Open Thread, 08/23/2015

Screenshot from 2015-08-23 12:32:24I get notifications for a lot of different things. Some of them are way off base (e.g., I think at some point a publicist sent me the contact information of a client who had written a book on homoepathy?). But some of them are spot on. I drink a lot of coffee. On the order of two to six large cups a day probably. So I was curious when I got a notification of a new KickStarter, Cultured Coffee: Reinventing Coffee. Of course for many people Folgers instant coffee will do, but that’s probably not most people who have the marginal income to engage in discretionary spending on coffee made from recently ground whole beans. Definitely curious where this will all go in the long run, though unlike the horrible “cupcake craze” it seems that coffee is here to stay.

k10255The author of A New History of Western Philosophy admits a fondness for medieval thought, which he believes has been undervalued. There is something of a backlash to the Renaissance way of thinking about the “Middle Ages” recently, but it can get a little out of control. I have to be honest and admit that for whatever reason, many, though not all, medieval philosophers and their thoughts seem to be no more than hilarious language games. Much of this has to do with the fact that their metaphysics were different from what take for granted today. Or, perhaps more accurately they took metaphysics seriously, so their linguistic analyses of terms were a very serious affair for them.

But I’m taking a break to check out Michael Cook’s Ancient Religions, Modern Politics: The Islamic Case in Comparative Perspective. I got this on the recommendation of T Greer, and he is correct that I disagree with some of the premises. But, it’s pretty interesting and detailed on facts. I doubt I’ll finish it before getting back to A New History of Western Philosophy, but it will probably be a quick read once I have time.

CLUMPAK, for model-based population structure analysis

This isn’t probably aimed at most readers, but I think it’s important to pass the word around, so, Clumpak: a program for identifying clustering modes and packaging population structure inferences across K. An ungated version. From the abstract:

The identification of the genetic structure of populations from multilocus genotype data has become a central component of modern population-genetic data analysis. Application of model-based clustering programs often entails a number of steps, in which the user considers different modelling assumptions, compares results across different predetermined values of the number of assumed clusters (a parameter typically denoted K), examines multiple independent runs for each fixed value of K, and distinguishes among runs belonging to substantially distinct clustering solutions. Here, we present clumpak (Cluster Markov Packager Across K), a method that automates the postprocessing of results of model-based population structure analyses. For analysing multiple independent runs at a single K value, clumpak identifies sets of highly similar runs, separating distinct groups of runs that represent distinct modes in the space of possible solutions. This procedure, which generates a consensus solution for each distinct mode, is performed by the use of a Markov clustering algorithm that relies on a similarity matrix between replicate runs, as computed by the software clumpp. Next, clumpak identifies an optimal alignment of inferred clusters across different values of K, extending a similar approach implemented for a fixed K in clumpp and simplifying the comparison of clustering results across different K values. clumpak incorporates additional features, such as implementations of methods for choosing K and comparing solutions obtained by different programs, models, or data subsets. clumpak, available at http://clumpak.tau.ac.il, simplifies the use of model-based analyses of population structure in population genetics and molecular ecology.

The website deploys the package as a web based application (kind of like Structure-harvester). I don’t do GUIs, but I thought I would mention it (the package is downloadable). I’ve shied away from posting admixture barplots not because I think they lack utility. Rather, over the years readers have had a hard time understanding their limitations, and tend to reify a little too much for my taste.

A Note on Uralic (& Finnish) genomics

609px-Fenno-Ugrian_languages

I was playing around with some data, and I saw a strange migration from Amerindians to Finns in one run. I looked through replicate runs the same pattern reoccurred. The weird thing is that I had a Siberian data set in there (Ngannassan, Koryak, and Chukchi). The Amerindians were a mix of Pima, Maya, and a few 1000 Genome Peruvians.

To explore this further I got ran TreeMix with progressively fewer populations. I got the Ancient North Eurasian genotype and also put it in there. Using various quality filters I got down to 112,000 SNPs. All of the plots are here, but representative ones are below.

As you can whatever I saw was an artifact. Probably due to merging the various Siberian populations together. Now there is a gene flow edge from at least near the Nganassans and Nenets toward the Finnic groups, or from the Finnic groups. The relationship of Mal’ta is complicated by the fact that it’s so old, and, the population structure of North-Central Eurasia seems to have changed several times over the past few tens of thousands of years.

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Selective sweeps on the X chromosome of homonoids

Screenshot from 2015-08-19 23:27:08About ten years ago David Reich and Nick Patterson were involved in a paper which posited “complex speciation” in the lineage that led to humans and chimpanzees. What that means is that there was some hybridization between the proto-chimp/bonobo lineage, and that leading to hominins. As the authors state: “These unexpected features [of the genome] would be explained if the human and chimpanzee lineages initially diverged, then later exchanged genes before separating permanently.” The primary result happens to be a disjunction between the patterns you see in the broader genome, the autosome, and the X chromosome. The divergence from the X chromosome is far less than it should be if you would set your expectation from the autosome, suggesting that it harbors signatures of recent gene flow across the two lineages.

A new paper in PLOS GENETICS, Strong Selective Sweeps on the X Chromosome in the Human-Chimpanzee Ancestor Explain Its Low Divergence, offers up a different set of possibilities. One of the authors, Thomas Mailund, has a write-up of where they were going with this paper and how they got there. Definitely read what he has to say.

The crux of the issue seems to be that the diversity on the X chromosome varies in a peculiar manner. In particular, incomplete lineage sorting, basically the overlap of variation across two species due to common ancestral alleles, seems to exhibit a bimodal distribution on the X chromosome (the bottom panel above). Going beyond just a chromosome-wide summary or average, the authors found that there were huge deserts where variation was gone, in contrast with broad swaths of the X chromosome genome where the variation is totally in light with roughly neutral assumptions (i.e., the effective population of the X chromosome is ~3/4 of the autosome, so that increases the power of drift, etc.).

