Recently I was at the supermarket, getting some shrimp at the fish counter. The clerk noticed I had some habanero peppers, and he asked if I’d checked out the ghost peppers. My interest was piqued, but I had no idea what he was talking about. He told me to look at again.
They were Frieda’s ghost pepper chilis. My first question: are these really ghost peppers? Comparing to the standard orange habaneros you’d get at the supermarket I’d stay these peppers were about three times as spicy. So probably real ghost peppers then. But here’s the great thing: there was a tangy astringency which made them much less bland that mass produced orange habaneros. The pepper was legitimately delicious.
The main caution I’d give is that what goes in easily may not come out with grace and comfort.
— Pontus Skoglund (@pontus_skoglund) July 26, 2016
A new paper on on archaic admixture in Andaman Islanders has come out. It’s in Nature Genetics, Genomic analysis of Andamanese provides insights into ancient human migration into Asia and adaptation. If you don’t have access, just read the supplements, they have the good stuff as usual.
The results here range from intriguing to clarifying. But I want to engage in a little post-publication criticism: I think the fact that the authors highlighted model-based admixture results is a disservice to the rest of their results. Daniel Falush will be out with a paper on best practices (or not) in relation to the utilization of model-based admixture soon enough, but the plot that is part of figure 1 is really in my opinion misleading in the broader context of their results. The JAR and ONG are Andamanese samples, while ILA and BIR are isolated tribal group in south to central India. These four groups are not very numerous, and, they are characterized by very small effective populations. In other words, the model-based admixture framework immediately infers these to be extremely close to idealized reference populations because they are so drifted. One can call this the “Kalash effect”, as the original STRUCTURE based analyses of the middle 2000s would routinely yield a “Kalash cluster.”
One consequence of the mix of populations that they have in this reference panel is some of the results are difficult to interpret. The Andamanese and Irula (a South Indian tribe) become nearly fixed for a major cluster respectively, and in the text the authors are interested enough to observe that these Andaman samples don’t show admixture because of this result. This is not necessarily true though. If these are the ‘purest’ of the samples that remain, then they will serve as the ‘pure’ reference. That doesn’t mean there hasn’t been recent gene flow into them. The same with the Irula. Because these two are highly drifted populations they are quite often going to arrive at these very high fractions in some particular K cluster.
Because of the large sample these rather obscure tribal groups, you have the result that Rajputs seem to share more ancestry with Chinese than the Bengalis (RAJ and BEN). This is in contradiction to everything we know. In reality, the Rajput samples have very little recent East Asian admixture, while the Bengalis are about ~10% East Asian on the time scale of the past one to two thousand years. I can offer a hypothesis for why the clustering algorithm converged on this result, but I’ll just suggest you read Lucy van Dorp’s Evidence for a Common Origin of Blacksmiths and Cultivators in the Ethiopian Ari within the Last 4500 Years: Lessons for Clustering-Based Inference.
But what of the results overall? The intriguing aspect is the evidence that there is archaic admixture into the Andamanese, Australian indigenous peoples, and to some extent Indians (via their “Ancestral South Indian”) form a mystery hominin. The time scale they infer is on the order of divergence at least several hundred thousand year ago in the past. Presumably these results became clear because they had good high quality whole genome sequences (~10x and more coverage) with millions of SNPs to work with (and well ascertained), as opposed to the few hundred thousand in earlier work.
One of the models the authors were testing is the idea that there were two waves out of Africa, with South Asian and Oceanian peoples in particular exhibiting hallmarks of admixture from an earlier migration. There are smattering of population genomics papers which support this proposition, but I will tell you most researchers who work with these data are skeptical. There were some methodological issues with some earlier findings, and limitations on the sample sizes and quality (whole genome sequence), or marker set (the SNP studies).
By and large these results support the idea of one migration. If one assumes Africans are one branch of the modern human race, all non-Africans are approximately equally related to Africans, because there is one major bifurcation between Africans and non-Africans. In contrast, the two migration thesis often posits that there was an earlier migration, that was later overwhelmed by a later migration. In that case, you might have scenarios where the second population shared more genetic drift with modern Africans because of a later separation. Or, there could be a scenario where the South Eurasian substrate shared more drift with Africans, shifting the affinities of the Andaman Islanders in that direction.
