I don’t listen to “bro country” often, but when I do it’s Brantley Gilbert

k10386After the events of today I’m going to curl up with Xunzi: The Complete Text. That’s just how I roll. Most of my friends are more outraged than I am. I don’t know why. It just is that way. It is heartening that people care about me, and I appreciate it. But there’s not much more to say than has been said, and perhaps even less. Things happen. If today I was a dying man, I would tell you that I was the child with a book in hand, not the proud one demanding that my views be heard because of the stridency of my voice. My views aren’t important, the truth as best as I can understand it is important. My friends know who I am, and that is all that matters to me. I regret the day that I am the story. That’s besides the point, and uninteresting to boot. Being at the center of a mini-media mini-controversy is rather tiring.

Yes, I just juxtaposed Brantley Gilbert with Xunzi. Nowhere else….

Open Thread, 3/15/2015

pkMost of you may guess that I’m not big into human interest stories (though I do follow celebrity gossip cursorily). But over the last week I’ve become moderately interested in the death of Paul Kalanithi. A little over a year ago his piece How Long Have I Got Left? was brought to my attention. The issue that he was confronting was that he was suffering from terminal lung cancer. It was particularly of note because Kalanithi was a neurosurgeon who was just ascending up the peak of his professional powers. Now, he was confronting disease and illness from the perspective of a patient, and it was making him reconsider some of the norms of medical practice. Despite his deteriorating health Kalanithi kept writing and speaking out in the media. His last piece, Before You Go, was written not too much before his death, on March 9th of 2015.

His story attracted my interest again because despite his terminal condition he and his wife decided to proceed with starting a family. On July 4th of 2014 his daughter Cady was born. He concluded his last piece of written work:

…There is perhaps only one thing to say to this infant [his daughter, Cady], who is all future, overlapping briefly with me, whose life, barring the improbable, is all but past.

That message is simple: When you come to one of the many moments in life when you must give an account of yourself, provide a ledger of what you have been, and done, and meant to the world, do not, I pray, discount that you filled a dying man’s days with a sated joy, a joy unknown to me in all my prior years, a joy that does not hunger for more and more, but rests, satisfied. In this time, right now, that is an enormous thing.

A minute after my daughter was born she opened her eyes, and looked straight at me. And at that moment I slipped beyond the event horizon. I am happy for Paul Kalanithi that he decided to embark on that last journey into the deep before his passing.

Second, does anyone know a good book about the “Age of Discovery”? I can’t think of one off the top of my head. A reader emailed me to ask, and I didn’t have a pat response.

Selection in Europeans, but it still sweeps!


David Reich’s lab has a new preprint out, Eight thousand years of natural selection in Europe, which serves as a complement to Massive migration from the steppe is a source for Indo-European languages in Europe. Where the previous work has focused on the relationships of ancient and modern populations, this research puts the spotlight on patterns of natural selection which have shaped ancient and modern populations. The method utilizes the explicit model which is supported by the previous work, that Europeans are best approximated as a three population admixture of a group represented by the hunter-gatherers of Western Europe, the first farmers which brought agriculture to Europe, and the peoples of Central Eurasia which likely brought the Indo-European languages to Europe. In the parlance of these sets of papers, WHG, EFF, and Yamnaya. Basically they have allele frequencies of these ancestral groups, thanks to ancient DNA techniques, and the frequencies in modern populations. By comparing the frequencies one can then infer if the deviations from expectation are large enough to satisfy the conditions you’d expect for a locus subject to a selective sweep of some sort which is changing proportions rapidly as a function of a given selection coefficient.

lctFirst, it is very obvious that lactase persistence in Europe has been under strong directional selection over the past 4,000 years. Even in the Bronze Age Central European samples did not exhibit frequencies of the derived variant common across Western and South-Central Eurasia on the LCT locus which is associated with persistence today. A quick survey of the 1000 Genomes data shows that this variant has wide variation in modern European populations which are phylogenetically close. The frequency in the Spanish data set is ~50 percent, but in the Tuscan Italian samples it is ~10 percent for the derived variant. In Denmark and Sweden the derived allele frequency goes up to ~75 percent (the phenotypic expression is dominant, so that means ~95 percent lactase persistence), though in the Finnish sample it is closer to the frequency of the Spanish data set. In South Asia the 1000 Genomes data as well as earlier work shows that frequencies are 25 percent or more in Northwest India, in the Punjab, where dairy culture is most pervasive. It drops as a function of distance from this zone, to 5 percent in the Southern and Eastern South Asia. The haplotype network around this particular mutation implies that it probably originated in Central Eurasia, so the varied frequencies across the Old World is suggestive of both migration and selection.  Intriguingly, the lactase persistence allele is not present  at appreciably frequencies in the Yamnaya. It begins to appear in cultures such as the Corded Ware Bell Beaker, though at far lower frequencies than is presently the case in this region.