Why this pattern? One explanation could be background selection. This is basically the removal of deleterious alleles as they arise, often resulting in reduced variation across a genomic region because of linkage. The X chromosome has a peculiar dynamic because in males normally recessive alleles, whether favored or disfavored, are subject to the full force of selection (since most recessive mutations are deleterious, they’d be purged more effectively). But background selection is a relatively gentle and continuous process. The width of the flanking regions impacted by selection against a focal mutant should be modest. What they found was that there were huge genomic blocks without any segments of incomplete lineage sorting in humans and chimpanzees. That is, variation was removed in some portions of the genome and not others. One process that can cause this are positive selective sweeps. The authors posit there were many of these to explain how many regions of the X chromosome seem to have been affected.

51x-WwY-sAL._SX387_BO1,204,203,200_What was driving these sweeps? At this point they’re really tentative. But they suggest meiotic drive. Meiotic drive is pretty famous from the deleterious t haplotype in mice, but there might be a major bias in when we see drive, because if it doesn’t have a deleterious drag it might result in such rapid sweeps to fixation that we won’t ever catch it in the act. It could be pervasive as a phenomenon, but we might have a skewed perspective of its basic nature.

Finally, they also report that these regions of reduced ILS correlate with regions of the X chromosome where there is very little Neanderthal admixture. So this might be part of a broader evolutionary dynamic among apes. Mailund promises more, and I’ll be waiting….

Old Europeans were old school thugs

14 – And Moses was wroth with the officers of the host, with the captains over thousands, and captains over hundreds, which came from the battle.

15 – And Moses said unto them, Have ye saved all the women alive?

16 – Behold, these caused the children of Israel, through the counsel of Balaam, to commit trespass against the Lord in the matter of Peor, and there was a plague among the congregation of the Lord.

17 – Now therefore kill every male among the little ones, and kill every woman that hath known man by lying with him.

18 – But all the women children, that have not known a man by lying with him, keep alive for yourselves.

– King James Bible, Numbers 31

In the 20th century the Lithuanian archaeologist Marija Gimbutas posited that the emergence of pre-Christian European culture went through two phases after the Mesolithic. First, there were the Neolithic Old Europeans who brought agriculture. Then there were the Kurgan people from the steppe, who brought Indo-European languages and warlike patriarchal values to the continent.By the 1990s many archaeologists had turned against the Kurgan model of Indo-Europeanization, leaning rather toward the proposition that the Old Europeans themselves were Indo-Europeans. I believe that the latest work in genetics, utilizing powerful statistical inference techniques leveraging genomics and computational biology, and ancient DNA, suggest that Gimbutas was right in terms of the role of the Kurgan people as promoters of Indo-European culture in Northern Europe. Even those who supported the Kurgan hypothesis, such as David Anthony, were apparently shocked at the magnitude of the genetic turnover.

warbeforeBut Gimbutas probably went very wrong is the idea that Old Europeans were a peaceful and matriarchal society. First, though there are matrilineal societies, and matrifocal societies, to my knowledge there are no matriachal societies which are analogs to the patriarchies you might find in the modern Arab world or ancient Athens (and frankly, most agricultural and post-agricultural societies). Certainly there were societies where powerful women were shaping the course of events. This influence may even be institutionalized (I’m thinking of the Iroquois as an instance of a case). But there were no societies where rulers were exclusively women and men were forced into roles of total passivity in matters of war and politics, and property as a class.

That’s the truism as informed by what we know from surveying cultures in the historical record and extant today. But there is a spectrum of empirical phenomena in terms of magnitude. During the Roman Empire the women of the Latin West continued to have liberties and freedoms that were customary for them during antiquity (the power of the Julio-Claudian women and Theodora seem less shocking when considering the public prominence of elite women during the Republican period, which some ascribe to the role of Etruscan women in their society). When the focus of Roman power shifted toward Constantinople in the 4th century, one visible marker distinguishing elite women of western cultural affiliation, as opposed to those who were of the Greek nobility, is that the latter were often veiled, perhaps echoing the seclusion of ancient Athenian women of good family.

Similarly, though Japanese civilization is influenced, perhaps even derived, in large part from Chinese civilization, one major distinction between the two is that the in the ideal and often in practice the Chinese have subordinated military values to civilian ones to an exceptional extent for a pre-modern society. In contrast, the Japanese developed a military aristocracy which eventually superseded the civilian nobility. This results in the anachronistic romanticization of a martial ethos such as in bushido, which has no clear analogy in the Chinese world view. Obviously here I am not saying that the Chinese were a purely pacific people. And there were ages when martial values were ascendant, for example the early Tang. But the fact that the founder of the Song dynasty, a general, encouraged a demilitarization of his ruling class makes much more sense in light of the ethos of Chinese elite culture going back to the end of the Warring States period. In contrast, the Western aristocracy, often directly descended from Germanic warlords, have retained an ethos where physical violence and competition is more meritorious. The emergence of firearms necessitated a shift away from direct front-line combat to minimize casualties, and a channeling of energies into patronage of high culture and foppish self-cultivation. But even today the princes of the House of Windsor continue to serve in military professions, putting the role of the soldier in Western society in stark relief as one of esteem.

51PS1EGohbL._SX309_BO1,204,203,200_I bring this up to reiterate that though we see the past through a dark mirror, we must filter its probabilities through what we know of societies today, and those that are historically attested. Human phenomena is not infinitely flexible, but exhibits modal peaks across the distribution of possibilities. Our expectations should not be uniform and agnostic. The Old Europeans may have been gynocentric pacifists, but if they were then they were sui generis among human societies. As time machines are not feasible we will never truly know in a direct sense what they were like. Rather, we must look to aligning material remains with theoretical expectations given what we know about the nature of human societies. Interpretation will always occur. The key is to obtain the proper framework to generate true inferences. In Lawrence Keeley’s War Before Civilization the author observes how the objects which might be useful as weapons in graves have often been interpreted as “ritual” markers of status, as if conspicuous consumption was always the primary form of status competition. Written in the 1990 War Before Civilization  was a seminal work taking on the neo-Rousseauan model head-on, that war was somehow a contingent invention of civilization. A terrible mistake.

