The Bronze age demographic transformation of Britain

In Norman Davies’ the excellent The Isles: A History, he mentions offhand that unlike the Irish the British to a great extent have forgotten their own mythology. This is one reason that J. R. R. Tolkien created Middle Earth, they gave the Anglo-Saxons the same sort of mythos that the Irish and Norse had.

But to some extent I think we can update our assessments. Science is bringing myth to life. The legendary “Bell Beaker paper” is now available in preprint form, The Beaker Phenomenon And The Genomic Transformation Of Northwest Europe. The methods are not too abstruse if you have read earlier works on this vein (i.e., no Nick Patterson authored methodological supplement that I saw). And the results are straightforward.

And what are those results?

First, the Bell Beaker phenomenon was both cultural and demographic. Cultural in that it began in the Iberian peninsula, and was transmitted to Central Europe, without much gene flow from what they can see. Demographic in that its push west into what is today the Low Countries and France and the British Isles was accompanied by massive gene flow.

In their British samples they conclude that 90% of the ancestry of early Bronze Age populations derive from migrants from Central Europe with some steppe-like ancestry. In over words, in a few hundred years there was a 90% turnover of ancestry. The preponderance of the male European R1b lineage also dates to this period. It went from ~0% to ~75-90% in Britain over a few hundred years.

If most of the genetic-demographic character of modern Britain was established during the Bronze Age*, then there has been significant selection since the Bronze Age. The figure to the left shows ancient (Neolithic/Bronze age) frequencies of selected SNPs, with modern frequencies in the British in dashed read. The top-left SNP is for HERC2-OCA2, the region related to brown vs. blue eye color, and also associated with some more general depigmentation. The top-right SNP is in SLC45A2, the second largest effect skin color locus in Europeans. The bottom SNP is for a mutation on LCT, which allows for the digestion of milk sugar as adults.

The vast majority of the allele frequency change in Britons for digestion of milk sugar post-dates the demographic turnover. In other words, the modern allele frequency is a function of post-Bronze Age selection. This is not surprising, as it supports the result in Eight thousand years of natural selection.

1000 Genomes derived SLC45A2 SNP frequency

At least as interesting are the pigmentation loci. The fact that the derived frequency in HERC2-OCA2 is lower in both British and Central European Beaker people samples indicates that the lower proportion is not an artifact of sampling. Britons have gotten more blue-eyed over the last 4,000 years. Second, SLC45A2 is at shocking low proportions for modern European populations.

HGDP derived SLC45A2 SNP frequency

In the 1000 Genomes the 4% ancestral allele frequency is almost certainly a function of the Siberian (non-European) ancestry. In modern Iberians the ancestral frequency is 18% (and it is even higher in Sardinians last I checked), but in Tuscans it is ~2%. Though not diagnostic of Europeans in the way the derived SNP at SLC24A2 is, SLC452 derived variants are much more constrained to Europe. Individuals who are homozygote ancestral for SNPs atSLC45A2 rare in modern Northern Europeans (pretty much nonexistent actually). But even as late as the Bronze Age they would have been present at low but appreciable frequencies.

This particular result convinces me that the method in Field et al. which detected lots of recent (last 2,000 years) selection on pigmentation in British populations is not just a statistical artifact. Though these papers are solving much of European prehistory, they are also going to be essential windows into the trajectory of natural selection in human populations over the last 5,000 years.

* In the context of this paper the Anglo-Saxon migrations tackled by the PoBI paper are minor affairs because the two populations were already genetically rather close. Additionally, the PoBI paper found that the German migrations were significant demographic events, but most of the ancestry across Britain does date to the previous period.

Synergistic epistasis as a solution for human existence

Epistasis is one of those terms in biology which has multiple meanings, to the point that even biologists can get turned around (see this 2008 review, Epistasis — the essential role of gene interactions in the structure and evolution of genetic systems, for a little background). Most generically epistasis is the interaction of genes in terms of producing an outcome. But historically its meaning is derived from the fact that early geneticists noticed that crosses between individuals segregating for a Mendelian characteristic (e.g., smooth vs. curly peas) produced results conditional on the genotype of a secondary locus.

Molecular biologists tend to focus on a classical, and often mechanistic view, whereby epistasis can be conceptualized as biophysical interactions across loci. But population geneticists utilize a statistical or evolutionary definition, where epistasis describes the extend of deviation from additivity and linearity, with the “phenotype” often being fitness. This goes back to early debates between R. A. Fisher and Sewall Wright. Fisher believed that in the long run epistasis was not particularly important. Wright eventually put epistasis at the heart of his enigmatic shifting balance theory, though according to Will Provine in Sewall Wright and Evolutionary Biology even he had a difficult time understanding the model he was proposing (e.g., Wright couldn’t remember what the different axes on his charts actually meant all the time).

These different definitions can cause problems for students. A few years ago I was a teaching assistant for a genetics course, and the professor, a molecular biologist asked a question about epistasis. The only answer on the key was predicated on a classical/mechanistic understanding. But some of the students were obviously giving the definition from an evolutionary perspective! (e.g., they were bringing up non-additivity and fitness) Luckily I noticed this early on and the professor approved the alternative answer, so that graders would not mark those using a non-molecular answer down.

