They’re not a gym

This week Planet Money had an episode about the economic angle of how gyms make money off you not using your services (transcript). The basics are easy enough to understand. If you buy a memership to a gym, and actually showed up every day, then you’d wear out the equipment. If you are a member and pay dues and don’t utilize the services then the costs are kept down. In fact it is obvious that gyms have many more members than they have capacity to service at any given time. The radio piece quotes one manager as saying that her Planet Fitness has 6,000 members, but a capacity of only 300 (and often it is rather empty). In fact the whole idea of gyms like Planet Fitness is to mix a portfolio of projecting the ideal of fitness while enabling your more slothful tendencies. People join for the cardio machines, but they stay for the pizza nights and socials.

In contrast another gym they profiled, Precision Athlete, serves an opposite clientele. While Planet Fitness charges $10 a month, Precision Athlete charges $500. Some of this has to be the fixed costs of a small operation with high level trainers, but it is also clear that their equipment gets used, a lot. This puts in stark relief the peculiarities of the normal gym, where there’s a power law distribution of utilization. About 10% of the members probably use 90% of the “gym time.”

Addendum: In some ways Planet Fitness perfectly encapsulates are our contemporary ethos among a certain set of middle class Americans. Since actually working out is “triggering,” they ban or discourage it.

Open Thread, 12/21/2014

165280Currently reading Mathematical Models of Social Evolution: A Guide for the Perplexed. Though there is a focus on the social aspect, this is really a book on evolutionary modeling more generally. And, it’s less daunting than many other works that I’ve run into. The authors also make a nice case for why analytical modeling is still important in an age of simulations.

Been very busy with stuff, trying to get as much work done as possible before Christmas. You know how it is.

Fear of race mixing in biodiversity


Abolishing diversity, one child at a time!

One of the often overlooked historical oddities in the development of the environmental movement in the United States was its close relationship to what we would today term white supremacy. Though many praise Teddy Roosevelt for his embrace of conservationism and evolutionary theory, he also adhered to racial beliefs of the day, which presumed the superiority of Anglo-Saxon people and couched it in Darwinian terms. Even less well known is the activism of race theorist Madison Grant, who was as much a conservationist as the intellectual for white supremacy that he is remembered for today (see Defending the Master Race: Conservation, Eugenics, and the Legacy of Madison Grant). In some ways the connection is reasonable, in that both are fundamentally conservative instincts. To preserve the environment and the racial order of the day. The connection was clear well into the 20th century, Charles Lindbergh was a prominent eugenicist, but later became an environmentalist, while Garrett Hardin, who originated the term “tragedy of the commons” opposed both high immigration levels and was skeptical of racial diversity.

Because of environmentalism’s association with the cultural Left in the United States these connections no longer apply so straightforwardly. In fact, the Sierra Club and other such organizations tend to be careful to not oppose immigration on environmental terms because of its racial implications. But, I’ve noticed that many people with an environmental orientation still use what strikes me as quite racialist language in the context of animals. I don’t think it is a problem.  Different moral and ethical standards apply to animals than humans. But I also think it is funny, as well as somewhat wrong-headed. This came to my attention because of an article in Nautilus, A Strange New Gene Pool of Animals Is Brewing in the Arctic. There’s a lot of talk about issues like hybrid zones, and pre- and postzygotic isolation (at least implicitly). But this section caught is just totally confused:

In September, in an inlet some 1,800 miles north of Fargo, North Dakota, where the North American landmass dissolves into the Arctic Ocean, the whales met in the middle. They spent two weeks together, and although not much happened before they turned around, the meeting was historic. The fossil record indicates the last time Pacific and Atlantic bowhead whales came into contact was at least 10,000 years ago.

While it’s tempting to imagine a strange new Arctic teeming with “grolar bears” and “narlugas,” hybridization comes at a cost. Arctic biodiversity will be reduced through gradual consolidation, taking with it a blend of genes that have evolved by natural selection over millennia. “There’s going to be a whole bunch of organisms containing genes that we’re going to lose,” Kelly says. Which genes, exactly, is unclear….

The problem here is that the terms are being mixed up. “Biodiversity” is often applied at the level of species or races, with a diversity index calculated from discrete numbers of population types. If you calculate a diversity index based on Swedish, Nigerians, and Chinese, you start out with three populations and look at their proportions. If you take them all and mix them so they are one population obviously the diversity is going to go down. But the genetic diversity is not going to down, because genes don’t “mix”. This is the blending theory of inheritance, and what Mendelian genetics overthrew with its understanding of discrete and particulate units of inheritance. The same confusion crops up with the idea of “disappearing blondes” and “disappearing redheads.” The phenotypes may change in frequency, but the understanding alleles, the genetic variants, remain. From a genetic perspective if you wanted to you could probably pull back out the original populations through selective breeding if you wanted to. Not only does the allelic diversity of the pooled populations not change, but the genotypic diversity increases, because of elevated heterozygosity. Finally, because of new potential combination genotypes the phenotypic diversity in totality also probably increases (example: Brazilians exhibit a wider range of skin color variation than Africans or Europeans).

Of course this is predicated on racial/subspecies level variation and divergence. If the populations are separated long enough then there will be barriers to easy gene flow. This is evident in the modern human-Neandertal event, where the X chromosome seems to have been purified of Neandertal alleles (this is a common tendency with hybridization events). But please note above that the people in the piece are concerned about populations of whales separated for 10,000 years. There are plenty of human populations separated for 10,000, and even 100,000 years. So this isn’t really a terrifying number of generations.

Most horse lineages are in heaven

wuwei_horseThe present is often only a faint echo of the past. That is why ancient DNA has totally revolutionized our understanding of the evolutionary past of many branches of the trees of life. The tips of the tree that we see around us today are all that remains of diverse and chaotic brambles which have been thoroughly pruned by chance and necessity. Utilizing present genetic variation researchers have been able to make some very interesting inferences, but you can’t infer that which you lack all evidence for. When it comes to the “megafauna” (i.e., anything bigger than a rat) the past two million years have been very trying, with cold alternating with short warm spells. This has no doubt resulted in thinning every so often as populations go extinct across vast swaths of Eurasia in the face of advancing glaciers. In time the range expands, as populations are re-founded by surviving lineages. But these oscillations drive down long term genetic diversity. In addition, the rise of modern humans has resulted in a great wipe out of whole lineages due to our predatory and avaricious behavior.

