Razib Khan One-stop-shopping for all of my content

April 23, 2017

The logic of human destiny was inevitable 1 million years ago

Filed under: Evolution,Genetics,Genomics,Human Evolution,Human Genetics — Razib Khan @ 1:11 pm

Robert Wright’s best book, Nonzero: The Logic of Human Destiny, was published near 20 years ago. At the time I was moderately skeptical of his thesis. It was too teleological for my tastes. And, it does pander to a bias in human psychology whereby we look to find meaning in the universe.

But this is 2017, and I have somewhat different views.

In the year 2000 I broadly accepted the thesis outlined a few years later in The Dawn of Human Culture. That our species, our humanity, evolved and emerged in rapid sequence, likely due to biological changes of a radical kind, ~50,000 years ago. This is the thesis of the “great leap forward” of behavioral modernity.

Today I have come closer to models proposed by Michael Tomasello in The Cultural Origins of Human Cognition and Terrence Deacon in The Symbolic Species: The Co-evolution of Language and the Brain. Rather than a punctuated event, an instance in geological time, humanity as we understand it was a gradual process, driven by general dynamics and evolutionary feedback loops.

The conceit at the heart of Robert J. Sawyer’s often overly preachy Neanderthal Parallax series, that if our own lineage went extinct but theirs did not they would have created a technological civilization, is I think in the main correct. It may not be entirely coincidental that the hyper-drive cultural flexibility of African modern humans evolved in African modern humans first. There may have been sufficient biological differences to enable this to be likely. But I believe that if African modern humans were removed from the picture Neanderthals would have “caught up” and been positioned to begin the trajectory we find ourselves in during the current Holocene inter-glacial.

Luke Jostins’ figure showing across board encephalization

The data indicate that all human lineages were subject to increased encephalization. That process trailed off ~200,000 years ago, but it illustrates the general evolutionary pressures, ratchets, or evolutionary “logic”, that applied to all of them. Overall there were some general trends in the hominin lineage that began to characterized us about a million years ago. We pushed into new territory. Our rate of cultural change seems to gradually increased across our whole range.

One of the major holy grails I see now and then in human evolutionary genetics is to find “the gene that made us human.” The scramble is definitely on now that more and more whole genome sequences from ancient hominins are coming online. But I don’t think there will be such gene ever found. There isn’t “a gene,” but a broad set of genes which were gradually selected upon in the process of making us human.

In the lingo, it wasn’t just a hard sweep from a de novo mutation. It was as much, or even more, soft sweeps from standing variation.

April 14, 2017

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

Filed under: EES,Evolution,Genetics,Neo-Darwinian Synthesis — Razib Khan @ 3:30 pm

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 succeed, 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 you can also read 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 since he 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 thing that is a bit surprising is the good work 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

Filed under: Evolution,Game Theory — Razib Khan @ 12:55 am

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.

April 10, 2017

Sexual selection decreasing difference

Filed under: Evolution,Genetics,Sexual Selection — Razib Khan @ 10:32 pm

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

Filed under: Evolution,Genetics,Neural Crest,Self-domestication — Razib Khan @ 8:17 pm


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

April 7, 2017

Why humans have so many pulse admixtures

Filed under: Admixture,Evolution,Genetics,Genomics — Razib Khan @ 5:38 pm

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.

April 4, 2017

How Tibetans can function at high altitudes

Filed under: Altitude Adaptation,Evolution,Genetics,Genomics,Human Evolution,Tibetans — Razib Khan @ 11:10 am


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

April 3, 2017

Jeepers creepers…those eyes

Filed under: Contigency,Evolution — Razib Khan @ 11:41 pm

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.

March 29, 2017

When the gods come crashing down

Filed under: Culture,Evolution,History — Razib Khan @ 9:03 pm

Sometimes the old gods slowly fade into oblivion. Contrary to popular perception this seems likely the case for ancient paganism. The conversion of Constantine to the Christian religion began the process of a hand-off and the commanding heights of classical culture that took over a century to complete. There were punctuating moments, such as the apostasy of Justinian in the 360s, or the mostly symbolic ban on public paganism by Theodosius in the 390s (the Serapeum was destroyed by a vigilante mob). But pagans in the form of the Neoplatonic school persisted into the 6th century, while elite pagans such as Marcellinus maintained power and influence deep into the second half of the 5th century.

Call this “normal” cultural evolution. Antiquity evolved from being predominantly pagan to predominantly Christian (though a small cultured pagan minority persisted even until the Islamic conquest in the Near East, such as the Sabians of Haran).

The Reformation period was different. In a single generation one thousand years of a coherent and unified Western Christian ideology collapsed, and was replaced by something very different.