But the story of lactase persistence is not entirely surprising. Its late evolutionary trajectory in relation to the rise of cattle culture and complex societies in Eurasia points to the reality that evolutionary change in the biological dimension requires a powerful cultural scaffold. That existed in the form of agro-pastoralism in Eurasia. Similar forces are at play across regions of Africa, where signatures of selection are even more evident in groups dependent upon cattle, likely because of the recency of the emergence of the trait, caught in mid-sweep.

A new face in the world?
A new face in the world?

There are few other signatures evident in these data. Three of them have to do with pigmentation, SLC24A5, SLC45A2, and HERC2. Ewen Callaway reported on the peculiarity last year that Paleolithic European hunter-gatherers may have had dark skin and light eyes. The reasoning here is that a large fraction of the complexion difference between Europeans and Africans is attributable to a derived mutation on SLC24A5, which is nearly fixed in modern Europeans. And yet ancient European hunter-gatherers on the whole were not fixed at this locus, and Western European hunter-gatherers, exhibited the ancestral variants. To get a sense of how peculiar this is the vast majority of the alleles in much of the Middle East are in the derived state, as are about half the alleles in South Asia (I am a homozygote for the derived allele for what it’s worth, and my skin is still notably brown, though obviously not extremely dark). The best available data suggests that the mutant allele emerged recently in the Middle East, and it has expanded out from that point of origin.

SLC45A2 is different in that its distribution is far more constrained to within Europe, though it is found at appreciable frequencies in the Middle East, and at lower frequencies in South Asia. The same for HERC2, though I was surprised to see that the “European” variant associated with blue eye color is actually found at a 0.10 proportion in the 1000 Genomes data in Bangladesh (I am a homozygote for the ancestral variant), the same fraction as the Punjabi sample.*

The results here seem to suggest that all these loci are under selection. The two SLC genes are under positive selection, though SLC24A5 probably got its first boost from EFF with the arrival of agriculture, and was subsequently fixed even when that group fused with the hunter-gatherers who lacked it. Curiously HERC2 is under some negative selection. Remember that all the hunter-gatherers seem to carry the derived variant, so the frequency could only but go down. But in Southern Europe it is likely being driven down in frequency, while it Northern Europe it has been maintained, or rebounded.

Of course one of the major issues we have when evaluating pigmentation loci and their relationship to selection is it’s not always clear if the target of selection is the trait of pigmentation, or something else which the locus modulates, and pigmentation just happens to be a salient side effect. There are many theories about why populations have become depigmented, but none of them are truly well supported in my opinion. Another question is whether we know the genetic architecture of pigmentation well enough to actually infer that these ancient populations are easily predicted in their trait character by modern models which map genotype to phenotype. In other words, were Paleolithic Europeans light skinned because of different alleles? The genetic architecture of skin color is relatively well understood in extant populations. Though it is possible, it so happens that modern Northern Europeans, and to a lesser extent Southern Europeans, harbor a substantial portion of European ancestry which is rooted in the Paleolithic. Studies in admixed African American populations, which are about ~20 percent European, indicate that the primary variants which determine complexion are the ones extant in modern populations, though it may be that there isn’t power to detect the ones from WHG, etc. Of course it could be that the lightening alleles of the Paleolithic Europeans were subject to negative selection, excepting the HERC2/OCA2 locus. But that’s not a particularly parsimonious solution from where I stand (by the way, if selection is targeting something other than pigmentation it is strange that pigmentation associated loci emerge in clusters as positive hits for selection tests).

A secondary issue in relation to pigmentation is that the Yamnaya population does not seem to have been particular fair of hair or azure of eye. The frequency of the derived HERC2 SNP is in the range of North Indian populations, while the SLC45A2 SNP is in the same frequency range as Middle Eastern groups. One might suggest that the Yamnaya are not representative of the population which was intrusive to Europe, but note that the frequencies of the alleles in question during the Late Neolithic and Bronze Age are intermediate between it and modern groups. These results imply in situ evolution within Europe over the Holocene, and down into historical times, toward the phenotype which we ascribe uniquely to Europeans. This is strange especially in light of the fact that a later eastern branch of Indo-Europeans seem to have been quite light. I don’t think we can make final inferences, but to me it is starting to look like the “Proto-Indo-European” complex of peoples was highly cosmopolitan and heterogeneous. Should we expect anything other? As the Mongols expanded in all directions their divergent tendrils were embedded in different ethnic substrate (e.g., Tatars, Khitai and Jurchen in China, Kipchak Turks in Russia, etc.).

