Open Thread, 1/17/2016

41Ryk7GgnlL._SX331_BO1,204,203,200_I’ve been very busy the past week or so. There’s a lot I could blog, but I just don’t have the time. I should mention that I’m now reading my friend Garett Jones’ book Hive Mind: How Your Nation’s IQ Matters So Much More Than Your Own. It’s a good complement to Joe Henrich’s The Secret of Our Success: How Culture Is Driving Human Evolution, Domesticating Our Species, and Making Us Smarter. Reading them in sequence reminds me of how One Explanation to Rule Them All is usually not a good fit with reality broken down into its more complex bits. I’m about ~2/3 of the way through Garett’s book, and it’s a pretty quick read. I feel a bit bad for Garett though because he has to spend so much time justifying the utility of intelligence testing (much of it reads like Intelligent: All That Matters). Like The Secret of Our Success I’d really recommend Hive Mind if you have a background that’s outside of its core area of economics and psychometrics; there’s a lot you’ll learn, and it’s not a heavy lift.

k10181One the issues that Garett mentions in Hive Mind is that IQ is only a modest (though robust) predictor of income. This explains why there are so many stupid people who happen to be well off, and vice versa. Much of where you end up in life is stochastic, in addition to other factors like personal background (i.e., “connections”), appearance, and personality. That being said when looking at groups of people as a unit IQ is much more predictive. It strikes me that this is just a lot of the random/stochastic effects being cancelled out, as they’re not systematically biased. I think there’s a relationship here to the dynamics that Greg Clark explored in The Son Also Rises: Surnames and the History of Social Mobility. While Garett surveys spatial patterns, Greg was highlighting temporal (inter-generational) patterns.

What else is going on?

How Europe was settled by farmers

41uhvVKVH+L._SX331_BO1,204,203,200_Over the past several years ancient DNA has opened a startling window onto the settlement of the European continent during the Holocene. The story is one of migration, replacement, and repeated pulsing of populations from the fringe toward the North Sea. In short, the model that farming spread to Europe predominantly through cultural diffusion is dead. Though the genetic legacy of the indigenous hunter-gatherers persists in modern Europeans, it is through their amalgamation into the populations of farmers with roots in the Near East, as well as later peoples who arrived from the Eurasian steppe. Not because they adopted the culture of the newcomers.

But while the cultural diffusionist model has been falsified, the customary alternative, demic diffusion, has not been entirely validated either. This model posits the expansion of farming as a mechanistic, mindless, process analogous to thermodynamics and the expansion and diffusion of heat. It is in many ways a “culture-free” model, as farmsteads expand in an ad hoc and uncoordinated fashion across an empty landscape. And, as L. L. Cavalli-Sforza pointed out it was actually compatible with a predominant Pleistocene period ancestry for modern Europeans, because as the wave of demographic advance proceeded it would mix with the indigenous peoples on the frontier, diluting the distinctive original genetic signal.

I won’t repeat what’s been stated a thousand times in this space. Basically, rather than a gradual movement, the DNA is suggesting that there were starts and fits, and later equilibrations. For a thousand years or so it looks as if in the region of modern Germany during the early Neolithic the farmers and hunter-gatherers remained apart, with genetic distances comparable to that between modern Northern Europeans and Han Chinese. To account for this I have presented a rough model which I termed “leapfrogging,” as farmers migrated to ecologically favored terrain, leaving much of the hinterland in the hands of Mesolithic hunter-gatherers.

It turns out that none of my ideas were original, down to the terminology! A book chapter in The Colonization of Unfamiliar Landscapes: The Archaeology of Adaptation, prefigures almost all of my thoughts. Additionally, though published in 2003 I would argue it was relatively prescient. Here is one section:

The Neolithic colonization of Europe was a complicated process that took more than 2,500 years to unfold. Analysis of calibrated radiocarbon dates reveals a series of punctuated, rapid expansions, interrupted by periods – 500 to 1,000 years long – of stasis and in-filling. The earliest colonists in Southeastern Europe sought out floodplains and lake basins that were close analogues to familiar ancestral habitats in Anatolia and optimal for their farming practices. The two-stage structure of the Early Neolithic expansion and the selectivity of initial settlement locations imply carefully planned colonizing ventures, based on detailed prior knowledge of the landscape. The second-stage farmers may have derived this vital geographic information from fishing groups that initially created settlement facilities on the Greek coast to support long distance fishing trips. These frontiersmen probably shifted opportunistically from hunting and fishing, to herding, to trading.

You can read the whole chapter, Deerslayers, pathfinders, and Icemen: origins of the European Neolithic as seen from the frontier, at

Open Thread, 1-10-2016

So Taylor Swift looks scary to Koreans? A couple of the guys seem to have been unaware that Beyonce Knowles is black (one of them commented on being ambivalent about her dark tan, only to be surprised when told that that wasn’t a tan, that she’s black).

51sdHZvYfTL._SX334_BO1,204,203,200_I’m done with Joe Henrich’s The Secret of Our Success: How Culture Is Driving Human Evolution, Domesticating Our Species, and Making Us Smarter. I would recommend it to anyone who wants to know more about the field of cultural evolution (the author is one of the major people behind the idea of WEIRD psychology). For myself, one of the main upsides was that the book had a lot of empirical illustrations I wasn’t familiar with. Unfortunately some of the references to genomics are out of date, because he was writing the book in 2014. Also, I found the chapter on language somewhat unsatisfying.

The best passages so far that I recall. Page 234:

…Even ultra-verbal academics frequently use air quotes, an iconic gesture derived from the use of scare quotes in writing, to imply some disagreement with their terminology or its implications. I’ve seen many a humanities scholar, with a latte in one hand and a book in the other, struggle to communicate, unable to deploy air quotes to shield themselves from any undesirable implications of their words.

And from page 95:

…What we need is a more evolution-grounded science on genes, culture, ethnicity, and race, not less.

These insights will continue to fuel the spread of a new social construct: the view that all people, perhaps some other species as well, are endowed with certain inalienable rights-we call these human rights. No new facts about genes, biology, or culture can alienate a person from these rights.