Note here that I said Western Christian ideology. The reality is that Western Christianity was never as unified or coherent as Western Christians themselves envisaged themselves to be (or aspired to be). There were episodes of hostility between particular kingdoms and the Roman papacy. Heresies such as that of the Cathars, and popular revolts with a religious tinge such as that of the Hussites. And finally, there were periods of multiple popes, which undermined the credibility of the institution of the Church in the medieval period.

But all this pales next to the magnitude and scope of the revolt against the establishment of the Western Christian church that occurred in the 1520s. Martin Luther went from being a Christian cleric within the established Church to declaring the pope the anti-Christian! Previously devout peasants in Switzerland turned on the relics and churches which they had only recently venerated, and engaged in mob iconoclasm. Whereas monarchs, such as Henry IV, ultimately compromised with the clerical estate (or, submitted), Henry VIII of England managed to destroy or subordinate the institutions of the church to his own will and pleasure.

There are many theories for why the Reformation occurred when it did. Some of them are rooted in technology, in particular the printing press. Others point to the development of proto-national identities, such as the rise of German nationalism and its leveraging by Luther against his “Roman” persecutors.

These specific issues are not interesting to me. Rather, what they point out to us that there can be cultural revolutions that occur very rapidly. One can point to the pacific post-World War II Japanese, and contrast them with the militaristic Japanese of the first half of the 20th century. Or the shift of Russia from being a conservative autocracy in the 1910s to a revolutionary society in the 1920s. But these are modern events, and moderns are liable to suggest that our own epoch is sui generis in these sorts of turnovers of values. But the Reformation shows that revolutionary changes in whole societies can occur rather rapidly even in a pre-modern context.

In other words, cultural revolution is not a derived characteristic of our species, but perhaps a very old one. The rapid expansion of the Austronesians. Or the radiation of non-African humanity. These come out of a vacuum, a cultural-demographic analog to the inflationary universe. But given enough time perhaps our species is simply subject to these sorts of explosions of creative change and innovation.

List of top 10 evolutionary biologists in history

Filed under: Evolution,Evolutionary Biologists,Genetics — Razib Khan @ 4:00 am

What is your list of the top 10 evolutionary biologists in history? I’m asking because this came up in a discussion with a friend. Obviously the composition of the list will have to do with disciplinary bias and geography and history (there are Russian population geneticists from the 20th century who should be more famous who aren’t).

Here are my top 10 (with two minutes thought given):

1. Charles Darwin
2. R. A. Fisher
3. Sewall Wright
4. J. B. S. Haldane
5. W. D. Hamilton
6. G. G. Simpson
7. John Maynard Smith
8. August Weismann
9. Motoo Kimura
10. Theodosius Dobzhansky

What’s your list? (in the comments)

March 19, 2017

10 things about human evolution (genetics) you should know (simpler)

Filed under: Evolution — razibk @ 3:25 am

In response to my earlier post some people suggested that the language was impenetrable. Nathan Taylor​ offered to make it more plain spoken, so here is this go at it. I think it’s pretty good.

(text below is from Nathan)  

1) Modern humans stayed in Africa for tens of thousands years of before expanding beyond it. Most of the ancestors of non-African humanity seem to have started expanding rapidly from a small founder group of less than 1,000 people, starting around 50-75 thousand years years ago. African humanity has a more complex pattern. Some groups diverged as early as 200,000 years ago, then mixed back together.


2) Don’t think of humanity as a branching tree. Rather think of humanity as groups of streams. Some streams end, many fold back on one another, and some suddenly have massive expansions. Surprisingly, all major human population groups we know today seem to be the product of relatively recent fusions. Even Africa, the source of modern humanity, has seen streams flow back from Eurasia.


3) Many of the characteristics people focus on today are of recent origin. At least as measured in thousands or tens of thousands of years. 8,000 years ago parts of Europe were populated by brown skinned hunter gatherers with blue eyes. Whiter skin is a (relatively) recent development. And the thick straight hair now common among East Asians is recent as well.

4) The genetic variant which helps Tibetans tolerate very high altitudes comes from a human lineage as divergent from modern humans as Neanderthals are. The Denisovans. This illustrates a general trend: we have adaptations from other very diverged human lineages in our genes today. Even if the genetic percentage is small.


5) The transition to agriculture and complex civilization seems correlated with the explosive growth of a few select male Y chromosomes. Think Genghis Khan.


6) It seems unlikely there is one genetic change which made humans humans. This is less certain than 1-5, but I’m pretty sure it’s true. Researchers have been looking for this for years and haven’t turned up anything definitive. I think the reason is simple enough: many genetic changes came together to make us distinctive.


7) A lot of variation between human groups is not due to novel genes. Rather it comes from increasing the popularity of pre-existing genetic variants. For example, the lightening of skin across parts of Eurasia is due to an increase of genetic variants which are common to many human populations. Height is another example.


8) Cultural flexibility does not means humans are not evolving. On the contrary, strong shifts in cultural norms seem to drive human evolution. Lactase persistence (the ability to drink milk as an adult) is a clear case. But even genetic tolerance to malaria was ultimately driven by human created environmental changes.