The other major locus that showed up was one related to fatty acid metabolism, FADS1. Many tests for selection in humans and domestic animals show changes in the ability to process nutritive inputs. It seems an eminently plausible candidate phenotype to target for selection since the relationship to fitness is straightforward. Using polygenic score methods they also find that there was selection for shorter stature in early Neolithic populations in places like Spain. I think in the future one area of investigation is going to be in the domain of biological adaptations on the margin of farming populations which are put into a Malthusian pressure cooker. Humans, on average, were getting smaller until recently in comparison to their average stature during the Last Glacial Maximum. The Yamnaya people, in contrast to the Neolithic Iberians, seem to have been rather tall. Perhaps it had something to do with the nature of agro-pastoralism? (though do note that without lactase persistence they’d miss out on about 1/3 of the calories in the form of lactose sugar, though not the protein and fat)

edarmotalaBut there’s a twist which I haven’t gotten to, and that’s the one in regards to the hunter-gatherers from the Scandinavian region. Unlike the WHG samples you can see that they exhibit mixed frequencies of derived and ancestral alleles at the SLC loci. That’s peculiar, since geographically they are more distant from the core region from which EFF issued. We do know that their ancestry is somewhat exotic, as paper on Indo-European migrations pointed out that they seem to carry the same ancestral component which the Indo-Europeans brought to most of Europe, that of the Ancestral North Eurasians (albeit at far lower fractions than the EHG group which was a partial precursor of the Yamnaya population).

The past is complex and doesn’t fit into a solid narrative. And yet the weirdest aspect of the Scandinavian samples is that they carry the East Asian/Native American variant of EDAR at appreciable frequencies! The figure to the right illustrates this. In blue you have the focal SNP (dark is homozygote, light is heterozygote, dark circle means only one allele was retrieved). In the Chinese from Beijing population (CHB) the derived variant is at high frequency. In the sample of Northwest Europeans from Utah (CEU) it is not present. You can confirm these findings in the 1000 Genomes and elsewhere. In European EDAR of the East Asian form seems only to be found in Finland and associated populations. Using ALDER the authors conclude that admixture occurred on the order of 1 to 2 thousand years before the present, from an East Asian-like group (in the Indo-European paper they found this source best matched the Nganasans of North Central Siberia). An interesting fact which also comes out of this finding is that the haplotype that the derived SNP arose against is relatively common in Northern Europe. The arrows in the figure point to individuals who carry the ancestral SNP, but exhibit the same haplotype which is dominant in East Asia (and also among the Scandinavian hunter-gatherers with the derived variant). The authors state that “The statistic f4(Yoruba, Scandinavian hunter-gatherers, Han, Onge Andaman Islanders) is significantly negative (Z=-3.9) implying gene flow between the ancestors of Scandinavian hunter-gatherers and Han so this shared haplotype is likely the result of ancient gene flow between groups ancestral to these two populations.” Though in earlier work on these data sets they left open the possibility of gene flow between Eastern and Western Eurasia during the Paleolithic as a way to explain some results, it was not offered as a result for the Scandinavian hunter-gatherers. I do not know what to think of the fact that the haplotype that the derived East Asian SNP arose in is common in Northern Europe (though without the derived SNP, which is likely only present in a few populations due to recent Siberian admixture). Could it be that ancient gene flow from Western Eurasian Paleolithic people occurred into East Asian populations, and that then this haplotype accrued the mutation which later swept to near fixation? If that is the case I’m curious about haplotype networks, as Northern Europeans should be more diverse when it comes to the haplotype in question.

In the near future we’ll probably have better and more numerous whole genome sequences of ancient samples. Some of the confusions engendered by this work will be cleared up, as better data renders paradox crisply coherent. The preprint is free to anyone, and I invite readers to dig deeply into it. Though the results yielded only a few positive signals of selection, they’re subtle and complex in their implications. I certainly haven’t thought through everything….

* The fraction of blue eyes is MUCH higher among Punjabis than Bengalis in my experience. It goes to the point that blue eyes likely expresses against the genetic background found in Europeans, where there are other depigmenting alleles near fixation.