Though Henrich is skeptical about the utility of the race construct, his thinking is in line with A.W.F. Edwards’ in his essay Human Genetic Diversity: Lewontin’s Fallacy. Grounding human rights in empirical facts which are subject to change is…problematic!

41Ryk7GgnlL._SX331_BO1,204,203,200_The emphasis on collective intelligence in The Secret of Our Success is an interesting complement to Hive Mind: How Your Nation’s IQ Matters So Much More Than Your Own. Though I was familiar with the model of technology loss because of drift, I was surprised how much return to population size there is in relation to the rate of innovation.

Glenn Reynolds often links to Amazon Kindle “Daily Deals”. I mostly ignore these though I’m a bit of a Kindle-holic. It’s for the same reason I canceled Kindle Unlimited, so many of the books on offer are just crappy (albeit, from my own subjective perspective). But on a lark, I clicked, and found some good stuff by drilling down to the subject categories.

61XC3xuXP2L._SY344_BO1,204,203,200_I purchased John Darwin’s The Empire Project: The Rise and Fall of the British World-System, 1830-1970. Since I enjoyed After Tamerlane I’m expecting to not regret ponying up $2.99 or whatever it cost (“for the price of a Starbucks coffee….”). I also got a biography, Elizabeth Cady Stanton: An American Life. I’ve always been sympathetic to her, but my knowledge of her views and life are rather superficial (sometimes you get unfortunately surprised, R. A. Fisher: Life of a Scientist seems to confirm that he was a major league asshole). Speaking of biography, some reviewers were irritated that Constantine The Emperor read less like a narrative about his life, and more like a monograph of the culture of the Roman Empire of the time.51YhNdG3q3L._SY344_BO1,204,203,200_ Of course all that did was induce me to purchase it! Finally, I got two science(ish) books. Longitude by Dava Sobel, and To Explain the World, a history of science by by Steven Weinberg. In general I find Weinberg’s quasi-scientistic social and historical analyses rather uninteresting, but it was cheap, and the summary indicates that he begins in Miletus, a city whose role as the midwife for proto-science has always been near to my heart.

PAG is going on. If you are interested in genomes not human, I recommend the you check out the #PAGXXIV hash-tag on Twitter. There is lots of good science being done, but if you are interested, check out my friend Dave’s poster, Genetic Characterization of Indicators for Diazotrophic Recruitment in Zea mays.

Speaking of posters, I’m trying to get my data analyzed well enough to have a poster for BAPG XIII in Berkeley on February 13th. #Excited

New dietary guidelines. Frankly, the US government doesn’t have a good track record on this. My main qualm is that Average is Over.

41f8rXshBRL._SX331_BO1,204,203,200_Rounding out my personal population genetics library, I purchased An Introduction to Population Genetics Theory, by James F. Crow and Motoo Kimura. This book was published in 1970, so 45 years ago, but pretty much everyone on Twitter who would be in a position to know stated that it was a worthy purchase for more than historical reasons. It goes to show the value of old theoretical books in the field. I also purchased a copy of Male, Female: The Evolution of Human Sex Differences, because the topic isn’t something that I take for granted anymore in the sort of society we live in, where “cis-heteronormative binaries” or whatever considered “problematic.” 51UUhrJMhpL._SY344_BO1,204,203,200_For more purely historical interest I also got a copy of The Monk in the Garden: The Lost and Found Genius of Gregor Mendel, the Father of Genetics About 15 years ago I read the first 1/3 of this book, but I never finished before I had to return it to the library. At this point I’m much more invested in genetics, so I figure I should give it a second go.

I watched Idiocracy. It was OK. My wife was disappointed by the lack of world-building. One thing to observe: no one is looking at their phone in the future, and there are still payphones around. The film was made in 2005, before that particular revolution.

CYQeUxuUwAAoelXSomeone on Twitter asked me to take the Political Compass test. I’m not a big fan of it, as I think it lacks subtly, and its libertarian-centric orientation is pretty obvious. But you can see my results. Probably not a big surprise. I’m moderately skeptical of democratic populism, so I’m not sure if many of these quizzes capture my own orientation correctly. But then again, everyone thinks they’re a special snowflake.

Screenshot from 2015-12-31 13:56:34There’s a new book, The South African Gandhi: Stretcher-Bearer of Empire, which got an interesting review in The Wall Street Journal. The subhead: “Gandhi fought for Indian rights in South Africa, but his concern for the black majority was minimal.” This has been known for a while, so why is this portion of Gandhi’s life so eternally controversial? I think it’s because Mohandas Karamchand Gandhi has gone through the apotheosis, and the reality that he was a man of his time is uncomfortable for many. The past today is populated by gods and devils, not men. But Gandhi was a man.

Like Slate I’m skeptical of Twitter’s latest moves. I’ll be pretty sad if Twitter turns into a form of Tumblr, and I might have to move on to something else. Which would be lame as I’ve invested a lot in my Twitter presence. As I’ve noted before at this point when I go to a scientific conference people know me more for my Twitter than my blog. Turning Twitter into a more full-fledged blogging platform is totally useless and counter-purpose for me, since I already have a blog….

Opinions on the best Szechuan in San Francisco?

The pull-up tower I purchased last week? It’s been awesome. My motivation remains pathetic, but the activation energy of just walking up to it and doing pull-ups and chin-ups is so minimal that I work-out every day now as a matter of course. Though as the New Year’s crowd clears out I’ll probably venture back to the normal gym, the tower is a great supplement and keeps me at a good baseline.

Why are Northeast Asians white-skinned?

koreanI am wont to say that the genomics of human pigmentation are solved. Arguably this has been one of the major successes of the early GWAS era. In 2005 the postscript to Mutants: On Genetic Variety and the Human Body alluded to the fact that the genetic architecture of pigmentation in humans was relatively mysterious. A year and a half later reviews such as A golden age of human pigmentation genetics where being published. What happened?

