping with the same sort of Protestant populism which inspired the Gordon riots a broad swath of American colonial opinion was critical of the Quebec Act for giving French speaking Catholics a modicum of religious liberty and equality before the law.

Despite this historical context the relationship between the Roman Catholic population and the American republic in the early years was relatively amicable. Most of the priests were French Canadians, and Catholic population was highly assimilated and integrated. The great change occurred with the arrival of large numbers of Roman Catholic Irish, as well as a Irish American clerical ascendency which drew upon a revival in the Church in Ireland.

John T. McGreevy’s Catholicism and American Freedom is probably the best history of the religion in the United States that I read during that period. Not because it’s comprehensive, it’s not. Rather, because it focuses on the tension between the Church and the American republic and society, and how it resolved itself, and how that resolution unravelled.

Periodically people in the media make allusions to the ability of the American republic and culture to assimilate Catholics and Jews, and how that might apply to Muslims today. The discussion really frustrates me because there is almost never an acknowledgement that Roman Catholics experienced various degrees of low-grade persecution during periods of the 19th century. The Ursuline Convent riots are just the most sensational incident, and the Know Nothing movement turned into a political party.

The expansion of public schooling in parts of this was country tied to anti-Catholicism. But the Catholics did not take this passively. The emergence of a whole counter-culture, and parochial schools, suggested that they were ready to fight back to maintain their identity. The powerful Irish clerics who served as de facto leaders of the Roman Catholic faithful seem to have wanted to establish a modus vivendi with the American government which recognized the Church’s corporate role in society. By and large American elites and culture rejected this attempt to import a European style model to the New World.

By the late 19th century a movement began in the American Roman Catholic Church which became labeled the Americanist heresy. Despite its official condemnation I would argue that “Americanism” eventually became the de facto ideology of most American Roman Catholics. As Catholics conceded and assimilated toward American liberal and democratic norms in their everyday life, the hostility from the general public declined, and by the middle of the 20th century Will Herberg’s Protestant, Catholic, Jew articulated a vision of religious harmony among white Americans.

It should be rather obvious from the above that I believe this religious harmony was achieved in large part through concessions that American Catholics made to the folkways of the United States. You see the same dynamic in Jonathan Sarna’s American Judaism. Second, in Catholicism and American Freedom McGreevy lays out the great unravelling of the Catholic hierarchy’s understanding with American society which occurred in the 1960s, as social liberalism went far beyond what even the most progressive Roman Catholic intellectuals were ready to countenance. And in this cultural revolution Catholics were shocked to find that their Jewish allies made common cause with mainline Protestants and post-Protestants.

The reason I am writing this is that the American landscape today is different in deep ways from that of the 19th and early 20th century. The lessons of Catholic and Jewish assimilation to a Protestant understanding of religion were achieved through bitter conflict, and the rejection of a corporatist accommodation between the American government and religious minorities, as was achieved in several European countries. The modern ideas of religious pluralism are fundamentally different from the explicit understanding of Protestant supremacy which ruled the day a century ago, and only slowly faded with assimilation of non-Protestants.

July 11, 2017

23andMe ancestry only is $49.99 for Prime Day

Filed under: 23andMe,D.T.C. Personal Genomics,Personal genomics — Razib Khan @ 11:10 am


23andMe has gone below $50 for “Prime Day”! For those of us who bought kits (albeit more fully featured) at $399 or even more this is pretty incredible. But from what I’m to understand these sorts of SNP-chips are now possible to purchase from Illumina for well less than $50 so this isn’t charitable.

At minimum a way to get a raw genotype you can bank later.

July 10, 2017

The sons of Ham and Shem

Filed under: Afro-Asiatic,History — Razib Khan @ 1:33 am


Recently I had the pleasure of having lunch with David Reich and he asked me about my opinions in relation to the Afro-Asiatic languages. I thought it was a strange question in that I get asked about that in the comments of this weblog too. Why would I have any particular insight? I gave him what I thought was the likely answer: Afro-Asiatic languages probably emerged from the western Levant. The ancient textual evidence indicates that to the north and east of Mesopotamia the languages were not Semitic. Though Akkadian, a Semitic language, was present at the dawn of civilization, Sumerian was the dominant language culturally in the land between two rivers, and it was not Semitic. As Lazaridis et al. did not detect noticeable Sub-Saharan African ancestry in Natufians, or later Near Easterners, I have become skeptical of any Sub-Saharan African origin for Afro-Asiatic.

But after the earlier post I made a few mental connections, and so I’ll put something up which pushes forward my confidence on a few issues. They lean predominantly on Y chromosomes. I understand that this sort of phylogeography has been shown to be not too powerful in the past, but in the scaffold of the ancient DNA framework it can resolve some issues.

About a decade ago study of Adolf Hitler’s paternal lineage (through male relatives) indicated that his haplogroup was E1b1b. Though reports that Hitler was non-European, because this is a very common lineage in non-Europeans, as well as Jews, were incorrect, it does turn out that Hitler’s paternal lineage is not associated with the Indo-European migrations. That is, unlike me, Adolf Hitler does not descend from the All-father, but rather one of the men who were conquered and assimilated by the steppe pastoralists.

But E1b1b is an interesting lineage. First, it is very common in much of Africa, especially the north. Second, it is common among the Natufian people according to Lazaridis et al. In contrast the Neolithic Iranian farmers seem to have harbored haplogroups J. Today the Near East is a mix of the two, which makes sense in light of the fact that reciprocal gene flow has occurred in the last 6,000 years.