My interested in epistasis was fed to a great extent in the middle 2000s by my reading of Epistasis and the Evolutionary Process. Unfortunately not too many people read this book. I believe this is so because when I just went to look at the Amazon page it told me that “Customers who viewed this item also viewed” Robert Drews’ The End of the Bronze Age. As it happened I read this book at about the same time as Epistasis and the Evolutionary Process…and to my knowledge I’m the only person who has a very deep interest in statistical epistasis and Mycenaean Greece (if there is someone else out there, do tell).

In any case, when I was first focused on this topic genomics was in its infancy. Papers with 50,000 SNPs in humans were all the rage, and the HapMap paper had literally just been published. A lot has changed.

So I was interested to see this come out in Science, Negative selection in humans and fruit flies involves synergistic epistasis (preprint version). Since the authors are looking at humans and Drosophila and because it’s 2017 I assumed that genomic methods would loom large, and they do.

And as always on the first read through some of the terminology got confusing (various types of statistical epistasis keep getting renamed every few years it seems to me, and it’s hard to keep track of everything). So I went to Google. And because it’s 2017 a citation of the paper and further elucidation popped up in Google Books in Crumbling Genome: The Impact of Deleterious Mutations on Humans. Weirdly, or not, the book has not been published yet. Since the author is the second to last author on the above paper it makes sense that it would be cited in any case.

So what’s happening in this paper? Basically they are looking to reduced variance of really bad mutations because a particular type of epistasis amplifies their deleterious impact (fitness is almost always really hard to measure, so you want to look at proxy variables).

Because de novo mutations are rare, they estimate about 7 are in functional regions of the genome (I think this may be high actually), and that the distribution should be Poisson. This distribution just tells you that the mean number of mutations and the variance of the the number of mutations should be the same (e.g., mean should be 5 and variance should 5).

Epistasis refers (usually) to interactions across loci. That is, different genes at different locations in the genome. Synergistic epistasis means that the total cumulative fitness after each successive mutation drops faster than the sum of the negative impact of each mutation. In other words, the negative impact is greater than the sum of its parts. In contrast, antagonistic epistasis produces a situation where new mutations on the tail of the distributions cause a lower decrement in fitness than you’d expect through the sum of its parts (diminishing returns on mutational load when it comes to fitness decrements).

These two dynamics have an effect the linkage disequilibrium (LD) statistic. This measures the association of two different alleles at two different loci. When populations are recently admixed (e.g., Brazilians) you have a lot of LD because racial ancestry results in lots of distinctive alleles being associated with each other across genomic segments in haplotypes. It takes many generations for recombination to break apart these associations so that allelic state at one locus can’t be used to predict the odds of the state at what was an associated locus. What synergistic epistasis does is disassociate deleterious mutations. In contrast, antagonistic epistasis results in increased association of deleterious mutations.

Why? Because of selection. If a greater number of mutations means huge fitness hits, then there will strong selection against individuals who randomly segregate out with higher mutational loads. This means that the variance of the mutational load is going to lower than the value of the mean.

How do they figure out mutational load? They focus on the distribution of LoF mutations. These are extremely deleterious mutations which are the most likely to be a major problem for function and therefore a huge fitness hit. What they found was that the distribution of LoF mutations exhibited a variance which was 90-95% of a null Poisson distribution. In other words, there was stronger selection against high mutation counts, as one would predict due to synergistic epistasis.

They conclude:

Thus, the average human should carry at least seven de novo deleterious mutations. If natural selection acts on each mutation independently, the resulting mutation load and loss in average fitness are inconsistent with the existence of the human population (1 − e−7 > 0.99). To resolve this paradox, it is sufficient to assume that the fitness landscape is flat only outside the zone where all the genotypes actually present are contained, so that selection within the population proceeds as if epistasis were absent (20, 25). However, our findings suggest that synergistic epistasis affects even the part of the fitness landscape that corresponds to genotypes that are actually present in the population.

Overall this is fascinating, because evolutionary genetic questions which were still theoretical a little over ten years ago are now being explored with genomic methods. This is part of why I say genomics did not fundamentally revolutionize how we understand evolution. There were plenty of models and theories. Now we are testing them extremely robustly and thoroughly.

Addendum: Reading this paper reinforces to me how difficult it is to keep up with the literature, and how important it is to know the literature in a very narrow area to get the most out of a paper. Really the citations are essential reading for someone like me who just “drops” into a topic after a long time away….

Citation: ScienceNegative selection in humans and fruit flies involves synergistic epistasis.

Beyond “Out of Africa” and multiregionalism: a new synthesis?

For several decades before the present era there have been debates between proponents of the recent African origin of modern humans, and the multiregionalist model. Though molecular methods in a genetic framework have come of the fore of late these were originally paleontological theories, with Chris Stringer and Milford Wolpoff being the two most prominent public exponents of the respective paradigms.

Oftentimes the debate got quite heated. If you read books from the 1990s, when multiregionalism in particular was on the defensive, there were arguments that the recent out of Africa model was more inspirational in regards to our common humanity. As a riposte the multiregionalists asserted that those suggesting recent African origins with total replacement was saying that our species came into being through genocide.

Though some had long warned against this, the dominant perception outside of population genetics was that results such the “mitochondrial Eve” had given strong support to the recent African origin of modern humans, to the exclusion of other ancestry. 2002’s Dawn of Human Culture took it for granted that the recent African origin of modern humans to the total exclusion of other hominin lineages was established fact.