In any case, they did not see evidence of any of this. Rather, Andamanese share no more ancestry with Africans than you’d expect of generic non-Africans…sort of. As it turns out when using an outgroup with only ancestral allelic states as inferred from using the chimpanzee reference Andamanese actually have fewer African alleles that Europeans and East Asians. The same is true of indigenous Australians, though the authors did not tackle this issue in detail. Of course this could be Neanderthal and Denisovan ancestry. But it isn’t. We have the ancient genomes of these populations, and the Andamanese seem typical for a East Eurasian population.
They make the inference of a few percent admixture from a population which diverged from modern humans on the order of ~300,000 years ago through a lot of testing of explicit models. Again, read the supplements. Unfortunately they don’t have the genome of the mysterious ghost population, so they can’t make definitive conclusions.
The fact that East Asians and Europeans both lack this ancestral element is peculiar, because all the evidence puts the Andamanese on the same branch as the East Asians. So you can have models whereby a composite East Asian/European population engages in back migration to Africa. Or, perhaps Ancient North Eurasians, who contributed to both Europeans and East Asians? In any case, of the models they tested it does seem that archaic admixture from a ghost population is the most likely, but that does not mean that that is the correct answer. Obviously they did not exhaust the possibilities of models and scenarios. For several years now people have been seeing strange things in the data from Australasian and isolated Southeast Eurasian groups. There’s a story here, we just don’t know much of the outlines, we’re just grasping. Both Mait Metspalu and Luca Pagani have papers in the works….
What about the clarifying? It strikes me that they used some stringent selection tests (e.g., focusing on hard sweeps?), and still hit pay-dirt on positive results for the Andamanese. Both selection tests, and polygenic scores, suggest there’s a bias toward being small in these two groups. I’m curious if the Sentinelese would be the same. The thesis here is that islands result in dwarfism. But I wonder if the selection here is very recent indeed. The authors note that some of the sweeps are not complete. In the last few hundred years there has been a massive demographic collapse of the Andaman Islanders, and only the Sentinelese preserve their lifestyle in a pristine fashion.
This relates to the question in regards to phylogenetics. The authors indicate the the phenotype of these Austro-Melanesian populations is not necessarily due to shared descent from Africans, but adaptation to local circumstances. I don’t think they’ve proven it as such, but they’ve definitely shown that there’s a lot of selection occur in their new habitats. Curiously they don’t detect that there’s been adaptive introgression from the archaic, but I’m not sure if they have the power to detect that sort of thing anyhow. But, it might indicate that the admixture occurred further north?
Finally, I should mention that the Andamanese genomes are now online.
One of Taleb’s hobby-horses in Fooled by Randomness is that the book The Millionaire Next Door was based on faulty inferences, and misleading many people. This was back in the heady days before the property bust, so many middle class individuals were investing in the “can’t miss” and eternally appreciating real estate bubble. In any case, The Millionaire Next Door had a simple strategy: observe the characteristics of millionaires, and so gain insight into what might make you a millionaire. The problem pointed out by Taleb is that the sample set is highly biased; you see all the millionaires with the characteristics of interest, but not the more numerous non-millionaires. One of the major variables, perhaps the major variable, in becoming a millionaire is what we’d all luck. There may be many necessary conditions, but luck is one we can’t cultivate. One might increase the chance that one is a millionaire…but The Millionaire Next Door misled many people into thinking that just by doing what millionaires had done any person could become on themselves.
So consider this from The Wall Street Journal, Best-Paid CEOs Run Some of Worst-Performing Companies:
The analysis, from corporate-governance research firm MSCI, examined the pay of some 800 CEOs at 429 large and midsize U.S. companies during the decade ending in 2014, and also looked at the total shareholder return of the companies during the same period.
