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Gene Expression Blog

51Odj8gZIeL._SY344_BO1,204,203,200_ On a plane trip I finally finished Heirs to Forgotten Kingdoms: Journeys Into the Disappearing Religions of the Middle East. It’s about equal parts travelogue, ethnography, and historical speculation. Though not a scholarly work there’s a lot of peculiar and fascinating data. I’d recommend the book, and will probably have a longer review up at some point. NPR had an interview with the author a while back, in part because he has a chapter about the Yezidis, who were in the news at the time because of the attack of ISIS on Sinjar.

So I have determined that I’m going to go to ASHG 2015 and PAG as far as conferences go in the near future, though I’m a little confused why ASHG decided to pick Baltimore rather than D.C.. I assume there’ll be a Bay Area Population Genomics meeting before that of course.

It’s strange, but I’ve noticed something about Twitter for me. I’ve been on since April of 2009. I finally topped 6,000 followers. That’s fine, but it’s literally ~1,000 followers per year. Below you can see the Twitter analytics, which dates to August of 2012. It’s basically a linear progression, except for a kink here and there.

Screenshot from 2015-04-25 22:51:21

Also, I’ll be on the third episode of Through the Wormhole. Premiers mid-May.

• Category: Miscellaneous • Tags: Open Thread 

South_Asian_Language_Families

51IZQjMbVlL._SY344_BO1,204,203,200_ I am often asked by people online to give an “elevator” pitch as to the genetic history of the Indian subcontinent. At this point we’ve got ~90 percent of the story I think. Modern humans arrived in the Indian subcontinent ~50,000 years ago, and pushed onward to East Asia, but over the past ~10,000 years massive changes have occurred genetically due to the intrusion of populations form the northwest and northeast, with likely total cultural turnover. What do I mean by this? First, it’s highly probable that all of the extant language families of the Indian subcontinent are rooted in lineages which were present outside of the Indian subcontinent before the Holocene. The only exception here are the languages of the indigenous peoples of the Andaman Islanders.*

516ma6FzHPL._SY344_BO1,204,203,200_ Older historical works on South Asia often have a preface which suggests that the Austro-Asiatic Munda languages, and those of the Dravidians were deeply indigenous to the region, to be marginalized in the north and west of the subcontinent by Indo-Aryan dialects which arrived relatively recently. This strikes me as likely wrong in terms of broad brush impressions. I now believe that Peter Bellwood was probably right to argue in First Farmers that the arrival of Dravidian languages to the subcontinent was mediated through the arrival of agriculturalists, and perhaps may not have predated the Indo-Aryans by very much time at all. I am even more confident that the Munda people are descended from a group with relatively recent origins on Southeast Asia, approximately contemporaneous with, though likely marginally preceding, the arrival of Indo-Aryans. What you see in South Asia today when it comes to linguistic-cultural agglomerations is the jostling of groups whose origins are all exogenous and date to the post-Neolithic period. Though the Pleistocene genetic heritage of South Asia persists to a great extent, as culturally coherent units I doubt there is much of the Pleistocene left in the region (with the exception again of the Andaman Islands).

51MGYd330tL._SY344_BO1,204,203,200_ Let’s take about the Munda people first. Most of South Asian cultural analysis focuses on a divide between two elements. Culturally, Indo-Aryan vs. Dravidian. Religiously, Hindu vs. Muslim. Genetically, Ancestral North Indian (ANI) vs. Ancestral South Indian (ASI). These dyads are useful analytically, but they elide the more richly textured diversity of the subcontinent (in the case of Muslim vs. Hindu, neither groups, especially the “Hindu” category, are very homogeneous). According to a new paper, A late Neolithic expansion of Y chromosomal haplogroup O2a1-M95 from east to west, as much as ~15% of the Y chromosomal lineages of South Asia may be attributed to these populations. This group uses quite old-fashioned methods. That is, they’re about 10-15 years old, an eon in modern genetics! Basically the focus is on fast evolving microsatellite lineages, and the patterns of variation thereof. But, the power of the paper is the massive data set. By looking at thousands of individuals from some regions they were able to observe patterns with a very high degree of confidence.

The following table illustrates what I’m talking about:

Austroasiatic-en.svg

The cultural-historical debate is whether the Austro-Asiatic languages are indigenous to South Asia or not. The balance of the evidence now seems to be that they are not.What likely occurred is that the Austro-Asiatic languages waxed with the rise of an agricultural Diaspora, whose locus of origin was in what is today the southern regions of China proper. More precisely, the Austro-Asiatic languages may have spread with rice farming across Southeast Asia and eastern South Asia. Likely they were the first on the scene in Southeast Asia, as Bellwood reports in First Farmers and First Migrants that archaeology and anthropometrics can detect admixture between the farmers arriving from the north and native hunter-gatherers in places like the Red river valley in northern Vietnam ~4,000 years ago. The frequency of O2a1-M95 for regions and populations is subdivided very precisely in the above paper, and it is clear that in island Southeast Asia its proportions match those in an earlier paper on autosomal inferences of Austro-Asiatic ancestry. Populations in eastern Indonesia and in the Philippines have minimal numbers of males carryin lineages of O2a1-M95, while the densely populated island land of Java has frequencies of ~50%.

The clincher for why O2a1-M95, and therefore Austro-Asiatic populations, are likely exogenous to India genetically would be the genetic diversity of the lineages. In short, there is tentative information from the variation on the microsatellites that the coalescence of the diverse lineages in Laos are the deepest by a few thousand years. But there was another paper from a few years back which makes my confidence in these results higher, Population Genetic Structure in Indian Austroasiatic speakers: The Role of Landscape Barriers and Sex-specific Admixture, which presented autosomal data which was very persuasive to me. In particular, the derived variation of EDAR which is present in very high frequencies among Northeast Asians and Amerindian populations, is present at about ~5% frequency among Munda groups. Among Dravidian populations in South India according to the 1000 Genomes Browser the frequency is less than 1%, while it is absent among populations in Northwest India, aside from those with clear East Asian admixture.

Next we address the issue of the Dravidian languages. A new paper in Human Genetics, West Eurasian mtDNA lineages in India: an insight into the spread of the Dravidian language and the origins of the caste system, points to an association between particular mtDNA lineages in South India and southern Iran, in particular the region which was once inhabited by the Elamites, who have been posited to have an association with the Dravidian languages. I don’t put particular stock in the philological association between Dravidian langauges today and Elamite; I can’t judge it with any degree of certainty or competency. But the genetic data is certainly suggestive. Here’s the portion which is relevant:

The autochthonous subhaplogroups—HV14a1 and U1a1a4 uniquely found in contemporary Dravidian speakers share their ancestry primarily with the Near East-Iran populations (Derenko et al. 2013). The coalescence times of HV14a1 and U1a1a4 were estimated to be ~10.5–17.9 kya. The shared ancestry of the Dravidian of South India and Iranian of Near East populations has been shown in the HV14 and U1a1 phylogeny (Fig. 1a) and their time estimates are consistent with the proto-Elamo-Dravidian language diffusion. hypothesis which emphasized that the proto-Dravidian language evolved over 15 kya, specifically in western Asia before the beginning of agricultural development ~11 kya. This language was introduced by Neolithic pastoralists, and was thought to be associated with the spread of these west Eurasian-specific mtDNAs to peninsular India (Pagel et al. 2013). The Y-chromosome haplogroup L1a has added a further dimension to this hypothesis. The subclades of haplogroup L such as L1a, L1b, and L1c were found predominantly in Iranian populations of western Asia (Grugni et al. 2012). In India, only the L1a lineage was observed and was largely restricted to the Dravidian-speaking populations of south India (Sahoo et al. 2006; Sengupta et al. 2006). The coalescence time (~9.1 kya) (Sengupta et al. 2006) and the virtual absence in Indo-Aryan speakers in north indicate that the L1a lineage arrived from western Asia during the Neolithic period and perhaps was associated with the spread of the Dravidian language to India

There has long been a presumption to assume that the Dravidian languages are primal to South Asia. But that was before modern genomics revolutionized our understanding of Indian genetic history. More or less all South Asian populations are a fusion between a deeply indigenous strain which distant affinities to the peoples of eastern Eurasia (ASI), and a group very close to the ones typically found in Western Eurasia (ANI). There are no pure indigenes. South Indian tribal populations, who are presumed to be the closest to indigenous groups are at least ~25% ANI, if not more. To presume that the Dravidian languages are indigenous to South Asia one would have to assume that this exogenous element was absorbed by the cultural substrate, something I find implausible on cross-cultural grounds (more dominant South Asian social elites, even ones of pure Dravidian extraction, such as the Reddy group, have higher fractions of ANI). Additionally, Dravidian languages themselves are not particularly variegated, as one might expect if there was deep local structure, as is the case in inland Papua and pre-Columbian America.