Domestic animals are arguably the most extreme case of this dynamic. A recent paper on the genomics of the domestic dog highlighted just how wrongheaded previous assumptions were. The standard thinking was that modern dogs are a derived form of wolf. In other words, dogs are simply a specialized subset of wolves. A domestic wolf as it were. Using whole genome sequencing it turns out that wolves that we see around us today are a sister lineage to dogs. Using wolves as the ancestral form of the dog may not therefore be quite as obvious as we’d thought. Of course it seems likely that the ancestors of the dogs were a wolf lineage of some sort, but we can’t assume that they resemble modern Holarctic wolves.

A similar, more complicated, dynamic is being illustrated by ancient DNA for our own lineage. And now a new paper in PNAS highlights similar dynamics to dogs in horses, Prehistoric genomes reveal the genetic foundation and cost of horse domestication. The authors sequenced two horses from the Taymyr regio
in Siberia with medium and high coverage. The horses were from 15 and 40 thousand years ago. That means they well predate domestication, which probably occurred in the 5 to 10 thousand year interval.

These results confirm that the wild Przewalski horses are not ancestral to the domestic lineages, and that rather they are simply the single wild lineage which persisted down to the modern period. The horses from Taymyr are more distantly related to modern horses than the Przewalski are, but intriguingly tests of admixture indicate that there was gene flow from lineages more closely related to the Taymyr individuals to the modern lineages. This gene flow has to be very close to the root of the origination of modern domestic horses since all breeds are equally represented in the signal of admixture. In short, the modern lineages of horse, wild and domestic, are but a fraction of the variation of the ancient populations.

They confirm this in a population genomic sense by looking at the enrichment for deleterious mutations. A major confound is that many lineages of horse are inbred, so they corrected for that. It turns out that all modern horses exhibit signs of being subject to a load due to accumulation of deleterious variants because of small population size (specifically, bottlenecks), as selection is less efficient at removing these mutations in small population because it is overwhelmed by random drift.

Finally, there is a lot in the paper on signals of selection around various causal alleles. It’s the typical laundry list. Many of the genes are associated with various pathologies and abnormalities, which shows you the cost of reshaping organisms and their behaviors which can occur due to domestication. Strong selection on major effect alleles often result in a cost due to antagonistic pleiotropy. If the selection benefit is high, then negative consequences be damned! Now, horses are notoriously dumb compared to donkeys, so I’d be curious of the cognitive/behavioral signals are found in humans another mammals, and how they may have changed over time.

Songs of Ancient Mesopotamia

I guess this is taking “world music” to the next level, going back to the ancient Mesopotamians. The artist is Stef Conner, and you can read about how this reconstruction was done over at Newsweek, where there is a Soundcloud preview of her full album, The Flood. I’d actually purchase it if I could find a full digital copy, but I don’t see any out there right now (the article says it will be on iTunes next month). You can buy a physical copy at her website, but the last time I purchased a C.D. was probably in the early 2000s, so that’s not happening. Anyway, do listen the preview on Soundcloud. The drinking song above is probably not representative.

Open Thread, 12/14/2014

513367In my books list below I tried to not focus too much on evolutionary genetics and genomics. But I still feel that I was a bit narrow. Over the years my interest in science has become rather narrow because of professional focus, but when I was younger I used to read quite a bit of popular physics, such as John Gribbin’s In Search of Schrodinger’s Cat. This sort of narrowing of focus is probably inevitable, but still pretty worrying for me. Probably the last popular physics book which I read front to back was Lee Smolin’s The Trouble With Physics, nearly 8 years ago.

In other news, I’m going to try and take a break from the internet for a few days around the New Year. More precisely, I’m going to try and take a vacation with my growing family somewhere sunny and hopefully warm. We’ll see how that works out. But please don’t be concerned if I don’t post on Twitter or have a blog update for a few days +/- January 1st of 2015.

The future of publishing (does it have a future?)

Founder of the Royal Society

Founder of the Royal Society

A few years ago Joe Pickrell wrote a very influential post, The first steps towards a modern system of scientific publication. Influential because it seems have to been a reason for the development of SciReader.The developers behind PubChase also took some lessons from it. Of course we know the role that “open access” and PLOS have played in shifting the ecosystem of the consumption and production of scientific knowledge (if you don’t know what I’m talking about, an Eisen will enlighten). And Haldane’s Sieve has been instrumental in bringing preprints to biology (in particular, evolutionary biology and genomics). Finally, events like the Bay Area Population Genomics meetings fill the gap between inter-personal relationships which are critical to scientific production, and massive conferences which have an enormous overhead in implementation for the organizers and non-trivial cost of attendance for the conference-goers.

a190So is there more to say? I think so. That’s why something I wrote with Laurie Goodman and David Mittleman just dropped in Genome Biology, Dragging scientific publishing into the 21st century. It’s open access, you can read it all, and I encourage you to do so. The question that framed my thought was a simple one: how can scientific publishing become more than simply a PDF delivery platform? Using the internet to delivery PDFs is like using a gasoline engine to draw a conventional carriage designed with horses in mind. And it’s feasible because scientific publishing is a profitable field dominated by a comfortable oligopoly which captures rents from the institutional structure of modern science. Remember, high impact journals are not high impact because they provide a better experience for scientists, who are the producers and consumers of the product. They’re high impact because they are impact, and as long as they are high impact people will need to publish in them to gain scientific credibility and prestige. Many researchers would label this a vicious circle. There’s a reason that they call Science, Nature, and Cell “glamor mags.” It’s about being seen. Ultimately, a matter of fashion, not substance.

What can not continue, will not continue. There isn’t a need to talk about creative destruction today as if it’s a novel concept, we’ve seen “smartphones” swallow the functionality of whole industries (e.g., watches and cameras), and it seems inevitable that ride-sharing will radically transform the nature of the taxi industry in the United States. I hold that the dominance and profitability of scientific publishing firms today is in large part a function of norms within modern science which enable and perpetuate a coordination problem. Once the norm starts shifting, it will change very fast, because many of the people who are publishing in the glamour magazines only do so begrudgingly because they feel they have to.

