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

April 28, 2017

Less intelligent people want to exclude racists from the public square

Filed under: Culture,GSS,Racism — Razib Khan @ 10:03 pm
Logit Coefficients  
  B SE(B) Probability
SEX 0.739 0.217 0.001
DEGREE -0.302 0.092 0.001
WORDSUM -0.338 0.068 0
POLVIEWS -0.078 0.078 0.317
INCOME -0.026 0.06 0.671
AGE 0.007 0.007 0.283
ATTEND 0.09 0.046 0.05
GOD -0.018 0.077 0.819
Constant 3.341 0.937 0

It’s been a while since I’ve done much GSS blogging. Part of it is that I’ve got only so much attention I can devote to things, and most of my focus has been on the area of science that I’m interested in, and one or two non-scientific topics. The second variable is that I started blogging about GSS data a long time ago (~2008), and there’s only so much interesting stuff you can talk about.

But over the past few years there have been some controversies related to speech in public spaces, and what is and isn’t acceptable. There has also been some chatter that young people today in particular are intolerant of freedom of speech. I’ve wanted to address this, so here I go.

The toleration of racists is in today’s America is like testing a boundary condition. If you are willing to tolerate racist speech if you are not a racist, then you are pretty likely to be a free speech absolutist. I am not interested in rehashing arguments, I support free speech in an absolutist sense personally. Rather, let’s look at some data.

The General Social Survey has a question up from 2014 for the variable RACEMEET that asks:

Should people prejudiced against any racial or ethnic group be allowed to hold public meetings?

The question was asked in 2010 and 2014, and 2,651 individuals answered this. The answer was converted to ordinal, so I decided to probe relationships between variables and the score of toleration through regression. Some independent variables, such as political viewpoint (POLVIEWS), were recoded in an ordinal fashion (so that “extremely liberal” = 1, “liberal” = 2, and so forth, to “extremely conservative” = 7). Others, such as age, do not require any recoding. RACEMEET itself was converted to an ordinal.

The above results suggest that political ideology does not predict your response to this question much once you account for other variables. In fact, I did a query on ideological views first, and the results indicated to me what was really going on.

  EXT. LIB. LIB. SLIGHTLY LIB. MODERATE SLGHTLY CONSERV. CONSERV. EXT. CONSERV.
1: Should definitely be allowed 39 24 17 15 22 17 20
2: Should probably be allowed 12 24 24 21 22 22 15
3: Should probably not be allowed 26 20 19 22 19 24 22
4: Should definitely not be allowed 23 32 40 43 37 38 43

As you can see moderates are relatively skeptical of allowing racists to have a public meeting. All of my analysis of the GSS indicates that moderates are not as smart as more liberal or conservative people.

Let’s go through the variables which were significant predictors above. First, sex.

Male Female
1: Should definitely be allowed 21 13
2: Should probably be allowed 22 21
3: Should probably not be allowed 20 23
4: Should definitely not be allowed 36 43

These results were expected. On the whole women tend to be more skeptical of absolutist free speech positions which allow offensive material to be promoted (women are more skeptical of allowing Communists to speak too in comparison to men, so it’s not because of the ideology of the speaker or viewpoint).

Then church attendance frequency:

Never attends church More than once a week
1: Should definitely be allowed 20 23 19 14 21 15 13 14 13
2: Should probably be allowed 21 21 27 24 13 16 26 22 20
3: Should probably not be allowed 21 17 20 18 28 24 18 24 23
4: Should definitely not be allowed 37 39 34 44 37 45 43 40 44

A modest difference.

Next, highest educational attainment:

No HS HS Some college College Graduate
1: Should definitely be allowed 7 14 11 26 32
2: Should probably be allowed 14 20 23 29 27
3: Should probably not be allowed 20 23 21 19 20
4: Should definitely not be allowed 59 43 45 26 21

The big gap here is between those with college and those without college educations.