Looking at E1b1b frequencies you notice a few things. The highest frequencies with large N’s are in the Cushitic and Berber languages. Haplogroup J has a different distribution, being skewed more to West Asia. In Ethiopia E1b1b is more common, but J is far more prevalent among the Semitic Amhara than the Cushitic Oromo. Though it is subtle autosomal DNA makes it clear that the Semitic speaking populations in Ethiopia-Somalia have more Eurasian ancestry than the Cushitic ones. I believe this is evidence of the multiple migration pattern discerned earlier.

If you go further south in East Africa and compare E1b1b and J you see a skew in the ratio. E1b1b declines in frequency, but J basically disappears. Among the Masai, who have a clear minor West Eurasian ancestral component, albeit far less than Ethiopians, 50% carry E1b1b. Among the Sandawe, who are a language isolate  with clicks, but exhibit Cushitic genetic affinities, 34% carry E1b1b. Among their Hadza hunter-gatherer neighbors, 15% do so. Among many Khoisan groups the frequency of E1b1b is 10%. Most of these groups exhibit no J haplogroup. This aligns easily with what Skoglund was reporting earlier: the first pastoralists had no “eastern farmer,” but did have “western farmer.” The Natufians were E1b1b. The wider reach of E1b1b in Africa in comparison to J is likely due to the fact that the admixed pastoralists were pushing into relatively virgin territories. Later Eurasian backflow events, which brought Semitic languages, encountered a much more densely populated Africa.

The hypothesis I present is that after the descendants of the Natufians made the transition to farming, some immediately pushed into areas of Africa suitable for farming and/or pastoralism. They quick diversified into the various Berber and Cushitic languages. The adoption of Nilo-Saharan languages, and later Khoisan ones, was simply the process of successive and serial admixture into local populations as these paternal lineages introduced their lifestyle. In the Near East many distinct Semitic languages persisted across the Fertile Crescent, and for whatever reason the various non-Semitic languages faded and Semitic ones flourished.

The great Bantu expansion was massive

Filed under: History,Human Genetics,Punt — Razib Khan @ 12:01 am

Lots of stuff at SMBE of interest to me. I went to the Evolution meeting last year, and it was a little thin on genetics for me. And I go to ASHG pretty much every year, but there’s a lot of medical stuff that is not to my taste. SMBE was really pretty much my style.

In any case one of the more interesting talks was given by Pontus Skoglund (soon of the Crick Institute). He had several novel African genomes to talk about, in particular from Malawi hunter-gatherers (I believe dated to 3,000 years before the present), and one from a pre-Bantu pastoralist.

At one point Skoglund presented a plot showing what looked like an isolation by distance dynamic between the ancient Ethiopian Mota genome and a modern day Khoisan sample, with the Malawi population about $\frac{2}{3}$ of the way toward the Khoisan from the Ethiopian sample. Some of my friends from a non-human genetics background were at the talk and were getting quite excited at this point, because there is a general feeling that the Reich lab emphasizes the stylized pulse admixture model a bit too much. Rather than expansion of proto-Ethiopian-like populations and proto-Khoisan-like populations they interpreted this as evidence of a continuum or cline across East Africa. I’m not sure if this is the right interpretation of the plot presented, but it’s a reasonable one.

Malawi is considerably to the north of modern Khoisan populations. This is not surprising. From what I have read Khoisan archaeological remains seem to be found as far north as Zimbabwe, while others have long suggested a presence as far afield as Kenya. Perhaps more curiously: the Malawi hunter-gatherers exhibit not evidence of having contributed genes to modern Bantu residents of Malawi.

Surprising, but not really. If you look at a PCA plot of Bantu genetic variation it really starts showing evidence of local substrate (Khoisan) in South Africa. From Cameroon to Mozambique it looks like the Bantu simply overwhelmed local populations, they are clustered so tight. Though it is true that African populations harbor a lot of diversity, that diversity is not necessarily partition between the populations. The Bantu expansion is why.

Of more interest from the perspective of non-African history is the Tanzanian pastoralist. This individual is about 38% West Eurasian, and that ancestry has the strongest affinities with Levantine Neolithic farmers. Specifically, the PPN, which dates to between 8500-5500 BCE. More precisely, this individual was exclusively “western farmer” in the Lazaridis et al. formulation. Additionally, Skoglund also told me that the Cushitic (and presumably Semitic) peoples to the north and east had some “eastern farmer.” I immediately thought back to Hogdson et al. Early Back-to-Africa Migration into the Horn of Africa, which suggested multiple layers. Finally, 2012 Pagani et al. suggested that admixture in the Ethiopian plateau occurred on the order of ~3,000 years ago.

Bringing all of this together it suggests to me two things

  1. The migration back from Eurasia occurred multiple times, with an early wave arriving well before the Copper/Bronze Age east-west and west-east gene flow in the Near East (also, there was backflow to West Africa, but that’s a different post….).
  2. The migration was patchy; the Mota sample dates to 4,500 years ago, and lacks any Eurasian ancestry, despite the likelihood that the first Eurasian backflow was already occurring.

Skoglund will soon have the preprint out.

July 9, 2017

Our civilization’s Ottoman years

Filed under: Culture,International Affairs,international relations — Razib Khan @ 9:29 pm

Some right-wing intellectuals are wont to say that multicultural and multiracial empires do not last. This is not true. Historically there are plenty which lasted for quite a long time. Rome, Byzantium, and the Ottomans, to name just a few of the longest. But, though they were diverse polities modern liberal democratic sensibilities would have been offended by them. That is because these empires were ordered and centered around a hegemonic culture, with other cultures accepted and tolerated on the condition of submission and subordination.