In 2008 I went to a talk where Svante Paabo presented some recent Neanderthal ancient mtDNA work. It was rather ho-hum, as Paabo showed that the Neanderthal lineages were highly diverged from modern ones, and did not leave any descendants. Though of course most modern human lineages did not leave any descendants from that period, Paabo took this evidence supporting the proposition that Neanderthals did not contribute to the modern human gene pool.

When his lab reported autosomal Neanderthal admixture in 2010, it was after initial skepticism and shock internally. I know Milford Wolpoff felt vindicated, while Chris Stringer began to emphasize that the recent African origin of modern humanity also was defined by regional assimilation of other lineages. The data have ultimately converged to a position somewhere between the extreme models of total replacement or balanced and symmetrical gene flow.

This is not surprising. Extreme positions are often rhetorically useful and popular when there’s no data. But reality does not usually conform to our prejudices, so ultimately one has to come down at some point.

The data for non-Africans is rather unequivocal. The vast majority of (>90%) of the ancestry of non-Africans seems to go back to a small number of common ancestors ~60,000 years ago. Perhaps in the range of ~1,000 individuals. These individuals seem to be a node within a phylogenetic tree where all the other branches are occupied by African populations. Between this period and ~15,000 years ago these non-Africans underwent a massive range expansion, until modern humans were present on all continents except Antarctica. Additionally, after the Holocene some of these non-African groups also experienced huge population growth due to intensive agricultural practice.

To give a sense of what I’m getting at, the bottleneck and common ancestry of non-Africans goes back ~60,000 years, but the shared ancestry of Khoisan peoples and non-Khoisan peoples goes back ~150,000-200,000 years. A major lacunae of the current discussion is that often the dynamics which characterize non-Africans are assumed to be applicable to Africans. But they are not.

A 2014 paper illustrates one major difference by inferring effective population from whole genomes: African populations have not gone through the major bottleneck which is imprinted on the genomes of all non-African populations. The Khoisan peoples, the most famous of which are the Bushmen of the Kalahari, have the largest long term effective populations of any human group. The Yoruba people of Nigeria have a history where they were subject to some population decline, but not to the same extent as non-Africans.

What do we take away from this?

One thing is that we have to consider that the assimilationist model which seems to be necessary for non-Africans, also applies to Africans. For years some geneticists have been arguing that some proportion of African ancestry as well is derived from lineages outside of the main line leading up to anatomically modern humans. Without the smoking gun of ancient genomes this will probably remain a speculative hypothesis. I hope that Lee Berger’s recent assertion that they’ve now dated Homo naledi to ~250,000 years before the present may offer up the possibility that ancient DNA will help resolve the question of African archaic admixture (i.e., if naledi is related to the “ghost population”?).

The second dynamic is that the bottleneck-then-range-expansion which is so important in defining the recent prehistory of non-Africans is not as relevant to Africans during the Pleistocene. The very deep split dates being inferred from whole genome analysis of African populations makes me wonder if multiregional evolution is actually much more important within Africa in the development of modern humans in the last few hundred thousand years. Basically, the deep split dates may highlight that there was recurrent gene flow over hundreds of thousands of years between different closely related hominin populations in Africa.

Ultimately, it doesn’t seem entirely surprising that the “Out of Africa” model does not quite apply within Africa.

Addendum: Over the past ~5,000 years we have seen the massive expansion of agricultural populations within the continent. The “deep structure” therefore may have been erased to a great extent, with Pygmies, Khoisan, and Hadza, being the tip of the iceberg in terms of the genetic variation which had characterized the Africa during the Pleistocene.

What if you call for a revolution and no one revolts?

When I was in 8th grade my earth science teacher explained he did not believe in Darwinism. He seemed a reasonable fellow so my first reaction was shock. My best friend at the time, who sat next to me, laughed, “Yeah, some people believe we’re descended from monkeys! Crazy, huh?” I didn’t really know what to say. But what followed was even more confusing to me: my teacher explained that he accepted punctuated equilibrium, not Darwinism. He did not elaborate much beyond this, though I tried to get at what he believed after class in the few minutes I had.

Later on I realized that he had drunk deeply at the well of Stephen Jay Gould, paleontologist and polymath. I will quote Richard Lewontin, Gould’s longtime collaborator and friend:

Now I should warn you about my prejudices. Steve and I taught evolution together for years and in a sense we struggled in class constantly because Steve, in my view, was preoccupied with the desire to be considered a very original and great evolutionary theorist. So he would exaggerate and even caricature certain features, which are true but not the way you want to present them. For example, punctuated equilibrium, one of his favorites. He would go to the blackboard and show a trait rising gradually and then becoming completely flat for a while with no change at all, and then rising quickly and then completely flat, etc. which is a kind of caricature of the fact that there is variability in the evolution of traits, sometimes faster and sometimes slower, but which he made into punctuated equilibrium literally. Then I would have to get up in class and say “Don’t take this caricature too seriously. It really looks like this…” and I would make some more gradual variable rates. Steve and I had that kind of struggle constantly. He would fasten on a particular interesting aspect of the evolutionary process and then make it into a kind of rigid, almost vacuous rule, because—now I have to say that this is my view—I have no demonstration of it—that Steve was really preoccupied by becoming a famous evolutionist.