Patriarchy came with Cain and Abel


figure1I do like to suggest that the genetic and archaeological record support the conjecture of Conan the Barbarian in terms of what our male ancestors thought was “good in life.” Basically, to conquer your enemies and seize their women, which is a distillation of a disputed quote from Genghis Khan. Conan may be fiction, but Genghis Khan is not. As it happens there is a fair amount of circumstantial evidence that the genetic legacy of Genghis Khan is enormous. Not only did Khan father many sons, but so did their sons, and so forth. Tens of millions of men around the world are direct paternal descendants of Genghis Khan and his family.

This is known. But now more is known, thanks to a new paper out of Genome Research, A recent bottleneck of Y chromosome diversity coincides with a global change in culture. The upside of this paper is that it uses whole genome sequence of Y chromosomes to generate phylogenetic inferences. This is important because the Y chromosome has very little genetic variation relative to much of the rest of the genome. The downside is that because techniques were utilized to perform whole genome sequencing of the Y, the sample size, at 299, is not as large as we’ve gotten used to for analyses of uniparental lineages. That will change in the future, as there are many thousands of whole genome sequences of the Y in databases around the world, though perhaps not enough computational power allocated by funding agencies to crunch through them in the fashion on display in the paper (they didn’t use the whole sequence for a lot of the analysis, but ~35,000 SNPs).

So what are the major findings of the paper? Using a Bayesian Skyline Plot (BSP) it is rather clear that 4-8 thousand years ago there was a sharp drop in male effective population sizes across many world populations. It is also clear that the female effective population did not experience the same drastic contraction. The supplements have individual figures, and many of the events of history and archaeology can be easily mapped onto these population size changes. For example, the later reduction of African population sizes probably is due to the later adoption of agriculture in that continent, and timed with the Bantu expansion. In the New World the data seem to show late and persistent reduction in effective population size. The Columbian Exchange and massive population contraction subsequent to that is probably being picked up by this result. figure3Intriguingly there is a detection of a two events in the European data, where the sample size is relatively large. The first major drop seems to coincide with the arrival of the “First Farmers” (e.g., LBK culture) in Northern Europe. In the Middle East (orange) you see collapse, and then a rapid ascent very early. This comports well with the early history of agriculture here. But in the European samples there is a rapid ascent, and then a level off ~3,000 years ago or so. This could be the arrival of Indo-European cultures to Europe. If the sample sizes for other regions were as large and representative as Northern Europe such subtle details might also have emerged there with the BSP method (to be clear, I suspect the crash in effective size in Europe is due to haplogroup I, while the delayed expansion is due to R1a and R1b arriving a few thousand years later).

Also of interest are is the deep structure of the different clades. Those of you stepped in Y chromosomal haplogroups can extract more from the figure to the top left, but it shows relationship of the primary groups as well as their recent expansion. The affinity of the Q and R clades to me indicate that those who argue that these are somehow related to the “Ancestral North Eurasians” are correct. Similarly, the position of I and J in the same clade points to their common descent from ancient West Eurasian Pleistocene groups. The I lineage is most exclusively associated with European hunter-gatherers, while J is traditionally associated with groups of farmers expanding out of the Middle East in all directions (note that one branch of J is found in the Middle East, Central Asia, South Asia, and Europe). I agree with Dienekes that the branch of E that corresponds to the lineages which span Sub-Saharan Africa and Western Eurasia are a indicating a back migration to Africa, probably in the Pleistocene. I do wonder as well whether they have some association with the mysterious “Basal Eurasians.”

An important part of the paper that they emphasize is that ~50,000 years before the present there was a profusion of haplogroups associated with the ones which are today common across Eurasia, and Y chromosomal Ne was ~100. This seems to agree with the rapid expansion of non-Africans in the wake of the “Out of Africa” event, though the authors note they don’t have enough power to reject a model of a separate “Southern Route” migration, which might be detected with autosomal data. This is a good caution on the limitations of Y and mtDNA data; archaic admixture was rejected by these two loci because the non-African hominin lineages went extinct (mtDNA and Y have higher turnover rates than the recombining autosomal regions). figure4Additionally there were some major lacunae in the sampling. For example, among the African populations it doesn’t seem like some of the hunter-gatherer groups, the Khoisan or eastern Pygmy, were included in the data set. The map also shows that Northeast Asia (China, Japan and Korea) and Oceania were not extensively sampled. But these are minor issues in the broader picture of the insights from the population coverage that they did have.