Of course the title of this post has to do with males, so with that, let’s look back to a paper which was first posted on the web last year (though finally “published” this March), The phylogenetic and geographic structure of Y-chromosome haplogroup R1a. Here’s the important part:

…Using the 8 R1a lineages, with an average length of 48 SNPs accumulated since the common ancestor, we estimate the splintering of R1a-M417 to have occurred rather recently, ~5800 years ago (95% CI: 4800–6800). The slowest mutation rate estimate would inflate these time estimates by one-third, and the fastest would deflate them by 17%.

With reference to Figure 1, all fully sequenced R1a individuals share SNPs from M420 to M417. Below branch 23 in Figure 5, we see a split between Europeans, defined by Z282 (branch 22), and Asians, defined by Z93 and M746 (branch 19; Z95, which was used in the population survey, would also map to branch 19, but it falls just outside an inclusion boundary for the sequencing data4). Star-like branching near the root of the Asian subtree suggests rapid growth and dispersal. The four subhaplogroups of Z93 (branches 9-M582, 10-M560, 12-Z2125, and 17-M780, L657) constitute a multifurcation unresolved by 10 Mb of sequencing; it is likely that no further resolution of this part of the tree will be possible with current technology. Similarly, the shared European branch has just three SNPs.

The authors emphasize that the TMRCA has a wide confidence interval. I don’t think so. There’s now a fair amount of work on sequencing R1b and R1a lineages which are very common across Eurasia, and one thing is xclear: they’re star-shaped phylogenies which are likely reflecting massive population expansions relatively recently (see A recent bottleneck of Y chromosome diversity coincides with a global change in culture). Additionally, they note that the “Asian” (which includes South, Central, Southwest Asia) and the European branches of R1a1a are relatively well separated, and, the greatest diversity of R1a1a can be found in Iran.

I doubt that R1a1a was associated with one ethno-linguistic group at the end of the last Ice Age. It is present at relatively high frequencies in low caste and tribal populations in South India, so I am skeptical of an exclusive association with Indo-Europeans, though in Europe it may actually be that it arrived only with Indo-Europeans. But, the fact that R1a1a is so common all across Eurasia points to a genetic-cultural revolution. Just as Haplogroup O2a1 is almost certainly rooted in populations outside of South Asia before the Holocene, so is the case with R1a1a. They came with groups of men who brought a new dominant lifestyle. From the west came wheat and cattle. From the east, rice.

The latest research suggests about half the ancestry of modern South Asians dates to the Pleistocene. That is, it predates 10,000 BC. The majority of the mtDNA lineages are from this ancestral element. But culturally this group likely had minimal influence. One question which comes to mind is whether the ASI ancestry is from many groups, or, from only a few which were assimilated into an expanding group of agriculturalists. If the former, then one expects that the ASI ancestral segments which exhibit a tendency toward regional structure. I suspect thought that this is not the case, that the genetic landscape of modern India is characterized by overlapping populations which are all hybrids of different regional groups which only recently expanded. The pattern of Munda groups in South Asia, surrounded by Dravidian and Indo-European speaking groups, points one to the possibility that these groups were pioneers of some sort, but eventually lost.

* Language isolates like Kusunda and Nihali may date to the era before the Holocene, but without relatives we can’t really make a good guess. Possible relationships of Kusunda to Andaman or Papuan languages strike me as implausible due to the time depth of separation.agglomeratio

• Category: History, Science • Tags: Genetics, Genomics 

Drakas_cover Everyone and their mother has heard of the story about the CRISPRed embryos by now. If you haven’t, the original paper is open access. Second, Carl Zimmer’s primer is excellent, Editing Human Embryos: So This Happened. For those who are overly alarmed by the non-ethical aspects, I think this is key:

Just because this experiment came out poorly doesn’t mean that future experiments will. There’s nothing in this study that’s a conceptual deal-breaker for CRISPR. It’s worth recalling the early days of cloning research. Cloned embryos often failed to develop, and animals that were born successfully often ended up with serious health problems. Cloning is much better now, and it’s even getting to be a business in the world of livestock and pets. We still don’t clone people, though–not because we can’t, but because we choose not to. We may need to make the same choice about editing embryos before too long.

Livestock and pets. And plants. I think CRISPR is going to be a big deal. It already is a big deal. But some people are worried now about a profusion of designer babies. We need to get calm here. For something to become a consumer product it needs to get much better in terms of probability of outcomes, and we’re a long long way from that. As Ramez Naam pointed out people are very risk averse with their children.

Rather, the real danger is more one of ethics. Something out of S. M. Stirling’s Draka series where a government or society isn’t bound by normal human ethical standards, and begins to basically treat their population like livestock. As is usually the case the major issues looming are not scientific, but have to do with human volition.

• Category: Science • Tags: Crispr 

41ncnodwApL._SY344_BO1,204,203,200_ Beauty can lie all too easily, while oftentimes truth is ugly on first inspection. I’ve been reading Inventing the Individual: The Origins of Western Liberalism, and it is a beautiful book, full of style and erudition, and paragraph after paragraph of mellifluous argumentation. It is far more gossamer than Victor Lieberman’s Strange Parallels, which is weighted down by turgid prose. But where Lieberman’s narrative is dense in unique and distinctive data, Larry Siedentop’s Inventing the Individual circles around the same big facts. Siedentop promotes a bold, if not original, thesis, that the Hebrew-Hellenic synthesis which became Christianity was the seed for the invention of liberal individualism, which reigns ascendant today, at least in name if not reality. Lieberman makes an observation about the parallel development of societies across Eurasia, even in its isolated and far-flung regions in the protected peninsulas and archipelagos of Southeast Asia, and gropes confusedly at overarching explanations. And yet it is the “ugly duckling” of Strange Parallels that is more satisfying than the crisp and elegant theses of Inventing the Individual. The latter is a joy to read, but if you know a fair amount of 61LXo6U7a4L._SY344_BO1,204,203,200_ history, and cross-cultural history at that (I do), a lot of it comes off as hot air and naked assertion. It’s a great read, but will only persuade the persuaded, and unfortunately is a little thinner on “dense description” than I would have liked for a work which I knew I was going to look at skeptically (that is, even if you find a work uncongenial on the whole, there are often great gains to be made in extracting nuggets of information).

The ultimate problem that confronts me when entertaining the core contention of Inventing the Individual is sentences such as the following on page 77: “But texts are facts. And the facts remain.” The question is whether they are non-trivial facts, and that is debatable. There is a school of thought that ideas are the drivers of history, and Inventing the Individual takes that position as a premise. If one is wobbly on that premise, the force of the argument falls flat.

Second, do readers have any particular papers/books on domestication that they think are particularly good? My professional research focus is in this area and I need to do a thorough survey of the literature.