MSCI found that $100 invested in the 20% of companies with the highest-paid CEOs would have grown to $265 over 10 years. The same amount invested in the companies with the lowest-paid CEOs would have grown to $367. The report is expected to be released as early as Monday.
The original report is also online. There are other studies which support this conclusion. The correlation between CEO pay and firm performance is relatively weak to non-existent.
Does this mean CEOs are worthless? Not necessarily. There’s some range constriction going on. The average person on the street wouldn’t have the minimum necessary skills and aptitudes to be a CEO of a large firm. But the variation among CEOs in pay might be due to a whole different set of skills than the characteristics which constrain the set of individuals who might become CEOs. For example, the average CEO might be far more conscientious and intelligent than the average person. But, it may be that the less conscientious CEOs actually get paid more. And then of course there is luck in falling into a good board situation, which anchors you to a particular set point in terms of future salary expectations. And the outcome of a firm may have only the most marginal relationship to the CEO performance (consider how we attribute macroeconomic performance to American presidents, when they probably have only marginal influence on the business cycle).
And once you make it into a particular class, social connections can help prevent you from sliding back down. To a great extent the same of Yahoo to Verizon is a failure for Marissa Mayer. But she’ll be fine, and obtain another CEO position if she so chooses. If she had turned around Yahoo, always a long shot, she would have been dubbed a genius. As it is, she’ll get a golden parachute and look to future opportunities.
What’s the take-home less? Social mobility is a thing in the United States. But the reality is that what you really need to do is somehow make it into a particular segment of the class structure. Once you are there, the reality is that your own competence probably matters less than chance and necessity. Even if you don’t become a superstar, the nature of the American class structure will probably make it so you’ll be shielded from the bracing consequences of creative destruction.
When people ask me what they should read to understand genetics, I don’t really know what to say. But An Introduction to Genetic Analysis is what I reviewed for my genetics qualifying exam. If you want to understand what PCA is, the Wikipedia page should suffice, especially if you have taken linear algebra. Perhaps ironically for someone interested in evolution and genetics I’ve read only a few textbooks devoted to these topics. Rather, I try and read papers. And with the preprint revolution there’s really far less of an excuse to not engage with the literature in such a direct fashion if you are interested.
re: question about inferring admixture from allele, as opposed to genotype data. One could convert to diploid genotype. Or, one could use a PCA based admixture method which takes allele data as inputs.
The Great Ordeal finished with a bang. I’d recommend it, though it is a difficult and frustrating read. Even being conditioned by the previous books that the protagonist is pretty creepy, it went even further in The Great Ordeal. But R Scott Bakker shines where you’d expect, in world-building and haunting evocations and expositions of what had heretofore been beyond the horizon. In particular the sections in Ishterebinth illustrate Bakker’s ability to take a tired trope, elves (he calls them nonmen), and transform it into something novel and multi-textured. Interestingly, as I was reading these sections I began to think that the nonmen looked just like the engineers in the world of the Alien films, and someone also added that observation to their entry in the wiki.
Congo: The Epic History of a People is kind of like reading Oedipus Rex. It’s hurtling toward tragedy. For the section on the “Great War in Africa” I’d just recommend Dancing in the Glory of Monsters. One might ask, why read books like this? Because to confront reality is hard, but to understand the world one must expose oneself to horrible truths.
One of the aspects of American culture that I have long disliked is the inability to acknowledge that democratic polities will naturally lead to an element of populism, and the people are often illiberal. The Founders were aware of the pitfalls of democratic populism, but the skepticism of the 18th century gave way to the embrace of democracy in the Age of Jackson. I’ve long been skeptical of this, but it’s interesting to watch people attempt to deny legitimacy to popular will where in other cases that is all that matters.
Joshua Schraiber is looking to get some post-docs.
In other news, why do people with Ph.D.s aim to get post-docs so that they can get a job in the private sector? Shouldn’t the 5+ years in a Ph.D. program in the biological sciences train you for jobs outside of academia? If not, then we’re doing it wrong.