The most important implication of these sorts of results have to do with the nature of the change of human social organization and behavior over the course of the existence of modern humans. The authors of the above paper seem to understand this, as there is extensive focus on the topic within the paper:

An increase in male migration rate might reduce the male Ne but is unlikely to cause a brief drastic reduction in Ne as observed in our empirical data…However, in models with competition among demes, an increased level of variance in expected offspring number among demes can drastically decrease the N e (Whitlock and Barton 1997). The effect may be male-specific, for example, if competition is through a male-driven conquest. A historical example might be the Mongol expansions (Zerjal et al. 2003). Innovations in transportation technology (e.g., the invention of the wheel, horse and camel domestication, and open water sailing) might have contributed to this pattern. Likely, the effect we observe is due to a combination of culturally driven increased male variance in offspring number within demes and an increased male-specific variance among demes, perhaps enhanced by increased sex-biased migration patterns (Destro-Bisol et al. 2004; Skoglund et al. 2014) and male-specific cultural inheritance of fitness.

To restate what’s being said here:

1) During the Holocene we saw the rise of powerful patrilineages which engaged in winner-take-all of inter-group competition.

2) Within the “winning” patrilineages there may have been winner-take-all dynamics, or at least high reproductive variance

When it comes to farmers and nomads against each other I do think a model of inter-demic competition is pretty realistic. But when it comes to farmers and nomads against hunter-gatherers I don’t think one can term it competition. The latter in most circumstances would be quickly overwhelmed by the farmers and nomads; eliminated, excluded, or at least assimilated (there are exceptions in areas where the hunter-gatherer density was high and they were sedentary). And as concerns the complex societies of farmers and nomads, even within them the rise of inequality and stratification mean that subordinate or secondary males and their lineages were marginalized, leaving few descendants.

Men are on average 15-20 percent bigger than women. Men are also stronger than women. But the sexual dimorphism is far less than one can find among gorillas. This suggests that intra-sex competition among males was attenuated, or at least it was not in the physical domain. Though I am not of the camp which believes that war as we understand it must necessarily be a feature of Holocene agricultural societies, it seems likely that the pressure cooker of high population densities resulted in a radical increase in the scale of inter-group atrocity. One way to react to this change would have been to grow larger physically, but there are limitations to how fast biological evolution can resculpt the human physique. Not only that, but larger humans presumably require more nutritional inputs, and the agricultural revolution in Malthusian conditions did not enable that on a mass scale. So humans did what they do best: innovate culturally.

The cultural innovations came as package deals. A central role for patriarchal lineages which tended to apply force to maintain social order, as well as take on the position as the tip of the spear in inter-group competition, eventually resulted in power accruing to those groups almost exclusively. The importance of patrilineages naturally resulted in an increased importance of paternity certainty, and therefore social mores which emphasized female chastity. These powerful lineages fixed upon a solution which gorillas had long ago arrived at: treat females as chattel and defend them as one would property.

The “men in groups” were evoked by particular social-cultural conditions of agricultural society which they themselves did not necessarily trigger in an any way. But once you had a small benefit to the emergence of a caste of men in groups, groups which developed this caste benefited. Within these groups eventually the caste took over the identity of the group, and made its own interests conterminous with the interests of the group. The Athenian polis was democratic, but only for free males who were born of Athenians. In other words, the most radical experiment in radical democracy in the ancient world was also still relatively exclusionary and delimited in the nature of political power and representation (also, recall that the power of freeborn males of lower economic status in Athens has been connected to their importance in the navy as oarsmen).

Speaking as someone with broadly liberal sympathies, economic and social forces over the past few centuries have resulted in an unwinding of the cultural innovations of the past 10,000 years which have put a straight-jacket on the forces of human liberty. This great unwinding to some extent can be understood as the shattering of the great patriarchal monopolies of old, reflected in the great families and lineages which spanned the world, and democratic representation first for all men and then women. In the West the period between 1800 and 1970 saw massive gains in income to unskilled workers, reversing the tendency toward winner-take-all dynamics which arose with the Neolithic.

That being said, the post-Industrial and post-materialist world, in full flower in places like North Europe, is not exactly like the Paleolithic. Some of the innovations of the post-Neolithic world, such as organized religion, are probably here to stay in a world of social complexity and density. The great devolution to power from the elite male lineages is one specific aspect where I believe the modern age more resembles the Paleolithic. More liberal sexual ethics is also another dimension where the modern world is more like that of hunter-gatherers. But the autonomous individual, an island unto himself, is a fiction. Hunter-gatherers were, and are, social creatures. No doubt they were bound by taboos and rules, just as modern hunter-gatherers are. The vision of egalitarianism promoted by many in the modern West is a reaction against the social controls of the post-Neolithic world, but those social controls themselves are rooted in human cognitive impulses. Competition did not come full formed in the world of grain, and the impulse toward violence and domination was present in man long before the scythe was re-purposed toward bloodier ends.