So is there a future for organizations such as the Nature Publishing Group? I think there is. The key is to take more to heart the idea that scientists are their customers. I don’t think the sector will be as awash in money in the future, so it needs to be leaner and more efficient. Publishers need to really start innovating so that scientists don’t just focus on something like “impact factor,” but also questions such as “is this journal going to package and present my results in a way that communicate well with my colleagues?” In other words, one needs to focus on the substance of what scientific publishing is supposed to be about, beyond obtaining a tenure track position, the furtherance of mutual understanding! Second, the journals can also invest in sharpening their style so that they always maintain some value-add over spare operations such as preprint servers. The ecosystem of scientific communication will remain vast, but it will evolve. Scientific publishers need to reposition themselves into a smaller but more specialized niche soon, because the market is likely to shift underneath their feet before they know it.

Razib’s 20 Holiday Books, 2014

41PHSZN6AELMy friend Randall Parker sent me an email where he suggested I should put up a post relating to books for the holidays. This makes sense, since I’m a book nerd. Over the years I’ve started to realize time is precious, and have offloaded a lot of the hard work of figuring out things to others who have domain specific specialties (e.g., I have friends who are into nutrition or exercise, and rely on them to give me appropriate pointers and direction). As implied by the title I’ll probably try and do this every year now. Also, I’ll avoid textbooks in the following list, and will attempt to be more diverse in my disciplinary focus than usual….

The Genetical Theory of Natural Selection. The variorum edition from 1958 with J. H. Bennett is what you want. R. A. Fisher is dense, but this isn’t a textbook. If you understand 10%, that’s a lot of understanding.

The Isles. Norman Davies’ magisterial narrative history of the British Isles.

In Gods We Trust. You won’t look at religion the same way after.

kwonhardcoverKnowledge and the Wealth of Nations. All about endogenous growth theory and its origins. More interesting than it sounds. As important as it sounds.

From Plato to NATO. This book has had many lesser copycats.

The Truth About Everything. A history of western philosophy. It has illustrations.

Prehistory of the Mind. Underrated hybrid of evolutionary psychology and paleoanthropology.

The Fall of Rome. A materialist take on the decline and fall of the Roman Empire. I’ve read this book three times.

The Number Sense. Like The Language Instinct for numeracy.

What_Hath_God_Wrought_-_The_Transformation_of_AmericaWhat Hath God Wrought. An anti-Jacksonian history of early America.

When Genius Failed. The template for “too big to fail.”

The Imitation Factor. Great short reader on behavioral ecology.

Mutants. Armand Leroi can write beautifully even about the grotesque.

Descartes’ Baby. The child is the father of the man.

downloadCalculus Made Easy. This is an old and chatty book. It’s not a text.

A Beautiful Math. Game theory and John Nash’s science.

Grand New Party. Not the Tea Party.

Genome. Compulsively readable.

The Human Web. One of William H. McNeill’s later books.

From Dawn to Decadence. Jacques Barzun’s magnum opus.

Readers are invited to offer their list of 20 in the comments. Randall has been challenged to put one up at his blog. Though I hope people will try and make the books at least somewhat accessible and relevant to a general intelligent audience (e.g., no books on Design Patterns or The Art of Computer Programming).

Haplogroups in the post-genomic era


Sometimes results precede an appropriate interpretative framework. I am beginning to think that that was the case with the explosion in analysis of Y and mtDNA phylogenies around the year 2000. This was a research program which took the direct male (Y) and female (mtDNA) lineages of humans, inferred a phylogenetic tree, and drew historical and demographic inferences. Part of the reason that this research program flourished is that these lineages are easy to model as a tree, because there isn’t recombination and sex on these lineages. The genealogy of these markers is actually a straightforward tree. And, in the case of mtDNA it is copious, so extraction was and is relatively easy.

The_Journey_of_Man_-_A_Genetic_OdysseyThis period not only resulted in an explosion of research, but also several seminal popularizations, in particular Spencer Wells’ Journey of Man, Bryan Sykes’ Seven Daughters of Eve, and Steve Olson’s Mapping Human History. The way this method worked involved taking the distributions and diversity of particular Y and mtDNA lineages present in the world today, and inferring back to the past routes of human expansions assuming that the tree-like model of genetic fission reflected a serial founder process of human migration. On the largest scale this work did confirm and extend previous research which implied a dominant signal “Out of Africa,” as well as broad geographic racial clusters. But on a finer scale the method likely led us astray, in large part because it seems that the model of human expansion and diversification was just too simple. Empirically, the rise of whole-genome analysis via SNP-chips in the middle years of the 2000s and today ancient DNA has revolutionized and clarified our understanding of the human past. Many of the inferences made from Y and mtDNA turn out to be wrong, even if the original results are broadly robust.

And that is a key point, because the original Y and mtDNA results are correct, and there has been an enormous body of research already in this area, they can be leveraged in understanding the human past when slotted into the framework sculpted on the edges by autosomal SNP data and ancient DNA. A serial founder model where the tree-like phylogeny was recapitulated spatially and temporally always had “anomalies.” In light of new results those anomalies may actually make much more sense. In particular, the common lineages which span Sub-Saharan Africa and western Eurasia (e.g., R1b above) are less perplexing in light of a model of periodic Eurasian back migration after the initial Out of Africa event. Admixture between long distinct lineages resolves issues relating to haplogroups with discordant geographic distributions. As long a the results are correct and methodologically sound, more data is better.

A form of eugenics people might not object to

Jalkh, Nadine, et al. "Genome-wide inbreeding estimation within Lebanese communities using SNP arrays." European Journal of Human Genetics (2014).

Jalkh, Nadine, et al. “Genome-wide inbreeding estimation within Lebanese communities using SNP arrays.” European Journal of Human Genetics (2014)., SH = Shia, MA = Maronite, GO = Greek Orthodox, SU = Sunni

The term “eugenics” has very negative connotations today. Nevertheless, in some ways society is moving in a direction which results in “eugenical” outcomes, insofar as allele frequencies and genotypes are skewed from what would otherwise be the case if natural processes operated without human volition.* Probably the most obvious case in modern medicine is the high rate of abortion of fetuses which are inferred to carry the genetic profile of an individual with Down Syndrome. In the future this sort of instance will be more general, as high quality prenatal genome sequencing along with progress toward understanding of the basis of inheritance of Mendelian diseases will avail parents of many choices. This will naturally result in a lot of discussion and debate about ethics and values.