The Ottoman example is the most stark because it was formally explicit under the millet system by the end of its history, though it naturally evolved out of Islamic conceptions of the roles of dhimmis under Muslim hegemony. For 500 years the Ottomans ruled a multicultural empire. Yes, it decayed and collapsed, but 500 years is a good run.

I bring up the Ottoman example because I was having a discussion with a friend of mine, an academic, and he brought up the idea that the seeming immiseration of the middle to lower classes in developed societies will lead to redistributive economic policies. Both of us agree that immiseration seems on the horizon, and that no contemporary political movement has a good response. But I pointed out that traditionally redistributive socialism seems most successful in relatively homogeneous societies, and the United States is not that. American society is diverse. Descriptively multicultural. There would be another likely solution.

Eleven years ago Amartya Sen wrote a piece for The New Republic which could never get published in the journal today, The Uses and Abuses of Multiculturalism. In it he looked dimly upon the emergence of plural monoculturalism. Today plural monoculturalism is the dominant ideal of the identity politics Left, with cultural appropriation in vogue, and separatism reminiscent of the 1970s starting to come back into fashion. Against plural monoculturalism he contrasted genuine multiculturalism. I think a better word for it is cosmopolitanism.

The Ottoman ruling elite was Sunni Muslim, but it was cosmopolitan. The Sultan himself often had a Christian mother, while during the apex of the empire the shock troops were janissary forces drawn from the dhimmi peoples of the Balkans. This was a common feature of the Islamic, and before them Byzantine and Roman empires. The ruling elites exhibited a common ethos, but their origins were variegated.

Many of the Byzantine emperors were not from ethnic Greek Chalcedonian Christian backgrounds (before the loss of the Anatolian territories many were of Armenian, and therefore non-Chalcedonian, origin). But the culture they assimilated to, and promoted, as the core identity of the empire was Greek-speaking and Chalcedonian, with a self-conscious connection to ancient Rome. I can give similar examples from South Asia or China. Diverse peoples can be bound together in a sociopolitical order, but it is invariably one of domination, subordination, and specialization.

But subordinate peoples had their own hierarchies, and these hierarchies interacted with the Ottoman Sultan in an almost feudal fashion. Toleration for the folkways of these subordinate populations was a given, so long as they paid their tax and were sufficiently submissive. The leaders of the subordinate populations had their own power, albeit under the penumbra of the ruling class, which espoused the hegemonic ethos.

How does any of this apply to today? Perhaps this time it’s different, but it seems implausible to me that our multicultural future is going to involve equality between the different peoples. Rather, there will be accommodation and understandings. Much of the population will be subject to immiseration of subsistence but not flourishing. They may have some universal basic income, but they will be lack the dignity of work. Identity, religious and otherwise, will become necessary opiums of the people. The people will have their tribunes, who represent their interests, and give them the illusion or semi-reality of a modicum agency.

The tribunes, who will represent classical ethno-cultural blocs recognizable to us today, will deal with a supra-national global patriciate. Like the Ottoman elite it will not necessarily be ethnically homogeneous. There will be aspects of meritocracy to it, but it will be narrow, delimited, and see itself self-consciously above and beyond local identities and concerns. The patriciate itself may be divided. But their common dynamic will be that they will be supra-national, mobile, and economically liberated as opposed to dependent.

Of course democracy will continue. Augustus claimed he revived the Roman Republic. The tiny city-state of Constantinople in the 15th century claimed it was the Roman Empire. And so on. Outward forms and niceties may be maintained, but death of the nation-state at the hands of identity politics and late stage capitalism will usher in the era of oligarchic multinationalism.

I could be wrong. I hope I am.

Open Thread, 07/09/2017

Filed under: Open Thread — Razib Khan @ 8:29 pm


I’m a sucker for the aesthetics of Norden. Why? I wonder if part of it is that the fringe of Northern Europe is a science fictional setting. The long dark nights during the cold winter, and the twilight during midsummer. The sun may be bright, it never gets too high in the sky. The 13th Warrior wasn’t the best movie, but it was evocative. One of the problems with the film depiction of the Lord of the Rings trilogy is that New Zealand seems too bright and airy (and also not decayed enough).

Because of the SMBE meeting I haven’t made much progress on The Enigma of Reason. Much of it has been reviewing the literature in cognitive psychology and reasoning which I’m familiar with (system 1 vs. system 2, Wason reasoning task, etc.). Though it is leading me up to the main thesis.

I remember years ago Matthew Yglesias mentioned he was going to do a bit more reading of books, as opposed to news, to differentiate himself from other pundits. Today he admitted he wasn’t going to make a show of having an informed opinion about the Frankfurt School. I suggested he take time out to read The Dialectical Imagination: A History of the Frankfurt School and the Institute of Social Research, 1923-1950. The modern campus Red Guards don’t know anything about Adorno, Marcuse, or Horkheimer. But the outlines of contemporary project toward cultural revolution and exaltation of the marginalized are all there. Rather than being the origin modern radical movements, I suspect that the Frankfurt School simply provides a useful tool and framework to go about its project.

I do know that some politically moderate scientists who read The Dialectical Imagination, and saw campus politics in a totally different, and more intelligible, light.

Joe Pickrell’s new company, Gencove, Improving ancestry estimates in South Asia.

I said on Twitter that “easiest way to make housing affordable for non-rich is to build more houses for the rich so they won’t buy houses built for non-rich.” What do I mean? It’s all about supply. The well-off will always be first in line for any supply of housing. If you allow for copious development, vertically and horizontally, then the rich can purchase the luxury condos and mansions that they crave, while the middle class and lower class can buy up the more normal housing stock.