A recent paper in PNAS puts the final nail in the coffin of this strong form of the neo-Roussseauan paradigm, which now has little support even from scholars such as Brian Ferguson. The paper is The massacre mass grave of Schöneck-Kilianstädten reveals new insights into collective violence in Early Neolithic Central Europe:

The Early Neolithic massacre-related mass grave of Schöneck-Kilianstädten presented here provides new data and insights for the ongoing discussions of prehistoric warfare in Central Europe. Although several characteristics gleaned from the analysis of the human skeletal remains support and strengthen previous hypotheses based on the few known massacre sites of this time, a pattern of intentional mutilation of violence victims identified here is of special significance. Adding another key site to the evidence for Early Neolithic warfare generally allows more robust and reliable reconstructions of the possible reasons for the extent and frequency of outbreaks of lethal mass violence and the general impact these events had on shaping the further development of the Central European Neolithic.

The body of of the text engages in a deep osteological analysis, but in the language of the street, “they fucked these people up.” In particular, the victims seem to have had their lower extremities maimed or crushed. If they were still alive when this occurred then it was clearly a form of torture. If they were dead, then it was clearly a spiteful mutilation of the dead, and the valence has to be symbolic rather than utilitarian. The victims in the assemblage exhibited a curious demographic pattern. There were infants below one year of age, as well as young children, but no older children or adolescents. The only two adult women were over the age of forty. The rest of the adults killed were men.

We can’t know what happened with certainty. These were preliterate people. But with what we know about the nature of human culture it seems that an obvious narrative presents itself. As noted in the paper this was an LBK site. But, it seems that the community was on the border of two LBK trade networks (as inferred from the distribution and character of material remains). On the frontier of agricultural production, when land is in surplus, one can imagine that there was little inter-group conflict between LBK coalitions. What we would probably term “tribes.” Additionally, there was almost certainly a “meta-ethnic frontier” which Mesolithic hunter-gatherers, who we now know were genetically and physically very distinct from the LBK people (naively projecting genetic variance statistics, their difference was in the ballpark as that between modern Chinese and Northern Europeans, Fst ~ 0.10).

But what happens when Malthusian constraints begin to close in? In the Moral Consequences of Economic Growth Benjamin Friedman suggests that in American history economic stagnation and stress lead to greater xenophobia, and reduced openness. And one doesn’t need a deep history lesson to observe what occurred in Europe during the 1930s. Retrenchment invariably leads to turning back to collective units of organization and protection. Once the LBK reached a stationary state, which reduced marginal returns to labor input, and likely produced increased sensitivity to environmental perturbations, then it is entirely expected that “inter-group competition” would emerge as one of the ways in which the carrying capacity would maintain a “check” on numbers. Sedentary agriculturalists must scramble for scarce resources. There’s no running off, at least at this stage of social complexity.

The fact that the LBK turned on each other should condition our understanding of how the transition to the Corded Ware may have occurred. The Y chromosomes of the LBK period are very different from what we find in Bronze Age Europe. The most reasonable model I believe is that these lineages did not go silently into the night. As they did to each other, so was done unto them. In J. R. R. Tolkien’s work there are allusions to the coming Fourth Age of Middle Earth, an age of men. The rise of agricultural mass society was the age of men in our world. Hunter-gatherer societies were no idyll, but due to their small scale, and complementarity in economic production, the relationship between the sexes was not one of male domination, where women were property to be traded as chattel. But concentrated and sedentary units of economic production that arose with village life became an inevitable target of extraction from collective groups of males, who translated their significant superior upper body strength into a reign of coercive terror. That coercion was translated into reproductive success, which is evident in the explosion of a finite set of Y chromosomal lineages on the order of ~5,000 years ago. The common R1a1a ancestor of Daniel MacArthur and myself was the original O G thug.

In evolutionary genetics R. A. Fisher introduced the idea that when selection pressures come to bear upon a population, large effect mutations may increase rapidly in frequency to increase population mean fitness. But, these mutations are not without cost, one reason that they were likely at low frequency in the first place. For example, one of the most well known adaptations to malaria famously has a very large segregation load in terms of a recessive disease. Evolutionary theory predicts over time that the adaptation will be less genetically disruptive. New mutations which allow for adaptation without the costs may emerge, or, other mutations may arise to “mask” and “modify” the deleterious effect of the initially favored allele.

When John Maynard Keynes purchased the papers of Isaac Newton he was shocked at the proportion of the great physicists writings devoted to matters occult and esoteric. Keynes declared that Newton was the ” last of the magicians, the last of the Babylonians and Sumerians, the last great mind which looked out on the visible and intellectual world with the same eyes as those who began to build our intellectual inheritance rather less than 10,000 years ago.” In opening the new age with his beautiful system of rational science, Newton nevertheless reflected an ancient ethos which persisted down into the modern period.

The Jewish people have been critical in the development of a universal ethical monotheism in the West, part of the broader evolution away from the supernatural systems of the Bronze Age that occurred across the Axial Age. But the Hebrew Bible preserves within it a world far removed from the divine Logos, a God of law and morality. The angry and jealous sky god of the Hebrews also enjoins upon them genocide of other tribes. Though the Hebrew Bible is pregnant with the possibilities of religious ethical universalism, the voice of the prophets’ righteous indignation raw with rage alive in our age, and channeled through the gentler voices of Hillel and Jesus, it also is a record of a parochial and peculiar people, who wash their hands of their atrocity by attributing it to the capricious and vindictive will of their god. If Moses and Joshua did exist, they almost certainly would have more in common with the war-chiefs of early Neolithic Europe, 4,000 years before their time, than men such as Constantine, who 1,300 years later promulgated a universal religion for a universal empire.