9) There are no “most ancient” human group. By definition, we are all equally separated in time from our common ancestors.


10) There are hints of possible new discoveries coming from ancient human DNA.  For example there is evidence of humans leaving Africa ~100,000 years ago into Eurasia in both genetic and fossil data. These earlier humans may have been overrun by a later group. But this is hard to determine with the current data. The DNA of current and ancient humans still has many stories to tell.

10 things about human evolution (genetics) you should know

Filed under: Evolution — razibk @ 1:53 am

In 2011 I had dinner with a friend of mine from college. He’s a smart guy. Ph.D. in chemistry form M.I.T and all that. I mentioned offhand how it was rather proven to good degree of certainty there was Neanderthal gene flow into modern humans (our lineage)[1]​. He was somewhat surprised by this information, and I was aghast that he didn’t know. 1It was one of the biggest science stories of the year. Right?

What that brought home to me is that something that seems revolutionary near to your heart or field of occupational interest may not be so visible to those who are not similarly situated. My friend is a well educated person with a science Ph.D., but it was just not on his radar. Similarly, I had very smart friends in college who were evangelical Christians who were surprised by the high degree of identity between the chimpanzee and human in regards to our DNA sequence (they were Creationists, and skeptical of any close kinship).

Here’s a final example that might interest readers. I had a long conversation with a relatively prominent journalist a month or so ago. Someone who writes in biology, and in particular genetics (who is not Carl Zimmer). I mentioned offhand to them that the work of various labs utilizing ancient DNA is showing rather conclusively that the vast majority of human populations are relatively recent admixtures between highly diverged lineages. To put it in plainer language: we are all mestizos! This journalist was totally surprised by this fact.

This indicates to me again that facts which are “known” in the “in-group” may be surprising to those who are not as hooked in. It isn’t a matter of being educated, smart, or interested. It’s a matter of narrowly constrained social channels.

Here are 10 facts that we’ve recently discovered about human evolution, with a focus on genetics since that’s what I know best, which you should probably know. Or might find interesting.

1) The expansion/development of modern humans occurred within Africa for tens of thousands of before their expansion “Out of Africa.” Most of the ancestors of non-African humanity seem to have started expanding rapidly from a small founder group of 100-1,000 50-75 thousand years years ago. African humanity has a different and more complex historical pattern, with lineages which began diverging as early as 200,000 years before the present, and then mixing back with each other.

2) Related to #1, we’re one species, so rather than an expanding “tree” from common ancestors, it’s better to think of a mesh which keeps coming back together, as some branches are pruned, and the whole pulses out periodically. All major human populations seem to be the product of relatively recent fusions between diverged branches. Africa was the source of modern humanity, but clearly there has been “back migration” from Eurasia.

3) Many of the phenotypes we define as characteristic of various human populations are relatively recent. E.g., the depigmented look of Northern Europeans, or the thick straight hair of East Asians.

4) The Denisovan version of EPAS1 which is found in Tibetans illustrates a general trend: we have adaptations from other very diverged human lineages through low levels of gene flow[2]​.

5) The transition to agriculture and complex “civilization” seems correlated to pulses of highly fecund male paternal lineages. Many of the common Y chromosomes today exhibit a pattern of diversification indicative of explosive population growth.

6) It seems unlike there is one singular genetic change which makes us sui generis or distinctive in relation to our hominin cousins. This is less certain than 1-5, but I’m pretty sure that this is so. Researchers have been looking for years, and not finding anything definitive, and I think there’s a reason. There isn’t anything definitive. Many genetic changes come together to make our lineage distinctive.

7) A lot of adaptation occurs through reemergence of old variation which is floating around in the human population. For example, the lightening of skin across parts of Eurasia co-opt common mammalian pigmentation pathways.

8) Cultural flexibility does not negate biological evolution. On the contrary, strong shifts in cultural norms seem to drive biology. Lactase persistence is a clear case, but even something like malaria adaptation is ultimately due to anthropogenic environmental changes.

9) We are all equally descended from common ancestors. There are no “most ancient” human lineages. We’re all equally recent by definition.

10) There are evolutionary genetic events in our history which are hinted at in the most recent data, so there are major lacunae in our knowledge. The picture is well formed, but not complete. E.g., there is evidence of pulses out of Africa ~100,000 years ago into Eurasia in both genetic and fossil data. These lineages may have gone extinct, or, their contribution may be difficult to detect with current data sets. But there is clearly more to be told in this story.