Third, I am not an “adaptationist” as Larry Moran has asserted. I’m “dynamic agnostic,” and am wary of null hypotheses of what drives variation in organisms as a whole (i.e., I think neutrality may be more justified for some branches of the tree of life than others).

Fourth, I should mention again that if you are following an RSS feed for my content, http://feeds.feedburner.com/RazibKhansTotalFeed is preferred. The reason is that it bundles all my content, and I don’t like to cross-post notifications across blogs. E.g., if I write for The Guardian again or something it will show up in that feed, and I’m liable not to mention it on this blog (though it will show up in Twitter since that pushes the above feed).

• Category: Miscellaneous • Tags: Open Thread 

22522805 Amazon believes that e-books are price-elastic. That is, the lower the price, the more units sell. The print list price for Kazuo Ishiguro’s The Buried Giant is $26.95. I noticed it was $5.99 in the Kindle version, so I purchased it on a whim. It’s basically cheaper than lunch. I can say with some confidence that if it was priced at “normal” e-book rates, which are still discounted, I probably wouldn’t have purchased it. I don’t read much fiction, and when I do I tend to shy away from material with too many mainstream plaudits because the mainstream often strikes me as banal in their preoccupations.

I stated last week I probably wouldn’t get to finishing The Buried Giant very soon. I was wrong. It’s a quick read, and I was just on an airplane, so the book is done. Overall I’d say it was worth the money. Ishiguro writes well and evocatively threads through his broader themes, while still allowing the narrative itself to have some drive to it.

The Buried Giant operates in the area between the literary allusive opacity of Gene Wolfe’s The Book of the New Son and the sort of sincere and transparent high fantasy you see in Brandon Sanderson’s The Way of Kings. Because it is notionally set in post-Roman but pre-Anglo-Saxon Britain you might think The Buried Giant exhibits some of the historical fantasy flavor you see in works such as Guy Gavriel Kay’s Sarantine Mosaic (or quasi-scholarship about this period, such as Nikolai Tolstoy’s The Coming of the King). But it does not.

Though the Saxons and the Britons are real people who coexisted in a real time, the world is anachronistic and laced through with fantastical elements. There are dragons and ogres, but also Norsemen and knights. The latter are features of periods centuries after the late 5th century. One aspect that is difficult to not acknowledge in a book about this time period is the foreshadowing of the Saxon conquest of lowland Britain, what became England. But, I do think as a point of historical fact one should note that as late as the early 7th century Celtic British kings such as Cadwallon ap Cadfan were conquering eastern areas of England, with armies reaching the North Sea. Though the Germanization of Britain seems inevitable now, it is possible to imagine a scenario where the late 6th century marked the low point from which Britons reconquered the islands, in a manner that the Christians in Spain reconquered their peninsula. But The Buried Giant operates under the assumption of Saxon inevitability, with the Britons being portrayed faintly as if they are a feckless and complacent people, with more civilized refinement than genuine honor.

68520 Finally, one aspect of this book that many readers of traditional fantasy will find disappointing is that its description of the world and the people within it is very understated. Ishiguro exhibits an admirable economy of prose, but at the sacrifice of a rich and deep color of character and landscape. For example, I can not tell you what the main characters looked like aside from the thinnest of generalities (e.g., two characters were aged, one was a strong warrior, etc.). Obviously this makes it difficult to conceptualize them in one’s mind’s eye, but perhaps the point was to identify with the character and their life rather than their embodiment. The fact that concrete aspects of character and landscape were put into the background probably allowed the broader themes to be more clearly obvious.

I can see why mainstream audiences might find The Buried Giant appealing, as it doesn’t push them too far. The fantastical elements are unobtrusive background furniture. But if you want real a real “Dark Age” Arthur, I highly recommend Bernard Cornwell’s Warlord Chronicles.

• Category: Miscellaneous • Tags: The Buried Giant 

weight

71qnces9omL._SX450_ Over a year ago at my friend David Mittleman’s recommendation I got a Fitbit Aria Wi-Fi Smart Scale. The reason was two-fold. First, I’d been monitoring my weight since 2010 by using a spreadsheet, but I liked the idea of just jumping on the scale, and having it automatically record the weight. Yes, definitely a “First World Problem”, but it reduces even the need to think about recording my weight. Second, the scale also purports to measure body fat percentage. I say purports because many people are skeptical of the results because it utilizes bioelectrical impedance. But I still thought it was worth it because as long as it was precise, even if not accurate, I could see a possible trendline. Over the past year my body fat percentage has declined from ~20% to ~18%. This seems validated by the fact that my waist has also gone down an inch, as I can easily fit into 29 inches instead of 30 (my target is 28, which is where I’m at when I’m genuinely lean).

Obviously what you look like and what you can fit into is the best measure of your body fat. But I’m a bit of a quant nerd, so when a reader suggested that the Omron Body Fat Loss Monitor was better than the Aria, I purchased it. It uses the same method, but while the Aria is a scale, the Omron is a device which you grip two-handed. Yesterday I tested the Omron three times. The results came back in the 17 to 18 percent range. Perfectly in line with the Aria. I also had a few friends of various sizes and male and female use the Omron, and it seemed to make sense. My friend who came back at 7%, is totally believable at 7%. And the women always came back with higher proportions for their build than the men.

webpreview_htm_be9c6222 So how do I measure up? Below is the data from the CDC drawn from a survey of American males in the early 2000s. I’m definitely below average in my age class, but the curve here is not particularly strenuous (in fact, I might just fall into the “ideal” range for my age, though that’s contingent on the reading being accurate and population typicality). My ultimate goal is get below 15%. At that point I’ll stop caring much besides maintenance. Most of the guidelines seem to suggest that the border between fit and average body type is 17%, but I’m of South Asian ancestry, so I’m at higher risk for metabolic diseases. I suspect I’ll have to reduce my body fat percentage down further than the population wide guidelines to obtain the same risk value as the average person. Contrary to Aaron Lewis’ song a few extra pounds could hurt. I still have too much fat around my mid-section.

• Category: Science • Tags: Health 

A-Game-of-Thrones-Bantam-Spectra On January 23rd of 1999 I had just finished Paul Gottfried and Thomas Fleming’s The Conservative Movement. My roommate was pretty high, as usual (it was a Saturday). A few weeks earlier I’d gotten a paperback of a fantasy novel, Game of Thrones. I read a few pages, and then went to sleep. The next morning, Sunday, I began to read more. I did not finish until very late Sunday evening/Monday morning. I happened to have had a midterm in a biochemistry course the next day. I did not do so well. In a month the first edition of the sequel, Clash of Kings, came out. Satisfaction! In the year 2000 the British edition of the third book, A Storm of Swords, was published a few months earlier than the American one. I special ordered it from England so I could read it ahead of time. After I read Game of Thrones I emailed George R. R. Martin, and he actually responded, though it took about a year. He apologized for being responsible for my difficult midterm. He also confirmed that Bernard Cornwell’s Warlord Chronciles were similar in feel, if not directly influential, to his series.

Like many I was patient, though frustrated, by the delays after A Storm of Swords. Like many readers I also believe that A Dance with Dragons and A Feast for Crows were somewhat inferior to his first three books. But I understand that the “middle books” of such an expansive series are often the least interesting. Bridges between the past and future. I am patient. When I first encountered Martin’s series I was a callow youth. I am now a father. Much has changed.

But now I read this post at FiveThirtyEight, We’re Going To Learn How The ‘Game Of Thrones’ Books End On HBO. I haven’t much paid attention to the show because I do not watch television, and film or television of science fiction and fantasy are usually inferior and compromised products. But the math is compelling. I had assumed that A Song of Ice and Fire would conclude in the early 2020s. But if the television show has nearly caught up with the books, and is already through 4 years of its run, it seems implausible that it won’t race ahead. I’m at a loss for what I can even say to this. Is our patience and forbearance for naught? Apparently.