The Austin skyline, then and now.

Yazidi sex slave had to choose between son and escape from Isis.

Bangladeshi students test into elite schools. This story is about the entrance examinations for the elite public high schools of New York City. In 2010 the average Bangladeshi family in New York City had a household income of $37,000. I believe in the near future the entrance exams will not be the only criterion for gaining admission. The reality is that Asian American students lack “leadership” and are not “well rounded,” and all the Asian American applicants “look the same.”

A large-scale genome-wide enrichment analysis identifies new trait-associated genes, pathways and tissues across 31 human phenotypes.

Racism Is Everywhere, So Why Not Move South? This article is written in the context of black Americans. But the insights are general. Houston has a cost of living that’s at the national average. It’s the fourth largest city in the United States, and there is a lot of good phở because of the large Vietnamese community.

Patrick Wyman, who sometimes comments on this blog, has a great Fall of Rome podcast.

The Sad, Sexist Past of Bengali Cuisine. Really upper caste Bengali Hindu cuisine.

Utilities fighting against rooftop solar are only hastening their own doom. Not surprised. I have been following Ramez Naam’s commentary on this for years. He’s been on this.

Islamophobes are attacking me because I’m their worst nightmare. Linda Sarsour.

I thought Hillary would win the election. But I told a long-time reader of this weblog who is a Democratic operative that BLM activists getting in Bernie Sanders’ face did not presage well for the direction of the party. Linda Sarsour as the face of progressivism is a massive boon for the Right and Republicans.

Sarsour has left a trail of obnoxious and offensive comments on Twitter. So have many people. For me personally the biggest issue is possible solidarity with Rasmea Odeh. The PFLP is the literal definition of a terrorist organization (though a Marxist, not Islamic, one). But the reality is that her enemies on the Right know that she and her compatriots in the “woke” movement would never exhibit charity toward their political opponents, so they are attempting to destroy her because they know she would do the same to them. That’s where we are in American politics today. You destroy your enemies, or they destroy you. Let’s have fun until the last battle though!

A combined analysis of genetically correlated traits identifies 107 loci associated with intelligence. I guess I’ll start paying attention to when they can explain ~25% of outgroup sample variance. They’re already further than the 7% in this preprint, though that will take a little longer to publish.

Procedures for enumerating and uniformly sampling transmission trees for a known phylogeny.

A reanalysis of Schaefer et al. does not indicate extensive CRISPR/Cas9 mediated off-target editing events.

Evolutionary Action of de novo missense variants across pathways prioritizes genes linked to autism and predicts patient phenotypic severity.

SLC24A5 is very important, but we don’t know why


The golden of pigmentation genetics started in 2005 with SLC24A5, a putative cation exchanger, affects pigmentation in zebrafish and humans. Prior to that pigmentation genetics was really to a great extent coat color genetics, done in mice and other organisms which have a lot of pelage variation.

Of course there was work on humans, mostly related to melanocortin 1. But more interesting were classical pedigree studies which indicated that the number of loci controlling variation in pigmentation was not that high. This, it was a mildly polygenic trait insofar as some large effect quantitative trait loci could be discerned in the inheritance patterns.

From The Genetics of Human Populations, written in the 1960s, but still useful today because of its comprehensive survey of the classical period:

Depending on what study samples you use variance on a locus of SLC24A5 explains less than 10% or more than 30% of the total variance. But it is probably the biggest effect locus on the whole in human populations when you pool them altogether (obviously it explains little variance in Africans or eastern non-Africans since it is homozygous ancestral by and large in both groups).

One aspect of the derived SNP in this locus is that it seems to be under strong selection. In a European 1000 Genomes sample there are 1003 SNPs of the derived variant, and 3 of the ancestral. Curiously this allele was absent in Western European Mesolithic European hunter-gatherers, though it was present in hunter-gatherers on the northern and eastern fringes of the continent. It was also present in Caucasian hunter-gatherers and farmers from the Middle East who migrated to Europe. It seems very likely that these sorts of high frequencies are due to selection in Europe.

The variant is also present in appreciably frequencies in many South Asian populations, and there seems to have been in situ selection there too, as well as the Near East. In Ethiopia it also seems to be under selection.

It could be something due to radiation…but the Near East and South Asia are quite high intensity in that regard. As are the highlands of Ethiopia. About seven years ago I suggested that rather that UV radiation as such the depigmentation that has occurred across the Holocene might be due to agriculture and changes in diet.

But a new result from southern Africa presented at the SMBE meeting this year suggests that this can not be a comprehensive answer. Meng Lin in Brenna Henn’s lab uses a broad panel of KhoeSan populations to find that the derived allele on SLC24A5 reaches ~40% frequency. Probably a high fraction of West Eurasian admixture in these groups is around ~10% being generous. Where did this allele come from? The results from Joe Pickrell a few years back are sufficient to explain: there was a movement of pastoralists with distant West Eurasian ancestry who brought cattle to southern Africa, and so resulted in the ethnogenesis of groups such as the Nama people (there is also Y chromosomal work by Henn on this).

Sad human with two derived alleles of SNP of interest

Lin reports that the haplotype around SLC24A5 is the same one as in Western Eurasia. Iain Mathieson (who is now at Penn if anyone is looking for something to do in grad school or a post-doc) has told me that the haplotype in the Motala Mesolithic hunter-gatherers and in the hunter-gatherers from the Caucasus are the same. It seems that this haplotype was widespread early in the Holocene. Curiously, the Motala hunter-gatherers also carry the East Asian haplotype around their derived EDAR variant.