November 13, 2013

The color of life as a coincidence

Filed under: Anthroplogy,Evolution,Evolutionary Genetics,Genetics of taste,Taste — Razib Khan @ 12:35 am

Credit: Eric Hunt

Credit: Eric Hunt

I do love me some sprouts! Greens, bitters, strong flavors of all sorts. I’ve always been like this. Some of this is surely environment. My family comes from a part of South Asia known for its love of bracing and bold sensation. But perhaps I was born this way? There’s a fair amount of evidence that taste has a substantial genetic component. This does not mean genes determine what one tastes, but it certainly opens the door for passive gene-environment correlations. If you do not find a flavor offensive, you are much more likely to explore it depths, and cultivate your palette.

220px-Durio_kutej_F_070203_ime

Dost thou dare?
Credit: W.A. Djatmiko

And of course I’m not the only one with a deep interest in such questions. With the marginal income available to us many Americans have become “foodies,” searching for flavor bursts and novelties which their ancestors might never have been able to comprehend. More deeply in a philosophical sense the question of qualia reemerges if there is a predictable degree of inter-subjectivity in taste perception (OK, qualia is always there, though scientific sorts tend to view it as intractable in a fundamental sense).


But there’s heritability, and then there’s genes. We know that perception in some ways is heritable, but what is perhaps more interesting is if you can peg a specific genomic location to it. Then the evolutionary story becomes all the richer. And so it is with the locus TAS2R16, where a nonsynonymous mutation at location 516 seems to result in heightened sensitivity to bitter tastes. More specifically, it’s rs846664, and the derived T allele is fixed outside of Africa, while the ancestral G allele still segregates at appreciable fractions within African populations. A new paper in Molecular Biology and Evolution puts this locus under a microscope, though it does not come up with any clear conclusions. Origin and Differential Selection of Allelic Variation at TAS2R16 Associated with Salicin Bitter Taste Sensitivity in Africa presents some interesting findings. First, let’s look at the distribution of the variation in their sample populations at the SNP of most particular interest:

Region Population T516G
Outside of Africa Non-Africans 0.000
Ethiopia Semitic 0.059
Tanzania Sandawe 0.083
Ethiopia Omotic 0.093
Ethiopia Cushitic 0.095
Tanzania Iraqw 0.111
West Central Africa Fulani 0.114
Kenya Niger-Kordofanian 0.133
Ethiopia Nilo-Saharan 0.156
Kenya Afroasiatic 0.162
West Central Africa Niger-Kordofanian 0.214
Kenya Nilo-Saharan 0.225
Kenya Luo 0.250
Central Africa Niger-Kordofanian 0.329
Tanzania Hadza 0.333
Central Africa Bulala 0.361
Central Africa Nilo-Saharan 0.367
West Central Africa Afroasiatic 0.462
West Central Africa Nilo-Saharan 0.500

As you can see T is fixed outside of Africa, and varies across many African populations  Previous work implied this, though coverage within Africa was not good. One thing to observe though is that the frequency of A within Africa can not be explained by recent Eurasian admixture. The frequency is way too high for that to be the sole explanation, and in any case there is no evidence that ~33% of the Hadza’s ancestry is of Eurasian provenance (the Hadza being one of the three major groups of African hunter-gatherers, along with the Bushmen and Pygmies).

Within the paper the authors resequenced ~1,000 base pairs across diverse African populations in an exonic region of this gene (the stuff that codes for amino acids). What they discovered is that of the SNPs segregating, 516 in particular was critical toward effecting phenotyping change. Not only did individuals with the T variant notably exhibit stronger bitter sensitivity, but in vitro expression with a reporter was elevated. Because they had such a dense genomic region they could perform various nucleotide based tests to detect natural selection, and, attempt coalescent models to infer genealogical history.

I’m going to spare you some of the gory details at this point. Here’s what they found. First, it does look like the region is under natural selection in many African populations, in particular, the derived haplotype with T at 516 at the center. But this result is not reproduced across all tests. The coalescent simulations make clear why: the mutation is an old variant with deep roots in the hominin lineage. In other words this variation pre-dates H. sapiens. It looks like the T allele has rapidly increased in frequency relatively recently, though more on the order of ~50,000 years, rather than ~10,000.* Basically around the time of the “Out of Africa” event. Additionally, there’s a tell-tale sign that this is being subject to selection within Africa: the genetic differences across populations at TAS2R16 far exceed the genome-wide values (the Fst at this locus is in the top 1% of loci within the African genome). Finally, one should note that the G allele haplotypes seem to be much more strongly constrained, as if they’re under purifying selection. This means that the switch to T is not all gain.

At this point you may be ready for a story about how some African populations, like Eurasians, underwent a lifestyle change, and diet changes resulted in a shift in sensory perception. That does not seem to be the story. Rather, the authors did not seem to be able to agree upon a neat explanation for what is driving these recent sweeps up from ancient standing genetic variation. They do observe that the variation does tend to cluster geographically, more so than the genome-wide results would imply. There’s likely some adaptation going on, they simply don’t know what. In the introduction and elsewhere you can see that variation at TAS2R16 does correlate with other traits. Not too surprising due to the relatively ubiquity of pleiotropy; one gene with many effects.