I agree with the suggestion o some: the HBO series and the books should explicitly “fork.”

• Category: Miscellaneous • Tags: Fiction 

41BlNMFJqNL._SY344_BO1,204,203,200_ A few separate pieces that I read today came together thematically for me in an odd confluence. First, an article in The Straits Times repeats the shocking statistics about the nature of modern academic intellectual production, Prof, no one is reading you, that you may be aware of. Here’s the important data:

Even debates among scholars do not seem to function properly. Up to 1.5 million peer-reviewed articles are published annually. However, many are ignored even within scientific communities – 82 per cent of articles published in humanities are not even cited once. No one ever refers to 32 per cent of the peer-reviewed articles in the social and 27 per cent in the natural sciences.

If a paper is cited, this does not imply it has actually been read. According to one estimate, only 20 per cent of papers cited have actually been read. We estimate that an average paper in a peer-reviewed journal is read completely by no more than 10 people. Hence, impacts of most peer-reviewed publications even within the scientific community are minuscule.

What ever happened to the “republic of letters”? Are humanists reading, but not citing, each other? Or is it that humanistic production has basically become a matter of adding a line to one’s c.v.? So the scholar writes the monograph which is read by their editor, and then published to collect dust somewhere in the back recesses of an academic library.

Second, an article in The New York Times, Philosophy Returns to the Real World, declares the bright new world in the wake of the Dark Ages of post-modernism. Through a personal intellectual biography the piece charts the turn away from the hyper-solipsistic tendencies in philosophy exemplified by Stanley Fish in the 1980s, down to the modern post-post-modern age. Operationally I believe that Fish is a human who reconstitutes the characteristics of the tyrannical pig Napoleon in Animal Farm. Despite all the grand talk about subjectivism and a skepticism about reality which would make Pyrrho blanch, Fish did very well for himself personally in terms of power, status, and fame by promoting his de facto nihilism. Money and fame are not social constructs for him, they are concrete realities. Like a eunuch in the Forbidden City ignoring the exigencies of the outside world, all Fish and his fellow travelers truly care about are clever turns of the phrase, verbal gymnastics, and social influence and power. As the walls of the city collapse all around them they sit atop their golden thrones, declaring that they are the Emperors of the World, but like Jean-Bédel Bokassa are clearly only addled fools to all the world outside of the circle of their sycophants. After all, in their world if they say it is, is it not so? Their empire is but one of naked illusions.

Finally, via Rod Dreher, a profile of David Brooks in The Guardian. He has a new book out, The Road To Character. I doubt I’ll read it, because from what I can tell and have seen in the domain of personal self-cultivation of the contemplative sort our species basically hit upon some innovations in the centuries around 500 B.C., and has been repackaging those insights through progressively more exotic marketing ploys ever since. Xunzi and Marcus Aurelius have said what needs to be said. No more needed for me.

But this section jumped out:

“I started out as a writer, fresh out of college, thinking that if I could make my living at it – write for an airline magazine – I’d be happy,” says Brooks over coffee in downtown Washington, DC; at 53, he is ageing into the amiably fogeyish appearance he has cultivated since his youth. “I’ve far exceeded my expectations. But then you learn the elemental truth that every college student should know: career success doesn’t make you happy.” In midlife, it struck him that he’d spent too much time cultivating what he calls “the résumé virtues” – racking up impressive accomplishments – and too little on “the eulogy virtues”, the character strengths for which we’d like to be remembered. Brooks builds a convincing case that this isn’t just his personal problem but a societal one: that our market-driven meritocracy, even when functioning at its fairest, rewards outer success while discouraging the development of the soul. Though this is inevitably a conservative argument – we have lost a “moral vocabulary” we once possessed, he says – many of the exemplary figures around whom Brooks builds the book were leftists: labour activists, civil rights leaders, anti-poverty campaigners. (St Augustine and George Eliot feature prominently, too.) What unites them, in his telling, is the inner confrontation they had to endure, setting aside whatever plans they had for life when it became clear that life had other plans for them.

Many of the ancients argued for the importance of inner reflection and mindful introspection. Arguably, the strand of Indian philosophical thought represented by the Bhagavad Gita was swallowed up by this cognitive involution, as one folds in upon one’s own mind.

But let me tell a different story, one of the outer world, but not one of social engagement, but sensory experience of the material domain in an analytic sense. Science. A friend of mine happens to be the first using next-generation sequencing technologies to study a particularly charismatic mammal. I reflected to her recently that she was the first person in the history of the world to gaze upon this particular sequence, to analyze it, to reflect upon the natural historical insights that were yielded up for her by the intersection of biology and computation. It is highly unlikely that my friend will ever become a person of such eminence, such prominence, as David Brooks or Stanley Fish. Feted by her fellow man. But my friend will know truth in a manner innocent of aspirational esteem totally alien to the meritocratic professionals David Brooks references. On the day that you expire, would you rather be remembered for a law review article, or discovering something real, shedding light on some deep truth (as opposed to “truth”)?

This perhaps offers up a possibility for why humanists don’t cite each other. Too many have been poisoned by the nihilism of the likes of Stanley Fish. They do not see any purpose in the scholarship of their peers, because humanistic scholarship of the solipsistic sort is primarily an interior monologue with oneself. The experiments of English professors always support their hypotheses. Their struggle is to feed their egos, they wrestle with themselves, Jacob’s own angel as a distillation of their self-essence. The limits of their minds are the limits of their world.

Finally, this filament threaded through, of a reality out there, the possibility of being made aware of it, even through the mirror darkly, is why I continue to do what I do, and aspire to what I aspire to. The truth is out there. It does not give consideration to our preferences. But it is, and we can grasp it in our comprehension. Over the past ten years in the domain of my personal interest, and now professional focus, genomics, we’ve seen a sea change. That which we did not even imagine has become naked to us. Before the next ten years is out who knows what else we’ll discover?

• Category: Ideology • Tags: Epistemology, Philosophy 

330px-KeiraKnightleyByAndreaRaffin2011 In the comments below someone asked if the model Bryan Sykes’ outlined in Seven Daughters of Eve (and later Saxons, Vikings, and Celts), that modern Britons descend predominantly from the Paleolithic stock which repopulated the island in the wake of the end of the last Ice Age (or fled Doggerland), is still tenable. I don’t think so much. First, the tripartite origin of modern Northern Europeans probably puts more of an emphasis on migration in the Western regions of the continent. Yes, in many groups the ancestry which derives from the small populations which followed as the glaciers retreated is overall predominant (that is, somewhat more than 50%). But that is distinct from the idea that the proportion of ancestry from hunter-gatherers in any given area, such as Britain, is from indigenous hunter-gatherers long resident. What I’m getting at is that socio-cultural groups, such as “Early European Farmers” (EFF) and the Yamna, which contributed a great deal of ancestry to modern people are themselves in origin compounds of disparate elements. Because of the seeming homogeneity of European hunter-gatherers, likely due to a Pleistocene bottleneck and then a rapid range expansion from small founder groups, earlier methods of aligning mtDNA and Y haplogroups may have misled because of the lack of power to distinguish between extremely close lineages (European hunter-gatherers are almost all mtDNA group U and predominantly Y group I). Therefore the predominant Paleolithic ancestry across Northern Europe may actually be a function of a few discrete pulse admixture events. Subsequently demographically successful groups then carried this ancestry where they went, possibly replacing natives in totality.