Finally, we look at WORDSUM, which is a proxy for intelligence. It’s a ten word vocabulary test. Below in the columns are the number of answers a respondent got correct:

<5 5 6 7 8 9 10
1: Should definitely be allowed 8 10 12 16 24 30 36
2: Should probably be allowed 13 22 18 24 26 34 33
3: Should probably not be allowed 27 20 23 22 21 18 18
4: Should definitely not be allowed 52 48 47 38 29 18 12

I combined those who scored below 5 out of 10 (0-4) into one class. You can see that as score on this vocabulary test goes up, the view that racists should be allowed to meet in public goes up. It’s almost monotonic. The smartest people are more tolerant than the next smartest people who are more tolerant than the next smartest people, with the dumb being the least tolerant.

I made the below chart to illustrate this:

Often when it comes to views associated with “smart” people when you put it into some regression eduction accounts for all of the difference. In other words, the less intelligent educated have the same views as the intelligent educated, and the more intelligent but less educated have the same views as the less intelligent less educated. There are more older people who are intelligent but not educated, so it could be generational too (though in this case age does not seem to matter). A plausible hypothesis is that in many cases it is social milieu. Even if you are not bright, being in college inculcates certain values.

And college is a predictor. But these data show that even if you account for college education the brighter you are, the more likely you favor allowing tolerance for views that most people find intolerable.

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

Filed under: Africa,Evolution,Genetics,Genomics,Human Evolution,Human Genetics — Razib Khan @ 4:14 pm

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

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

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

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

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

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

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

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

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

What do we take away from this?

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

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

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

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

April 26, 2017

“Out of Africa” bottleneck is what really matters for mutations

Filed under: Africa,Genetics,Genomics,Human Evolution,Pygmies — Razib Khan @ 10:49 pm


At least in relation to mutational load, if you read a new preprint in biorxiv, The demographic history and mutational load of African hunter-gatherers and farmers:

The distribution of deleterious genetic variation across human populations is a key issue in evolutionary biology and medical genetics. However, the impact of different modes of subsistence on recent changes in population size, patterns of gene flow, and deleterious mutational load remains to be fully characterized. We addressed this question, by generating 300 high-coverage exome sequences from various populations of rainforest hunter-gatherers and neighboring farmers from the western and eastern parts of the central African equatorial rainforest. We show here, by model-based demographic inference, that the effective population size of African populations remained fairly constant until recent millennia, during which the populations of rainforest hunter-gatherers have experienced a ~75% collapse and those of farmers a mild expansion, accompanied by a marked increase in gene flow between them. Despite these contrasting demographic patterns, African populations display limited differences in the estimated distribution of fitness effects of new nonsynonymous mutations, consistent with purifying selection against deleterious alleles of similar efficiency in the different populations. This situation contrasts with that we detect in Europeans, which are subject to weaker purifying selection than African populations. Furthermore, the per-individual mutation load of rainforest hunter-gatherers was found to be similar to that of farmers, under both additive and recessive modes of inheritance. Together, our results indicate that differences in the subsistence patterns and demographic regimes of African populations have not resulted in large differences in mutational burden, and highlight the role of gene flow in reshaping the distribution of deleterious genetic variation across human populations.

There’s two major moving parts in this preprint. First, they using phylogenomic methods to explicitly model population history. Second, they integrated their demographic results in generation and interpreting the distribution of mutations within the exomes of these populations. That is, they combined phylogenomics to gain insight into population genomics, as the latter focuses more on the parameters which define variation with a population.

The data they worked with was from the exome. The regions of the genome which translate into genes. That’s ~30 million bases. They get really good precision due to high coverage, hitting site about 70 times. Their sample was about 300 Africans and 100 Europeans, and they got ~500,000 polymorphisms or variants for their trouble.

The populations were labeled by subsistence and provenance. The Europeans were Belgians. For the Africans they had two groups of hunter-gatherer Pymgies, and two groups of Bantu agriculturalists, sampled from western and eastern locations as you see on the map above.