Stepping outside of the implications of this specific result, let’s think about what might be a takeaway: something as essential as taste perception might be a side effect of other aspects of evolutionary processes. In other words, we don’t know what the phenotypic target of selection is in this case, but we do have a good handle one of the major side effects, which is sensory perception. How one taste seems like a big deal.** Andthere have been many theories propounded that variation in bitter sensitivity is due to adaptation to poisonous plants and such, but really no one knew, and that was just the most plausible of low hanging fruit. With these results from Africa, where there is more variation in the trait and genes, and good geographic coverage, that seems to be an implausible model to adhere to (one would think the hunter-gatherer Hadza would exhibit the most sensitivity, no?). Many of the traits and tendencies which we humans see as fundamental, essential, and of great import, many actually be side effects of powerful evolutionary forces hammering at the genetic-correlation matrices which define the hidden network of co-dependencies within the genome. So there, I said it. Life is an accident. Enjoy it.

Citation: Campbell, Michael C., et al. “Origin and Differential Selection of Allelic Variation at TAS2R16 Associated with Salicin Bitter Taste Sensitivity in Africa.” Molecular biology and evolution (2013): mst211.

* If it was closer to ~10,000 I think haplotype based tests would come back with something, but they do not.

** Some Epicureans might be accused of reducing the good to taste!

The post The color of life as a coincidence appeared first on Gene Expression.

The color of life as a coincidence

Filed under: Anthroplogy,Evolution,Evolutionary Genetics,Genetics of taste,Taste — Razib Khan @ 12:35 am

Credit: Eric Hunt

Credit: Eric Hunt

I do love me some sprouts! Greens, bitters, strong flavors of all sorts. I’ve always been like this. Some of this is surely environment. My family comes from a part of South Asia known for its love of bracing and bold sensation. But perhaps I was born this way? There’s a fair amount of evidence that taste has a substantial genetic component. This does not mean genes determine what one tastes, but it certainly opens the door for passive gene-environment correlations. If you do not find a flavor offensive, you are much more likely to explore it depths, and cultivate your palette.

220px-Durio_kutej_F_070203_ime

Dost thou dare?
Credit: W.A. Djatmiko

And of course I’m not the only one with a deep interest in such questions. With the marginal income available to us many Americans have become “foodies,” searching for flavor bursts and novelties which their ancestors might never have been able to comprehend. More deeply in a philosophical sense the question of qualia reemerges if there is a predictable degree of inter-subjectivity in taste perception (OK, qualia is always there, though scientific sorts tend to view it as intractable in a fundamental sense).


But there’s heritability, and then there’s genes. We know that perception in some ways is heritable, but what is perhaps more interesting is if you can peg a specific genomic location to it. Then the evolutionary story becomes all the richer. And so it is with the locus TAS2R16, where a nonsynonymous mutation at location 516 seems to result in heightened sensitivity to bitter tastes. More specifically, it’s rs846664, and the derived T allele is fixed outside of Africa, while the ancestral G allele still segregates at appreciable fractions within African populations. A new paper in Molecular Biology and Evolution puts this locus under a microscope, though it does not come up with any clear conclusions. Origin and Differential Selection of Allelic Variation at TAS2R16 Associated with Salicin Bitter Taste Sensitivity in Africa presents some interesting findings. First, let’s look at the distribution of the variation in their sample populations at the SNP of most particular interest:

Region Population T516G
Outside of Africa Non-Africans 0.000
Ethiopia Semitic 0.059
Tanzania Sandawe 0.083
Ethiopia Omotic 0.093
Ethiopia Cushitic 0.095
Tanzania Iraqw 0.111
West Central Africa Fulani 0.114
Kenya Niger-Kordofanian 0.133
Ethiopia Nilo-Saharan 0.156
Kenya Afroasiatic 0.162
West Central Africa Niger-Kordofanian 0.214
Kenya Nilo-Saharan 0.225
Kenya Luo 0.250
Central Africa Niger-Kordofanian 0.329
Tanzania Hadza 0.333
Central Africa Bulala 0.361
Central Africa Nilo-Saharan 0.367
West Central Africa Afroasiatic 0.462
West Central Africa Nilo-Saharan 0.500

As you can see T is fixed outside of Africa, and varies across many African populations  Previous work implied this, though coverage within Africa was not good. One thing to observe though is that the frequency of A within Africa can not be explained by recent Eurasian admixture. The frequency is way too high for that to be the sole explanation, and in any case there is no evidence that ~33% of the Hadza’s ancestry is of Eurasian provenance (the Hadza being one of the three major groups of African hunter-gatherers, along with the Bushmen and Pygmies).