I don’t talk about contemporary politics much. That’s because I don’t have much to say. On some topics, such as international affairs, not to be immodest, I’m actually more well informed on history and ethnographic detail than many people who write columns. But because I know a fair amount I’m also conscious of how little we can say concretely. Stuff happens. Big coarse heuristics are probably for the best, because this isn’t like sending a probe to Jupiter. We just don’t have a good grasp of mechanics. As for domestic politics, my current attitude is to ask my friends every now and then what’s happening. My time is better spent on intellectual interests, working, and spending time with my family.
So are there neighborhoods where kids hang around on the block? A suburban cul-de-sac? That’s the childhood I want for my kids, but the streets seem to be empty of children. Are they playing video games?
Someone asked me about Game of Thrones a few weeks back. Everything seems to moving in directions you’d predict. I suspect that much of the narrative in the book is not going to be so pat. The show-runners for the HBO series seem to want to squeeze an incredible amount into the last two seasons, while Martin has at least two books to go, and probably three (his books are barely physically feasible, there are so many pages).
One thing watching the television show has impressed upon me: the average IQ of people watching television is much lower than those who read books. The “theories” promoted by those who primarily watch the television show are often far stupider than anything I remember from the message boards of the late 1990s and early 2000s, when those who read the books came up with plausible models such as R+L=J.
Unlike most of my friends I don’t have a problem with gentrification. If a city is expensive, then only people who can afford there should be able to live there. That might impact the cost or availability of services provided by low wage earners, but that’s just how life goes. But being a gentrifier myself it’s interesting to see neighborhoods in transition. The demographic switch can happen very rapidly (e.g., if I see young white women on a block I assume it’s safe). But there is the phenomenon of established businesses often being geared toward the lower-income population that was previously dominant. Eateries and churches might still be frequented by old-timers, who hang around in some way almost as ghosts, strangers in the neighborhoods that grew around them.
The Kindle version of The High Frontier: Human Colonies In Space was free yesterday, so I bought it. There are some awesome things going on in space right now, and it’s fascinating to look back to a time when this was the science which captured the public imagination. It strikes me we are in the golden age of planetary probes, so who is the Richard Dawkins of this field?
The whole DNC email leak and Debbie Wasserman-Schultz resignation strikes me as strange. Obviously I don’t follow politics, because everyone knew they were engaging in these shenanigans. Is it different because we know for a fact?
Detecting Heterogeneity in Population Structure Across the Genome in Admixed Populations. I think the method is a bit under-powered…but I think that’s because local ancestry deconvolution hasn’t progressed that far in the past 3-4 years. I hear things will change soon. Also, high-quality whole genome sequences will change things.
I’ve started a Blue Apron subscription. Pretty impressed so far in that it has “nudged” me to start cooking.
One of the interesting things about genetics, and population genetics even more specifically, is how the theory and analysis outran the biophysical mechanism of the phenomenon. By this, I mean that the Mendelian laws inferred from transmission of physical characteristics predate any understanding about how genes were embedded within chromosomes, let alone the structural nature of DNA.
Population genetics, which fused the quantitative evolutionary thinking of the biometrical school with Mendelism, arguably outran the data by decades. Until the molecular evolution revolution of the 1960s controversies such as the role of selection and drift in shaping variation were rhetoric rich and data poor. Though the allozyme era was clarifying, I do think people who were shaped by that era get a bit fixated on being a particular camp. In contrast, with the genomics revolution many researchers seem to be more willing to let the data speak, because the data is so copious. A model that is relevant in one part of the tree of life may not be as predictive in another portion of it.
The rise of data makes old questions live again. With that, I present a paper in PNAS where the first author is Jonathan Wakely, a pioneer of coalescent theory, Effects of the population pedigree on genetic signatures of historical demographic events:
Genetic variation among loci in the genomes of diploid biparental organisms is the result of mutation and genetic transmission through the genealogy, or population pedigree, of the species. We explore the consequences of this for patterns of variation at unlinked loci for two kinds of demographic events: the occurrence of a very large family or a strong selective sweep that occurred in the recent past. The results indicate that only rather extreme versions of such events can be expected to structure population pedigrees in such a way that unlinked loci will show deviations from the standard predictions of population genetics, which average over population pedigrees. The results also suggest that large samples of individuals and loci increase the chance of picking up signatures of these events, and that very large families may have a unique signature in terms of sample distributions of mutant alleles.