The elves of the dark forest

The Smithsonian Magazine has a nice report, Humans Relied on Rainforest Riches 12,000 Years Earlier Than Thought. The original paper is in Science, Direct evidence for human reliance on rainforest resources in late Pleistocene Sri Lanka:

Human occupation of tropical rainforest habitats is thought to be a mainly Holocene phenomenon. Although archaeological and paleoenvironmental data have hinted at pre-Holocene rainforest foraging, earlier human reliance on rainforest resources has not been shown directly. We applied stable carbon and oxygen isotope analysis to human and faunal tooth enamel from four late Pleistocene–to–Holocene archaeological sites in Sri Lanka. The results show that human foragers relied primarily on rainforest resources from at least ~20,000 years ago, with a distinct preference for semi-open rainforest and rain forest edges. Homo sapiens’ relationship with the tropical rainforests of South Asia is therefore long-standing, a conclusion that indicates the time-depth of anthropogenic reliance and influence on these habitats.

The idea that humans only inhabited the deep rainforest would seem strange to me form a human historical genetic perspective, there’s evidence that the Pygmy peoples of Africa are deeply diverged. That is, the western groups and the eastern groups separated tens of thousands of years ago. This needn’t imply that this divergence occurred within the rainforest context, but it seems more plausible to me that the low population densities and delimited ranges of this environment would be more conducive to reducing gene flow across populations than if the two populations developed their structure in the savanna.

The Smithsonian piece ends in a strange way to me though:

“If our ancestors were able to gain such crucial knowledge and respect for these ecologies throughout these long periods of time, then it is somewhat arrogant that we think we can now go and change them significantly without there being considerable consequences for animal or human populations living within them, or our species more widely,” says Roberts.

1491-coverThis imputation of post-materialist values upon hunter-gatherers of the forest seems to me to be unwarranted. In 1491 Charles C. Mann reports on evidence that the “primal” rainforest of the Amazon was widely utilized by native peoples before the arrival of Europeans. Its relative emptiness and occupation by less advanced populations may have been a function of collapse induced by the introduction of European disease. In parts of western North America, such as the Willamette valley of Oregon, the same dynamic occurred. The great forests of the bottomlands that the white settlers encountered were relatively recent secondary growth which had developed in the wake of the population declines of native groups in the because of diseases introduced by the Europeans, which outran the extend of white occupation (though in some cases Europeans also consciously spread disease; e.g., distributing blankets of people who had survived smallpox).

51CvHNNZ6DL._SY344_BO1,204,203,200_The trail of megafaunal extinction from Australia to the New World suggests to me that pre-modern people were just like modern people in how they respected or conceived the environment. That is, their view was one driven by short term concerns of survival, which one would assume from standard evolutionary theory. Over time cultures could iterate and converge upon more sustainable solution, but the initial waves of human refashioning of the ecology through continuous burning and one time pulse extinction of large organisms fit for consumption suggests a mindset which is easy for moderns to imagine I’d think. I doubt the boom and bust cycle driven by irrational manias emerges in a vacuum, the Malthusian conditions which are the consequence of intra-specific competition are a deep part of the nature of most organisms.

The Fourth Law of Behavior Genetics

Citation: The Fourth Law of Behavior Genetics, Chabris et al.
Figure citation: Marigorta UM, Navarro A (2013) High Trans-ethnic Replicability of GWAS Results Implies Common Causal Variants. PLoS Genet 9(6): e1003566. doi:10.1371/journal.pgen.1003566

The above is a figure from The Fourth Law of Behavior Genetics (ungated), accepted for publication in Current Directions in Psychological Science. It’s an excellent overview of the intersection of behavior genetics and genomics over the past 10 years or so. The full story is outlined in the paper, fleshed out by the copious and informative citations which litter the text. The point of the above figure is to show how robust many inferences from small effect genome-wide associations are. In particular, there is the standard caveat that a variant which is correlated with disease X in population 1 may not be correlated with disease X in population 2. It actually turns out that in most cases they are correlated across populations. Above you see the correlation in effects (odds ratios) between variants and traits between East Asians and Europeans (common variants are also predictive within families).