Within the paper the authors resequenced ~1,000 base pairs across diverse African populations in an exonic region of this gene (the stuff that codes for amino acids). What they discovered is that of the SNPs segregating, 516 in particular was critical toward effecting phenotyping change. Not only did individuals with the T variant notably exhibit stronger bitter sensitivity, but in vitro expression with a reporter was elevated. Because they had such a dense genomic region they could perform various nucleotide based tests to detect natural selection, and, attempt coalescent models to infer genealogical history.

I’m going to spare you some of the gory details at this point. Here’s what they found. First, it does look like the region is under natural selection in many African populations, in particular, the derived haplotype with T at 516 at the center. But this result is not reproduced across all tests. The coalescent simulations make clear why: the mutation is an old variant with deep roots in the hominin lineage. In other words this variation pre-dates H. sapiens. It looks like the T allele has rapidly increased in frequency relatively recently, though more on the order of ~50,000 years, rather than ~10,000.* Basically around the time of the “Out of Africa” event. Additionally, there’s a tell-tale sign that this is being subject to selection within Africa: the genetic differences across populations at TAS2R16 far exceed the genome-wide values (the Fst at this locus is in the top 1% of loci within the African genome). Finally, one should note that the G allele haplotypes seem to be much more strongly constrained, as if they’re under purifying selection. This means that the switch to T is not all gain.

At this point you may be ready for a story about how some African populations, like Eurasians, underwent a lifestyle change, and diet changes resulted in a shift in sensory perception. That does not seem to be the story. Rather, the authors did not seem to be able to agree upon a neat explanation for what is driving these recent sweeps up from ancient standing genetic variation. They do observe that the variation does tend to cluster geographically, more so than the genome-wide results would imply. There’s likely some adaptation going on, they simply don’t know what. In the introduction and elsewhere you can see that variation at TAS2R16 does correlate with other traits. Not too surprising due to the relatively ubiquity of pleiotropy; one gene with many effects.

Stepping outside of the implications of this specific result, let’s think about what might be a takeaway: something as essential as taste perception might be a side effect of other aspects of evolutionary processes. In other words, we don’t know what the phenotypic target of selection is in this case, but we do have a good handle one of the major side effects, which is sensory perception. How one taste seems like a big deal.** Andthere have been many theories propounded that variation in bitter sensitivity is due to adaptation to poisonous plants and such, but really no one knew, and that was just the most plausible of low hanging fruit. With these results from Africa, where there is more variation in the trait and genes, and good geographic coverage, that seems to be an implausible model to adhere to (one would think the hunter-gatherer Hadza would exhibit the most sensitivity, no?). Many of the traits and tendencies which we humans see as fundamental, essential, and of great import, many actually be side effects of powerful evolutionary forces hammering at the genetic-correlation matrices which define the hidden network of co-dependencies within the genome. So there, I said it. Life is an accident. Enjoy it.

Citation: Campbell, Michael C., et al. “Origin and Differential Selection of Allelic Variation at TAS2R16 Associated with Salicin Bitter Taste Sensitivity in Africa.” Molecular biology and evolution (2013): mst211.

* If it was closer to ~10,000 I think haplotype based tests would come back with something, but they do not.

** Some Epicureans might be accused of reducing the good to taste!

The post The color of life as a coincidence appeared first on Gene Expression.

October 27, 2013

Our forefathers were fierce & our foremothers were faithful

Filed under: Cuckoldry,Evolution — Razib Khan @ 5:51 pm

Credit: Chineeb

Credit: Chineeb

One of the peculiarities of human historical genetics is that people can simultaneously accept the existence of aggressive polygynous males such as Genghis Khan, and promiscuous females who give rise to the idea that 1 out of 10 children have an incorrect assigned paternity. I’ve mentioned the cuckoldry myth before. It is a common evolutionary myth; I’ve heard many biologists quote the 1 out of 10 number, and have often made myself obnoxious by pointing to the contradictory literature in this area. This isn’t to say that cuckoldry doesn’t exist. There’s certainly an evolutionary reason so many males engage in “mate guarding.” But you don’t need a high frequency of a trait to allow it to be selectively constrained. If it’s deleterious, then it will be driven down in frequency rather quickly. Whenever you get outbreaks of males who are sanguine about providing resources for offspring who are not their biological issue, natural selection will kick in and guarantee that this generous spirit toward their cheating partners and the delinquent cads does not persist.


The way that modern genetics adds value to this area is that one can compare Y chromosomal lineages to surnames. The logic is simple. If you have a constant frequency of misattributed paternity per generation over time the correlation between a surname and a Y chromosomal lineage will weaken. In addition, because the interlopers are likely to be different from each other you’ll have a pattern with (for example) ~50% of the male individuals of a given surname may carry one haplotype, while the other ~50% are distributed across hundreds of other haplotypes (one can imagine twists on the scenario, for example an early interloper might result in a secondary highly frequent haplotype).