The paper is open access, so read the whole thing. The major math is tucked away in the extended material. Many of the formalisms in the text are those you’d regularly encounter in population genetics. The issue they’re addressing here is the fact that real populations exhibit pedigree structure, and even unlinked loci, which we treat as independent evolutionary histories, share a pedigree history.
If you read the text though it is notable how robust standard population genetic inferences are to the fact that in a literal sense they’re based on false assumptions. Massive demographic expansion (e.g., Genghis Khan haplotype) and unrealistic selection coefficients don’t seem to disturb the lineages enough so that the assumption of independent assortment starts to become misleading.
This shouldn’t be entirely surprising. I would argue that genomics has not really revolutionized evolution or population biology. The big frameworks are vindicated because nature is one, and the glimmers of reality you see in sparse data nevertheless sample from a comprehensible underlying distribution. As we get more data we’re getting more clarity, but the overall picture is not shocking or surprising.
Citation: John Wakeley, Léandra King, and Peter R. Wilton, Effects of the population pedigree on genetic signatures of historical demographic events
Reading The Essential Talmud about ten years ago I vaguely recall the author stating that it was common for working class males to devote each day to one page of one a tractate from the commentaries on the oral law of the Jewish religion. As I am not religious, and look dimly on excessive orthopraxy, it struck me as a depressing thought.
But I am not entirely different. I often will relax at some point in the day and open up a random page of a population genetics textbook. Just as those Jewish men attempted to gain insight into the divine intent for how they should live their life, so with population genetics I am attempting to refine the theory which allows me to interpret the world around me.
It would probably help anyone who reads many of my posts as well, as it develops particular habits of mind. Though I often recommend Principles of Population Genetics, Elements of Evolutionary Genetics is also excellent. So in the future I’ll try to write up short insights which are pretty banal to most population geneticists, but which might be interesting to a motivated public, if my modest readership can be considered the “public.”
Page 100 has a section, “Selection in inbreeding populations.” The most important formal relationship on this page is:
Δq ≈ qs[h(1 -f) + f]
q = minor allele frequency on a biallelic locus, that is, the remainder from 1 – p
h = dominane coefficient , so that h = 0 means q is totally recessive and h = 0.5 means that the locus is additive in regards to allelic effect.
f = inbreeding coefficient, a basic measure of two alleles at the same locus sharing recent common ancestry (and therefore, rendering the genotype likely homozygous). From 0 to 1, with 1 meaning totally inbred and homozygous.
s = selection coefficient against the population mean fitness. Usually the value is near zero, though not exactly zero. A positive selection coefficient of 0.01 is considered very favorable for a new mutant.
What you see here is that in an instance where q is entirely recessive, inbreeding increases the selection on the locus. In a normal population with lots of random mating homozygous recessive genotypes are rare. When f ≈ 0 the change in the frequency of q is just a function of the selection coefficient and the dominance. As inbreeding increases, the importance of alleles (or lack thereof) in heterozygote genotypes decreases. For recessive traits inbreeding is another way to expose the novel alleles to selection.
This is one reason that unscrupulous breeders of animals sometimes utilize very close relatives in programs to change traits. The problem is that inbreeding has an effect across the whole genome, even if you are interested in particular loci. And that effect on the whole genome is often very bad, as lots of deleterious alleles with recessive expression are present in populations which are normally outbred. Of course in plants this also results in purging of genetic load, as alleles get flushed out of the system. Unfortunately for mammals, and complex metazoans in general, this doesn’t seem to work to well for out lineage. If it did work well zoological veterinarians, who I’ve talked to, would be a lot more hopeful about what they’re trying to do by mating near relations in the hopes that they can get a large enough population to maintain a viable breeding program.