But there is a less high-tech and ethically fraught form of eugenics, which is nevertheless culturally controversial. One of the overlooked aspects of the 2009 paper Reconstructing Indian population history is that it found that many Indian populations had an excess of homozygosity, likely due to long standing endogamous practices encouraged by the caste system. This, despite cultural towards which enforce exogamy between Hindus across much of India (in particular, the North). Within the abstract the authors suggest then that “there will be an excess of recessive diseases in India.” Recently I spoke to a young woman of Jat background whose parents are very traditional. I told her the issue relating to homozygosity, and communicated that to gain the benefits of masking genetic load one need not go genetically and culturally very far. An individual of the same ethnicity and religion would be sufficient, so long as they were not of the same caste (jati).**

This is not only a South Asian issue, as evident in a recent paper in The European Journal of Human Genetics, Genotyping of geographically diverse Druze trios reveals substructure and a recent bottleneck. Following up on earlier work it confirms some structure within the Lebanese Arab population. This should not be surprising, as the distribution of ethno-religious groups within Lebanon is not geographically arbitrary. Whether they live in and around Beruit today, the Maronite Christians for example often have a ancestral background from around Mount Lebanon. Additionally, it seems likely that the Muslim groups within Lebanon have been subject to a proportion of admixture with foreign populations over the past ~1,000 years. Nevertheless, it does seem that overall the Lebanese of all sects derive from a common ancestral group, and exhibit more affinities with each other on the whole than with non-Lebanese populations (the Druze have been subject to a stronger bottleneck than the other sects, explaining why they are distinct genetically).

In any case, the major finding in these results is that there are elvated levels of homozygosity in individuals who are Lebanese who are the product of “unrelated” papers. Additionally, individuals of Muslim background who are the product of first cousin marriages show evidence of being descended from common ancestors recently across multiple paths, suggesting a more ubiquitous practice of cousin marriage within this group. This mean that “first cousins” in the Muslim community often exhibit a relatedness greater than that of idealized first cousins because they are part of an extended inbred lineage.

ROHIn the figure to the right you can see the distribution of runs of homozygosity for different Lebanese sects comparing individuals who are the product of unrelated parents and those who are first cousin offspring (against a reference set of Europeans). You note that in the 0.5 to 1 Mb range of homozygosity tract length Europeans are highly enriched in comparison to Arab Lebanese. This is almost certainly due to the bottlenecks that Europeans have been subject to over the past ~50,000 years. Most Middle Eastern populations a priorishould have a higher long term effective population size assuming a serial founder effect, as well as the ecological context of the Ice Ages. But at 1-2 Mb you see that long term inbreeding shows up in all the Lebanese groups. Notice that the further you go up in tract length the more unequal the ratio between the first cousin offspring (FCO) and those who are the products of “unrelated individuals” (URO). This is what you expect. But even at greater than 16 Mb you see that Lebanese who are unrelated still have many more of these segments than Europeans.

Shakira, half-Lebanese

Shakira, half-Lebanese

The recommendation here then would be simple: Lebanese Arabs should marry individuals who are culturally aligned with them (e.g., Greek Orthodox Lebanese marrying Greek Orthodox Palestinians, Maronites with individuals from other Arab Christian groups in alignment with Rome, etc.), but have a different genetic history. This shouldn’t be controversial, but it can be (e.g., warning about the dangers of cousin marriage in terms of birth defects has resulted in accusations of Islamopobhia). Yet to some extent I believe that first cousin marriages will decline throughout the Middle East because of the demographic transition. If you don’t have many first cousins, then the potential for first cousin marriages declines greatly. But as I noted above in many Indian Hindu groups exogamy is normative, but there is still an issue with elevated homozygosity, so even without first cousin marriages there could be some gains in utility on the margin from outbreeding further than just near relatives.

Finally, aside from the straightforward genetic issues, there may be social benefits to the breakdown of clan structures which are the driving force behind population wide elevated homozygosity. Keeping it “all in the family” may not be conducive to broader national trust and cohesion.

* In a narrow sense eugenics should actually result in allele frequency changes, but in modern practice this is not always the case. E.g., the screening for individuals with Tay-Sachs carrier alleles changes the genotype frequency in the population so it is not in Hardy-Weinberg Equilibrium.

** Another thing that might be feasible to be to attempt to infer potential enrichment of homozygosity by looking at genotypes of pairs of potential mates within the same caste.

Population genomics’ end

Nice review, Advances and limits of using population genetics to understand local adaptation. In particular the focus here is on the insights one can derive from new genomic methods (e.g., think of SFS analysis). But they on a cautious, perhaps even down, note:

Many of the important questions in local adaptation being pursued with population genetics approaches begin – rather than end – with identifying loci responsible for variation. It is therefore important to realize that a full accounting of local adaptation at the molecular level goes beyond having high-quality data to analyze and statistical methods to identify causative genes. The crux of the challenge is that most ecologically important traits responsible for local adaptation are quantitative, and identifying all of the genes responsible for variation in quantitative traits is likely not possible. Even the cumulative explanatory power of individual loci identified in human genotype–phenotype association studies, which often involve tens of thousands of individuals, is generally only a small percentage of the phenotypic variation….

But I want to note that they cite a paper from 2012, and the work in capturing the fraction of phenotypic variation from genomic variation for height has gotten much better since then. So perhaps in that way that is a reason for optimism. Though, as they note, humans are in some ways a best case scenario since the sample sizes are enormous.

Cultural evolution exists

9780226520438A very fertile area of evolutionary science is the understanding and modeling of human culture. But it’s hard, which is why my aspiration is to be an evolutionary geneticist in a more classical sense. Not only is it hard, but people don’t appreciate it, because they think they understand “culture.” Robert Boyd and Peter Richerson’s The Origin and Evolution of Cultures is an excellent introduction (with Not by Genes Alone for a more popular audience), but Alex Mesoudi’s Cultural Evolution: How Darwinian Theory Can Explain Human Culture and Synthesize the Social Sciences is a more recent survey which I think is very worthwhile. 0226712842Complementary to the modelers, who draw from classical genetic frameworks (going back to Cultural Transmission and Evolution by Cavalli-Sforza and Feldman), are the cognitive anthropologists, represented by Dan Sperber and his colleagues (Explaining Culture: A Naturalistic Approach). Another way to look at this is that it is cultural anthropology without the Post-Modern Voodoo. In other words, it strives for disciplinary relevance through a fidelity to reality, rather than political and social impact.