Gould succeeded, after a fashion. His reputation within evolutionary biology is mixed, at best. Just look at what someone who thinks he made genuine original contributions to science admits above. But in the mind of the public Stephen Jay Gould was an oracle of sorts.

A revolution is sexy. A revolution sells. Having read both of them, I would say that Richard Dawkins is the better stylist when compared to Gould. Additionally, though some might disagree with this Dawkins is closer to the mainline of the modern evolutionary biological tradition than Gould. But in the United States Gould far overshadowed Dawkins…until the latter began to make a name for himself as an anti-religion polemicist in the 2000s. Revolution. Controversy. They’re salient. The press eats it up, and the public trusts the press.

And some things never change. Every few years there is an impending “revolution” in evolutionary biology or genetics. But the revolution is mostly in the minds of a few journalists, and a public that reads a little too much into a puff piece here and there. The sort of well educated public woolly on what the “central dogma” is, but clear that it has been overthrown.

Sometimes this gets out of control. Suzan Mazur’s The Altenberg 16: An Exposé of the Evolution Industry is probably the weirdest instance of this genre of “the sky is falling in evolutionary theory!” But of late some scholars have been coming out with more sober critiques, arguing that the Neo-Darwinian Synthesis needs to be extended or modified significantly. Kevin Laland’s Darwin’s Unfinished Symphony: How Culture Made the Human Mind is the latest instance of this, but this was preceded by Evolution in Four Dimensions: Genetic, Epigenetic, Behavioral, and Symbolic Variation in the History of Life. You can also read David Dobbs’ sympathetic treatment from a few years back around this issue.

I can communicate to you what seems to be the majority view among the evolutionary biologist I know: there isn’t a need for a revolution in conceptual thought, just a working out of details and reallocation of resources. Many who are sympathetic to Kevin Laland’s argument still believe that it’s about emphases and semantics. There’s no reason to put out a clarion call that evolution needs to be rethought in its conceptual foundations.

Honestly I don’t know if there’s been much that is revolutionary conceptually since the original period of the synthesis. Perhaps the rise of molecular evolution and neutrality as a null hypothesis? But even I’m not sure about that.

Erik I. Svensson has put up a preprint which speaks for many people, On reciprocal causation in the evolutionary process. Read the whole thing, it’s thorough, and accessible to a lay audience. The main aspect a bit surprising to me is the good word put in for The Dialectical Biologist, which I have heard is an interesting book:

Recent calls for a revision the standard evolutionary theory (ST) are based on arguments about the reciprocal causation of evolutionary phenomena. Reciprocal causation means that cause-effect relationships are obscured, as a cause could later become an effect and vice versa. Such dynamic cause-effect relationships raises questions about the distinction between proximate and ultimate causes, as originally formulated by Ernst Mayr. They have also motivated some biologists and philosophers to argue for an Extended Evolutionary Synthesis (EES). Such an EES will supposedly replace the Modern Synthesis (MS), with its claimed focus on unidirectional causation. I critically examine this conjecture by the proponents of the EES, and conclude, on the contrary, that reciprocal causation has long been recognized as important in ST and in the MS tradition. Numerous empirical examples of reciprocal causation in the form of positive and negative feedbacks now exists from both natural and laboratory systems. Reciprocal causation has been explicitly incorporated in mathematical models of coevolutionary arms races, frequency-dependent selection and sexual selection. Such feedbacks were already recognized by Richard Levins and Richard Lewontin, long before the call for an EES and the associated concept of niche construction. Reciprocal causation and feedbacks is therefore one of the few contributions of dialectical thinking and Marxist philosophy in evolutionary theory, and should be recognized as such. While reciprocal causation have helped us to understand many evolutionary processes, I caution against its extension to heredity and directed development if such an extension involves futile attempts to restore Lamarckian or soft inheritance.

The origin of organismic gangs

When W. D. Hamilton was a student he expressed an interest in exploring the problem of altruism in an evolutionary context. His struggles in getting anyone interested in the issue and supporting his study of the topic is extensively detailed in Narrow Roads of Gene Land. But he persevered and for his efforts he came up with the framework of inclusive fitness (John Maynard Smith’s term was kin selection). To a great extent it was a revolutionary model, formalizing what he been roughly understood verbally.

But could inclusive fitness explain the social structure we see around us? Hamilton attempted to extend the framework to humans in the 1970s, but that was not particularly fruitful. Other dynamics which emerged on the scene drew more from game theory. Again, John Maynard Smith loomed large, but Robert Trivers also introduced reciprocal altruism into the lexicon. These sorts of processes were much favored by thinkers such as Richard Dawkins because they are simple elementary strategies and relations that are tractable, and can be programmed dand simulated (or analytically explored).

Other researchers have different ideas and appeal to alternative traditions. David Sloan Wilson, along with E. O. Wilson, have been trying to revive models predicated on higher levels of organization. Though often termed “group selection,” the first Wilson correctly labels it “multi-level selection theory.” Though I am willing to agree that the pendulum swung too far in favor of individual level game theory and inclusive fitness in the last few decades, I do find David Sloan Wilson’s triumphalism a bit much (though his books are worth reading, and I think this is a personality issue with David, as he engages in the same triumphalism with economists).