The admixture plots, which separate out individuals into K numbers of populations break out in a way that makes sense. First, Europeans separate, and the eastern agriculturalist populations have a little bit of evidence of European-like ancestry. This is almost certainly Middle Eastern farmer, which has been found in many East African populations, and those populations which have mixed with them. Then the hunter-gathers separate from the agriculturalists. This is in line with expectation and earlier research; the hunter-gatherers of Africa seem very different from the agriculturalists, and are actually more closely related to each other than the agriculturalists in their neighboring regions.

The exception to this pattern is caused by recent gene flow, which is clearly evident above. Due to population size differences it looks like there is more agricultural ancestry in the Pygmies than vice versa. I wish that they had sampled Mbuti Pygmies. I’m told that this group has the least agricultural admixture.

But then they decided to get fancy and explicitly model demographic histories with fastsimcoal2. What does this do? From the website for the software:

While preserving all the simulation flexibility of simcoal2, fastsimcoal is now implemented under a faster continous-time sequential Markovian coalescent approximation, allowing it to efficiently generate genetic diversity for different types of markers along large genomic regions, for both present or ancient samples. It includes a parameter sampler allowing its integration into Bayesian or likelihood parameter estimation procedure.

fastsimcoal can handle very complex evolutionary scenarios including an arbitrary migration matrix between samples, historical events allowing for population resize, population fusion and fission, admixture events, changes in migration matrix, or changes in population growth rates. The time of sampling can be specified independently for each sample, allowing for serial sampling in the same or in different populations.

The models you see that were tested are pretty simple, and they all seem plausible I suppose. Their simulations suggested that the three above scenarios, with alternative branching patterns and various gene flows, were all of equal likelihood. That is, given the models and the data that they had (4-fold synonymous sites which are likely to be neutral) you can’t distinguish which is right.

In all the models hunter-gatherers diverged relatively recently and so did the agriculturalists. Europeans, who are stand-ins for all non-Africans in this scenario, diverged pretty early from the Africans. But how the Africans relate to each other and Europeans is not totally clear. Why? Because ancient population structure. It is becoming rather obvious now that ~100,000 years ago, and earlier, there were many different modern human lineages which had already diversified. The Khoisan seem to have diverged from other human lineages closer to 200,000 thousand than 100,000 years ago. What this means is that for most of the history of anatomically modern humans population structure  existed between distinct lineages. And some of that persists down to today within Africa.

I’ll bullet point some of their inferences from these models (verbatim quotes below):

  1. Our results suggest that the ancestors of the contemporary RHG, AGR and EUR populations diverged between 85 and 140 thousand years ago (kya), from an ancestral population that underwent demographic expansion between 173 and 191 kya
  2. After the initial population splits, the Ne of AGR and RHG (NaAGR and NaRHG) remained within a range extending from 0.55 to 2.2 times the ancestral African Ne (NHUM), whereas EUR (NaEUR) experienced a decrease in Ne by a factor of three to seven.
  3. The ancestors of the wRHG and eRHG populations diverged 18 to 20 kya (TRHG), and underwent a decreased in Ne by a factor of 3.8 to 5.7 for the wRHG (NwRHG) and 7.1 to 11 for the eRHG (NeRHG), regardless of the branching model considered.
  4. The ancestors of the AGR (NaAGR) split into western and eastern populations 6.7 to 11 kya (TAGR), and underwent a mild expansion, by a factor of 2.3 to 3.1 for the wAGR (NwAGR) and 1.2 to 2.2 for the eAGR (NeAGR).
  5. The EUR population experienced a 7.1- to 8.3-fold expansion (NEUR) 12 to 22 kya (TEUR).

No results are perfect. But some of these dates do not make sense. There’s a lot of circumstantial evidence that the ancestors of European populations began to expand over the last 10,000 years. The dates above suggest there was a Pleistocene expansion. Basically you can divide that value by half, and then you get a reasonable range.

Second, both the agriculturalists sampled here are Bantu speaking, and there’s a good amount of cultural and genetic data for recent shared ancestry of the Bantu over the last 3,000 years. I understand that admixture with a very diverged lineage (e.g., eastern Bantu agriculturalist samples mixing with Nilotic populations, which is how they got some non-African ancestry, as well as local Pygmy groups) can inflate these divergence dates. If that’s the case, they should note that in the text.