This is all to highly recommend you read an excellent post on cultural evolution, Why Cultural Evolution Is Real (And What It Is). I don’t link to blogs much because it is usually more useful to read the paper, or the book, but in this case I think the writer really reduced the essentials of the field down to a manageable extent. Hopefully it will encourage readers to pursue their own avenues of inquiry.

I doubt the ancestors of the Khoisan were ever the most numerous human population on this planet


Adapted from Khoisan hunter-gatherers have been the largest population throughout most of modern-human demographic history

It is common for strong results from population genetics to be confused when it is translated for public consumption. The best example is that of “mtDNA Eve.” Despite the big warning label that mtDNA Eve is one of many female ancestors, the public has gained the impression that she is the female ancestor. A similar problem is cropping up with the Khoisan paper which reports that they went through a relatively mild bottleneck in comparison to other modern human populations. There’s a reason I titled the post The Least Bottlenecked Humans of All. It’s a defensible reduction of the results. In contrast many popular treatments are translating the results into the conclusion that “the Khoisan had the largest population of all human groups at some point in the past.” The reason I avoided this formulation is that plainly stated I doubt that at any time the Khoisan as we understand them, a genetically-culturally coherent group in southern Africa, had the largest population of all. Humans of various sorts have been common across Afro-Eurasia for over a million years. Is it plausible that ancestors of the Khoisan had the largest populations of all? Anne Gibbon’s somewhat cautiously stated piece in Science, Dwindling African tribe may have been most populous group on planet, relays the sentiment which I share:

Other researchers agree that it’s likely that the Khoisan descend from a large population. But because sampling of African genomes is still so spotty, not everyone is yet convinced that the Khoisan “was the largest population on Earth at some point,” says evolutionary geneticist Pontus Skoglund of Harvard University. “Many African populations are not included for comparison,” he says, so it is possible that some of the diversity seen in the Khoisan was inherited from recent interbreeding that cannot yet be detected.

Either way, the study makes it clear that even though the Khoisan are genetically diverse by today’s standards, even they carry just a fraction of our ancestors’ genetic legacy over the past 120,000 years. “It is quite staggering how much extraordinary genetic variation and ethnic diversity was present but is now lost,” Skoglund says. The Khoisan, retaining more than the rest of us, offer a rare window to look back in time at some of that diversity.

The biggest gap in the current study is that many extinct lineages were not included. Obviously they couldn’t be included, because they’re extinct, though at some point in the future ancient DNA or (more likely in the African context) reconstruction of ancient genomes from extant populations which have absorbed them, might allow for a better understanding of Pleistocene human population sizes. Population genomics is powerful, but it has limits. We need to be cautious about assuming that what we can illuminate with current methods is all that can be conceived in our natural philosophy.

Y chromosomes as a window into cultural evolution

Citation: The Y-chromosome tree bursts into leaf: 13,000 high-confidence SNPs covering the majority of known clades

Citation: The Y-chromosome tree bursts into leaf: 13,000 high-confidence SNPs covering the majority of known clades

There’s a new open access paper on human Y chromosome phylogenies, The Y-chromosome tree bursts into leaf: 13,000 high-confidence SNPs covering the majority of known clades, which is just as interesting because of a reference than the paper itself. The paper cited is “Batini, C, P Hallast, D Zadik, et al. submitted. Large
-scale recent expansion of European patrilineages shown by population resequencing. Nature Comms.” As I’ve mentioned earlier it was clear from several posters at ASHG that whole genome sequencing of larger sample sizes is making much more clear how recent and rapid the expansion of several of the common lineages across Eurasia was. In particular I’m thinking of R1a and R1b. We know this already from earlier work, but these latest results just confirm it. The truth is visually obviously. Notice in the figure above how R1b fans out in an instant from a single node. This reflects recent rapid population expansion.

The_Journey_of_Man_-_A_Genetic_OdysseyBut when The Journey of Man and The Seven Daughters of Eve were being written in the early 2000s it was assumed that Y and mtDNA phylogenies could tell us about human prehistory in totality. In hindsight that was probably asking for too much. But because they are sex specific these two lineages can inform us a great deal about social structures. In particular, rapid expansion of Y chromosomal lineages in the recent past may indicate the rise of patriarchy, as powerful males began to see polygyny as a viable strategy due to their monopolization of the resources of whole societies.

If I had to predict, I believe that female lineages tend to be characterized by isolation by distance dynamics. In contrast, male lineages are pruned periodically by rapid expansions and admixtures by groups which are able to marginalize or extermination competitors over vast swaths of territory. The Genghis Khan effect is just the most prominent of this sort of phenomenon. It is certain that in prehistory this occurred as well, as new technologies such as agricultural triggered social revolutions, and the rise of specialization and stratification among humans.

I don’t care about Strunk & White

sense_of_style_book_coverMaking my way through Steve Pinker’s The Sense of Style: The Thinking Person’s Guide to Writing in the 21st Century, one thing I really appreciate is his lucid deconstruction and refutation of the tyranny of The Elements of Style, also known as “Strunk & White”. It’s not that I haven’t run into this line of thinking before from linguists. But it’s interesting to note that Pinker points out that Strunk & White violate the very maxims they promote in a sentence asserting the importance of particular grammatical constructions (e.g., using passive voice to exhort active voice). From what I can gather part of the issue is that the authors themselves were not linguistic scholars, so lacked the expertise to pass judgments on issues which t hey were only vaguely aware of. Nevertheless, they’ve attained a certain oracular status among many Americans. I know this because over the years of my blogging many readers have exhorted me to read Strunk & White to remedy my deficiencies as a prose stylist. At some point in the mid-2000s I tried, but found it all rather tedious. This makes sense, as I always detested the grammar section of English class. My teachers were sometimes perplexed, because I obviously read and wrote with a high aptitude.

Here’s a recent comment that I trashed:

Dear Mr Khan:

I offer to you this friendly advice: Proofread your work much more slowly and carefully than you do now. You are doubtless an intelligent man, but your English (clearly not your mother tongue, as one would expect of a South Asian) needs a lot more polishing than you seem to think.