First, and foremost, the genetic architecture of human pigmentation variation is characterized by the reality that most of the variation is due to a handful of loci. In other words, skin color is not monogenic Mendelian, but neither is it highly polygenic in the same fashion as height or IQ, where variation is distributed across so many loci that alleles have nearly an infinitesimal effect size. The small sample sizes and simple methodologies of aught era genomics were sufficient to capture the relatively large effect variants segregating in many populations. A second major aspect to pigmentation genomics is that the pathways seem strikingly conserved across vertebrates. That means that pelage color research could inform human genetics, and vice versa.Some of the most interesting confirmations of the power of loss of function mutations in humans occurred by inducing a similar change in zebrafish! One inference that I think one might take away from this is that ancient human populations likely exhibited variation due to polymorphism around the same set of loci as modern humans.

But, and there’s a big but, is that though the set of loci which are responsible for pigmentation variation across human populations are familiar, finite, and well characterized, the particular mutations responsible within a given locus varies quite a bit. Because derived mutations which result in reduced pigmentation are mostly loss of function all you need to do is “break” the functionality in some manner. Therefore, you might target a regulatory element, or, the exonic sequence itself, but the possibilities are rather numerous. Heather Norton’s publication from 2007, Genetic Evidence for the Convergent Evolution of Light Skin in Europeans and East Asians, is still rather relevant. For various reasons the pigmentation of Europeans has been well elucidated. That means that to a great extent the variation in West and South Eurasians more generally (and North Africans) is well understand because most of the same variants seem to be at play. The big lacunae, as pointed out by Norton et al., concerns East Asians. This is a population which is light-skinned, but lacking in the typical set of European “light” alleles.

Unlabeled_Renatto_Luschan_Skin_color_map.svgThe title of the post is “white-skinned”, and not “white”, because the conventional understanding is that East Asians are not white. That term is reserved in world-wide usage for people of European descent (or to a lesser extent related peoples, such as Turks) for historical and cultural reasons.

But this is a recent development. From what I am to understand historically the peoples of Northeast Asia did refer to themselves as white in contrast to the browner people of Southeast Asia (in an analogous fashion, the people of West Asia as far east as Afghanistan consider themselves white, in contrast to the black people of South Asia). Additionally, when Europeans first encountered Northeast Asians in large numbers in the 16th century they observed that physically the people of nations such as Japan and Korea were white in color. Only with total domination of the globe by Europeans in the 19th century did the identification of white and European become such as that Northeast Asians were classed among the “colored” peoples (the appellation “yellow” was taken up by early 20th century East Asian intellectuals). But both quantitative empirical evidence and simple visual inspection can remind us that many Northeast Asians are as light in complexion as many Europeans, albeit never as pale as many Northern Europeans.

A new paper in Molecular Biology and Evolution, A genetic mechanism for convergent skin lightening during recent human evolution, goes a major step toward pinpointing what is going on in a functional sense in relation to East Asians. In fact they’re doing what occurred ten years ago for Europeans. First, they’re finding the variant through GWAS, and second, they are confirming through molecular methods and animal models that the variant of interest is actually the causal mechanism. And, they are also attempting to establish a temporal narrative by adducing signatures of selection.

rs180014The major finding is that variation on a particular SNP in OCA2 is responsible for differences in pigmentation across many groups in eastern Eurasia. You should remember OCA2, since the region that spans it and HERC2 accounts for the pattern of blue and brown eye variation in Europeans. The SNP, rs1800414, is in the ancestral state in Europe and Africa, but derived in Northeast Asia. The results from the left are from the HGDP browser. The only thing is that I can’t find the SNP on the browser. So I looked for that particular SNP on my own HGDP data sets, and couldn’t find it. The SNP is in ALFRED, and you can see that the results are somewhat different. OCA2_labels_SThe HGDP results (which for whatever reason I can’t replicate) show that the derived allele is modal in Northeast Asia, and, that it is present in the New World. In contrast, the ALFRED map shows that the derived allele is modal among more southerly groups (including indigenous non-Han groups in South China), and absent in the New World. The 1000 Genomes has fewer populations, but large sample sizes. The allele frequency in Japan in the 1000 Genomes matches Alfred more than the HGDP results.

All that being said, the general stylized facts are in alignment. The derived allele is common on the eastern coastal region of Eurasia, and nearly absent in Africa, Europe, and West and South Asia. But a curious aspect to me is that in the 1000 Genomes data the allele is nearly as absent in the Bangladeshi samples as it is in other South Asians. In contrast, the derived variant of EDAR, which is diagnostic of East Asian or Amerindian ancestry, is present at 5% frequency in Bangladeshis, about what you would expect assuming the attested levels of gene flow from an East Asian population. While the authors in the above study found that the effect of the allele is additive, it is curious that in the 1000 Genomes there is no variation across Japanese, North and South Chinese, and Vietnamese. The implication is that the average between group differences across these populations has to be due to variation on other loci. The indigenous Dai people in fact had the highest frequency of the derived allele in the 1000 Genomes.

Austroasiatic-en.svgA final issue that is important to note is that the phylogenetic framework the authors are using is probably wrong. The major value-add of this paper is that they include several Austro-Asiatic populations to the data set, and compared individuals phenotypically between the Austro-Asiatic group and among the Han Chinese. Because the supplemental information isn’t online I don’t know which Austro-Asiatic groups they included in China, but there aren’t too many, so one can guess. The main problem though is that they presume these Austro-Asiatic are basal to the Han. This probably isn’t true. Rather, there was probably a migration of early rice farmers from what is today China proper southward, that resulted in the spread of the Austro-Asiatic languages to Southeast Asia and further west toward India. Vietnamese and Cambodian are two numerous languages which are Austro-Asiatic. Bringing together all the genomic evidence, it seems that a substantial minority of the ancestry of these Austro-Asiatic people are from the descendants of hunter-gatherers who were resident in Southeast Asian during the Pleistocene, but the majority of their ancestry derives from farmers who pushed south.