We don’t have much historical or archaeological clarity from what I know about divergences between Pygmy groups. This particular group has studied the topic and published on it before, so I’m inclined to trust them more than anyone else. But, the above dates for groups we do know make me a bit more skeptical of a simple divergence around the Last Glacial Maximum.

Then there are the earliest divergences. And 85 to 140,000 year interval is huge for when non-Africans split off from Africans. If closer to 140 than 85, then that means that non-African divergence from Africans preserves ancient African diversity. That is, non-Africans descend from an African group that no longer exists (or has not been sampled in this study at least!). I’ve poked around this question, and when you take into account recent gene flow, it is hard to find the specific African group that non-Africans descend from, though there is some consensus that they branched off from the non-Khoisan Africans later than from the Khoisan.

But there is also a lot of archaeological and some ancient genetic DNA now that indicates that the vast majority of non-African ancestry began to expand rapidly around 50-60,000 years ago. This is tens of thousands of years after the lowest value given above. Therefore, again we have to make recourse to a long period of separation before the expansion. This is not implausible on the face of it, but we could do something else: just assume there’s an artifact with their methods and the inferred date of divergence is too old. That would solve many of the issues.

I really don’t know if the above quibbles have any ramification for the site frequency spectrum of deleterious mutations. My own hunch is that no, it doesn’t impact the qualitative results at all.

Figure 3 clearly shows that Europeans are enriched for weak and moderately deleterious mutations (the last category produces weird results, and I wish they’d talked about this more, but they observe that strong deleterious mutations have issues getting detected). Ne is just the effective population size and s is the selection coefficient (bigger number, stronger selection).

Why are the middle two values enriched? Presumably it’s the non-African bottleneck. This is where another non-African population would have been a nice check to make sure that it was the “Out of Africa” bottleneck…but it’s probably asking a bit much to sequence more individuals to 70x coverage.

The lack of difference between the African populations is an indication that recent demography is not shaping the distribution much. Additionally, they note that gene flow between the African groups probably increased diversity in some ways, so that as long as a group is connected with other populations it will probably be rescued (note that none of these in their data were particular inbred as judging by runs of homozygosity).

Finally, they found that the number of homozygote mutations that were deleterious is higher in their model results for Europeans than the African groups. This is not surprising, and what one expects. But, they found that this is a function likely of continuous gene flow between the African groups. Without gene flow homozygosity would have been much higher. This gets back to the fact that gene flow is a powerful homogenizing tool, and the lack of gene flow has to be pretty extreme for divergence to occur.

Which brings us back to the “Out of Africa” event. The next ten years are going to see a lot of investigation of African phyologenomics and population genomics. Basically, the relationships, and selection pressures. It is totally implausible that Bantu groups in Kenya and Tanzania did not absorb local non-Nilotic populations. We’ll figure that out. Additionally, selection pressures are probably different between different groups. We’ll know more about that. But, ancient DNA will probably give us some understanding of why non-Africans went through such a massive demographic sieve. We know in broad sketches. But most people want to fill in the details.

Citation: The demographic history and mutational load of African hunter-gatherers and farmers, Marie Lopez, Athanasios Kousathanas, Helene Quach, Christine Harmant, Patrick Mouguiama-Daouda, Jean-Marie Hombert, Alain Froment, George H Perry, Luis B Barreiro, Paul Verdu, Etienne Patin, Lluis Quintana-Murci, doi: https://doi.org/10.1101/131219

Why do you read me and who are you

Filed under: Blog,Unlurk — Razib Khan @ 8:20 pm

The first time I tried to get through Scott Atran’s In Gods We Trust: The Evolutionary Landscape of Religion, I gave up because it seemed so pretentious and impenetrable. My curiosity was piqued by the fact that the subtitle alluded to evolution, and I was interested in evolutionary psychology. But though In Gods We Trust does talk somewhat about the evolutionary origins of religion, fundamentally it’s a work of cognitive anthropology.