Cases in point:
“Lines on a map does [sic] not an equivalency make.”
“…in the states of Punjab, West Bengali [sic]…”
“…the fertility in the BIMARU states is in the range as [sic] Pakistan…”
“…Guanyin is pervasive across Chinese the breadth of civilization [sic]…”
“This does not mean that modeling them in [sic] intractable…”
“…it manifests in more conventional class, sect, and ethnic lines [sic]…”
“…and it is disappears [sic] without the foundational support.”
“…even though though [sic] it is embedded in their customs.”

Not to be too cruel, but your writing suffers a bit from the all-too-Indian vice of excessive wordiness: Why use fifteen words where twenty will serve as well? Betake thyself unto a used book store in the Amazon; there seek and find Strunk and White’s Elements of Style (it’s time someone clued you in).

Warmest regards,

Mr Chips

The comment is a little on the patronizing side, but it’s pretty typical. Perhaps ~10 years ago I’d be more likely to take this sort of advice in stride, but at this point I think I’m doing OK. These comments are invariably from anonymous people leaving remarks on the internet.

Open Thread, 12/7/2014

BAPG XI, Credit, Graham Coop

BAPG XI, Credit, Graham Coop

Spent much of yesterday at BAPG XI. Pops to the Coop lab for putting it on. And speaking of which, want to give a special shout out to Gideon Bradburd, who presented his “SpaceMix” method. The preprint will be out soon, but I think the best way to understand it is what TreeMix is to standard phylogenetic trees, SpaceMix is to standard PCA. SpaceMix attempts to fit pulse admixture events against a landscape defined by geographic isolation by distance dynamics.

Props to Dmitri Petrov for starting the BAPG meetings over four years ago (along with sponsors, such as and CPB at Davis). From what I’m to understand the various regional meetings took their inspiration from BAPG, so it’s kind of a big deal. Though no doubt BAPG benefits from the high density of research universities from UCSC to UDC south to north, with Stanford and UCB anchoring in the middle, all in a small commutable area.

Note: In case readers aren’t clear, “open thread” means you can talk about/ask about anything (within reason).

Human is as human does

Credit: Luke Jostins

Credit: Luke Jostins

Human lineages as a whole have been tending toward increased cranial capacity over the past 2 million years, including the one that led to modern people. That is the finding of Luke Jostins several years back when he crunched the paleoanthropological data. This is one major knock at our specialness as humans, since it seems our cousins were progressing through the same stages of development as our own ancestors, before they were swept away by and large. A new paper in Nature reports that H. erectus engaged in more cleverness than we had expected, Homo erectus at Trinil in Java used shells for tool production and engraving. John Hawks has already commented on it so I won’t offer my two cents, as they aren’t worth much. But, it does suggest that we’ve underestimated “early humans.” John points out that many ancient finds might be reinterpreted with a different set of expectations.

On a related note, a new paper attempted to find evidence for classic selective sweeps in our lineage comparison to the Neandertal and Denisovan populations, something feasible because of the existence of high quality ancient genomes. Let me quote from the abstract:

… We tested sites at which humans are fixed for the derived (i.e., nonchimpanzee allele) whereas the Neanderthal and Denisovan genomes are homozygous for the ancestral allele. We observe only weak differences in statistics indicative of selection between functional categories. When we compare patterns of scaled diversity or use our ABC approach, we fail to find a significant difference in signals of classic selective sweeps between regions surrounding nonsynonymous and synonymous changes, but we detect a slight enrichment for reduced scaled diversity around splice site changes. We also present a list of candidate sites that show high probability of having undergone a classic sweep in the modern human lineage since the split from Neanderthals and Denisovans.

As the heirs of the snottily termed “anatomically modern” humans it is hard for us to not think that we came and conquered due to some glittering genetic mutation. The lack of pervasive classic sweeps since the divergence of “us from them” confirms that evolution didn’t go into magical overdrive in our lineage. We are not “more derived” on the Great Chain of Being with chimpanzees as a reference, but simply different. The laundry list of candidate sites will be interesting, but must always be interpreted cautiously. These sorts of results dovetail nicely with the reality that the behavioral chasm between “archaic” and anatomically modern humans until about ~50,000 years ago wasn’t that large at all. Though changes in the fossil and archaeological record can seem punctuated and is discontinuous, I wouldn’t bet against the possibility that genomics points to a dynamic where change between the lineages was driven by gradual evolution via selection on standing variation.

Finally, there’s a recent paper on the nasal anatomy of Neandertals which made some media headlines recently. The most sensational conclusion drawn from nasal architecture is that Neandertals were a separate species from us. As I don’t know much about anatomy, and I don’t care much about species status, this isn’t something I’ll explore beyond just reporting that. But, another aspect is the fact that it seems the morphology of Neandertals has often been compared to modern humans, and judged by modern human standards. It seems entirely likely that Neandertals had different adaptations and an alternative morphological trajectory from our own lineage. Though I don’t think they were as different as some scholars would like to think, we need to be cautious about turning them into a version of ourselves, or at least our Out of Africa selves. The hominin lineage contains multitudes, and we are but one.

The least bottlenecked humans of all

inferred effective population size over time

inferred effective population size over time

600px-Namibian_Bushmen_GirlsThe Khoisan are not the oldest people on the face of this earth, they simply have been the lest impinged by population crashes over the past ~200,000 years. This is not a shocking assertion, but it is supported with greater robustness by a new paper in Nature Communications, Khoisan hunter-gatherers have been the largest population throughout most of modern-human demographic history. Unfortunately the standard tropes that come to the fore whenever the Khoisan are the objects of genetic scrutiny have emerged fully formed. But the worst problem is that one of the authors seems to be contributing to the misleading perceptions. Here are the press release

“Khoisan hunter/gatherers in Southern Africa have always perceived themselves as the oldest people,” said Prof Schuster, an NTU scientist at the Singapore Centre on Environmental Life Sciences Engineering (SCELSE) and a former Penn State University professor.

“Our study proves that they truly belong to one of mankind’s most ancient lineages, and these high quality genome sequences obtained from the tribesmen will help us better understand human population history, especially the understudied branch of mankind such as the Khoisan.