I grant that this is speculative and not certain. For example, one assumption I’m making is that the density of hunter-gatherers was rather low across Europe. But clearly there were marine environments where they seem to have been thicker on the ground, particular zones where agriculturalists seem to simply stop their advance abruptly The ultimate answer will probably be through ancestry deconvolution methods. Basically, looking at the distribution of lengths of distinct ancestral elements, and seeing which model the empirical patterns fit. If I’m correct, then the distribution of lengths for hunter-gatherer ancestry in Northern Europe will be narrower than if you had a scenario of continuous regional expansion. It’s certain that someone is working on this.

Genetically the two scenarios don’t make that much of a difference, because European hunter-gatherers were probably a very homogeneous bunch (though this might be generally true for Eurasian hominins, as Neandertals and the Denisovan sample also exhibit low genetic diversity in comparison to modern populations). But anthropologically it is critical, because it fleshes out the processes of potential cultural change and turnover in the transition between societies and modes of production.

• Category: Science • Tags: European Genetics, Genetics 

41v0RwMV8OL._SY344_BO1,204,203,200_ I have an old friend from college who I’m in touch with via Facebook. He looks great. In fact, he looks like how I’d like to look. After a year of running and lifting I’m noticeably more muscular. I’m 150-155 pounds at 5’8, and according to my Aria I’ve lost about ~3% body fat (I’m not reporting the absolute value because it’s not that accurate, though the readings seem consistent day to day). But, since I’m South Asian and tend toward a “baby face” mien I’m not where I want to be in terms of definition. In contrast my friend is very toned. I asked him how he had changed his physique so much over the years, since in college he was rather “soft” looking. His response? Gay peer pressure.

This is why articles like this in Salon drive me crazy, You should never diet again: The science and genetics of weight loss. It’s excerpted from the book Secrets From the Eating Lab: The Science of Weight Loss, the Myth of Willpower, and Why You Should Never Diet Again. The author, Traci Mann, is a professor at the University of Minnesota, as she proudly notes:

To tease apart the effects of genes from the effects of the shared environment, researchers located identical twins that were raised in separate homes without knowing each other. It may seem surprising that there are enough sets of twins that meet this criteria, but there are. This type of twin research was partly pioneered in the very psychology department in which I work, at the University of Minnesota (coincidentally located in the twin cities of Minneapolis and St. Paul). If you go up to the fifth floor, the walls are covered with photographs of identical twins that were separated at the age of five months (on average) and had been apart for about thirty years before being reunited as adults. The visible similarities are remarkable, as are the many documented behavioral similarities.

The crucial twin study of body weight (which comes from the Swedish Adoption/Twin Study of Aging) included 93 pairs of identical twins raised apart (and 154 pairs of identical twins raised together). Sure enough, the weights of identical twins, whether they were raised together or apart, were highly correlated. That study, along with several others, led scientists to conclude that genes account for 70 percent of the variation in people’s weight. Seventy percent! What is truly remarkable is that this is only slightly lower than the role genes play in height (about 80 percent of the variation). Don’t get me wrong. I’m not saying you can’t influence your weight at all, just that the amount of influence you have is fairly limited, and you’ll generally end up within your genetically determined set weight range.

41nk1RoCEWL._SY344_BO1,204,203,200_ Many readers will be familiar with twin studies. If you aren’t, read Born that Way by William Wright. The strange thing about this reference to this scientific project is that it’s incongruous to see it in a Left-wing publication like Salon. The more moderate Slate trashed twin studies about four years ago, even though cutting edge genomic methods are now validating their results. Why all the hostility? Mostly it has to do with non-trivial heritabilities for intelligence and personality which come out of this type of research, which are not congenial to a particular sort of Left-wing mentality (see Steven Pinker’s The Blank Slate). I suspect the issue here is that the political valence is not alarming to the readers of Salon, who are very open arguments about “thin privilege”, and the idea that the heavy might be considered another protected class. The analogy then in terms of heritability and a biological basis for this trait is with homosexuality, where the Left favors genetic determinism. The same studies also come with high heritabilities for traits such as weight in developed world populations. The quoted results above are correct, but the implications that the public takes from them are misleading.

I’m pretty sure that Traci Mann knows the technical definition of heritability by the way she writes. That is, the proportion of phenotypic variation that can be explained by genetic variation within the population. The problem is that the general public is going to see “70 percent heritable” and think “70 percent genetic,” when that’s not even wrong. The way the piece is written also misleads in this fashion. One thing to note is that even though height is 80 to 90 percent heritable, the correlation between full siblings for this trait is only 0.50. I suspect this would surprise people since it is such a heritable trait, but that goes to show that a population wide heritability statistic has only modest utility on the individual scale. More importantly by analogy to height the norm of reaction matters a great deal. We know empirically that genetically similar populations vary in mean and variance of weight and height over time and in different environments.

Which goes back to social context. My friend now works out a lot and watches what he eats. It’s something that he does every day, and something that is enabled by the social environment in which he is embedded (see this music video about “Mean Gays”). Weight varies in the United States by class and region, and from what I recall this remains after you control for demographic variables. What this probably means is that it takes a village to sustain weight loss. So in a way those who argue that dieting is useless are correct. But they’re being misleading when they imply that your weight is ultimately “genetic.” It’s social.

Update: A friend emailed me and pointed out figure 2 in a recent Nature paper. It gets at what’s producing the heritability statistic:

nature14177-f2 (1)

• Category: Science • Tags: Heritability 

22522805 I listened to an interview with Kazuo Ishiguro over at Wired with the title “Why Are So Many People Snobby About Fantasy Fiction?” After hearing what Ishiguro had to say I decided to check out reviews for his new novel, The Buried Giant, and noticed it was $5.99 in the Kindle version. So of course I bought it.

I’m not sure if I’ll be satisfied. The premise somewhat reminds me of Gene Wolfe’s Soldier of Arete, though obviously most of the major elements differ. I don’t know if I’ll get to reading The Buried Giant anytime soon, as I’m behind on various projects relating to my real professional life and will be rather busy for a while. Additionally, I have other books that I’d like to get through, such as Inventing the Individual, a work that I’m pretty sure I’m not going to much like if the first 20% or so is a guide. The author basically asserts a lot of things about the antique past with support from literary references that I’m often not personally deeply knowledgeable about (to be clear, there are factual issues I know about, such as comparisons between Greeks and Romans, where I think the author is basically wrong in eliding important distinctions among these cultures before Christianity). Additionally, the conclusions grate a bit on my priors. I really dislike works of the form, such as “How Love was Invented in 13th Century Provence.” Giving something a label does not something make (i.e., defensible to say love as we understand it). But I am the type of person who reads things he disagrees with, because new arguments are often informative. So I’ll finish it.

In other news, I’ve been using SciReader for a while now and I like it quite a lot. It’s a nice complement to PubChase. For nonacademic readers PubChase is pretty handy for trying to locate copies of PDFs that you can access. If you are a regularly reader of this weblog you should try them out.

One of the major ways I find scientific literature is Twitter (which SciReader has a pretty tight integration with right now). My old rule-of-thumb was that I’d maintain a 10:1 follower-to-follow ratio. I’m nearing 6,000 followers (thanks The New York Times, sort of!), and until recently I kept the follow count to around ~300. The past few days though I’ve been following people who look interesting, and will continue to do so until I hit 600. Mostly I follow individuals who work in genomics and evolution, because when it comes to “big Twitter” those all get re-tweeted anyhow if they are interesting. But I’m curious if readers have particular suggestions for whom I should follow. In particular, data Tweeters like Conrad Hackett, I really appreciate. I’m also curious about scholars in fields like history, philosophy, and economics. Also, please note that I’m looking for Twitter users who actually post somewhat frequently.