51w0iMybWyL._SY344_BO1,204,203,200_Ancient Egypt, with its autocratic god-kings, was arguably one of the end-points of the Neolithic experiment with mass culture and ideology. So were Shang China and Mycenaean Greece, with their human sacrifices to propitiate the gods. Increasing primary productivity by an order of magnitude, which farming did, resulted in the emergence of huge amalgamations of humanity, and we as a species are culturally creative enough to have come up with adaptations. Literacy, cities, and social stratification, were all responses to the stresses and pressures that the opportunity of mass society presented. The emergence of powerful menacing and extortionate patrilineages was another. This was a world of gangs, thugs, and the question was not whether you would become a thug, it was whether you would be a thug or a victim of a thug. They were necessary, inevitable, cultural mutations against the background pressures that agricultural imposed upon humanity.

But as per Fisher’s model, mutants with deleterious consequences invite their own response. They are tamed and civilized by a scaffold of modifiers. The brutal gods which were but reflections of human vice and caprice were drafted in the service of primal human psychological impulses forged during the Paleolithic, reciprocity and egalitarianism arose against the background of brutality beyond imagining unleashed by the social dislocation that was a consequence of agricultural society. The men and women shaped by the Hebrew prophets and Christian Church Fathers, the rishis of the Upanishads and the Chinese sages, they are all closer to us 2,000 years later, then they were to their own forebears only a few hundred years earlier in their own past.

These models operate in the world between one of naive innate cognitive reflexes and pure cultural inventions generated without reference to the functional constraints of our minds and environments. The independent experiment of the Aztec Mesoamerican society suggests that the same stage of brutal social order that had occurred during the Neolithic was playing out in the New World. The Aztecs were engaging in ritual cannibalism and human sacrifice in a manner not seen in Old World civilizations since the Bronze Age. Some inventions are inevitable, emergent properties of the intersection of our biobehavioral toolkit and our species’ incredible cultural flexibility. Though we may believe ourselves to be far beyond the LBK people, the Nazi gas chambers or the more recent events in Rwanda suggest that the same mental reflexes of coalition-building and competition can be co-opted toward organized violent ends even today. Peace is possible, but violence is always imaginable.

Addendum: This Azar Gat article argues for the reality of war among hunter-gatherers, extensively citing what we know about Australian Aboriginal culture on the eve of European settlement. It would indicate that the only thing separating our Pleistocene ancestors from ourselves in terms of violence would be scale and organization, with ideology a novel handmaid.

Selection is often a mystery

Credit: Graham Crumb
Credit: Graham Crumb

If population genetics is “study of the distributions and changes of allele frequency in a population,” then the understanding of the maintenance of variation (or lack thereof) is one of the major topics of focus. In the first half of the 20th century when there was a lot more theory than data there were arguments about whether polymoprhism (in this era they’re talking about classical markers) was maintained through balancing selection or whether it was just a transient phenomena, and that at any given moment you’re just getting a snapshot of alleles sweeping up to fixation, or being purged out of the gene pool. In the second half of the 20th century it was all about neutral theory, and its discontents. Then the post-genomic era showed up, and geneticists had access to a lot of data and computational power to analyze it. Rather than relying on older molecular tests which were geared toward detecting inter-specific selection events population geneticists began scouring haplotype structure.

But even now there’s a lot of mystery. First, you might be able to adduce that selection is highly likely in a given region, but you may have no clue what that region does functionally (in some cases the region may not even be genic, in which case it has be a mysterious regulatory element). There are some good case studies where the mystery has cleared. Lactase persistence. The ways you can fight malaria. But over the past day I’ve been having to admit that it sure looks like the regions of the genome around pigmentation function are the targets of selection. But we don’t really know what selection is selecting for. And this is actually a set of selection events that I can imagine some day reaching a resolution into their probable cause. But we’re far from that.

A few years ago Eimear Kenney and company solved the mystery of why some Melanesian populations had very dark skins but blonde hair. I blogged about it, but didn’t read the paper too closely. Looking at the publication date, May 2012, I realize I was busy studying for some really big end of first year exams at that time, so that explains my lack of attention. In any case they found that a mutation, rs13289810 in TYRP1, results in blonde hair when it’s a homozygote. They didn’t find strong evidence for recent selection. That is there wasn’t a long haplotype block indicating a sweep in the past 10,000 years. The allele frequency difference across populations as well as long range linkage disequilibrium was suggestive of past selection.

map2This was in the Solomon Islands. Today I decided to see if there was any follow up on this work. Well, Heather Norton’s group published a paper, Distribution of an allele associated with blond hair color across Northern Island Melanesia. It’s on a different set of islands, but the same results pretty much hold. The allele has a recessive effect on hair color, not much on skin color (there was a small effect in the original paper, so it seems it’s not wholly tissue specific in expression). But I just kept staring at this map and the frequencies. Look at the derived proportions…they don’t get above 0.50. But in most of the populations they’re around in appreciable proportions. I had a hard time not thinking there wasn’t balancing selection going on here. That this was something old that was persisting, but not fixing.