So here’s an new study to bury this tired old urban myth, Low historical rates of cuckoldry in a Western European human population traced by Y-chromosome and genealogical data:

Overall, our results provide the first large-scale, unbiased genetic study of historical EPP rates in a human Western European population, with two independent estimation methods giving largely concordant results. Using the most direct estimation method, based on pairs of males that had a GCA in the last few centuries, we estimated the average EPP rate at 0.91% per generation (95% CI: lower bound 0.41% and upper bound 1.75%). This method took advantage of the hypervariability and mutability of Y-STR haplotypes, and the high phylogenetic resolution of the used Y-SNP haplogroups, which allowed paternally unrelated males to be easily recognized as such [35]. In addition, using a second method that was based on the population genetic traces of a past immigration event which happened at the end of the sixteenth century, we estimated the EPP rate at around 2%. Although this estimate had a broader CI (upper 95% confidence limit = 8%), the actual estimate was close to the first one.

Both of our methods therefore estimated a substantially lower historical EPP rate for Flanders than the 8–30% per generation suggested by previous studies based on behavioural data on rates of EPCs in Western Europe and given the absence of reliable contraceptive methods [30–33]….

It’s open access, so read the whole thing if you aren’t convinced.

The authors are clear that this is from a sample in Flanders, but I do not find that this population should be that exceptional across the Eurasian Ecumene. In other words, I’ll be willing to put down money that Indian gotras and Chinese patrlineal clans will exhibit the same pattern of cuckoldry frequency. Additionally, the authors note that this pattern of high paternity confidence is paired with male investment in offspring. That seems relatively typical among many members of our species, though the extent seems to vary by population and environmental condition.

The post Our forefathers were fierce & our foremothers were faithful appeared first on Gene Expression.

Our forefathers were fierce & our foremothers were faithful

Filed under: Cuckoldry,Evolution — Razib Khan @ 5:51 pm

Credit: Chineeb

Credit: Chineeb

One of the peculiarities of human historical genetics is that people can simultaneously accept the existence of aggressive polygynous males such as Genghis Khan, and promiscuous females who give rise to the idea that 1 out of 10 children have an incorrect assigned paternity. I’ve mentioned the cuckoldry myth before. It is a common evolutionary myth; I’ve heard many biologists quote the 1 out of 10 number, and have often made myself obnoxious by pointing to the contradictory literature in this area. This isn’t to say that cuckoldry doesn’t exist. There’s certainly an evolutionary reason so many males engage in “mate guarding.” But you don’t need a high frequency of a trait to allow it to be selectively constrained. If it’s deleterious, then it will be driven down in frequency rather quickly. Whenever you get outbreaks of males who are sanguine about providing resources for offspring who are not their biological issue, natural selection will kick in and guarantee that this generous spirit toward their cheating partners and the delinquent cads does not persist.


The way that modern genetics adds value to this area is that one can compare Y chromosomal lineages to surnames. The logic is simple. If you have a constant frequency of misattributed paternity per generation over time the correlation between a surname and a Y chromosomal lineage will weaken. In addition, because the interlopers are likely to be different from each other you’ll have a pattern with (for example) ~50% of the male individuals of a given surname may carry one haplotype, while the other ~50% are distributed across hundreds of other haplotypes (one can imagine twists on the scenario, for example an early interloper might result in a secondary highly frequent haplotype).

So here’s an new study to bury this tired old urban myth, Low historical rates of cuckoldry in a Western European human population traced by Y-chromosome and genealogical data:

Overall, our results provide the first large-scale, unbiased genetic study of historical EPP rates in a human Western European population, with two independent estimation methods giving largely concordant results. Using the most direct estimation method, based on pairs of males that had a GCA in the last few centuries, we estimated the average EPP rate at 0.91% per generation (95% CI: lower bound 0.41% and upper bound 1.75%). This method took advantage of the hypervariability and mutability of Y-STR haplotypes, and the high phylogenetic resolution of the used Y-SNP haplogroups, which allowed paternally unrelated males to be easily recognized as such [35]. In addition, using a second method that was based on the population genetic traces of a past immigration event which happened at the end of the sixteenth century, we estimated the EPP rate at around 2%. Although this estimate had a broader CI (upper 95% confidence limit = 8%), the actual estimate was close to the first one.

Both of our methods therefore estimated a substantially lower historical EPP rate for Flanders than the 8–30% per generation suggested by previous studies based on behavioural data on rates of EPCs in Western Europe and given the absence of reliable contraceptive methods [30–33]….

It’s open access, so read the whole thing if you aren’t convinced.

The authors are clear that this is from a sample in Flanders, but I do not find that this population should be that exceptional across the Eurasian Ecumene. In other words, I’ll be willing to put down money that Indian gotras and Chinese patrlineal clans will exhibit the same pattern of cuckoldry frequency. Additionally, the authors note that this pattern of high paternity confidence is paired with male investment in offspring. That seems relatively typical among many members of our species, though the extent seems to vary by population and environmental condition.