I don’t know what to make of this. My intuition is that if a haplotype like this is so widespread nearly ~10,000 years ago recombination would have broken it apart into smaller pieces so that haplotype structure would be easier to discern. As it is that doesn’t seem to be the case.

And we also don’t know what’s going on withSLC24A5. Obviously it impacts skin color. It has been shown to do so in admixed populations. But it is hard to believe that that is the sole target of natural selection here.

July 2, 2017

Rome fell fast, and so did we

Filed under: History — Razib Khan @ 11:46 pm

The fall of Rome has obviously been a topic of much interest and discussion. It is, after all, a conversation about the fall of civilization as we knew it.

If you read my blog you are probably aware that I lean toward a thesis of genuine and rapid fall. One of the most revelatory books I’ve read in the past 20 years is Bryan Ward-Perkins’ The Fall of Rome: And the End of Civilization. Ward-Perkins’ tale is an apocalyptic one. The material basis of Roman civilization the West collapsed. Perhaps the most relevant and evocative fact for me is that pollution due to manufacturing production in England did not match that of the Roman period until the industrial revolution. Though the Roman economy never achieved the industrial revolution’s gains in productivity, it did attain a level of Smithian efficiency and interdependence on the margins of the factors of production.

From a totally different perspective Peter Heather in The Fall of the Roman Empire broadly agrees with Ward-Perkins’ contention. The Roman Empire fell, and it fell fast, and the imperial elites didn’t see it coming. Remember, the Roman Empire was dismembered and disordered during the “crisis of the third century”. Under Diocletian and his successors in the 4th century it came back to health and strength before the distress of the 5th century in the West. But at the time contemporaries did not view the shocks and exigencies of these decades as any more distressing then the events of the 3rd century, and the Eastern Empire around Constantinople was reasonably robust.

Ultimately though 476 was a coup de grace to the Western Empire. The Gothic wars tore apart the fabric of the Italian peninsula in the 6th century, and the substantive reality of the old empire faded away. There was no going back. Of course I’m well aware of the argument that the Roman world evolved, that it did not collapse. And Late Antiquity and its continuities with the Classical world, and how it bridged itself to the Medieval world, are fascinating. But I do not accept that the preservation of Roman motifs and ideals in the courts of barbarian German warlords is evidence that substantively nothing changed.

Much of it depends on how you weight material vs. ideological parameters. The idea of Rome cast a shadow centuries beyond its substantive material integrity. After, the Byzantines called themselves Romans until the conquest of their city-stateless in 1453. But no matter the name, they were not Romans as the Romans were in 400 A.D.

The theoretical context of all this is that it strikes me cultures can go through rapid nonlinear shocks which induce very quick and unexpected changes. In the human past this would often entail collapses and regressions. The “Dark Age” after the chaos of the late Bronze Age is a case in point. In one generation the citadel society of Mycenanean Greece disappeared across much its extant range. The gap between 1966 and 1969 in much of the West was arguably greater than between 1956 and 1966.

The United States today is the most powerful nation in the world. And our cultural centrality and ascendency is such that we don’t challenge our implicit position as the premier power in the world. But I believe that we’ve become a inward looking involuted culture. There’s no point in litigating this, and obviously I may be wrong. But too often we confuse our own petty internecine squabbles with the concerns of the world. The world is passing us by….

Open Thread, 7/3/2017

Filed under: Open Thread — Razib Khan @ 10:25 am

Reading The Enigma of Reason. Pretty good so far. Not incredibly surprising to me so far. To be clear, their argument is somewhat orthogonal to the whole ‘rationality’ debate you may be familiar with from Daniel Kahneman and Amos Tversky’s work (e.g., see Heuristics and Biases).

One of the major problems in analysis is that rationality, reflection and ratiocination, are slow and error prone. To get a sense of that, just read ancient Greek science. Eratosthenes may have calculated to within 1% of the true circumference of the world, but Aristotle’s speculations on the nature of reproduction were rather off.

You may be as clever as Eratosthenes, but most people are not. But you probably accept that the world is round and 24,901 miles around. If you are not American you probably are vague on miles anyway. But you know what the social consensus is, and you accept it because it seems reasonable.

One of the points in cultural evolution work is that a lot of the time rather than relying on your own intuition and or reason, it is far more effective and cognitively cheaper to follow social norms of your ingroup. I only bring this up because unfortunately many pathologies of our political and intellectual world today are not really pathologies. That is, they’re not bugs, but features.

But I do suspect that the human bias toward trusting social wisdom is less useful in a world as fast changing and protean as ours. The math is pretty clear that in a stable environment there is no gain to reinventing wheels, as opposed to learning and believing what always works. Where individual learning and cognition are useful is in a situation where parameters are changing constantly, and folk wisdom leads you astray.

The Languages of Political Islam in India c.1200–1800 is only $5.99 on Kindle. I have no idea how Amazon figures out which academic books to discount highly, and which not to, but it’s always something I keep an eye out for.

RV dwellers in Palo Alto neighborhood forced to motor on and a reflection by a Stanford post-doc how difficult it is to make ends meet. One response is “we need affordable housing.” The reality is that you don’t need anything targeted, and special-built housing for the poor inevitably is subject to shortages. What is needed is more housing. But for various reasons incumbents between San Francisco and San Jose don’t want development.

Viral NRA ad sparks controversy. People are very freaked out on my Twitter timeline (I mostly follow liberals since I mostly follow scientists). Some people are saying that this is white supremacy in action. At this point it is useful to step outside of your socio-political bubble. For the past few years the dominant Left discourse has suffused all injustice with the term “white supremacy” and “systemic racism.” At some point you desensitize people who aren’t already fully on board with you

If 2011’s Rise Of The Planet of the Apes was filmed today I wonder if CRISPR/Cas9 would play a role?