I asked Carlos Bustamante, and he got back me on Twitter:

I also had an exchange with the first author, and she pointed out in the supplements that the frequencies in the Solomons were quite curious too:

Region Genotype counts Frequency of 93C
  CC CT TT
Central 126 80 22 0.27
Choiseul 17 2 0 0.05
Guadalcanal 33 33 13 0.37
Isabel 23 17 7 0.33
Makira 13 11 3 0.31
Malaita 98 185 92 0.49
Polynesian
Outliers
40 11 0 0.11
Temotu 13 11 3 0.31
Western 40 22 2 0.2
Total 405 374 142 0.36

 

When they looked in the HGDP data set it’s ancestral everywhere else. The derived variant isn’t floating around at low frequencies. One might naively think that it’s overdominance, but I suspect we’re looking at some negative frequency dependent selection. In the 2014 paper by Norton et al. it’s pretty clear that this is distributed across rather disparate populations. It is unlikely in my opinion to be purely due to population structure, as diverse islands have been sampled. It looks to be an old variant that’s persisted, so it dates to the Pleistocene settlement of Near Oceania. It’s also found in Australia, though we don’t know the genetic basis.

Ten years ago I would have been super excited to know the genetic basis of an interesting trait like this. But now I’m left with why? Why? We’ll be grappling with a lot of why’s in the next few decades.

Tamil Brahmins are alien & native to South India

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admixethn_htm_m25d90b04Whenever I post about Indian genetics there are really weird comments that pop up which go like this: “this guy doesn’t know anything about genetics, he totally ignores the research [usually published in the late 2000s and utilizing mtDNA haplgroups] of [Indian researcher that I don’t really know] who has proven [something which has been superseded long ago].” Usually these are at my Facebook account, though they also pop-up on Twitter. Often I’ll indulge this people, but usually I just ignore them. If your world-view needs to be supported by mtDNA haplogroup analyses published in Human Biology, more power to you! Or if eight marker autosomal microsatellite studies from 2005 is the last you want to hear about genetics…by all means.

As it is today in a few hours you can really resolve what’s going on with questions about Indian genetics, or whether the Chinese are genetically differentiated, as long as you don’t have too strong of an agenda, can get data, and don’t go sniffing for particular results. A few weeks ago a friend who is from a Tamil Brahmin background asked me if I knew anything about the genetics of this group. Well, a bit. Above and to the left is a bar plot with admixture fractions from Harappa DNA Project . You can see that the Tamil Brahmins are homogeneous. This suggests that they’re an endogamous community with genetic coherency.

But how do they relate to other South Indians and other Brahmins? This is a question that is politically fraught. I really don’t care though, because I’m not Indian, and even if I was, I still wouldn’t care. I don’t have Zack’s data set, but I do have three Tamil Brahmin genotypes. You can see them on the PCA plot above. The North Indian data set is all Punjabi, while the South Indians are a mix of non-Brahmin Tamils and Telugus, from the 1000 Genomes. The rest is from the Estonian Biocentre data. The results are clear, you can see that Tamil Brahmins are strongly shifted toward the North Indian cluster but in comparison to Uttar Pradesh Brahmins they are South Indian skewed. The most parsimonious explanation taking into account their generally agreed upon communal history of migration from northern India is that they are predominantly a northern origin caste with some admixture from the local substrate. This seems entirely reasonable with how we know demographic processes work.

Using TreeMix I ran 20 plots each of two different data sets with Tamil Brahmins. All the plots are here (tar.gz). But below are two representative plots.

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In the first set of plots the Tamil Brahmins tend to be near the positions of the North Indian groups, but have a consistent migration edge from near the Velamas. From what I can tell the Velamas are not a marginal group, but somewhat elite. It seems entirely reasonable that native gene flow into Brahmins coming from the north would be from local high status populations, since the Brahmins themselves were coming into the region as a priestly elite to serve the rulers of South India and sanctify their domains. Usually I read something about the assimilation of local religious elites, so that’s probably what happened. Also, note that Uttar Pradesh Brahmins consistently receive gene flow from Chamars, a Dalit caste in Uttar Pradesh. I suspect what’s going on her is that the Chamars are representative of the pre-Indo-Aryan population, and the Indo-Aryans amalgamated with local elites as they pushed the Aryavarta beyond the Punjab. There are allusions which can be interpreted this way in the older Hindu texts.

The second set of plots is a little more confused. The positioning of the various groups is a little schizophrenic, and you can see gene flow edges back and forth attempting to make the “fit” of the topology better. The position of the Tamil Brahmins is next to the Chamar here, but they are getting a lot of gene flow (nearly 50%) from the Uttar Pradesh Kshatriya, again indicates that the group is a composite. The Chamar make direct contributions to both Uttar Pradesh high castes.

A major shortcoming of these analyses is a paucity of good source populations for these gene flow edges. A lot of the public data is from obscure tribal groups who are somewhat inbred, and so often drift into long branches. The 1000 Genomes data has no ethnic label, so you are pooling a lot of different groups together. For whatever reason we know a lot more about the genetics of the Tharu people or the Kol than we do about the Brahmins of Tamil Nadu or Uttar Pradesh, or the Kayastha of West Bengali.

Finally, I was curious about runs of homozygosity. If the South Indian Brahmins went through a bottleneck of some sort, and have been endogamous, they’d have built up some of these. I have three 23andMe South Indian Brahmin samples, along with a Kayastha from Uttar Pradesh, and myself. I took the HapMap populations and intersected SNPs so that I got 750,000. Below is a density plot of total kb of runs of homozygosity of HapMap populations, as well as vertical lines which show where some individuals come out. I was struck that the South Indian Brahmins had 24, 25, and 26, runs respectively using default cut offs. The Kayastha from UP had 19. And I had 11. I think my relative lack is due to two factors. First, the last few generations above me in my pedigree have seen a lot of intermarriage between what in different parts of India would be different jatis (it doesn’t map totally to Muslims, but I do have a fair number of Hindu ancestors in the last few hundred years and sort of know their caste by the surname). Second, I’m Bengali, with a lot of East Asian ancestry, so without inbreeding that’s going to break apart a lot of blocs which might otherwise exist in the genome because of population admixture. If you are curious about the GIH, Gujarati population, there are a lot of Patels in that sample. They’re skewing the distribution up.