Because I did not know about this field, its lexicon struck me as totally opaque, and there seemed something almost Post-Modern and French about Atran’s prose. Actually though this perception made some sense, Atran, Dan Sperber, Pascal Boyer, and Larry Hirschfeld actually came up with the naturalistic paradigm in anthropology while meeting at Sperber’s home in Paris in the early 1980s.

I did end up reading In Gods We Trust front to back a year after I initially tackled it, along with some other books on religion from this perspective (e.g., Religion Explained by Pascal Boyer). Up until 2007 or so I would write extensively on cognitive anthropology and religion, but I got what I wanted to in terms of insight after period and do not write much on this topic (in 2006 I actually got invited to a conference with a press pass on the topic of religion and evolution, my interests had become so well known in this domain).

So I was surprised to see this comment:

I’ll give it a go. I tried starting with Principles of Population Genetics but found it heavy going (Ive only been reading here for a few years and mainly got into it for the posts about religion, but the genetics stuff is quite interesting)

I suppose I still write about religion enough that that might hook some people. Though honestly I don’t have anything original to say…it’s just that much of mainstream commentary strikes me as totally dumb and uninformed.

But that prompts me. Consider this an “unlurk” thread. Two questions:

1) Why do you read me? (and implicitly, what should I write about more?)

2) Tell me anything about yourself that you think would be of interest to me or other readers (some of you are not anonymous, so I know those who are lawyers in Colorado or engineers in Australia; that sort of thing)

The anti-“End of History and the Last Man”

Filed under: Adam K Webb,Culture,History — Razib Khan @ 6:42 pm

Francis Fukuyama’s The End of History and the Last Man has often been misconstrued. But, it did argue for the long term trend of the ascendancy of democracy and market values. Though Fukuyama did not necessarily predict the universal dominance of Western liberalism, that is one of the corollaries many associate with The End of History and the Last Man.

About 10 years ago I read a book which in many ways stood at total odds with Fukuyama’s thesis, Beyond the Global Culture War by Adam K Webb. I was very skeptical of Webb’s thesis, but intrigued by it. So much so that I did a 10 questions with him.

With hindsight I now believe that many of Webb’s contentions are much more relevant today in 2017 than they were when he wrote Beyond the Global Culture War. Though Webb was not prescient in the details, I think he did get at the fundamental limits of the Western liberal paradigm which were beginning to be exposed in the wake of 9/11.

(note, he has a newer book, Deep Cosmopolis: Rethinking World Politics and Globalization, which I have not read)

April 25, 2017

Austin vs. Portland

Filed under: Austin,Culture,Portland — Razib Khan @ 6:12 pm


The above video is from a Portlander who is quite anti-Austin, though in a tongue-in-cheek fashion.

The issue of cross-city comparisons was on my mind for two reasons. First, Joel Kotkin wrote an article last fall in Forbes, America’s Next Great Metropolis Is Taking Shape In Texas, that friends are sharing on Facebook. Second, I’m someone who has lived in both cities (around downtown Austin and the Hawthorne neighborhood in Southeast Portland). I still travel between Texas and Oregon, and it’s pretty interesting how people react when they find out that I live in Texas or that I’m from Oregon in the other locale. Kind of a wary curiosity about my opinions (in Austin one is careful to mention one’s California days lest the wrath of the native be triggered).

In Oregon it rains gently at an angle; raincoat, not umbrella.

First thing, though the video above is kind of silly and not too serious, I do want to address one thing. Texas is not more arid than Oregon. I’m actually originally from eastern Oregon, so I have to remind people that 2/3 of the state is quite dry, whether it be semi-arid or arid. Inspection of the above map shows that a much larger portion of Oregon is extremely arid than Texas. Also, Portland gets 41 inches per year. Austin? 37. The difference is that Portland’s is frontal precipitation that is dispersed over much of the year in drizzles and overcast skies, while Austin is subject to more convective bursts. Where there are 145 sunny days in Portland per year (remember there is summer drought), there are 230 such days in Austin.