The germline mutation rate has long been a major source of uncertainty in human evolutionary and demographic analyses based on genetic data, but estimates have improved substantially in recent years. I discuss our current knowledge of the mutation rate in humans and the underlying biological factors affecting it, which include generation time, parental age and other developmental and reproductive timescales. There is good evidence for a slowdown in mean mutation rate during great ape evolution, but not for a more recent change within the timescale of human genetic diversity. Hence, pending evidence to the contrary, it is reasonable to use a present-day rate of approximately 0.5 x 10−9 bp−1 yr−1 in all human or hominin demographic analyses.
Even since this review came out there has been new work. Fast changing.
The Ashkenazi Jewish (AJ) population is important in medical genetics due to its high rate of Mendelian disorders and other unique genetic characteristics. Ashkenazi Jews have appeared in Europe in the 10th century, and their ancestry is thought to involve an admixture of European (EU) and Middle-Eastern (ME) groups. However, both the time and place of admixture in Europe are obscure and subject to intense debate. Here, we attempt to characterize the Ashkenazi admixture history using a large Ashkenazi sample and careful application of new and existing methods. Our main approach is based on local ancestry inference, assigning each Ashkenazi genomic segment as EU or ME, and comparing allele frequencies across EU segments to those of different EU populations. The contribution of each EU source was also evaluated using GLOBETROTTER and analysis of IBD sharing. The time of admixture was inferred using multiple tools, relying on statistics such as the distributions of segment lengths and the total EU ancestry per chromosome and the correlation of ancestries along the chromosome. Our simulations demonstrated that distinguishing EU vs ME ancestry is subject to considerable noise at the single segment level, but nevertheless, conclusions could be drawn based on chromosome-wide statistics. The predominant source of EU ancestry in AJ was found to be Southern European (≈60-80%), with the rest being likely Eastern European. The inferred admixture time was ≈35 generations ago, but multiple lines of evidence suggests that it represents an average over two or more admixture events, pre- and post-dating the founder event experienced by AJ in late medieval times. The time of the pre-bottleneck admixture event was bounded to 25-55 generations ago.
I think this preprint is coming close to the answer. Why does a small ethno-religious minority in Europe matter? Well, that’s a matter of historical contingency.
In any case, there were some good papers on Ashkenazi Jewish genetics which came out in the spring of 2010. They really moved the ball forward from the uniparental work. But they suffered from two major problems. First, the putative “parent” populations of Ashkenazi Jews are not that genetically distinct. Second, the hypothesized parental populations were often implausible; e.g., Northern Europeans and modern Levantines.
The likely parental populations of Ashkenazi Jews are Roman period peoples of the eastern Mediterranean, particularly the swath of territory from Alexandria up to Anatolia, and, the peoples of the western Mediterranean. That is, Levantines and Iberians & Italians. These two groups are distinct, but they’re not that distinct.
Additionally, the more and more we learn about the Middle East, the more likely it seems that Muslim populations, who are often modeled as a parental group, are highly cosmopolitan compared to ancient groups. Recall that Neolithic farmers from the Levant resemble Sardinians more than they do locals, because of later migration from further east in Eurasia, as well as later African gene flow. Using imperfect reference populations will probably skew the results appropriately.
The major change in the past few years is the usage of more genetic information than common genotypes. This paper for example looks at haplotype information. Sequences of variants across the genome. This preserves more recent genetic variation. In other cases you can look at whole genome sequences, and focus on low frequency variants which are extremely informative of recent population differentiation.
Ultimately the only reason I’d suggest that this paper is lacking is the imperfection of Middle Eastern source populations. That’s probably increasing the European and decreasing the Middle Eastern fraction somewhat on the margins. The contemporary populations of the Near East have changed a fair amount over the past 2,000 years, though there is still some continuity.
Been busy with work. Lots of data coming in. Will be good to turn around some science.
But I’m eating OK. Location matters….
Here’s a FB post from a researcher on Eran Elhaik’s weird results which regularly make press. I’ve started ignoring Elhaik’s stuff because it’s also so crazy.
I’ll try to monitor the open thread better this week and respond to questions.