These details matter because the authors estimated how deep the selection sweeps around this locus must be in terms of time. Using two methods they arrive at a figure between 10 and 15 thousand years (one method is closer to 10, another to 15). That implies that selection began before the Holocene. The interpretation the authors put on these results is that the northern East Asian groups experienced selection as they migrated up from Southeast Asia during the Pleistocene, with the Austro-Asiatic groups being basal and reflecting the ancestral state. The problem, as I suggest above, is that the Austro-Asiatic populations are a compound of genuinely basal groups (their minority ancestry) to the Northeast Asians, and a population to which other Northeast Asians further north may be basal!

One thing Eight thousand years of natural selection in Europe tells us using ancient DNA that a history of admixture is important to understanding the specific dynamics of selection. Though the haplotype based methods were roughly correct, they did not exhibit the granularity necessary to make fine-grained inferences, and did not totally predict what the empirical ancient DNA is telling us about allele frequencies across time. For example, earlier attempts to infer the selection sweep which resulted in high frequencies of SLC45A2 in Europe arrived at a figure a bit north of ~10,000 years. But it seems that a great deal of selection on this locus has been occurring more recently than 5,000 years.

And on a final note, I would point out that the intermediate frequencies of the derived allele in much of East Asia are suggestive to me that the genuine target of selection here is not skin color, but a dominant trait. The fact that the derived allele is nearly absent in Bangladeshis indicates that either the sweep up in frequency is very recent, so that not all East Asian populations experienced it, or, more likely to my mind, there is constraining selection on the trait which is the genuine target of interest in other genetic backgrounds. To decrypt what I’m saying, the derived allele is probably useful in East Asia, but entails some cost. South Asians may already have another allele which gains the same function, and so the cost resulted in purification of the derived allele in Bangladeshis (who are ~10% derived from a group very similar to the Dai).

As should be clear, this paper has some confusions. But it’s a taste of things to come. There are many Chinese who are interested in the genomics of their region, and ancient DNA should begin to unveil the past in the next few years.

Admixture vs. introgression, is there a difference?

plant-introductions-evolution-hybrid-speciation-and-gene-transfer-18-728nature09103-f3.2Is there a difference between admixture and introgression? I think there is. Or have always assumed there is. But of late I’m wondering if a distinction is widely accepted, and what sort of distinctions people make. That is, in some cases it seems clear that admixture and introgression are used interchangeably as meaning the same thing. I’ve seen this in scientific papers, and often just do a mental substitution. But in other cases I’m wondering if people are using the terms in a different sense than I am. Probably the latter is more worrisome.

The figure to the left was generated by Admixture, a software package which takes population genetics assumptions (models) and data, and shows you the best fit of the data to a particular model. In this case the bar plot shows you the admixture of a given individual when you posit them to be a combination of K ancestral populations. The individuals are clustered by population, so you see population-wide profiles. The details of the model, and whether the model accurately captures reality (i.e., were there actually K populations at any time in the past?), is less important for this post than the fact that Admixture is reflecting admixture on a genome-wide scale between two or more populations. The input data are represented by hundreds of thousands of single nucleotide polymorphisms distributed across the whole genome. The question of interest is whether a population can be represented as a pulse mixing even between two hypothetical groups, which were at some point phylogenetically distinct.

Introgression in contrast focuses on the question of genetic variants which are penetrating one population from another, and becoming common in the target population. A classical method of generating introgression in plant genetics was to engage in extensive backcrosses of mixed lineages with a trait of interest against a parental population. If one continued to select for a particular trait among the progeny one could introgress the trait and allele in a daughter population which was almost identical to one of the parent populations on a genome-wide scale, but identical to the other at one gene of interest. The practical reason for this is obvious. Imagine you have a variety of cold adapted rice which is susceptible to a particular type of fungal infection. Then, you have a heat adapted rice which is resistant to the fungal infection. All you want is fungal infection resistance, maintaining all the other characteristics that keep the cold adapted rice optimal for its climate. So you cross the two, and continue to cross progeny against cold adapted rice while selecting for the resistance phenotype. Eventually you’ll get the allele you want introgressed while maintaining the genetic background you want. In contrast, if you just allowed for admixture between the two lineages, you might get a population which was in between on a whole host of phenotypes which make them suboptimal for any climatic regime.

An example from human population genomics can be found in the paper Altitude adaptation in Tibetans caused by introgression of Denisovan-like DNA. What occurred here is that a very common variant in Tibetans implicated altitude tolerance and adaptation seems to be phylogenetically closer to those you find in the Denisovan hominins than in other human populations. This, despite the fact that Denisovan ancestry is nearly nonexistent in Tibetans (the latest work suggests admixture in East and Southeast Asia on the order of 0.1 to 0.5%, with the highest fractions being among certain Southeast Asian and South Asian groups).

nature13408-f3The network plot to the right illustrates the issue. On a genome-wide admixture plot Tibetans look like any East Asian population. They seem to be a mix of farmers related to the Han to the east and indigenous groups long resident at these high altitudes. But on the region around EPAS1 their genetic variation matches not modern humans, but the Denisovan hominin, which diverged ~500,000 years ago from the population gave rise to 90 to 99% of the ancestry of our own lineage.

So what happened? We know that there were low levels of hybridization between very diverged human lineages in the past. Because of genetic incompabilities it seems that in fact there was some selection against distinctive alleles from archaic lineages in our own genome. That is, the percentage of Neanderthal ancestry on the genomic level is probably lower than you’d get from doing a genealogical analysis of all lines of ancestry back to 100,000 years ago, because there has been selection against Neanderthal variants in the dominant human genetic background. But not in 51r8Ph-vcaL._SY344_BO1,204,203,200_all cases. In a minority of instances the Neanderthal and Denisovan variants were not less fit, nor were they neutral, but rather, they were favored!