The post Our forefathers were fierce & our foremothers were faithful appeared first on Gene Expression.

November 11, 2012

Reflections on the evolution at ASHG 2012

As most readers know I was at ASHG 2012. I’m going to divide this post in half. First, the generalities of the meeting. And second, specific posters, etc.

Generalities:

- Life Technologies/Ion Torrent apparently hires d-bag bros to represent them at conferences. The poster people were fine, but the guys manning the Ion Torrent Bus were total jackasses if they thought it would be funny/amusing/etc. Human resources acumen is not always a reflection of technological chops, but I sure don’t expect organizational competence if they (HR) thought it was smart to hire guys who thought (the d-bags) it would be amusing to alienate a selection of conference goers at ASHG. Go Affy & Illumina!

- Speaking of sequencing, there were some young companies trying to pitch technologies which will solve the problem of lack of long reads. I’m hopeful, but after the Pacific Biosciences fiasco of the late 2000s, I don’t think there’s a point in putting hopes on any given firm.

- I walked the poster hall, read the titles, and at least skimmed all 3,000+ posters’ abstracts. No surprise that genomics was all over the place. But perhaps a moderate ...

September 17, 2012

The feathery Neandertal

Filed under: Evolution,Neandertal — Razib Khan @ 10:11 pm

Birds of a Feather: Neanderthal Exploitation of Raptors and Corvids:

The hypothesis that Neanderthals exploited birds for the use of their feathers or claws as personal ornaments in symbolic behaviour is revolutionary as it assigns unprecedented cognitive abilities to these hominins. This inference, however, is based on modest faunal samples and thus may not represent a regular or systematic behaviour. Here we address this issue by looking for evidence of such behaviour across a large temporal and geographical framework. Our analyses try to answer four main questions: 1) does a Neanderthal to raptor-corvid connection exist at a large scale, thus avoiding associations that might be regarded as local in space or time?; 2) did Middle (associated with Neanderthals) and Upper Palaeolithic (associated with modern humans) sites contain a greater range of these species than Late Pleistocene paleontological sites?; 3) is there a taphonomic association between Neanderthals and corvids-raptors at Middle Palaeolithic sites on Gibraltar, specifically Gorham’s, Vanguard and Ibex Caves? and; 4) was the extraction of wing feathers a local phenomenon exclusive to the Neanderthals at these sites or was it a geographically wider phenomenon?. We compiled a database of 1699 Pleistocene Palearctic sites based on fossil bird sites. We ...

September 16, 2012

What the substrate tells

Filed under: Evolution,Evolutionary Genetics,Genetics,Genomics — Razib Khan @ 7:26 pm

One of the weird things about genetics is that it encompasses both the abstract and the concrete. The formal and physical. You can talk to a geneticist who is mostly interested in details of molecular mechanisms, and is steeped in structural biology. For these people genes are specific and material things. In contrast there are other geneticists who focus more on genes as units of analysis. In this case genes are semantic labels for the mediators within an intersection of phenomena. Recall that genetics predates the knowledge of its concrete substrate by 50 years! By the 1920s Mendelian genetics had been fused with evolutionary biology to create a systematic framework in which we could understand the patterns of inheritance across the generations. In the 1950s the DNA revolution was upon us, but as W. D. Hamilton recalls this had only a minimal impact on the evolutionary genetic thinkers of the era. With the Lewontin and Hubby allozyme paper in the mid-1960s this sort of benign disciplinary evasion was no longer possible; the field of molecular evolution came into its own.*

Today with genomics these human-imposed artificialities are fading away. Consider the concept of genetic recombination. Originally an ...

September 12, 2012

An ontology of genetic diversity

Filed under: Evolution,Evolutionary Genetics — Razib Khan @ 11:23 pm

Implicit in the title The Origin Of Species is the question: why the plural? In other words, why isn’t there a singular apex species which dominates this planet? One can imagine an abstract system where natural selection slowly but gradually sifts through variation and designs a best-of-all-replicators. And yet on the contrary it seems that our planet has exhibited an overall tendency of going from lower to higher diversity. The age of stromatolites may be the last epoch when we had the best-of-all-replicators.


These sorts of deep questions about variation drive many of the research projects in evolutionary biology. Often one focuses on a narrow zone of interest. An organism for example which might serve as an illustrative model for more general processes. Or, a particular dynamic which interlocks with other processes to form a whole phenomenon. But on occasion you have to sit and ponder the whole shebang. Why genetic diversity? More specifically, why not more diversity of genetic diversity? The issue here is what is sometimes termed Lewontin’s paradox.

Consider two populations. One population goes through an extreme bottleneck, while the other maintains a large population over the generations. What would you presume in regards to ...

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