A lot of work still needs to be done to explain social organization and behavior, even in social insects! With that, two preprints in biorxiv caught my attention.

First, Co-evolution of dispersal with behaviour favours social polymorphism. In it the authors model a system where there are dispersing individuals and sessile individuals, and show that cooperative behavior and the sessile morph and selfish behavior and the dispersing morph can persist as two alternative strategies. The paper makes the assumption that the sets of behaviors are caused by different genes which are linked, and show that low recombination is necessary to maintain the linkage. This does not seem genetically realistic.

The second paper is of a broader purview, Stags, hawks, and doves: Social evolution theory and individual variation in cooperation:

One of the triumphs of evolutionary biology is the discovery of robust mechanisms that promote the evolution of cooperative behaviors even when those behaviors reduce the fertility or survival of cooperators. Though these mechanisms, kin selection, reciprocity, and nonlinear payoffs to cooperation, have been extensively studied separately, investigating their joint effect on the evolution of cooperation has been more difficult. Moreover, how these mechanisms shape variation in cooperation is not well known. Such variation is crucial for understanding the evolution of behavioral syndromes and animal personality. Here, I use the tools of kin selection theory and evolutionary game theory to build a framework that integrates these mechanisms for pairwise social interactions. Using relatedness as a measure of the strength of kin selection, responsiveness as a measure of reciprocity, and synergy as a measure of payoff nonlinearity, I show how different combinations of these three parameters produce directional selection for or against cooperation or variation in levels of cooperation via balancing or diversifying selection. Moreover, each of these outcomes maps uniquely to one of four classic games from evolutionary game theory, which means that modulating relatedness, responsiveness, and synergy effectively transforms the payoff matrix from one the evolutionary game to another. Assuming that cooperation exacts a fertility cost on cooperators and provides a fertility benefit to social partners, a prisoner’s dilemma game and directional selection against cooperation occur when relatedness and responsiveness are low and synergy is not too positive. Enough positive synergy in these conditions generates a stag-hunt game and diversifying selection. High levels of relatedness or responsiveness turn cooperation from a fitness cost into a fitness benefit, which produces a mutualism game and directional selection for cooperation when synergy is not too negative. Sufficiently negative synergy in this case creates a hawk-dove game and balancing selection for cooperation. I extend the results with relatedness and synergy to larger social groups and show that how group size changes the effect of relatedness and synergy on selection for cooperation depends on how the per capita benefit of cooperation changes with group size. Together, these results provide a general framework with which to generate comparative predictions that can be tested using quantitative genetic techniques and experimental techniques that manipulate investment in cooperation. These predictions will help us understand both interspecific variation in cooperation as well as within-population and within-group variation in cooperation related to behavioral syndromes.

I haven’t dug into the formal models in the methods sections of either preprint, so I won’t say much more. But, I will offer that as someone who has long been interested in this field there is a surfeit and not enough data to test the models. It is time for someone ambitious to figure out how to make these areas more empirically testable.

Sexual selection decreasing difference

Sexual selection is often considered a driver of diversification of a lineage. I was introduced to the concept in Jared Diamond’s The Third Chimpanzee, where he suggested that racial differences in appearance might be due to sexual preference, following a suggestion originally made by Charles Darwin. Though sexual selection emerges now and then as a deus ex machina in discussion sections of papers, in general it hasn’t panned out addressing this topic.

But a new paper using shorebirds offers results which oppose this sort of inference, in that sexual selection may be a homogenizing force. Basically the authors used the fact that shorebird lineages have related monogamous and polygamous species. They looked at species richness and genetic diversity using STRUCTURE and microsatellites.

Polygamy slows down population divergence in shorebirds:

Examining microsatellite data from 79 populations in 10 plover species (Genus: Charadrius) we found that polygamous species display significantly less genetic structure and weaker isolation-by-distance effects than monogamous species. Consistent with this result, a comparative analysis including 136 shorebird species showed significantly fewer subspecies for polygamous than for monogamous species. By contrast, migratory behavior neither predicted genetic differentiation nor subspecies richness. Taken together, our results suggest that dispersal associated with polygamy may facilitate gene flow and limit population divergence. Therefore, intense sexual selection, as occurs in polygamous species, may act as a brake rather than an engine of speciation in shorebirds.

A reminder that lots of theorizing may lead you nowhere fast, but a quick empirical check can be very humbling. I’m not sure as to the generality of this result, and ultimately it probably has to do with reproductive variance. But it is a starting point.

Addendum: Overall Geoffrey Miller’s The Mating Mind is probably wrong in most of the details, though perhaps on the most general level there may be something there (I’m wondering particularly in regards to mutational load). But it’s a decent introduction to sexual selection theory in  human context, and has a lot of interesting ideas. And Miller is actually a good writer as far as scientists go.

The human extended phenotype


I think there is something to the hypothesis that we as a species are self-domesticated, but a new preprint really doesn’t change my probability up or down, Comparative Genomic Evidence for Self-Domestication in Homo sapiens. Notwithstanding my own participation in some comparative genomic work, a lot of the conclusions from this field are as clear and obvious to me as the above figure, not very.

To be fair at least the authors of the preprint have a hypothesis they’re testing, the “domestication syndrome” as cause by the neural crest gene modification. Two major issues I’d bring up: it’s comparative genomic because of a paucity of samples, and, tidy explanations often don’t pan out.