I will be filling up the #SMBE17 hashtag tomorrow.

Bringing Neanderthals to Life: The Sculptures of Elisabeth Daynès. Neanderthals are depicted as having straight hair and African hominins with wooly hair. Is this justified? Is wooly hair the ancestral state?

Since wooly hair is found in many disparate human populations it probably is ancestral. But it would be nice to have more than a hunch or phylogenetic inference based on extant distributions of the trait.

July 1, 2017

How much bigger Americans are in two generations

Filed under: fitness,Health,Ketogenic Diet — Razib Khan @ 2:24 pm

 

Average American Size 2015
  Men Women
Height 69.2 inches (175.8 cm) 63.7 inches (161.8 cm)
Weight 195.7 lbs (88.8 kg) 168.5 lbs (76.4 kg)
Waist 40 inches (101.5 cm) 38.1 (96.9 cm)
     
Average American Size 1960
  Men Women
Height 68 inches (173 cm) 63 inches (160 cm)
Weight 166.3 lbs (75.3 kg) 140 lbs (63.5 kg)

The film WALL-E came out in 2008, and at this point it seems already quaint. Remember, when WALL-E was in theaters smartphones were not ubiquitous. Today it is not abnormal for people in social situations to always have one eye on their phone, or for people to text each other in close proximity.

Another aspect of WALL-E is that it depicted future humans as obese unitard wearing consumers. If such a film came out in 2017 I do wonder if it would be accused of being fatphobic and fat-shaming. WALL-E‘s general critique of post-industrial gluttony seems to be spot on.

Some of this is on my mind because I’ve gained 5-10 pounds over the past year due to new jobs and a move. As some of you know I’ve been trying out the ketogenic diet. In just a few weeks I’ve shed enough water weight to make a difference.

I would recommend it to someone trying to kickstart a change in their lifestyle for a simple reason: it does take care of the satiety aspect. If you work long hours it reduces the urge to snack on something. But if you are a social eater it will be difficult for it to be sustainable. I’m going to go off the diet for SMBE.

After joining a gym recently I got a full body analysis of my fitness level. At 5’8 and at 165 pounds I feel rather large for me. My body fat percentage was estimate at around 17%, which sounds right (I fluctuate between 14 and 18 depending on my fitness level). Recently my waist has gone up to 31 inches from 29 or 30. But I was surprised that my percentiles were not that bad.

That’s because the average American man is rather overweight.

Look at the statistics above. You probably know this, but let’s reiterate: the average American woman in 2015 is heavier than the average American man in 1960.

June 30, 2017

Bret Weinstein talks about being hunted on campus

Filed under: Bret Weintsein — David Hume @ 8:37 pm

Does Tad Williams still have game?

Filed under: Fantasy,Tad Williams,The Witchwood Crown — Razib Khan @ 12:38 am

Like many people I was quite taken with Tad Williams Memory, Sorry, and Throne, when they came out in the years around 1990. George R. R. Martin has admitted that Williams’ trilogy helped awaken him to the possibilities of the fantasy genre.

I tried to read his Shadowmarch series, but I didn’t find it as original so gave up after one and a half books. So I was excited for Williams to go back to a world where he seemed to shine. The first reviews for The Witchwood Crown make it seem like it’s actually pretty good, and perhaps even might be better then the original series. Not sure frankly I’ll ever get to reading it, but who knows.

Addendum: In the fall Brandon Sanderson is coming out with Oathbringer, and R. Scott Bakker’s Unholy Consult will be out at the end of July. I preordered the latter because I thought Bakker’s second book in the tetralogy was actually better than the first two so I have hopes the fourth will be best of all.

Basal humans in our evolutionary closet

Filed under: Basal Humans,Neanderthal — Razib Khan @ 12:19 am

The ancient genome from South Africa was of not because it confirmed what many had long suspected: the deep structure of modern humans in Africa goes back quite a bit further than we had been assuming. A few years ago I co-wrote an op-ed for USA Today where I initially wrote that the Khoisan divergence from other humans was around ~200,000 years ago. For various reasons I let a “fact-checker” change that to ~150,000 years ago. But as I told my co-author Alex Berezow people had access to whole genomes just leaning toward an older date than in the current literature.

Now we know that the date of divergence may be closer to ~300,000 years. Both because of the ancient DNA, and the Moroccan fossils which make it obvious that morphology associated with our own lineage was already beyond incipient before 300,000 years ago.

The past was more complicated than we think. Ancient DNA has made us toss many of our preconceptions out. For example, several years ago researchers concluded that the Out of Africa populations exhibited a different structure than we had thought. Populations of the Near East and Europe had ancestry from a group that was basal to all other non-Africans. That is, if you have a family tree then Oceanians, East Asians, Amerindians, Siberians, and European hunter-gatherers would be on one branch. On the other branch would be “Basal Eurasians” (BEu), named due to their basal position on the tree in comparison to all other non-Africans. Ancient DNA has not uncovered any population which is mostly BEu. Early Holocene Near Eastern populations, the various first farmers, invariably seem to show mixture between BEu and a West Eurasian element similar to what gave rise to the Mesolithic hunter-gatherers of Europe.

It seems possible we may never find “pure” BEu samples. We know that 10,000-15,000 years ago in Europe there was a massive expansion of a population of hunter-gatherers with stronger affinities to modern Middle Easterners than in the past. Perhaps this was part of a broader expansion of this group of hunter-gatherers across vast swaths of Western Eurasia, and in the process they absorbed the BEu populations until there were no pure populations left?