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CEU = Utah White

GIH = Gujarati

CHB = Beijing, Chinese

ASW = African Americans from Oklahoma City

Multi-level selection, red in tooth & deme

41lYx8Va7WL._SY344_BO1,204,203,200_People routinely mistake the action of adaptive evolutionary process as occurring on the level of the species. Not only is this a misunderstanding that crops up in the general public, but I’ve talked to biologists who make the same mistake. The reality is that the mainstream tradition in modern evolutionary biology is very skeptical of “for the good of the species” arguments. For me one simple reason is that I don’t think species are necessarily a clear and distinct taxonomic class. But the major factor is the reality that altruism of this sort is vulnerable to being superseded by an invading selfish free-riding strategy. As a matter of pervasive phenomena much of the “struggle for survival” that an organism experiences won’t be due to exigencies of environment or the threat from other lineages, but rather within one’s own species. Though this can be conceptualized in terms of violence, more often one can chalk it up to competition for finite resources in a Malthusian world at carrying capacity.

417SDKP-XhL._SX323_BO1,204,203,200_The logical conclusion leads to the sort of individual-level focus that is at the heart of The Selfish Gene, though Richard Dawkins’ book is to a large extent an exposition of a Neo-Darwinian tradition which goes back to R. A. Fisher, and matured with W. D. Hamilton and George Williams. But over the past few decades there has been a small group of biologists who have rebelled from the focus on individuals and genes, and made the case for selection operating at multiple levels or biological organization, from the intra-genomic all the way to “super-organisms” such as ant colonies. Rather than old-style species/group selection, the new theorists refer to “multi-level selection.” The primary force behind this movement has been David Sloan Wilson. I like David personally and he’s a great scientist (I did a BloggingHeads with him 6 years ago). But he has a tendency in my opinion of declaring unilateral victory when most people would argue that there’s still a lot to hash out, and the war continues. His new book, Does Altruism Exist?, is in my Kindle “to-read” stack, but from what I’ve seen of the reviews he does do this again! (no worries, the rest of the book looks interesting anyway)

41z97bDZvUL._SY344_BO1,204,203,200_My own views have evolved…over the years I have realized I am not entirely satisfied with models of human cultural variation that are individual level or entirely non-adaptive. I have long been broadly sympathetic to the project of Peter Richerson and Richard Boyd of using the frameworks developed in evolutionary biology to understand cultural processes. Additionally, I’m a big fan of Joe Henrich’s research, to the point of pre-ordering his book The Secret of Our Success: How Culture Is Driving Human Evolution, Domesticating Our Species, and Making Us Smarter six months ahead of time. There are good reasons why above-the-individual level selection would be able to operate in humans. The reduction in a verbal sense is that human cultural phenomena are such that between group variation can dwarf within group variation. The canonical example of this is language, where differences between groups are very large, and rather smaller within groups. This is simply a function of how culture, and language in particular, spreads in a population: it can be asymmetric in terms of vertical transmission. This is in contrast to genes, where you have equal contributions from both parents. One can imagine a population expanding into another where it absorbs individuals from hostile groups, changes its own genetic makeup, but by and large maintains its cultural integrity. To give a concrete example, the Xhosa people of South Africa are approximately ~25 percent Khoisan in genetic ancestry. But their culture is not “25% Khoisan.” There are influences, such as click sounds in their language, but those are accents on the basic Bantu cultural substrate which is preserved, and ties them with populations in Central and Eastern Africa.

51aEM-jiATL._SX323_BO1,204,203,200_It is a rather different matter with biological processes because of the enforced symmetry in transmission. Maintaining between group variance requires ingenious processes, which some find implausible. But ultimately it’s an empirical matter on a species-by-species basis. I would commend readers to look through first half of Wilson’s Unto Others to get a sense of how inter-demic selection processes might be ubiquitous. My position on the role that biological above-the-level-of-individual selection plays in evolution is to be skeptical in the generality but open-minded in the specifics. After all, bdelloid rotifers show that there are cases where complex asexual species can persist, even if the general rule about asexual lineages is that they are prone to extinction.

For whatever reason arguments about multi-level selection get rather heated among evolutionary biologists. It’s often closely related to the debate about kin selection (see this post from Jerry Coyne, and follow the links). I suppose David Sloan Wilson would suggest that it’s an illustration of inter-group competition, as individuals conform to particular positions due to their identity as members of a coalition.

coverWith the preliminaries out of the way, I’d like to recommend a series of papers in the Journal of Evolutionary Biology which are open access to readers if they want to dig further (especially for those with a formal bent). First, The genetical theory of multilevel selection. The title should give some readers a clue as to the tradition which this theorists works in! Charles Goodnight makes a spirited response in Multilevel selection theory and evidence: a critique of Gardner, 2015 (his point about some researchers who come out of quantitative genetics has always been obvious to me when I read their papers; it’s a different tradition). Finally, the original author responds: More on the genetical theory of multilevel selection.

I’m not an evolutionary theorist, so I’m not going to take sides (though to be honest I always find Goodnight to be a little too vociferous for my taste, but perhaps that’s just how it comes across in print). Rather, I’m chewing through some of the ideas, and find that these papers are excellent starting points to explore the literature. It’s also nice that they’re open access, as there are people who are not in academia who might have some things to say about these topics, or, who might pursue research as a career after stumbling upon these sorts of papers.

Note: If the copious references to the Price Equation confuse, try this paper.