Though I think I know what Dr. Schuster is saying, I also believe that it is important remember that both you and I are also descendants of one of mankind’s most “ancient lineages.” We’re all equally descended from ancient lineages, because we’re all descended from ancient proto-humans. The Khoisan are not fossils preserved from a bygone age, they’re a modern people who descend from those same archaic Africans that we descend from. The phylogenetic distinction of the Khoisan is that their ancestors seem to have diverged from other human beings rather early on. In fact, it is defensible to suggest that they departed from the family tree of other humans at the first fork in the road, with the ancestors of Nilotic and Bantu Africans separating from the ancestors of Eurasians rather later on (also, it seems that the lineage that led up to the Khoisan after their divergence from the proto-non-Africans/agriculturalist Africans diversified and are represented by the Hadza and Pygmies, in addition to the Khoisan).

So what is the figure at the top of this post telling us? It’s showing you the effective population in the past by using the variation within the genome of individuals. In any given generation only a fraction of the population reproduces, and among the fraction which reproduces there is variation in output (e.g., some have one offspring live to adulthood, others have four). This increases random genetic drift by reducing population size and increasing variance of the sampling outcome. Drift tends to remove variation as some alleles fix and others go extinct due to the fluctuations that it produces. What happens when populations go through a bottleneck is that a lot of the variation that was present in a population can be squeezed out of it, and it takes a long time for that variation to replenish itself through mutation alone. This is why the long term effective population of the Khoisan is so much larger than the Han Chinese, despite there being four orders of magnitude more Han Chinese in the world today than Khoisan. As you can see in the figure the Khoisan were not subject to nearly as strong a bottleneck in the past. The small long term effective population size of non-Africans, reflected in their relative genetic homogeneity in comparison to Africans, is due to the bottlenecks that occurred as the ancestors of non-Africans were migrating across the world. About ~30,000 years ago the effective population of the Khoisan was ~10,000, while that of the ancestors of Eurasians was ~1,000. Both groups were going through a bottleneck, but the proto-Eurasians were experiencing a much stronger one. The ancestors of agriculturalist Africans, the vast majority of Sub-Saharan Africans today, were also experiencing a bottleneck, but a milder one.

One major caveat with the time scale above is that it is sensitive to the mutational rate. The figure above uses ~2.5-8 value, while some estimates are close to ~1.25-8. Though the authors brush this problem off, arguing that paleoclimate models can fit both parameter values in terms of explanations for the demographic patterns, from what I know the paleonathropology more neatly fits the dates from the higher mutation rate. With the lower value the divergence between Khoisan and non-Khoisan is almost contemporaneous with the first fossil evidence of anatomically modern H. sapiens in Africa. But it is true that in either scenario non-Africans are subject to a strong bottleneck, long evident from the genetic data, and that the Khoisan have relatively large long term effective populations.

To put my cards on the table I do not accept the paleoclimatic explanation for why the Khoisan in particular had a large population while the ancestors of agriculturalist Africans and non-Africans did not. First, in Science Pontus Skoglund observes that “Many African populations are not included for comparison….” Yes. He also points out that the Khoisan could have gotten their diversity from interbreeding, something that has support in the literature. That being said, that’s not my biggest problem with the explanatory model outlined in the paper. In the blog post yesterday I reviewed results which imply that the Igbo of Nigeria have some admixture from a hunter-gatherer group genetically closer to the Khoisan than to to the Pygmies. This is peculiar because geographically the Igbo are far closer to the Pygmy populations. So what’s going on here?

Human populations move. Paleoclimate models are often predicated on the idea that populations were geographically fixed for eons. But there’s a fair amount of circumstantial evidence that Khoisan-like people were extant as far north as Ethiopia in the recent past. The major element of the ancestry of the Bantu speaking majority in South Africa was resident in Cameroon ~3,000 years ago. A hybrid Eurasian-Sub-Saharan African populations in the highlands of Ethiopia only emerged in the past 3,000 years. And so on. We don’t know that the ancestors of agriculturalist Africans were resident in the northern fringe of Sub-Saharan African ~100,000 years ago. We don’t if the ancestors of the modern Khoisan have such deep time history in southern Africa.

In light of evidence of Eurasian back-migration into Sub-Saharan Africa in deep antiquity it is quite reasonable to suggest that the intermediate population dynamics of the agricultural Sub-Saharan populations in this paper is simply due to the fact that they are a hybrid between long resident hunter-gatherer populations with some affinity with Khoisan and Pygmies, and descendants of the original Out of Africa migration. The blogger Dienekes Pontikos has been proposing a flavor of this model for a long time. Initially I thought it was a cranky fixation of his which had little basis in reality, but over the years I’ve come around to the position that it’s a plausible theory. At least as plausible as the myriad attempts to reconcile genetic patterns with paleoclimate models.

Citation: Khoisan hunter-gatherers have been the largest population throughout most of modern-human demographic history.

Science practiced as if it’s 1995

Screenshot 2014-12-04 02.30.05Today we’ve gone much further in terms of utilizing the internet then just sending emails. In fact academics are so overwhelmed by emails that it’s not often the best way to reach them, because the noise level in their inbox is so overwhelming. That’s why I was confused a bit disturbed by this sentence from the supplements of the paper I blogged below, “All source code for analyses is available on correspondence with authors.” The sentence is on page 7 if you care. Two things. First, with services like GitHub you should be put together a repository of all your code and data pretty easily. Likely it would save time in terms of not having to respond to disparate emails (and finding the files, etc.). Yes, the one time investment to comment the code and clean it up a bit might be non-trivial, but you only have to do it once. Second, this is a Nature paper. In fact, it was a thorough Nature paper. Why this specific oversight? Perhaps the authors didn’t think it mattered.

It matters. Not making distribution of code in public repositories upon publication habitual and reflexive slows down science, and keeps it bogged down in the past. In fact, I’d argue that for non-computational papers there should be ways of uploading unfiltered data too.

Back to Africa and the Bantu Explosion

Adapted from The African Genome Variation Project shapes medical genetics in Africa

Adapted from The African Genome Variation Project shapes medical genetics in Africa

Ten years ago the story of how modern humans expanded across the face of the world ago would have been a relatively simple one. The story generally recounted for popular consumption was most forcefully articulated in Richard Klein’s The Dawn of Human Culture. Around ~50 thousand years ago a small group of Africans resident in the east of the continent changed in some sense. The mostly likely cause for this change was presumably a mutation which conferred upon this group the ability to engage in fully fluent language, and therefore engendered cultural flexibility previously unseen in our lineage.* The rest, as they say, was prehistory. These Africans expanded across the whole Afro-Eurasian zone, replacing archaic hominins, such as the Neandertals, in totality.