Genomic analysis of ancient genomes is very preliminary. Phylogenomic work, which establishes relationships between lineages, can accept a noisy and poor marker set with only a few representative samples. But when looking at population genomics one should at least have either really good data on a small number of individuals, or, more preferable, good-enough-data on lots of individuals. The ancient genomic data set for hominins is not rich enough that I’m confident about any but the most obvious and clear differences between our closest relations and ourselves. The reality of gene flow across populations also adds a confounding element, because it might not be implausible that “modern” alleles actually derive from another ancient lineage, and our modern forebears exhibited the ancestral state.

Second, the neural crest hypothesis and a general model of domestication is rather attractive. I myself find it intriguing, and am curious from a professional scientific perspective. But, attractive hypotheses often do not pan out, and gain early attention because scientists are human, and exhibit some bias and hope. A case in point, mirror neurons has stalled as a silver bullet to explain all sorts of unique aspects of human cognition. Neural crest models are part of the long quest to establish the genes which make us unique and human, even though I’m not even sure this is a wrong question.

The preprint did remind me of an excellent book I read over 10 years ago, The Cultural Origins of Human Cognition. I am much more well disposed toward the thesis now than I was then, in large part because I now longer hold to a “big bang” theory of the origin of modern humanity due to a behavioral revolution triggered by a rapid suite of genetic changes. Rather, I suspect a cultural model where there is reciprocal feedback with genetic changes in a sort of ratchet has a lot more utility, in part because the gap between “archaic” H. sapiens and our own ancestors was I believe much smaller in many ways in relation to behavior than we’ve assumed until lately. Finally, the genetic evidence of lots of lateral gene flow across these distinct branches is indicative of more complexity in the origin of humanity than we had previously understood.

There is also the whole idea of “self-domestication.” I think perhaps it needs to be more explicitly formulated in an ecological sense. Rather than self-domestication, what occurred is that a host of species began to inhabit an evolving “extended phenotype” which humans were a motive engine within. But we need to be cautious about overemphasizing our agency. Once human societies became agricultural beyond a certain point it is not not possible to revert back to hunter-gathering lifestyles without migration or mass die off. In some ways we are as much pawns in the forces unleashed by our original choices and actions as the domestic animals and plants and parasites which have come along for the ride.

Citation: Comparative Genomic Evidence for Self-Domestication in Homo sapiens, Constantina Theofanopoulou, Simone Gastaldon, Thomas O’Rourke, Bridget D Samuels, Angela Messner, Pedro Tiago Martins, Francesco Delogu, Saleh Alamri, Cedric Boeckx, doi: https://doi.org/10.1101/125799

Why humans have so many pulse admixtures

The Blank Slate is one of my favorite books (though I’d say The Language Instinct is unjustly overshadowed by it). There is obviously a substantial biological basis in human behavior which is mediated by genetics. When The Blank Slate came out in the early 2000s one could envisage a situation in 2017 when empirically informed realism dominated the intellectual landscape. But that was not to be. In many ways, for example in sex differences, we’ve gone backward, while there is still undue overemphasis in our society on the environmental impact parents have on children (as opposed to society more broadly).

But genes do not determine everything, obviously. Several years after reading The Blank Slate I read Not by Genes Alone: How Culture Transformed Human Evolution. In this work Peter Richerson and Robert Boyd outline their decades long project of modeling cultural variation and evolution formally in a manner reminiscent of biological evolution. Richerson and Boyd’s program does not start from a “blank slate” assumption. Rather, it is focused on broad macro-social dynamics where cultural variation “swamps” out biological variation.

Recall that in classic population genetic theory a major problem with group level selection is that gene flow between adjacent groups quickly removes between group variation. One migrant between two groups per generation is enough for them not to diverge genetically. For group selection to occur the selective effect has to be very strong or the between group difference has to be very high. Rather than talking about genetics though, where the debate is still live, and the majority consensus is still that biological group selection is not that common (depending on how you define it), let’s talk about human culture.

Here the group level differences are extreme and the boundaries can be sharp. Historically it seems likely that most groups which were adjacent to each other looked rather similar because of gene flow and similar selective pressures. Even though in medieval Spain there was a generality, probably true, that Muslims were swarthier than Christians*, there was a palpable danger in battle of identifying friend from foe because the two groups overlapped too much in appearance.

This brings up how one might delineate differences culturally. In battle opposing armies wear distinct uniforms and colors so that the distinction can be made. But obviously one change uniform surreptitiously (perhaps taking the garb from the enemy dead). This is why physical adornment such as tattoos are useful, as they are “hard to fake.” Perhaps the most clear illustration of this dynamic is the Biblical story for the origin of the term shibboleth. Even slight differences in accent are clear to all, and, often difficult to mimic once in adulthood.

Biological evolution mediated through genes is relatively slow and constrained compared to cultural evolution. Whole regions of central and northern Europe shifted from adherence to Roman Catholicism to forms of Protestantism on the order of 10 years. Of course religion is an aspect of culture where change can happen very rapidly, but even language shifts can occur in only a few generations (e.g., the decline of regional German and Italian dialects in the face of standard forms of the language).