So, imagine a scenario where in the initial generation admixture between a large human population and a small Neanderthal population leads to admixture on the order of ~5% in the descendants. Over the generations due to selection against Neanderthal alleles the genomic ancestry from this group converges upon ~2.5%. But, on a subset of loci the Neanderthal alleles will have increased in frequency, and in some cases introgressed to high levels. This could be due to randomness; in a genome with billions of base pairs and tens of millions of nucleotide polymorphisms some alleles will drift up to higher frequencies randomly. But it is in the set of high frequency alleles from Neanderthals that you might find variants that have become common due to adaptive introgression. See this paper in AJHG, Introgression of Neandertal- and Denisovan-like Haplotypes Contributes to Adaptive Variation in Human Toll-like Receptors. Immunological variation is always an excellent candidate because genetic diversity at these loci are highly favored, and long resident populations often have local adaptations.

Because my focus is generally in microevolutionary process, the sort of thing population geneticists are interested in, I’ve really not been talking about species-level dynamics (though the hominins are arguably distinct species). Much of the work on admixture and introgression is done by biologists focused on inter-specific differences, but the general framework holds I believe (in fact, questions of admixture and introgression and more clear and distinct across diverged lineages). In plants in particular hybridization and introgression are common in wild and domestic lineages.

I’m not putting this post up as definitive. When I read papers where there is talk about “introgression of ancestry” it is clear that today people are merging and bleeding the definitions. I actually checked for definitions of introgression and admixture in . Principles of Population Genetics and Elements of Evolutionary Genetics. There wasn’t anything, because debate on this issue isn’t/wasn’t very live in these fields. At this point I’m really curious what other biologists think. I still find the distinction important, and more critically, useful. If one doesn’t, I’d like to hear opinions. If one has different definitions, I’d like to hear opinions.

Open Thread, 1/3/2016

The Goat?

A friend of mine, a man-in-tech of eminently WASP background of moderately liberal orientation in case you care, has been bemoaning the downstream consequences of the floundering of Marissa Mayer of Yahoo!, the confused direction of 23andMe under Anne Wojcicki, and finally, there is Elizabeth Holmes and Theranos. These are three separate cases. I don’t believe that Mayer ever had a high probability of success at Yahoo!; it was a legacy of the late 1990s that had never managed to pivot and find a new direction. Even a company with as many resources as Microsoft has been having difficulties finding domains where it can both be dominant and produce growth. Yahoo! never had the success of Microsoft, and so doesn’t have as much margin.

Of course long odds does not mean that a turnaround was impossible. I’m old enough to remember when Steve Jobs came back to Apple and many people shrugged, as it looked inevitable that the firm’s future was in diminishing returns on the margins of the consumer and educational PC market in the shadow of Microsoft and PCs (at one point Microsoft was making more profits on sales of Apple computers than Apple because of the Office productivity suite from what I recall). Obviously it didn’t play out like that. If Marissa Mayer had turned around Yahoo! she’d be a genius. If she failed, as she seems likely to at this point, there will be some sort of exit strategy where she will save face, and there will be no threat to her solid position among the firmament of American oligarchs. The likes of Mayer are seeking glory like the Roman Senators of yore. Only a few will go down in history as men or women of renown, but all will die rich and comfortable.

As Marissa Mayer is a beautiful and intelligent woman who will reproduce above replacement, of course I was always rooting for her. Beauty and intelligence are good. In some measure ambition is as well. And when was being coldly analytic an insult? I couldn’t care less about Yahoo!, as it’s irrelevant to the American economy as a whole. But I cared a bit about Mayer’s success, though I was always pessimistic. Probably some of the same dynamic applied to my attitudes toward Elizabeth Holmes, who seemed smart and attractive, though I didn’t pay attention closely to her claims or business. The issue which many, including Steve Sailer, have suggested, and which my friend agrees with, is that because of the cultural expectation that the tech sector promote “diversity”, Holmes went somewhat under the radar due to dampened due diligence. An extreme case of this sort of thing occurred with Jayson Blair at The New York Times, where Howell Raines admitted that as a liberal white Southerner he was inclined to treating Blair “gently”. Ballooning of reputations and media hagiographies of tech visionaries are not without precedent (it’s a substantial proportion of the copy of glossy business magazines), but some have wondered if Elizabeth Holmes’ story was just too good to inquire too closely. Not only did she fit the stereotypical motif of Silicon Valley entrepreneurs (e.g., Stanford dropout attempting to “disrupt” a sector with innovation), but she also served as an exemplar of a young woman who falsified the idea that the sector was doomed to remain a man’s game.

With 23andMe and Anne Wojcicki, I have no idea what’s going on, but it is, and always has been, confused. I found out from inside sources what happened with the initial FDA letter, and what I can say is that it wasn’t part of the plan in any way but a total f**k up. 23andMe has a high valuation, and an incredible database, and seems totally pivoting to the health market, shaking off its past in recreational genetics (read: genealogy, etc.). But from what I’ve heard Ancestry has surpassed, or is close to surpassing, 23andMe’s database (speaking of, as of this writing Ancestry has a 20% of sale, on checkout at Amazon). I wonder if 23andMe isn’t getting a bit overconfident, as Ancestry is going to shift into the health space too.

Obviously biases are real. CEOs tend to look a certain way. They’re far taller than average. And in Silicon Valley they’re disproportionately white males, as in the rest of corporate America (though less so). The die is probably loaded in favor of white males in relation to getting to the top of management. I’ve had enough experience in “industry” (i.e., the real world), as they would say in academia, to know that “corporate culture” often does have connotations which exclude particular groups naturally. If, for example, you are a business person in South Korea, the marathon drinking sessions are going to disadvantage many women and teetotalers. I think one of the reasons that Asian Americans, and in particular East Asians, are under-represented in management roles in Silicon Valley in relation to their representation in engineering positions has to do with personality, cultural norms (e.g., Asian parents not emphasizing sports and the sort of comradeship that it engenders and translates into the business world), and just the “look” (too many Asian American engineers are short and not fit).*

But I think the example of Elizabeth Holmes suggests that shifting the playing field a bit in business journalism does no one a service. The next time a young blonde attractive woman makes a pitch to investors no doubt one prior that is going to rattle in their brains is going to be “is she going to be another Elizabeth Holmes?” That’s just a cognitive bias. Though privately people will likely state this openly.