That was in some important aspects wrong. First, the expanding African population mixed with other groups, including likely within Africa. Though less than ten percent of the ancestry outside of Africa, some of it was functionally very important. Second, the demographic expansion ~50-100 thousand years ago more accurately captures the dynamics of non-Africans, than Africans, who were characterized by much larger ancestral populations when the 100 to 1,000 ancestors of modern non-Africans left the continent. Third, modern populations seem to be to a large extent the product of fusions across the Pleistocene branches of humanity, brought together during the Holocene by rapid demographic expansion triggered by cultural innovations such as agriculture. Finally, these dynamics were not limited to populations outside of Africa.

Human_migration_out_of_AfricaFor far too long Africa was conceived of as a blackbox in genetic terms, eternally useful as an outgroup, basal to the rest of humanity. Yes, there were platitudes about how most human genetic diversity was localized in African populations due to the bottleneck during the Out of Africa event, but beyond that maps of human migration implicitly left one the impression that after the ancestors of modern humans left little occurred within Africa. Yes, everyone could agree that there were back migrations along the periphery of the continent, the great swath north of the Sahara around to the Horn of Africa, but Sub-Saharan Africa was neglected in these treatments. No more.

A new paper in Nature is a major step forward in bringing together a lot of the elements of new findings we’ve seen in other work. The African Genome Variation Project shapes medical genetics in Africa. The medical genetics part is important downstream. It doesn’t loom large in the paper itself. I recommend you check out the supplementary info and supplementary data, it has a lot of the meat of the paper. For me the big topline result is in the figure above, where you see the collection of results suggestiong admixture into African populations from Eurasia and also between agriculturalists and hunter-gatherers.

On the Eurasian admixture, the authors confirm what we always knew about Ethiopia and the Horn of Africa, that it was the scene of a relatively recent admixture event between an Afro-Asiatic people, and a group related to modern Nilotic peoples. What is more interesting is that they observed Eurasian admixture within Yoruba people. This admixture has been suggested by others, as the Yoruba have traces of Neandertal ancestry. This group dates the admixture back to nearly 10,000 years ago, so it as likely associated with goings on that were trans-Saharan. If that is the case these were almost certain quasi-Eurasian hunter-gatherers, and their ancestry might have been diminished in current North African groups subject to waves of farmers issuing from the east during the Neolithic. But there is also admixture with Eurasians further east in Uganda among Bantu groups. Reading the details of the supplements there is a chance that this was mediated through admixture of Eurasians with hunter-gatherer populations, and then the absorbtion of this hybrid group into the expanding wave of Bantu farmers. Speaking of which, this issue is solved and resolved, it is clear that the Bantu expansion was a major demographic transformation of eastern and southern Africa. The genes speak loudly and clearly. Additionally, the Sub-Saharan African admixture of Ethiopians is clearly more closely related to that of the Nilotic people than the Bantus. The paper didn’t tease out the details archaeological and historically, but if you look at the dates all this was going on in eastern Africa during the rise and fall of ancient Egypt. In other words, within historical memory the whole demographic landscape of Africa was reshaped. Contrary to the idea that Africa was static, there are indications here of massive transformations.

Though the Eurasian admixture story among these populations is fascinating, there is also nuance in the input of hunter-gatherer ancestry within West African and Bantu populations. First, I suspect that these estimates are low bounds, because they don’t have exact reference populations. Some of the hunter-gatherers mixed into the Igbo and Bantu groups may have been more like agriculturalists than the extant hunter-gatherer groups within Africa. One of the peculiarities of the genetics is that it looks as if the hunter-gatherers of Sub-Saharan Africa, the Khoisan in the south and the Pygmies in the center, share more recent common ancestors than they do with the agriculturalists. This may simply be due to the fact that the agriculturalists went through rapid expansion, and this whole constellation of peoples derive from a group which was an outgroup to extant hunter-gatherers. The only complicating issue is that of Eurasian admixture; it seems likely that for very old admixture events we’re seeing underestimates, or they aren’t picked up. In other words, the “reference” Sub-Saharan Africans themselves are compounds of people who remained within Africa, and Out of Africa. The eastern Pygmies may be the only people in the world without much Out of Africa input (recall that the Khoisan have some level of Out of Africa input mediated by East African pastoralists).

A second interesting aspect of the paper is about selection within African populations. As I said above you can find much in the supplements, so I won’t review that laundry list. But, it is interesting that many of the signatures disappeared once Eurasian ancestry was “masked.” That is, within the genomes of individuals you have a mosaic of ancestries, and high genetic distances between populations at particular loci turn out often to be simply due to historical demography. Once you remove this confound you pick out signals of selection which might be due to local adaptation (though some of the Eurasian alleles might also have been subject to selection, so in some ways the filtering might be too stringent). But the masking of Eurasian ancestry also highlighted something important: the genetic variation across African populations once you remove Eurasian ancestry is not that high. This is curious in light of the truism that most genetic variation in humans is found within Africa, but as Nick Patterson pointed out to me years ago: this applies to variation within populations, not across them. Since most variation is not partitioned across populations that explains why Africans can be so genetic varied despite exhibiting not too high between population variation. After masking Eurasian ancestry the mean pairwise Fst was ~0.015. To give a sense of perspective, the Fst between Northern Italians and Lithuanians is 0.01. The Fst between the Ethiopian African ancestry (so Eurasian segments are masked) and other African populations is still 0.027, on average (the distance between Lithuanians and Southern Italians is 0.015). This reinforces the fact that the African ancestors of Ethiopians are somewhat atypical (further confirmed by the relative inaccuracy of imputation from public data sets).

The result that the Igbo seem to have ancestry from a hunter-gatherer group genetically closer to the Khoisan than the Mbuti Pygmies makes a lot more sense when you accept that much of the genetic population structure within African disappeared with the rise of agriculturalist groups which demographically swamped them. It seems plausible that the preexistent variation can be reconstructed to some extent by analyzing patterns within agriculturalists, as they likely absorbed hunter-gatherer groups over time. Within the paper the authors suggest that whole genome sequencing of more populations should be high on the priority list, and I agree. The future is going to e interesting.

Citation: The African Genome Variation Project shapes medical genetics in Africa.

* Klein appealed to some of Stephen Jay Gould’s more macromutationist/saltationist speculations.

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