Cultural evolution as a formally modeled neofunctionalism is credibly outlined in works such as Peter Turchin’s Ultrasociety: How 10,000 Years of War Made Humans the Greatest Cooperators on Earth. That’s not what I want to focus on here. Rather, I contend that the reality of massive pulse admixtures evident in the human genome over the past 10,000 years, at minimum, is a function of the fact that human cultural evolutionary processes result in winner-take-all genetic consequences.

A concrete example of what I’m talking about would compare the peoples of the Italian peninsula and the Iberian peninsula around 1500. The two populations are not that different genetically, and up to that point shared many cultural traits (and continue to do so). But, a combination of geography and history resulted in Iberian demographic expansion in the several hundred years after 1500, whereby today there are probably many more descendants of Iberians than Italians. This is not a function of any deep genetic difference between the two groups. There aren’t deep genetic differences in fact. Rather, the social and demographic forces which propelled Iberia to imperial status redounded upon the demographic production of Iberians in the future. In addition, the New World underwent a massive pulse admixture between Iberians, and native Amerindians, as well as Africans, usually brought over as slaves, due the cultural and political history of the period.

The pulse admixture question is rather interesting academically. To some extent current methods are biased toward detection of pulse admixtures, and even fit continuous gene flow as pulse admixtures. A quick rapid exchange of gene flow and then recombination breaking apart associations of markers which are ancestrally informative haplotypes is something you can test for. But I think we can agree that the gene flow triggered by the Columbian Exchange was a pulse admixture, and there’s too much concurrent evidence from uniparental lineage turnover in the ancient DNA to dismiss the non-historically corroborated signatures of pulses as simply artifacts.

Nevertheless continuous gene flow does occur. That is, normal exchange of individuals between neighboring demes as a slow simmer over time. But the idea that we are a clinal ring species or something like that isn’t right in my opinion. Part of the story are strong geographical barriers. But another major part is that cultural revolutions and advantages introduce huge short-term demographic advantages to particular groups, and the shake out of inter-group competition can be dramatic.

Therefore, I make a prediction: the more cultural evolutionary dynamics a species is subject to, the more pulse admixture you’ll be able to detect. For example, pulse admixture should be more important in social insects than their solitary relatives.

* Not only was some of the ancestry of Muslims North African, Muslim rule was longest in the southern and southeastern regions, where people were not as fair as in the north.

How Tibetans can function at high altitudes


About seven years ago I wrote two posts about how Tibetans manage to function at very high altitudes. And it’s not just physiological functioning, that is, fitness straightforwardly understood. High altitudes can cause a sharp reduction in reproductive fitness because women can not carry pregnancies to term. In other words, high altitude is a very strong selection pressure. You adapt, or you die off.

For me there have been two things of note since those original papers came out. First, one of those loci seem to have been introgressed from a Denisovan genetic background. I want to be careful here, because the initial admixture event may not have been into the Tibetans proper, but earlier hunter-gatherers who descend from Out of Africa groups, who were assimilated into the Tibetans as they expanded 5-10,000 years ago. Second, it turns out that dogs have been targeted for selection on EPAS1 as well (the “Denisovan” introgression) for altitude adaptation as well.

This shows that in mammals at least there’s a few genes which show up again and again. The fact that EPAS1 and EGLN1 were hits on relatively small sample sizes also reinforces their powerful effect. When the EPAS1 results initially came out they were highlighted as the strongest and fastest instance of natural selection in human evolutionary history. One can quibble about the details about whether this was literally true, but that it was a powerful selective event no one could deny.

A new paper in PNAS, Genetic signatures of high-altitude adaptation in Tibetans, revisits the earlier results with a much larger sample size (the research group is in China) comparing Han Chinese and Tibetans. They confirm the earlier results, but, they also find other loci which seem likely targets of selection in Tibetans. Below is the list:

SNP A1 A2 Frequency of A1 P value FST Nearest gene
Tibetan EAS (Han)
rs1801133 A G 0.238 0.333 6.30E-09 0.021 MTHFR
rs71673426 C T 0.102 0.013 1.50E-08 0.1 RAP1A
rs78720557 A T 0.498 0.201 4.70E-08 0.191 NEK7
rs78561501 A G 0.599 0.135 6.10E-15 0.414 EGLN1
rs116611511 G A 0.447 0.003 3.60E-19 0.57 EPAS1
rs2584462 G A 0.211 0.549 3.90E-09 0.203 ADH7
rs4498258 T A 0.586 0.287 1.70E-08 0.171 FGF10
rs9275281 G A 0.095 0.365 1.10E-10 0.162 HLA-DQB1
rs139129572 GA G 0.316 0.449 5.80E-09 0.036 HCAR2
P value indicates the P value from the MLMA-LOCO analysis. FST is the FST value between Tibetans and EASs. Nearest gene indicates the nearest annotated gene to the top differentiated SNP at each locus except EGLN1, which is known to be associated with high-altitude adaptation; rs139129572 is an insertion SNP with two alleles: GA and G. A1, allele 1; A2, allele 2.

Many of these genes are familiar. Observe the allele frequency differences between the Tibetans and other East Asians (mostly Han). The sample sizes are on the order of thousands, and the SNP-chip had nearly 300,000 markers. What they found was that the between population Fst of Han to Tibetan was ~0.01. So only 1% of the SNP variance in their data was partitioned between the two groups. These alleles are huge outliers.