51sdHZvYfTL._SX334_BO1,204,203,200_Speaking of cognitive biases, I’m about halfway through The Secret of Our Success: How Culture Is Driving Human Evolution, Domesticating Our Species, and Making Us Smarter. Yes, it’s as good as readers have told me. But, I’ll be honest and state that I knew most of it already in the generality, though not the ethnographic details (for example, I did not know that Inuit ate deer feces like “berries”; thanks for that Joe!). Part of this has to do with the fact that I’ve kept up on the author’s research since 2004, when I encountered his models of skill decay in Tasmanian Aboriginals. And, I’m familiar with the fields of cultural evolution more broadly. Additionally, I’ll bring it up in my review, but I think that he wrote at an unfortunate time when it comes to drawing lessons from human genomics, because some of his assertions have been falsified! (he wrote the preface in January of 2015, a year ago).

Reading The Secret of Our Success after I finished Consciousness and the Brain was also pretty lucky, as some of the assertions made in the former book seem much stronger and robust after the background provided by the latter. In the near future I plan to re-read both Origin of Mind: Evolution of Brain, Cognition, and General Intelligence and The g Factor: The Science of Mental Ability. Sometimes re-reading is about refreshing, but I don’t feel that in this case I understood human evolution well at all when I read these previously.

Steve Pinker has something out in The Wall Street Journal, Steven Pinker on New Advances in Behavioral Genetics:

But new studies looking for small effects of thousands of genes in large samples have pinpointed a few genetic loci that each accounts for a fraction of an IQ point. More studies are in the pipeline and will link those genes to brain development, showing that they are not statistical curiosities. The emerging picture is that most behavioral traits are affected by many, many genes, each accounting for a tiny percentage of the variance.

51Y4n2TIgiL._SY344_BO1,204,203,200_When Pinker says that studies are in the pipeline, he’s thinking of concrete studies which are in review, and which will blow your minds (though the usual suspects will obfuscate and ignore).

In relation to Steven Pinker, he gets a lot of hate and dismissal. Even Joe Henrich in The Secret of Our Success uses him as somewhat of a foil, though in a good-natured manner (Henrich and Pinker are now colleagues at Harvard, so collegiality is probably for the best). I still think that for writing The Blank Slate alone Steven Pinker will go down in history as an important thinker (though The Language Instinct was the most revelatory book of Pinker’s for me).

When I run TreeMix I often get gene flow edges from Africans or to Africans from a region of the graph basal in eastern Eurasians. I ignore these because they don’t make sense. But they don’t make sense because I’m missing something in the bigger picture. I’m sure a year or two years or three years from now it will all make sense. Just filing this away as results which I can’t make heads or tails of, but which are telling us something with Delphic clarity.

On to genetic data sets. I’ll post on this soon. But the 1000 Genomes are a disparate bunch when it comes to South Asians. The Tamils and Telegu speakers have three Brahmins each in them. Also, both groups have rather endogamous low caste populations as a small subset, distinct from the broader mass. The Gujaratis are highly structured, with a large cluster of Patels, but also various other groups in the mix in a cline out toward Northwest Indians (so I assume middle castes and Guju Brahmins). The Punjabis, sampled from Lahore, are also strange, because they exhibit a very extreme cline, from near the Gujaratis all the way toward West Asian/European populations as far as Pathans. Does this have something to do with people of Muhajir background or mix identifying as Punjabi? Finally, the Bengalis are curious, because they are different from the other South Asian groups in exhibiting minimal structure. These were people sampled in Dhaka, but the cluster is very tight, except five individuals who are closer to the South Indian groups. Two of these five have sample numbers adjacent, so I wondered if they were collected together. Unlike the other Bengalis these individuals don’t seem to have substantial East Asian admixture. I have no idea what group this might be, but I have a hunch that they’re derived from an endogamous caste (probably Hindus) who migrated to the area of Bangladesh in the last few hundred years from another region of South Asia. Finally, I have to note that the Bengali populations exhibit far fewer individuals with long runs of homozygosity than the other South Asian groups. Less than the Punjabis or South Indians, which stands to reason since these groups engage in high levels of consanguinity. But also lower than Gujaratis. The implications of this later….

Xinjiang Seethes Under Chinese Crackdown. I wish the media would explore the relationship of Uighurs, and Hui Muslims, in Xinjiang (the latter are called Dungans in Central Asia). That would get at the ethnic vs. religion tensions. Though in China proper the Hui are often proud of their Islamic identity, in Turkestan their affinities to the Han group, both physically and linguistically, become salient. Because of their Muslim religion and martial character the Hui/Dungans were often used as enforcers of Chinese hegemony by the Manchus. A somewhat greater number of Muslims in China are Hui than Uighur.

10403266_10153388206137984_3744690303848345018_nI stole my kids’ candy-canes. It was for their own good! Am I a bad person? Christmas was fun. My wife read Selfish Reasons to Have More Kids, but I did not (aside from a chapter Bryan Caplan asked me to read to check for any issues). I don’t need selfish reasons to have more kids. I like kids. Christmas was fun when I was a kid. But it’s more fun by far when you have kids. sequencedOneWatching my ~1.5 year old son sit down with his new board book is pretty awesome. The world is his oyster. Or at least toy truck.

I haven’t read the GCTA isn’t all that paper in PNAS. Yes, it’s not titled that, and also, am I a bad person? Yaniv Erlich is a good person, as he has read and responded. The Twitter reaction seems to be skeptical, but cautious. The reality is when the great Alkes Price or Michael Goddard weighs in we’ll know if this is simply a pretender to the throne.

A big deal at some point: phenopredict21.

Uncovering the genetic architectures of quantitative traits. On my “to-read” after the GCTA-sucks papers. (if you don’t know what GCTA is, shame on you! Read this: GCTA: A Tool for Genome-wide Complex Trait Analysis).