The Fourth Law of Behavior Genetics makes no sense unless you know the first three laws outlined by Eric Turkheimer:

* First Law. All human behavioral traits are heritable.

* Second Law. The effect of being raised in the same family is smaller than the effect of genes.

* Third Law. A substantial portion of the variation in complex human behavioral traits is not accounted for by the effects of genes or families.

By heritable you simply mean that some of the variation of the trait in the population is explained by variation in genes in the population (you see it in the standard parent-offspring regression). The second law refers to the fact that on many behavior genetic traits the influence of shared family environment in explaining variation can be surprisingly small. The final law points to the reality that a lot of the variation we see in people in outcomes seems pretty much random. It’s labeled non-shared environment, but we should think of it more as a noise factor. These “laws” are robust regularities which you need to take into account when considering the likelihood of any given result. What is the fourth law? It’s pretty straightforward: “A typical human behavioral trait is associated with very many genetic variants, each of which accounts for a very small percentage of the behavioral variability.” To give a concrete example, it looks like the largest effect common variants for behavioral traits explain about 10% the variance as the largest effect variant for complex disease or morphological traits, on the order of 0.01% as opposed to 0.1%.

That’s a mighty small effect. To make sense of the heritabilities estimated using classical methods that means that genetic variation is partitioned across many many genes, on the order of thousands. This is why methods to ascertain loci of effect utilizing small sample sizes (e.g., candidate gene studies) were bound to fail, because they didn’t have the power to detect true results. Rather, many of the hits were simply noise which got published because of low stringency of statistical significance.

One objection then might be that the missing heritability consists of very low frequency (i.e., far less than the 1% threshold used to define common variants in terms of minor allele frequency) mutations which have a larger effect. The authors claim that the research currently does not support that finding. That implies that high coverage whole genome sequencing at reasonable sample sizes won’t make a big difference. Second, there are the results out of the GCTA framework. I won’t go into the details, though check out the paper in AJHG. It’s a powerful way to explore heritabilities using genomic data across unrelated individuals that’s rapidly converging on the heritabilities estimated from classical behavior genetic methods.

Finally, in a similar vein, Dominance Genetic Variation Contributes Little to the Missing Heritability for Human Complex Traits:

For human complex traits, non-additive genetic variation has been invoked to explain “missing heritability,” but its discovery is often neglected in genome-wide association studies. Here we propose a method of using SNP data to partition and estimate the proportion of phenotypic variance attributed to additive and dominance genetic variation at all SNPs (Math Eq and Math Eq) in unrelated individuals based on an orthogonal model where the estimate of Math Eq is independent of that of Math Eq. With this method, we analyzed 79 quantitative traits in 6,715 unrelated European Americans. The estimate of Math Eq averaged across all the 79 quantitative traits was 0.03, approximately a fifth of that for additive variation (average Math Eq = 0.15). There were a few traits that showed substantial estimates of Math Eq, none of which were replicated in a larger sample of 11,965 individuals. We further performed genome-wide association analyses of the 79 quantitative traits and detected SNPs with genome-wide significant dominance effects only at the ABO locus for factor VIII and von Willebrand factor. All these results suggest that dominance variation at common SNPs explains only a small fraction of phenotypic variation for human complex traits and contributes little to the missing narrow-sense heritability problem.

This moral panic shall end too

tnapb4From Tablet, Letting Go of Our Kids Isn’t a Form of Neglect:

…Kidnapping by strangers is wildly uncommon; in New York State, for instance, the Division of Criminal Justice Services announced that 20,309 children were reported missing statewide in 2011; exactly one of those children was confirmed abducted by a stranger. Most—94 percent—were runaways, most of them teenagers.

The article is in response to the state of Maryland’s horrified response in relation to the existence of a family which practices “free range” parenting. Free range being what used to be called normal parenting as far back as the 1980s. Looking at the statistics above this is a clear case of moral panic. It will abate. Too many cultural forces, from overtaxed working mothers to libertarians and Christian parents’ rights sorts, object to the dominant ethos. But, I suspect that technology, the ubiquity of phones with GPS and tracking technology, will play a role in the changing of the Zeitgeist.

Scions of the hairy Ainu, not Amaterasu


A few thousand years ago the islands of Japan were settled by a group of rice farmers, ushering in the Yayoi period. Prior to this Japan was home of the Jomon culture, which is notable for being a pre-agricultural society which may have innovated to produce the world’s earliest pottery. Because everything before ~500 A.D. in Japan is prehistory (this date being generous) the relationship of the Jomon and Yayoi, and the ethnogenesis of the Japanese people as a homogeneous group, is somewhat speculative. But, it does seem one group of Jomon descended people persisted in northern Honshu, the Emishi. Finally, it is usually understood that the indigenous people of Hokkaido, the Ainu, have some relationship to the Jomon.