Going back to fantasy and science fiction, I have no idea why the haters hate. One of my pet theories is that less intelligent liberal arts majors are not very intellectually curious outside of the prosaic. They’re just not creative types, and don’t have the requisite imagination to process speculative fiction. But that’s probably not generous (in any case, some serious hard science fiction writers, such as Greg Bear and C. J. Cherryh, come out of liberal arts backgrounds), not to mention self-serving. Though I do admit that that a lot of science fiction and fantasy is crap, that’s true of fiction more generally. For some reason the crap sticks to the whole genre. Or genres, as the same disdain is aimed at mysteries or romance novels, neither of which I care for, but neither of which I go out of my way to dismiss since I don’t read them. My identity isn’t bound up in the idea of the Book and Literature.

• Category: Miscellaneous • Tags: Open Thread 

journal.pbio.1002112.g003

$_35 Very important paper in PLOS BIOLOGY just out, Natural Selection Constrains Neutral Diversity across A Wide Range of Species. Important enough that the journal commissioned this article: Lewontin’s Paradox Resolved? In Larger Populations, Stronger Selection Erases More Diversity. The paradox is pretty straightforward. Assuming the neutral theory of molecular evolution you’d expect that you’d have more genetic diversity in species with larger population sizes, because the larger the population size the longer it would take for mutations to transition from novelty to fixation. More formally the time until fixation of a neutral polymorphism is ~4N e, with N e being the effective population size. In small populations mutations will emerge and fix rather quickly due to the generation to generation volatility of drift being so powerful, and therefore keeping down the total diversity. In large populations mutations will take a long time to traverse the frequency range from 0 to 100% because of the weakness of inter-generational random drift. The paradox was a big deal because for the past 30 years or so the neutral (or nearly neutral) has been the implicit null model, and I’d argue broadly supported as such, albeit with strong dissents.

41TCN6WTB4L._SY344_BO1,204,203,200_ The “controversies” that occurred from the 1970s onward about the role of selection and and its enemies are somewhat notorious. Some of the figures are well known to the public. Richard Dawkins and Stephen Jay Gould both had cameos because of their differing views about the pervasiveness of adaptation in evolutionary process more generally. But the geneticists at the heart of the major disagreements are more obscure to the general public, though in the early 1990s the Sacramento Bee reported on the beef between John Gillespie and Motoo Kimura (Gillespie was based out of UC Davis, near Sacramento). From what I can tell, and who I know, it strikes me that genomics has now somewhat mitigated the role of rhetoric in the debate, and at the same time fostered an abating of the extremism of some of the anti-selectionists. Leibniz’s stance of “let us calculate” has now become more important than a turn of the phrase or evocative metaphor. With data there is less of a role for posturing. Additionally, the fact is that many researchers did not follow mathematical theoretical proofs very closely or with genuine comprehension, so empirical results are really what is changing the terms of the debate. The Drosophila world has long been a redoubt for selectionism, but now you see papers such as Genome-wide signals of positive selection in human evolution, which argue for the importance of that population genetic parameter even for small effective population size organisms such as humans.

187874 What the authors did in the above paper was leverage the fact that with genome-wide data they could test the theoretical propositions empirically. In particular, they looked at regions with reduced recombination,* and therefore should be subject more strongly to selection (whether selective sweeps, which allow for the hitchhiking of regions around the target of selection and generate long haplotypes, or background selection, which constrains genomic variation due to negative pressures against mutation). As the figure above shows there is a correlation between the power of selection on the genome and inferred effective population size. I say inferred because they had to use species range and size as proxies. Obviously this isn’t perfect, but I suspect that the utilization of these proxy variables only diminishes the correlation. The authors admit that there is a lot of work to be done, but this is just the first step. Perhaps the results will change somewhat with a different selection of organisms (N = 40), but I’m moderately skeptical. Probably the most important line in the paper is “it seems clear that, in most cases, BGS [background selection] is a more appropriate null model for tests of natural selection than strict neutrality.”

* Recombination shuffles the association of variants across the genome, and so separates their destiny, whether good (positive selection) or bad (negative selection).

• Category: Science • Tags: Evolutionary Genetics, Genetic Draft, Selection 
miscarriage

Blue variant derived, correlated with higher anueploidy rates

A quick follow up to my previous post. To recap, a new paper in Science reports high (20-40%) derived frequencies for an allele which seems correlated with higher rates of aneuploidy. Anueploidy is bad, because often it results in nonviable offspring (individuals with Down syndrome have a viable anueploidy). The strange thing about this region of the genome is that it looks like modern humans have harbored this variant since the divergence from Neandertals. But, it has not gone to fixation. Its frequency in the intermediate range all this time, segregating in pretty much all populations from what it looks like, suggests balancing selection.

41ePHetk1dL._SY344_BO1,204,203,200_ Most of the paper is focused on medical genetics and the genome-wide association. The evolutionary aspect is interesting, but struck me as something of an afterthought. I made some chit-chat with the first author at the Bay Area Population Genomics meeting last December, and he didn’t let on that he had any good idea for why this allele was persisting. So I doubt that the group is wedded to the idea that miscarriage is a strategy for masking paternity and encouraging male investment. I’ve asked around people who work in behavioral ecology and they’re skeptical too. There’s a mystery here, and it’s kind of a big deal in my opinion, but there’s not much clarity.

On Twitter Vincent Lynch pointed out that the locus in question, PLK4, has been implicated in testes development. So one possible answer that crops up is that it is some form of sexually anatongistic selection. Meanwhile, Greg Cochran posits that we’re seeing some sort of meiotic drive, where there is selection pressure operating on the level of the genome itself (e.g., “selfish genetic elements” type dynamics). These are both plausible to me, and suggest that there needn’t be an explanation rooted in our human uniqueness to answer this particular genomic mystery.

hominids A common tendency among genomicists, who are modern humans, is to always highlight variants which have been selected in our lineage in comparison to nearby lineages. Before ancient DNA this usually meant chimpanzees, but now we’re talking Neandertals and Denisovans. Humans are a pretty big deal, and intuitively we think that our genomics are also a pretty big deal. There must be a key that unlocks our uniqueness, so searching through the 3 billion base pairs in our genome we stumble upon distinctive evolutionary histories, and think “eureka, this is It, the ultimate locus of our genius!” In pre-modern language, our souls. But the fact is that over tens of millions of polymorphisms in the genome you are naturally going to find regions where we are unique in relation to our relatives, and the broader mammalian family tree, just as a matter of chance. If we lived in the world of the Neanderthal Parallex no doubt Neandertal genomicists would be engaging in the same search for the uniqueness of their lineage, and discover regions where they are sui generis in relation to other hominins and mammals more broadly. The few times I’ve been to ASHG I stumble onto talks where the authors present evidence of genomic regions which are unique in our species, the implication being that this might be somehow responsible for the nature of who we are. Of course the researchers in question are usually not interested in that topic that much, rather, it is an interesting side element that adds to the sexiness of their results, and the glamour usually fades over time.

There is the quest for the the gene for everything. It’s a major problem with media representations of behavior genetics. But a lot of interesting traits are polygenic. We’ve long known this from classical genetics, and genomics is confirming this. There’s not a gene for anything, but a host of genes. Quantitative genetics is banal, but it is powerful. We need to be more open to the possibility that humanity as we understand it isn’t a clear and distinct thing, but the end of a distribution of possibilities long pregnant in our lineage of apes.

• Category: Science • Tags: Genetics, Human Evolution 

defect

The above figure is from Common variants spanning PLK4 are associated with mitotic-origin aneuploidy in human embryos. The author has presented this work at meetings, so I knew it was pending. One of major angles here is that you now have an actionable genotype whereby one can make calculations of likelihood of aneuploidy.. If you are female, and have a 23andMe account, just click here. In accord with the results above the risk for aneuploidy is as follows AA > AG > GG. If you don’t have access, the supplements have a lot of interesting stuff. There you can see that there’s no discernible geographical distribution of the minor allele, which is present in ranges from 20 to 40 percent (here it is at the 1000 Genomes Browser).