Edge, 2016 : WHAT DO YOU CONSIDER THE MOST INTERESTING RECENT [SCIENTIFIC] NEWS? WHAT MAKES IT IMPORTANT? To some extent if it doesn’t match =~ /CRISPR/ somewhere I’m underwhelmed. Did you see In vivo genome editing improves muscle function in a mouse model of Duchenne muscular dystrophy?

Michael Shermer: Murdering the facts about Homo naledi? Shermer also parrots those who criticize the H. naledi team for not publishing in Nature or Science. I happen to have been in Washington, D.C., when Lee Berger gave a private presentation on the findings over two years ago. And he already told me that the key was getting this research out quickly, and, dumping the data out there so that others could have access to it. It’s not just about H. naledi, it’s about changing how palaeoanthropology is done.

For those of you in Houston, I know that Cooking Girl has better Yelp reviews than Mala. Doesn’t deserve it in my opinion, though I’ll have to sample Cooking Girl more than once….

Also, I’ve spent some time in Austin, TX, recently. I lived in Portland, OR, years ago. Those who say that Austin is like the Texas version of Portland seem to totally capture it.

* I say Asian Americans, because internationals have obvious cultural handicaps in an American corporation.

The Dravidian migration theory vindicated!

ncomms9912-f451IZQjMbVlL._SX346_BO1,204,203,200_Update: Here is a post that you must read, A note on the early expansions of the Indo-Europeans. The post dates to the middle of December, and is similar in many ways to my own thoughts. But, the author rejects a two wave model where the first wave has a deep time history, and seems to give the balance of opinion that agriculture is predominantly indigenous in development to South Asia, and not primarily an exogenous event. Rather, they suggest that there were multiple waves of Indo-Aryans into South Asia, with the steppe cultures being parallel and pulses from the Indo-Iranian ur-heimat. The primary criticism of the genetic interpretation that I would make is that from what I am to understand LD decay methods seem to catch the last admixture event and/or underestimate time since initiation of mixture. Therefore, though I accept a substantial mixture event ~4,000 years before the present, my own model present below suggests that older ones occurred thousands of years earlier.

That being said, I have updated my own views to rather uncertain at this point. I would not be surprised if on the whole a model as the one proposed in the blog post is closer to the truth than the one below. My reasoning has less to do with the details of the argumentation, and more to do with authority.

1) the individual who wrote the above post has comparable mastery of the historical genetic descriptive results.

2) but, the individual has far superior understanding of the archaeology and philology in comparison to me.

Ignoring the details of any argument, on a priori grounds I find that the individual above could give a better appraisal of the probabilities in regards to South Asian archaeogenetics than I could. The main thing that is holding me back from suggesting that I now find their model more probable than mine is the issue in regards to LD and rolloff methods. But I’ve definitely increased my uncertainty, from ~25% to ~50%, with the balance split between the two models (or some combinations thereof).

End Update

Sometimes you see things in fragments, disparate threads, which only snap into focus in hindsight. In this post I will hazard a prediction of results which are going to come out of remains from Indus valley sites in South Asia, which will confirm that there were two major demographic pulses which entered the subcontinent from the Northwest over the past 10,000 year. The first wave was the dominant one in comparison to the second genetically, and began at Mehrgarh 9,000 years ago. Its locus of origin was in the highlands of Western Asia, between the Caucasus and the Fertile Crescent. The second wave though left its mark culturally, as it is associated with Indo-Aryans, and likely derives ultimately from the trans-Volga steppe societies. The genetic signatures of the former people are found in nearly every indigenous South Asian group, as they amalgamated with a deeply entrenched local group of peoples who were distantly related to those of Oceania and eastern Eurasia. In short, the latter are the “Ancestral South Indians” (ASI) and the former are the “Ancestral North Indians” (ANI, see Reconstructing Indian Population History).

Screenshot - 01022016 - 09:46:36 PMThe figure above is from Upper Palaeolithic genomes reveal deep roots of modern Eurasians (open access), which found that ancient DNA from two samples in the northern Caucasus region are representatives of a population which contributed to the origins of the steppe people who swept into Northern Europe ~4,500 years ago. It shows how contemporary populations are best modeled as admixture events between reference populations. What you see is that most South Asian groups are well modeled as a mixture between “Caucasian hunter-gatherers” (CHG), and another element which is labeled “South Asian” because it is mostly restricted to the subcontinent. But wait there’s more! In the supporting materials the statistics show that though most South Asian groups have more potential mixture from the high quality CHG sequence, Kotias, a subset, unspecified Gujarati groups and Tiwaris, share more drift with the Afanasevo culture, which flourished in the Altai region of Central Asia between 5,500 and 4,500 years ago. We have enough ancient DNA to infer that the Afanasevo basically the same people as the Yamna culture, who were present between the Volga and Dnieper, far to the west. The Tiwari are an upper caste group which is present across Northern India. The second wave component is clearly strongest in the Northwest, as indicated by the Kalash sharing so much drift with Ma’lta. Before subsequent waves  of gene flow into the steppe people, which brought dollops of European farmer and hunter-gatherer ancestry into the mix, they had a higher fraction of Ancestral North Eurasian (ANE) than any contemporary Northern European population. Their contribution to South Asian groups on the Northwest fringe of the subcontinent explains then the presence of high fractions of ANE there.

A final aspect which needs to be mentioned is that the Z93 subclade of R1a1a is found across much of South Asia. Though it is correlated with higher caste, and Indo-Aryan speaking, populations, it is not exclusive to them. In fact it is found in substantial fractions among notionally primal tribal people in South India who traditionally practice primitive slash and burn agriculture and engage in extensive hunting and gathering. Ancient DNA results from the Sbruna culture of Central Eurasia have yielded Z93 among buried males. This subclade is rather rare in this region today, and, it succeeded groups which were carrying R1b, today dominant across Western Europe. The details are to be worked out, but, I believe that are associated with, but more expansive than, the Indo-Aryans. Beyond the limits of the folk migrations were outrider groups of males who integrated themselves into indigenous societies, often taking elite positions as members of a dominant patrilineage. If there was a strong bias for male descendants of a small number of these individuals, but not female ones, to have higher reproductive fitness, than over time their Y chromosomes might be far more common than their total genome contribution (to illustrate what I’m talking about, a recent paper in Australian Aboriginals admits that 56% of their Y chromosomes introgressed over the past 200 years from Europeans!).