The authors used some sophisticated statistical methods to correct for exigencies of population structure, drift, admixture, etc., to converge upon these hits, but even through inspection the deviation on these alleles is clear. And as they note in the paper it isn’t clear all of these genes are selected simply for hypoxia adaptation. MTFHR, which is quite often a signal of selection, may have something to due to folate production (higher altitudes have more UV). ADH7 is part of a set of genes which always seem to be under selection, and HLA is never a surprise.

Rather than get caught up in the details it is important to note here that expansion into novel habitats results in lots of changes in populations, so that two groups can diverge quite fast on functional characteristics.  The PCA makes it clear that Tibetans and Hans have very little West Eurasian admixture, and the Fst based analysis puts their divergence on the order of 5,000 years before the present. The authors admit honestly that this is probably a lower bound value, but I also think it is quite likely that Tibetans, and probably Han too, are compound populations, and a simple bifurcation model from a common ancestral population is probably shaving away too many realistic edges. In plainer language, there has been gene flow between Han and Tibetans probably <5,000 years ago, and Tibetans themselves probably assimilated more deeply diverged populations in the highlands as they expanded as agriculturalists. An estimate of a single divergence fits a complex history to too simple of a model quite often.

The take home: understanding population history is probably important to get a better sense of the dynamics of adaptation.

Citation: Jian Yang, Zi-Bing Jin, Jie Chen, Xiu-Feng Huang, Xiao-Man Li, Yuan-Bo Liang, Jian-Yang Mao, Xin Chen, Zhili Zheng, Andrew Bakshi, Dong-Dong Zheng, Mei-Qin Zheng, Naomi R. Wray, Peter M. Visscher, Fan Lu, and Jia Qu, Genetic signatures of high-altitude adaptation in Tibetans, PNAS 2017 ; published ahead of print April 3, 2017, doi:10.1073/pnas.1617042114

Jeepers creepers…those eyes

I take some interest in the old debate about contingency and some aspect of determinism in evolutionary processes. Basically the debate is whether the basic morphology and mechanism of life on earth would exhibit the same patterns we see around us today if we rewound the clock. Stephen Jay Gould, most extensively in The Structure of Evolutionary Theory, argued for radical contingency. In Life’s Solution Simon Conway Morris takes a very different view. From what I can tell Richard Dawkins actually takes a somewhat middle perspective, though generally he is chalked up in the anti-Gouldian position (see The Ancestor’s Tale).

But ultimately this is all jaw-jaw. Real science deals in facts adduced and theories propounded. The great “debates” between “schools” of thought in the natural sciences usually suggests to me a paucity of data and method for the purposes of analysis. When it comes to contingency and inevitability that’s changing. Though I usually focus on the molecular evolutionary aspects of the scholarship (see Joe Thornton’s work), a new preprint in biorxiv utilizes phylogenetic reconstruction to indirectly addresses this question, Temporal Niche Expansion In Mammals From A Nocturnal Ancestor After Dinosaur Extinction:

Most modern mammals, including strictly diurnal species, exhibit sensory adaptations to nocturnal activity, thought to be the result of a prolonged nocturnal phase or ‘bottleneck’ during early mammalian evolution. Nocturnality may have allowed mammals to avoid antagonistic interactions with diurnal dinosaurs during the Mesozoic. However, understanding the evolution of mammalian activity patterns is hindered by scant and ambiguous fossil evidence. While ancestral reconstructions of behavioural traits from extant species have the potential to elucidate these patterns, existing studies have been limited in taxonomic scope. Here, we use an extensive behavioural dataset for 2415 species from all extant orders to reconstruct ancestral activity patterns across Mammalia. We find strong support for the nocturnal origin of mammals and the Cenozoic appearance of diurnality, although cathemerality (mixed diel periodicity) may have appeared in the late Cretaceous. Simian primates are among the earliest mammals to exhibit strict diurnal activity, some 52-33Mya. Our study is consistent with the hypothesis that temporal partitioning between early mammals and dinosaurs during the Mesozoic led to a mammalian nocturnal bottleneck, but also demonstrates the need for improved phylogenetic estimates for Mammalia.

The results from this analysis aren’t revolutionary. Through fancy rjMCMC they infer a posterior probability of 0.74 for the nocturnal hypothesis. As someone who knows very little about this topic I’d probably have guessed such a number. But at least the discussion is happening on a formal basis.

But first, this analysis highlights the likelihood that the tens of millions of years our mammalian ancestors spent as nocturnal creatures still redound to non-nocturnal lineages today, over 60 millions years beyond the end of the Age of Dinosaurs. Presumably in all this time mutation could have random-walked itself into some other optimum and moved beyond those nocturnal adaptations, but it seems that that legacy is with us still. Strike one for contingency.

Without knowing anything I’d predict birds would be the opposite, with nocturnal lineages derived from diurnal ancestors.

A final gripe about this preprint: data and code are available after publication. This is really a methods based paper and I did toy with the idea of trying to reanalyze the data. Oh well, I guess not.

Citation: Temporal Niche Expansion In Mammals From A Nocturnal Ancestor After Dinosaur Extinction, Roi Maor, Tamar Dayan, Henry Ferguson-Gow, Kate Jones
bioRxiv 123273; doi: https://doi.org/10.1101/123273