From an evolutionary perspective the strange thing is that the derived allele seems to reduce reproductive potential. Neandertals don’t carry the derived variant. But the presence of this derived allele isn’t a coincidence, the authors detect an ancient selection event around this region. So either the variant is beneficial in some way, or, aneuploidy as a trait has hitchhiked. I’ll post the explanation in the paper here, because I honestly don’t even know what to say:

The fact that the haplotype bearing the derived allele did not sweep to fixation and is present at similar frequencies across human populations is consistent with the action of long-term balancing selection. We speculate that the mitotic-error phenotype may be maintained by conferring both a deleterious effect on maternal fecundity and a possible beneficial effect of obscured paternity via a reduction in the probability of successful pregnancy per intercourse. This hypothesis is based on the fact that humans possess a suite of traits (such as concealed ovulation and constant receptivity) that obscure paternity and may have evolved to increase paternal investment in offspring (24). Such a scenario could result in balancing selection by rewarding evolutionary “free riders” who do not possess the risk allele—and thus do not suffer fecundity costs—but benefit from paternity confusion in the population as a whole

Whatever is happening is very strange. The authors make the case that there ascertainment bias is such that they’re underestimating effect of the derived variant. All things equal the selection coefficient should be strongly negative.

• Category: Science • Tags: Genetics, Human Evolution 

height

The above figure is from a paper in Proceedings B which shows a Dutch data set from right after World War 2. Controlling for several variables taller men and average height women have maximal fertility. The authors contrast the results from the United States, where it seems that shorter women and average height men have maximal fertility. This is kind of a big deal. The reasons for why the Dutch, who were the shortest Europeans two centuries ago, are the tallest nation in the world today, have been a matter of public discussion for over ten years (see this article in The New Yorker).

In the 19th century American whites were far taller than Europeans. European elites who toured the United States were reputedly shocked by the fact that American yeoman farmers were no shorter than them, as was the norm among the peasant classes in their lands of origin. This lack of size differential due to surplus of land in the early American republic was often compared with the relative social egalitarianism of the United States, along with its broader democratic ethos.

Obviously things have changed since the 19th century. The Malthusian conditions which ground down Dutch peasants in the 18th century no longer applied in the 20th century, and definitely not in the 21st century. Modern agricultural techniques mean that Northern Europeans are no longer nutritionally constrained. Not only that, but one could argue that today Northern European societies are more egalitarian than the the United States. Naturally there has been a focus on the environmental factors which might have shaped this difference in the distribution of heights between Northern Europeans and American whites of Northern European heritage.

But there are some biological issues which are likely relevant. Average human size, including height, actually peaked in the wake of the Last Glacial Maximum, ~20,000 years ago. Some of this is likely due to the nutritional changes enforced by the Neolithic Revolution, but the decrease in sizes predate that. Likely standard dynamics common to mammals, such as Bergmann’s rule, have also affected humans. The recent increases in height across the developed world have still not produced a population as imposing as that of late Pleistocene humans. Second, over the past few years plenty of genomic work has now argued for selection on height in Europe, explaining why there are small but persistent differences between populations in the north and south. Ancient DNA analysis has now confirmed this broadly result, as populations diverged in size due to local ecological pressures.

These new results suggest that selection is driving change in allele frequencies which control for height even today among the Dutch. The methods were pre-genomic. Basically they tracked fertility of individuals along with a bunch of variables, including height. There was no need to go into genomic details because there is a wide body of research which indicates that 80-90% of the variation in height in developed societies is controlled by variation in genes. In other words, height is a highly heritable trait. As per the breeder’s equation all you need to change a trait value for a highly heritable trait is selection:

Selection × Heritability = Response to selection

If there is selection but no heritability, then there is no response. If there is heritability but not selection, then there is no response. In this case the heritability is well known, and now they have shown selection in the Dutch population as an implication of differential fertility that tracks this heritable variation.

This framework is true for quantitative traits more generally. I wouldn’t be surprised to see that there is a fair amount of evolution going on in modern human populations, which large and robust data sets might be able to capture in the near future.

Citation: Does natural selection favour taller stature among the tallest people on earth? Gert Stulp, Louise Barrett, Felix C. Tropf, Melinda Mills, Proc. R. Soc. B: 2015 282 20150211; DOI: 10.1098/rspb.2015.0211. Published 8 April 2015

• Category: Science • Tags: Quantitative Genetics 

41o2X6mtArL._SY344_BO1,204,203,200_ Another article, More scientists doubt salt is as bad for you as the government says, in the respectable Washington Post, arguing that the salt dietary guidelines in vogue for the last generation were not based on strong science. The problem here is that bureaucratic organizations are making decisions about the health of hundreds of millions on correlational science. The incentives are skewed, and the decisions are not without cost. In the piece the journalist reports on studies which suggest that excessively low sodium content might be associated with health problems, but perhaps more important than that is that most people love salty food. Withholding salt is another way to diminish the simple pleasures of life from the populace at large.

An interesting twist on this public health issue is that it turns out that some of the original scholars argued against salt on “Paleo” grounds. That is, the small-scale and Pleistocene societies likely had very low salt intake, suggesting we were not well adapted for it. But the fact that until recently the salt guidelines for African Americans and those over 50 were more stringent implies that even then there are individual differences. Populations likely vary on “optimal” salt (or fat or sugar) intake.

• Category: Science • Tags: Health 

Print A few days ago I mentioned bioRxiv to a friend of mine who is a graduate student. She didn’t know of what I spoke, so I enlightened her. Since many of the readers of this weblog don’t have academic access, and pay journals like Nature come after you if you upload PDFs (though the open access via link option is now obviating that), it is often very nice when people originally post preprints on bioRxiv. Sometimes I even link to the bioRxiv version (or the latest) because believe it or not VPN’s can be kind of annoying even if you have access.

On one of the e-lists that I am on there was a conversation about the scientific literature that one reads (see a blog post on the topic). Because the scientific literature in an area like “evolutionary genetics” is an eternal tsunami now you need various filters and aids. PubChase, SciReader and Genomics-Twitter are pretty essential. Recently on bioRxiv I noticed an alerts page. So I am now subscribed to this on my RSS:

http://connect.biorxiv.org/biorxiv_xml.php?subject=genomics+genetics+evolutionary_biology.

Just change the parameters, and you get different subject areas.

Update: Also, I should mention Haldane’s Sieve. I think one major argument for how success that site is is that many people have no idea who is actually running the site, even if they are at the same institution. The message has become bigger than the messengers. And also a mention for Dmitri Petrov, who pushed for the Bay Area Population Genomics meetings, which is another way that scholars push friction costs down and continue the process of disintermediation.

• Category: Science • Tags: bioRxiv 
SELECTION

Is ADSL the locus of human genius?

God knows I would sleep more if it weren’t for bioRxiv. A new single author preprint debuts a new method, 3P-CLR, which extends XP-CLR, as a method to detect natural selection. The key is that it uses an explicit three-population tree to pick up selection events after the most recent, and second most recent, divergence events. So in the tree of ((Eurasians , Africans)Archaic Humans), this method can pick up perturbations which suggest selection after the emergence of a coherent anatomically modern population, but before it differentiated into its gorgeous mosaic.