Open Thread, 8/16/2015

About a year ago I heard a pop song on my Pandora that was a little less annoying than Ke$sha, and I looked up the singer up. Her real name was Jessica Malakouti. My immediate though was “that last name sounds Iranian.” Then I watch the video above, and my revised thought with the new priors (i.e., what she looks like) was “well, she’s probably of Lithuanian heritage, and that’s an archaized surname that sounds vaguely Iranian.” For reasons I don’t even recall somehow I stumbled onto this singer’s Wikipedia page recently, and it had been updated with the fact that she is of Iranian heritage. It turns out her father is from Iran, and she is a product of the greater Los Angeles Iranian Diaspora community. The citation for the Wikipedia entry is a Youtube interview where she refers to herself as “mixed-race” and talks about rapping in Farsi (I guess she’s a wannabe Arash).

If someone who looks like this refers to herself as “mixed-race” this country is going to need to update its 1960s era Civil Rights framework soon. One of the podcasts I listen to is On Point with Tom Ashbrook, and a week it ago it had a show with the title Race In America, From Watts To Ferguson And Beyond. Actually, on the podcast version it was shortened to “Race in America.” Despite the fact that less than 40 percent of people who are in some way not non-Hispanic white (which includes people from the Middle East, like Jessica Malakouti’s father in any case) are of black American heritage, they loom large enough in this nation’s history and consciousness that I knew that “Race is America” was going to be about two races, with the rest of us rendered invisible. Of the guests on that particular show only John McWhorter even grappled with the fact that there were groups outside of the black-white dichotomy. When I was a kid in the 1980s this was how it went too. And to a great extent it was how it should have gone. Black Americans have been in this country since the Founding, and most of their ancestry dates to before the Founding. They were the largest racial minority for most of its history, and were when I was a child. Things are different now on the ground. But you wouldn’t know that from the media. 15 years ago The New York Times published its prize winning series How Race is Lived in America. I thought that that was going to be the last testament to the old biracial America due to the nation’s changing demographics. I was wrong.

51aBlSPDX8L._SX342_BO1,204,203,200_After finishing The Making of Modern Japan, Japan is big in the media this week. There are yearly stories on the apology, but there is a new twist with the current Prime Minister’s attempts to modify the hyper-pacifist orientation of the Japanese state and society (more precisely, it strikes me that he wants to make it so that the “Self Defense Forces” have some real bite and can be more flexible in their operations internationally). After reading a book which outlines how Japan got to where it is today, I really value the importance of dense historical knowledge. It’s like going from sepia photographs to high resolution digital color imagery. I had been meaning to get back to A New History of Western Philosophy, which I dropped in the medieval section when I switched to reading The Indo-European Controversey, but now I am curious as to whether I should fill in my blank spot (in relative terms) in regards to modern Chinese history. Perhaps it’s the antiquarian in me, but I’ve never been much curious about Chinese history beyond the reign of the Qianlong Emperor. Now I’m inclined to pick up Jonathan Spencer’s The Search for Modern China, though part of me wants to finally learn about the Taiping Rebellion through God’s Chinese Son. Recommendations are welcome.

Recently I posted some analysis where it seems pretty clear that there’s Indian admixture into the Cambodian population. The main issue that I have when trying to get a fix on this is whether it’s deep common shared ancestry via the South Eurasian substrate which was present from India all the way to the South China Sea and down toward maritime Southeast Asia, or, whether it was more recent, on the edge of historical times (and whether it was connected to the cultural impact of India on Southeast Asia). I think I presented persuasive evidence that it was in part more recent. Yesterday I stumbled onto a smoking gun which was right in the literature all along. In the supplementary table for Norton et al.’s 2007 paper on convergent light skin adaptation it reports that of 22 Cambodians the frequency of the derived variant of SLC24A5 is 9% (so 4 allele copies out of 44). They are the only East Asian group south of the Yangzi with this allele. One hypothesis is that it could be French admixture. But there are no copies of SLC45A2 derived allele. The sample size is small, but I checked the 1000 Genomes, and the Vietnamese have very low frequencies of both alleles, consistent with French admixture. The best candidate for a donor group is obviously a South Asian one. It is interesting that the allele frequency is pretty low, probably consistent with overall admixture proportion, consistent with no selection in situ.

In January I wrote that op-ed in The New York Times last year so that the debate would be a little less “battle of the sexes” in rhetoric about abortion. But whenever I read/listen to liberals talk about it they often fallback on the trope that women implicitly support abortion rights and men do not. I have no idea what the point of this caricature is, because if you are talking to your own side everyone already agrees, while pro-life people are probably going to be pretty annoyed by your blatant mischaracterization. Perhaps I’m wrong, but I think part of it is that some people feel better about their own viewpoint when they can couch it in anti-sexism, where they (often these are liberal men) are on the side of women and their opponents are not.

Over the last year and a half or so I’ve gotten more into my fitness. Partly it was for reasons of health. I’m South Asian, and we have issues with morbidity relating to metabolic disease. It runs in my family. I have kids now and I want to be around for them. I was never that fat. Probably the highest my BMI ever got was 26 in March of 2002 (I’m 5’8, that’s 170 lbs), when I pretty much cut out all soft drinks from my diet (I was never a big consumer, but I went from occasional to literally zero). Since then I’ve been as light as 140 lbs (spring of 2008), but have veered between 150 and 160 in graduate school. My weight had has not shifted much since I began to make changes, but I’ve been lifting, so losing fat and gaining muscle. This has really helped the second, and not secondary, reason that I am working out, and that is aesthetic. It is really nice not to be soft anymore!

In any case, there was a recent link posted about low fat vs. low carb diets. The problem is that nutrition is basically a semi-science, and people rightly can offer their own opinions. Personally I find cutting carbs the main way I can sustain cutting calories, but the robotic pattern of responses by low-carb folks is too reminiscent of low-fat propoganda. For a balanced, and striving toward scientific view, I’d suggest you check out my friend Kevin Klatt’s blog (or send him questions on Twitter, that’s what I do).