220px-Bjs48_02_AinuThe Ainu are of interest because they do not exhibit many of the traditional characteristics of Northeast Asian people in their phenotype. Ergo, they are termed the “hairy Ainu.” Early anthropologists noting the physical uniqueness of the Ainu speculated that they were a lost branch of the white race. But even early ABO blood group analysis suggested that this was not the case. Rather, the closest relatives of the Ainu were the peoples of Northeast Eurasia. Nevertheless, it does seem striking that the Ainu do not exhibit the distinctive features of many other East Asians. I think this makes more sense though when you consider that it is likely that the East Asian physical type is not quite as primal as we might think. The latest work from genetics indicates very rapid population expansion out of the loci of agricultural activity on the North China plain over the past 10,000 years. The relatively uniformity of physical type and genetic relatedness across East Asia today may have more to due with demographic expansion that genetic connectedness through gene flow over long periods of time.

Much of this can be gleaned by inference, implication, and intuition. A new paper in Molecular Biology and Evolution uses explicit model testing to infer whether the modern Japanese the products of population replacement, admixture, or cultural diffusion. In other words, are the Japanese total cultural and biological descendants of the Yayoi. Are the Japanese total cultural and partial biological descendants of the Yayoi. Or, are the Japanese total cultural descendants of the Yayoi, but total biological descendants of the Jomon. The paper, Model-based verification of hypotheses on the origin of modern Japanese revisited by Bayesian inference based on genome-wide SNP data, reports that the middle hypothesis, genetic admixture, is highly supported when compared to the other two.

There are few interesting points. First, reference population matters. I’m rather sure that the Ainu samples they used as proxies for Jomon are imperfect because the Ainu today have recent Japanese admixture, and, as they note the Jomon themselves exhibit population structure (i.e., the Ainu are one lineage of post-Jomon people). This structure goes back to the late Pleistocene, over 10,000 years ago. The divergence between the ancestors of the Jomon and the Ainu goes back ~20,000 years ago, about when East Asian peoples began to diversify in the wake of the Last Glacial Maximum. The estimates for Jomon ancestry are probably inflated by the admixture in the Ainu, but dampened by the fact that the Ainu are not prefect proxies for the Jomon. Additionally, the reference population for the Yayoi, whether Koreans or North Chinese, has an effect.

But these are minor details. The major conclusion in a qualitative sense is that the modern Japanese are predominantly descended on the whole from the Yayoi farmers, but have a substantial minority component of indigenous Jomon ancestry. This almost certainly varies as a function of geography, the modern Japanese people likely can be used to obtain a “ghost phylogeography” of the Jomon whom they absorbed, as presumably admixture occurred locally a fair amount.

The past shall be naked to you

41ePHetk1dL._SY344_BO1,204,203,200_Most readers are aware that ancient DNA has revolutionized historical inference of the past, particularly prehistory. In 15 years we’ve gone from draft genomes of one living human being, to genomes of humans who have lived tens of thousands of years ago! But by and large the ancient DNA revolution has been one of temperate and boreal climates, because of the reduced degradation of DNA in such circumstances. A new paper in PNAS opens up a sliver of a possibility of expanding the purview of this analysis, Genome-wide ancestry of 17th-century enslaved Africans from the Caribbean:

Between 1500 and 1850, more than 12 million enslaved Africans were transported to the New World. The vast majority were shipped from West and West-Central Africa, but their precise origins are largely unknown. We used genome-wide ancient DNA analyses to investigate the genetic origins of three enslaved Africans whose remains were recovered on the Caribbean island of Saint Martin. We trace their origins to distinct subcontinental source populations within Africa, including Bantu-speaking groups from northern Cameroon and non-Bantu speakers living in present-day Nigeria and Ghana. To our knowledge, these findings provide the first direct evidence for the ethnic origins of enslaved Africans, at a time for which historical records are scarce, and demonstrate that genomic data provide another type of record that can shed new light on long-standing historical questions.

Hopefully this is just the beginning. Part of this the economics of innovation. The best ancient DNA labs are training others in their techniques. From what I’m to understand at this point there’s a backlog of remains to be analyzed. As the expertise becomes distributed labor and capital will no longer be the rate limiting step.