In any case, the most recent version of the preprint, Testing for ancient selection using cross-population allele frequency differentiation:

A powerful way to detect selection in a population is by modeling local allele frequency changes in a particular region of the genome under scenarios of selection and neutrality, and finding which model is most compatible with the data. Chen et al. (2010) developed a composite likelihood method called XP-CLR that uses an outgroup population to detect departures from neutrality which could be compatible with hard or soft sweeps, at linked sites near a beneficial allele. However, this method is most sensitive to recent selection and may miss selective events that happened a long time ago. To overcome this, we developed an extension of XP-CLR that jointly models the behavior of a selected allele in a three-population tree. Our method – called 3P-CLR – outperforms XP-CLR when testing for selection that occurred before two populations split from each other, and can distinguish between those events and events that occurred specifically in each of the populations after the split. We applied our new test to population genomic data from the 1000 Genomes Project, to search for selective sweeps that occurred before the split of Africans and Eurasians, but after their split from Neanderthals, and that could have presumably led to the fixation of modern-human-specific phenotypes. We also searched for sweep events that occurred in East Asians, Europeans and the ancestors of both populations, after their split from Africans.

The software will be posted on the author’s github when the manuscript is accepted somewhere.

A minor note is that the data set used was from the 1000 Genomes. The Sub-Saharan Africans then are not from the hunter-gatherer populations, the Khoisan and the Pygmy, who seem to have the largest reservoir of genetic variation. The figure above is from a major signal of selection which is specific to modern humans, but excluded from the Neandertal populations. That is, fixed in us for a derived mutation, fixed in our cousins for the ancestral type (ancestral as judged by reference to the chimpanzee outgroup). My main curiosity is to push the three-population model so that it is ((Khoisan, non-Khoisan)Archaic Humans). I know from ASHG that there are now a fair amount of good quality whole genomes from African hunter-gatherers, so no doubt people are looking for these signatures.

The holy grail here for some geneticists (e.g., Svante Paabo) is to find that gene or genes which changed in us to make us sui generis. I no longer believe that this will ever be found. Assuming tens of millions of polymorphisms floating around in the genome no doubt candidate genes will emerge, just like FOXP2 did all those years ago. But I no longer believe that there is a necessary or sufficient genetic variant for our humanity. It’s a quantitative trait, and many of the hominin lineages were actually stumbling in the same direction.

On a more optimistic note, those of us who work on non-human genomes will also have data sets to rival those who are savants of humanics in the near future, so these methods are generally useful.

Citation: Testing for ancient selection using cross-population allele frequency differentiation, Fernando Racimo, bioRxiv doi: http://dx.doi.org/10.1101/017566

• Category: Science • Tags: 3P-CLR, Human Evolution, Selection 

razib Years ago I recall a reader (perhaps Ikram or Conrad Barwa?) quip that I was basically Magid Iqbal from the novel White Teeth. Probably the biggest similarities are the fact that Magid is an atheist with a pro-Western outlook, and, he’s a geneticist. But a major difference is that the Magid depicted in White Teeth strikes me as a prig. And, there are obvious biographical discrepancies. Despite my parents threatening to send me back to Bangladesh periodically for impudence, they never did. I grew up in the United States, and have the citizenship of that country, as well as Bangladesh. And I’m quite glad to be an American right now, because of articles such as this: Atheists are being hacked to death in Bangladesh, and soon there will be none left. The sad conclusion:

This weekend I arrived in Bangladesh with the naïve hope of writing about wide-eyed idealists fighting the fight no matter what, fuelled with the zeal of Je Suis Charlie. The reality on the ground is much harsher: atheists are being hunted down for both religious retribution and political gain. Washiqur Rahman was right: words cannot be killed. But a struggling movement can only take so much battering, and Bangladeshi atheism is fighting to survive.

I’m not much interested in a “movement” of atheists. Bangladesh has other problems, and in some ways it is making progress. As I may have mentioned my mother was impressed and confused by the rapid economic development she saw across the country when visiting a few months ago (my parents left Bangladesh when the nation was only about a decade old). But these recent developments sadden me greatly, because when basic liberty of thought is an offense, then we see a society regressing. Mind you, I am not much the Whig, so this does not surprise me, nor does it strike me as unnatural. I think organized Islamism is atavistic in only a rhetorical sense. The reality is that it is a feature of modernity, or at least a reaction to modernity.

Words are cheap. And “solidarity” across the oceans is pretty much worthless. But I think it is something to at least say that there, but for the grace of God go I, ironically in this particular case. To me a measure of the worth of a society is its ability to tolerate heretics. That is why I sympathize with the ancient Hellenists, and not the waxing homogeneity of Christendom über alles. And that is why I think the world of Islam is today by and large an inferior vessel for human possibility. Not to sound too much a Spenglerian, but I do hope that this flare-up of Islamic violence is simply a reaction to the inevitable liberalism which is being ushered in by the demographic transition and economic growth evident across Bangladeshi society.

• Category: Foreign Policy • Tags: Bangladesh 

mammothIt seems strikingly obvious that modern humans are a pretty big deal. In Pat Shipman’s The Invaders she argues that H. sapiens can be thought of as a top predator which is so efficient that it rearranges the whole ecosystem, wreaking havoc with the conventional trophic cascades. We can see this in the archaeological record. Humans arrive in Australia, and all sorts of cool marsupial species disappear. A similar phenomenon is attested for the New World. The more recent extinctions on islands such as Madagascar and New Zealand are well attested.

Nevertheless, many people still argue that the pattern of extinctions which we see over the Pleistocene and Holocene is not the outcome of human expansion, but climate change. In other words, they are not anthropogenic. Don’t believe me? Here’s a paper from a few years ago, Serial population extinctions in a small mammal indicate Late Pleistocene ecosystem instability:

Examination of an under-exploited source of ancient DNA—small-mammal remains—identified previously unreported and unprecedented temporal population structuring of a species within Europe during the end-Pleistocene. That we identify a series of population extinctions throughout the Pleistocene from a small-mammal species demonstrates an extensive and prolonged diversity loss and suggests a nonsize-biased reduction in ecological stability during the last glaciation, a pattern consistent with climatic and environmental change as key drivers for changes in Late Pleistocene biodiversity.

You can find similar arguments for other particular regions and areas. For example, in North America. The mysterious hand of climate is everywhere. To some extent it reminds me of arguments about the Indo-European languages, and their origin. “Out of India” proponents make points which would be just as valid for the Greeks, e.g. the early Indians and Greeks did not have a memory of being from anywhere else. Obviously the Indo-European languages are unlikely to both originate in India and Greece, but when examining just one area the arguments can seem persuasive. What needs to happen when assessing probabilities though is to get a sense of the broader framework of prior information. The same applies to the mass extinctions of the past few hundred thousand years. A new preprint on bioRxiv tries to do this, Historic and prehistoric human-driven extinctions have reshaped global mammal diversity patterns:

…Results: We find that current diversity patterns have been drastically modified by humans, mostly due to global extinctions and regional to local extirpations. Current and natural diversities exhibit marked deviations virtually everywhere outside sub-Saharan Africa. These differences are strongest for terrestrial megafauna, but also important for all mammals combined. The human-induced changes led to biases in estimates of environmental diversity drivers, especially for terrestrial megafauna, but also for all mammals combined. Main conclusions: Our results show that fundamental diversity patterns have been reshaped by human-driven extinctions and extirpations, highlighting humans as a major force in the Earth system. We thereby emphasize that estimating natural distributions and diversities is important to improve our understanding of the evolutionary and ecologically drivers of diversity as well as for providing a benchmark for conservation.

It’s a preprint, you can read the whole thing. Of course I’m broadly persuaded, since it only confirms rigorously what I already believed impressionistically.

Citation: Historic and prehistoric human-driven extinctions have reshaped global mammal diversity patterns, Søren Faurby , Jens-Christian Svenning, doi: http://dx.doi.org/10.1101/017368

• Category: Science • Tags: Ecology, Extinction 
Razib Khan
About Razib Khan

"I have degrees in biology and biochemistry, a passion for genetics, history, and philosophy, and shrimp is my favorite food. If you want to know more, see the links at http://www.razib.com"