Bringing it together one implication of the above is that the Dravidian languages of the Indian subcontinent were probably brought by the West Asian farmers (perhaps confirming an ancient link to Elamite?). Therefore, the language(s) of the Indus valley civilization was probably a form of Dravidian. Another aspect to consider is that no South Asian population lacks the genetic imprint of these West Asian farmers. It seems likely that as in Europe the farmer populations which entered the subcontinent via the northwest totally marginalized most of the hunter-nihms137159f3gatherer groups, which were numerically less substantial in any case. But, why do all South Asian groups also exhibit ASI ancestry, which is deeply rooted in the subcontinent? Just as in Europe the initial populations of farmers on the fringes of the subcontinent mixed with the local hunter-gatherers, producing a synthetic population which over time evolved its cultural toolkit to become more well adapted to South Asian geographies. Once the crucial cultural adaptations occurred then the synthetic population underwent a phase of massive demographic expansion beyond its delimited ghetto on the fringes, where West Asian climatic parameters allowed for the initial phase of near total cultural transplantation. As in Europe the expanding South Asian farmer groups absorbed hunter-gatherer substrate, accruing greater and greater ASI fractions on the wave of demographic advance, and so generating the ANI-ASI cline evident in genetic analyses. The presence of ASI in groups like the Pashtuns in Afghanistan is probably due to the fact that the synthetic populations, what we now term “South Asians” or “Indians” or “desis”, exhibited enough cultural hegemony and influence to reach deep into the plateau of modern Afghanistan and impacted both the pre-Iranic and East Iranic people of Afghanistan (also, note that Indians were very common as slaves in the cities of Afghanistan during the early Islamic period).

The reason I took time to put this post up now is that it looks like the publication of ancient South Asian genomes from the Indus valley period is imminent. From The Guardian on December 30th, Rakhigarhi: Indian town could unlock mystery of Indus civilisation:

One has stood out: who exactly were the people of the Indus civilisation? A response may come within weeks.

“Our research will most definitely provide an answer. This will be a major breakthrough. I am very excited,” said Vasant Shinde, an Indian archaeologist leading current excavations at Rakhigarhi, which was discovered in 1965.

Shinde’s conclusions will be published in the new year. They are based on DNA sequences derived from four skeletons – of two men, a woman and a child – excavated eight months ago and checked against DNA data from tens of thousands of people from all across the subcontinent, central Asia and Iran.

They looked somewhat like a recent Miss America!
They looked somewhat like a recent Miss America!
I predict that the Y chromosomal haplogroups will be H or J2. Both these are common in Dravidian speaking groups of Southern India, and, are found at some fractions in West Asia. I predict that these individuals who share gene flow with Kotias, and not with Central Eurasian groups. I predict that these individuals will not be enriched for ANE ancestry. I predict these individuals will have mtDNA lineages present in modern Indian populations, probably M. Though excavated in a region of South Asia where today lactase persistence (LP( is common, none of the individuals with carry the common derived Eurasian haplotype conferring LP. They will segregate for the derived variant of SLC24A5. On a PCA plot these individuals will cluster with non-Brahmin upper/middle caste South Indian populations, such as the Reddys of Andhra Pradesh.

Note: I’ve been told by friends for two years and more that there are efforts to sequence and type Indus valley individuals. But I have no inside information. If you are an individual in the media who has early access feel free to send me a PDF with the understanding that I will honor the embargo! (if you don’t send me the PDF I’m mildly confident I’ve already hit the major themes you are safeguarding)

George R. R. Martin confirms the great fork

A-Game-of-Thrones-Bantam-SpectraI’ve been talking about A Song of Ice and Fire as long as I’ve been blogging. I purchased the first book as a paperback in December of 1998 because of the cover and some blurbs from authors that I found credible (Tad Williams?). In 2000 I ordered the British edition of A Storm of Swords because it came out earlier than the US one by a few months. So in a little over three years I read the first three books of A Song of Ice and Fire. Over 15 years later we’ve gotten through the next two books!

Back when I read Usenet I recall someone observing that there was something like Egwene’s rule in the Wheel of Time novels of Robert Jordan. Basically as the series progressed Egwene and her entourage moved toward the White Tower of the Aes Sedai at slower and slower pace, so World_of_Ice_and_Fire_coverthat it was as if Jordan was trying to illustrate Zeno’s Paradox in his plotting often(I stopped reading after book six). I hate saying this, but Martin may have out done Jordan in that his books four and five had less narrative progress (Martin’s characters and world-building exhibit much more verisimilitude, so I cut him some slack; Jordan admitted that all the primary female characters in his books were extrapolations of his wife). Instead of a gradual exponential decay A Song of Ice and Fire crashed after 2000.

And now we have the television shows, to the point where I almost wrote A Game of Thrones to label the series, as the show is named after the first book, though its narrative arc covers the whole series. Yesterday George R. R. Martin explained on a blog entry that his books were going to definitely be outpaced by the HBO series. For years there were those of us who read the books who ignored the television series, or at most laughed and rolled our eyes as people who watched the HBO depiction without prior exposure were shocked, appalled, and amazed. Sean Bean’s Eddard Stark will always be Boromir to me! Martin confirms now that the shoe is on the other foot. But, he does note that the show and books will diverge in many ways. Because the television series will go first I can not but now wonder if it will influence the trajectory of the books (e.g., Martin might consciously or unconsciously deviate from the HBO series in future installments in ways he might not have otherwise done so). Honestly the whole situation strikes me as worthy of a short story, as it’s really unprecedented. Books are turned into television shows or films. Or, shows or films are novelized. What is going to happen now is a synthetic hybrid process.