Preemptive apology if I can’t respond to all your comments, though I try to read the “open threads.” I’ve got a lot of responsibilities in “real life” as I attempt to be a “grown-up,” so don’t take it personally.

The genetic architecture & natural history of pigmentation

516JD1M3N5L._SX323_BO1,204,203,200_I got curious about pigmentation about ten years when reading the coda to Armand Leroi’s Mutants: On Genetic Variety and the Human Body, where he observes curiously that after all these decades geneticists still didn’t understand very well the basis of normal variation in skin color. I read that in the summer of 2005, so Armand had probably written it in 2004 (he can correct me if he has time, he occasionally comments here). Depending on how you view it, it was a fortunate or unfortunate time to write something like this. Over the past ten years geneticists have solved the basis of normal variation in human pigmentation. In fact, most of the major work was completed between 2005 and 2007. In December of 2005 Science published SLC24A5, a Putative Cation Exchanger, Affects Pigmentation in Zebrafish and Humans. The authors reported that rs1426654 was nearly disjoint in distribution between Africans and Europeans, and, that it explained on the order of 1/3 of the variance in pigmentation between the two populations (European populations are fixed for the A allele, Africans for the G allele).

41h+3YmTZRL._SX329_BO1,204,203,200_There are several facts just within that statement that illustrates why pigmentation genomics has been such a success in comparison to other domains tackled by the new methods. First, pigmentation pathways seem to be somewhat constrained across animals, so model organisms can given us a lot of insight and clues. A lot of the pigmentation genes, such as KITLG, TYR, and SLC24A5, actually increase or decrease melanin production and alter tissue specific expression just as they do in humans, across vertebrates. Second, the fact that I just named genes off the top of my head highlights the fact that are a few conserved loci that explain most of the variance, crop up in study after study. This is in contrast to height, where the variance is distributed across thousands of genes, and the only one I can name off the top of my head is HGMA2. And it explains a princely ~0.3% of the variance of the trait.

This wasn’t entirely a surprise. I happen to have had a copy of The Genetics of Human Populations. In it, L. L. Cavalli-Sforza reported on a classical pedigree analysis of individuals in Britain of varying levels of African ancestry dating to the 1950s. In particular, in genetic jargon the study focused on the variance in trait values between parentals, F1 individuals, and “back-cross” individuals (as well as a few F2 individuals from what I recall). The research concluded that pigmentation was probably controlled by on the order of 10 genes or so. In particular, the authors suggested that the trait was unlikely to be highly polygenic, which for the designs of that period really meant more than a dozen loci or so, beyond which they lacked the power to differentiate the number of independent effects with any precision (i.e., they wouldn’t be able to distinguish between a trait where 25 loci explain 90% of the variance, and a trait where 500 loci explain 90% of the variance). Third, pigmentation loci exhibit a relatively high pairwise Fst. That is, most of the variation on many of these alleles is partitioned between populations, rather than within them. Obviously that is convenient when you are trying to detect associations between genes and phenotypes which are partitioned on an inter-continental scale.

The illustration with SLC24A5 is pretty straightforward; the frequency of the derived allele is 100% in Europeans, and over 99% ancestral in unadmixed Sub-Saharan Africans. In the 1000 Genomes frequency in the Utah white American sample of the derived A allele is 100% (out of 99 individuals). In the 91 British individuals it is 100%. In the Tuscan set of 107, there are 213 A alleles, and 1 G allele. In the 107 Spanish individuals, the A allele is at 100%. In contrast, for the Yoruba Nigerian data set, there are 3 A alleles for 213 G variants. For the Esan of Nigeria, it is 5 A for 193 G. For the Chinese samples from Beijing, 6 A alleles, and 200 G. At this point you might think that the A variant at this SNP position is diagnostic of European ancestry, but it is not. I, for example, am homozygous for the A variant, as are both of my parents. In the 1000 Genomes data there are 25 Bengalis who are AA, 42 who are AG, and 19 who are GG. In the Sri Lankan Tamil population A is at 49% frequency.

F1.mediumThe figure to my left is from Heather Norton’s Genetic Evidence for the Convergent Evolution of Light Skin in Europeans and East Asians, and it uses neighbor-joining trees to represent genetic distances at particular loci then known (2007) to be implicated in inter-continental variation in pigmentation. The abbreviations are pretty self-evident, WA=West African, NA = Native American, EA = East Asian, IM = Island Melanesian, SA = South Asian, and EU = European. What you see is that pigmentation genes are not particularly phylogenetically representative. That is, whole genome relationships, whereby all non-Africans form one clade set against Africans, are not reflected here. Looking at these patterns, you would have inferred that Europeans were the outgroup. And, the lowest genetic distance from West Africans are Island Melanesians. What’s going on here is Island Melanesians and West Africans have similar phenotypes in skin color, and that is being reflected in these genes. Roughly, Melanesians and West Africans exhibit a fair amount of functional constraint around pigmentation genes. They haven’t changed much. In contrast, East Asians and Europeans actually are not too different in their pigmentation on a world-wide scale, but that is not reflected in these trees. Why? As is made clear in the title of Norton et al.’s paper East Asians and Europeans arrived at their phenotypes via different mutational paths. I say different mutational paths because there is a broad overlap in genes, but, the alleles are often different (different SNPs or regulatory elements within the gene).

One of the questions that I often get is how to translate genetic variation into realized trait value shifts in individuals, as opposed to simply proportion of variation explained within the population. Luckily, geneticists who study pigmentation have a quantitative unit, a “melanin index” (MI), which naturally utilizes the fact that individuals with darker skin exhibit less reflectance. But there are two problems giving a simple answer to these sorts of questions. First, a substitution of an allele may have an average effect, but, that effect may not be realized for various reasons (e.g., epistasis). And there are still individual differences between people with the exact same genotype. Second, that effect manifests within a population, and different populations have different mixes of alleles.

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