These questions were triggered by novel results which couldn’t be accommodated by current accepted models. This reminds me of a paper from over a year ago which presented some puzzling results which make much more sense now, Ancient gene flow from early modern humans into Eastern Neanderthals. The authors compared the Altai Neanderthal genome, the Denisovan genome, and those of modern humans (as well as a European Neanderthal). The stylized phylogenetic tree is one which the Neanderthal-Denisovan clade spits off from African proto-modern humans ~600,000 years ago. Then around ~400,000 years ago you see the divergence between Neanderthals and Denisovans. This gives us rough expectations as to the nature of the genetic variation in these populations, as they shared quite distinct periods of evolutionary history together and apart.

What the authors found is that a small minority of the Altai Neanderthal genome exhibited much stronger affinities to modern African populations than to the Denisovan. On the order of ~5%. Looking at the length of the haplotypes they estimated that the admixture occurred ~100,000 year ago. Curiously, at least at the time, this modern human population was basal to all modern humans. The authors estimate that the divergence from modern lineages occurred about ~200,000 year ago based on what was understood about modern human differentiation at the time.

At the time that was pushing it, though not unreasonably so. Now that number is probably comfortably defensible. One important point to note is that the modern human admixture was from a group equally related to all Africans. This implied that this group separated before the division of the Bantu and the Yoruba. So if you accept the most recent genomics then this group may date to closer to 260,000 years before the present. And in fact if the fossil record is correct they might have separated as early 350,000 years before the present. Additionally, the group which published the South African genome study posited another group, Basal Africans (BA), who diverged far earlier than the Khoisan from most African (and also non-African) groups.

Maximal Neanderthal range

The Neanderthals are a well studied group. We know what their range was. One can spit all sorts of speculative scenarios, from wide range proto-modern humans pushing deep in Eurasia during the Eemian interglacial 130,000 years ago. Or, it may have been through contact in the Near East and expansion of a somewhat admixed Neanderthal population north and east over time. Who knows? At least until there’s more ancient DNA….

June 29, 2017

Desperately seeking the secret of FOXP2

Filed under: FOXP2,Human Evolution — Razib Khan @ 6:04 pm


Since the early 2000s FOXP2 has shown up again and again in the press and scientific literature. Dubbed the “language gene” it exhibits evidence of accelerated evolution in the human lineage after it split from other apes. Additionally, a homolog of the same gene shows evidence of evolutionary change distinctive to songbirds and whales. Obviously this locus is involved in vocalization. Mutated mice on FOXP2 can even sing.

It isn’t difficult to connect the dots here. From 2002:

Dr. Paabo says this date fits with the theory advanced by Dr. Klein to account for the sudden appearance of novel behaviors 50,000 years ago, including art, ornamentation and long distance trade. Human remains from this period are physically indistinguishable from those of 100,000 years ago, leading Dr. Klein to propose that some genetically based cognitive change must have prompted the new behaviors. The only change of sufficient magnitude, in his view, is acquisition of language.

Klein’s thesis, advanced in The Dawn of Human Culture, is that a singular genetic change resulted in some sort of developmental cascade that allowed for the emergence of syntactically rich recursive language. And from language comes culture, and from culture comes world domination.

It was a clean and powerful hegemony while it lasted, but genomic and archaeological findings of the last decade have put such a elegant and simple model under a harsh light. With genomic technology even FOXP2 turns out to be much more complex and rich than the earlier reports had suggested. Neanderthals exhibited all the same mutations as modern humans to make them distinctive from chimpanzees. In other words, the changes on FOXP2 by and large predate the emergence of modern humanity, and go back closer to the root of the hominin lineage (Neanderthals and modern humans diverged ~600,000 years ago).

But FOXP2 keeps coming back. Why? It is an important gene. But another issue is that researchers still perceive in it the key to the holy grail of finding out what makes us distinctively human.

A new preprint (which is somewhat peculiarly formatted), takes another look at FOXP2, Human-specific changes in two functional enhancers of FOXP2:

Two functional enhancers of FOXP2, a gene important for language development and evolution, exhibit several human-specific changes compared to extinct hominins that are located within the binding site for different transcription factors. Specifically, Neanderthals and Denisovans bear the ancestral allele in one position within the binding site for SMARCC1, involved in brain development and vitamin D metabolism. This change might have resulted in a different pattern of FOXP2 expression in our species compared to extinct hominins.

The big picture is now the authors are focusing on gene expression levels as what might allow for modern human traits to be distinctive. Basically the DNA does not magically turn into protein. Biological machinery has to transcribe the sequence, and to transcribe it it has to bind to a particular region, a transcription factor binding site.

Most of the analysis involves comparing genomes of Neanderthals, Denisovans, and the human reference. I would be curious if they looked across lots of whole genomes to check if there was polymorphism in modern human populations. If modern humans with Neanderthal and Denisovan mutations had perfectly fine speech, that would be interesting.

Also, they spend a lot of time talking about how other genes interact and express with FOXP2, and all the other functions that are implicated. This is important, because of course selection may have nothing to do with speech, though perhaps speech changes are a side effect? Remember to that the Altai Neanderthal had some modern human admixture, and that one of the introgressed regions turns out to be FOXP2.

This sort of comparative genomic style research is interesting and suggestive. But we need more population wide analysis.

But, the authors do allude other work using genetic engineering where cell lines did show radically difference gene expression based on the mutation above. I do believe that CRISPR/Cas9 technology is cheap enough and going to be widespread enough that someone’s going to play around with splicing in “human” variants into primate models. Meanwhile, bioethicists will furrowing their brows about sequencing humans….

June 27, 2017

Why you should learn some population genetics

Filed under: Population genetics — Razib Khan @ 10:03 pm

From reader surveys I know a substantial portion of the people who will see this post are financially well off (of those who aren’t, a large number are students). Therefore, you can invest in some books.

Often people ask me questions related to population genetics in the comments (sometimes I get emails). That is all well and good. But it is always better to be able to fish than have to ask for fish. Additionally, learning some population and quantitative genetics allows you to develop some tacit schemas through which you can process information coming at you, and through with you can develop some general intuition.

If you have a modest level of mathematical fluency and and the disposable income, here are three indispensable books which are like the keys to the kingdom:

* Elements of Evolutionary Genetics
* Principles of Population Genetics
* Introduction to Quantitative Genetics.

If you don’t have the cash to spare, there are online notes which are pretty good:

* Graham Coop’s Population Genetics notes
* Joe Felsenstein’s Theoretical Evolutionary Genetics

There are others online resources, but they are not as comprehensive. John Gillespie’s Population Genetics: A Concise Guide is good as very gentle introductions go, but if you are going to spend money, I think just plumping down for a more comprehensive textbook (which will have more genomics in it) is better over the long run.

The goal of getting these books isn’t to make you a population geneticist, but, if you are interested in evolutionary questions it gives you a powerful toolkit. Really nothing in evolutionary process makes sense except in the light of population genetics.

Genome sequencing for the people is near

Filed under: Genomics,Personal genomics — Razib Khan @ 7:22 am

When I first began writing on the internet genomics was an exciting field of science. Somewhat abstruse, but newly relevant and well known due to the completion of the draft of the human genome. Today it’s totally different. Genomics is ubiquitous. Instead of a novel field of science, it is transitioning into a personal technology.

But life comes at you fast. For all practical purposes the $1,000 genome is here.

And yet we haven’t seen a wholesale change in medicine. What happened? Obviously a major part of it is polygenicity of disease. Not to mention that a lot of illness will always have a random aspect. People who get back a “clean” genome and live a “healthy” life will still get cancer.

Another issue is a chicken & egg problem. When a large proportion of the population is sequenced and phenotyped we’ll probably discover actionable patterns. But until that moment the yield is going to not be too impressive.

Consider this piece in MIT Tech, DNA Testing Reveals the Chance of Bad News in Your Genes:

Out of 50 healthy adults [selected from a random 100] who had their genomes sequenced, 11—or 22 percent—discovered they had genetic variants in one of nearly 5,000 genes associated with rare inherited diseases. One surprise is that most of them had no symptoms at all. Two volunteers had genetic variants known to cause heart rhythm abnormalities, but their cardiology tests were normal.

There’s another possible consequence of people having their genome sequenced. For participants enrolled in the study, health-care costs rose an average of $350 per person compared with a control group in the six months after they received their test results. The authors don’t know whether those costs were directly related to the sequencing, but Vassy says it’s reasonable to think people might schedule follow-up appointments or get more testing on the basis of their results.

Researchers worry about this problem of increased costs. It’s not a trivial problem, and one that medicine doesn’t have a response to, as patients often find a way to follow up on likely false positives. But it seems that this is a phase we’ll have to go through. I see no chance that a substantial proportion of the American population in the 2020s will not be sequenced.

June 25, 2017

Over the long term civilization matters

Filed under: Culture — Razib Khan @ 9:09 pm

In Peter Turchin’s work modeling human historical dynamics he introduces the idea of a “meta-ethnic” identity. Quite often this is synonymous with a world religion. These identities emerged in the last few years as human polities scaled so large as to expand beyond tribal-national boundaries.

These sorts of dynamics are clear when we think about the Crusades, the defense against the Ottomans in the 17th century, or the Iberian “division” of the world between Castile and Portugal. Common ties of civilization and identity allow for ingroup cohesion, as well as heightening hostilities against outgroups.

Of course there many exceptions. When reading The Great Sea: A Human History of the Mediterranean I recall being struck by how southern Italian city-states like Amalfi opportunistically allied with Muslim pirates against other Christian powers. Similarly, during the Battle of Vienna Protestant Hungarians marched with the Ottomans against the broader Christian alliance which came to the aid of the Habsburgs.

These are two instances which show short term self-interest or necessity driving choices of group coalitions. Amalfi, like later Italian city-states, found it in their interest to do business with Muslims, even if it was to the detriment of their co-religionists. This did not mean they were no longer Christians. But in many instances they put that identity aside for their own gains. In the case of the Protestant Hungarians there’s was an alliance of necessity.

As recounted in Divided by the Faith the decades leading up to the Battle of Vienna the Hungarians experienced a concerted campaign of conversion and persecution of the part of the Habsburg monarchy in concert withe Roman Catholic Church. The Habsburg’s Austrian lands were brought back fully into Catholicism, as was most of Imperial Hungary. It is no coincidence that Hungarian Reformed Protestantism was strong in the east, which had been under Ottoman influence. The arrival of an expansive Austrian monarchy was an existential threat for them.

The flip side are cases where groups with the same civilizational identity engage in wars over resources or boundaries. The conflict between Ethiopia and Eritrea would certainly fit into this mold, and to some extent the Great War in the Congo which has flared for two decades now.

This sort of dynamic has been used to argue that Samuel P. Huntington’s The Clash of Civilizations and the Remaking of World Order is not a useful framework. But on the contrary what Turchin and colleagues have shown is that over the long run civilizational fissures tend to result in the most vicious and dehumanizing wars.

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