Austin combines a vertical downtown with huge expanses of quasi-suburban sprawl.

Austin still has a lower cost of living, mostly because of housing. Due to its rapid population growth, Austin’s transportation infrastructure and supply of health professionals is far inferior to Portland. But, the population growth is obviously due to an economic dynamism which Portland can’t match; unless you work at Intel it seems most educated young people in Portland are retired and working as a barista on the side (this is an exaggeration, but you get the point).

Can you name Portland’s iconic food?

I’d say Austin’s food is definitely better and cheaper. For beer, I will give the nod to Portland, which has a more well developed scene for microbrews. The same with coffee. It’s hard to compare outdoor amenities. The Pacific Northwest has real trees. The rest of the country has bushes. Austin is near the Texas hill country, but Oregon has hills, mountains, and gorges. It has Crater Lake. But because of the warm weather you can go swimming and enjoy the outdoors the whole year without much

Vistas

preparation in Austin. The Colorado river in Austin is less geologically impressive than the Willamette, but there’s a lot more recreational activity because it’s warm and dry so much of the year.

A major difference between Portland and Austin is the university scene (or lack thereof). Portland State University has about half the student body of UT Austin, but its prominence within the city (and nationally) is far less than that simple quantitative measure. UT is located right north of downtown, so it’s an integral part of the Austin scene. In contrast, though PSU is located just south of downtown Portland, it is a much lower key presence. UT Austin is the flagship campus of the state university system of Texas. In contrast, PSU did not initially offer doctoral programs, and is a Research 2, a opposed to a Research 1, institution. Its roots were as a commuter school, and it still has many non-traditional students. In contrast UT Austin students are some of the most academically talented kids from all over Texas, which does not have large elite private universities, like California (Stanford and USC are both much larger than Rice).

Oregon has good beer

Finally, the arts & entertainment scene. This is really about taste obviously. Portland has a more artisanal arts scene, if that makes sense. More off the wall, homegrown, and organically and haphazardly presented. I didn’t really take advantage of it much when I lived in Portland, but honestly I’m not big into the arts scene here in Austin. But I’ve gone to shows now and then. It’s hard not to in Austin, which is crawling with musicians, and where live music is blasting up and down 6th street. But as Austin has gotten more popular and well known, it has also gotten more commercial and commoditized. National acts like Taylor Swift an Adele swing through town, and SxSW and ALC are huge draws. It’s easy to take it for granted, and honestly now it’s just part of the background furniture of my life.

Ritz beats the Baghdad

Note: I don’t have much to say about the fact that Austin is the capital of Texas. For me the main consequence of this fact is that perhaps this is one of the major reasons that the flagship university of the state system was located here (though usually it doesn’t work out like that). The Capitol is downtown, and there’s some political stuff going on there. But it’s pretty sealed off from the rest of the town. In contrast, Sacramento, probably is more affected by being the capital of California, since the city is less distinctive. And Albany is totally overshadowed by being the capital (I am naming three cities where I have actually lived at some point).

Dost thou know the equilibrium at panmixia?

Filed under: Genetics,Population genetics — Razib Khan @ 3:58 pm

If you read a blog about Biblical criticism from a Christian perspective it would probably be best if you were familiar with the Bible. You don’t have to have read much scholarly commentary, rather, just the New Testament. Barring that, at least the synoptic gospels!

At this point, with over 400 individuals responding to the reader survey, it is strange to consider that more people believe they have a handle on what Fst is than the Hardy-Weinberg Equilibrium. First, Fst is a more subtle concept than people often think it is. And second, because the HWE is so easy, important, and foundational to population genetics. I mean p^2 + 2pq^2 + q^2 = 1. Could it be simpler???

So a quick ask. If you are one of the people who doesn’t understand HWE or why it is important, please get yourself a copy of John Gillespie’s Population Genetics: A Concise Guide. I understand that not everyone has the time, interest, or money for Principles of Population Genetics, or any of the more “hardcore” texts. But Population Genetics: A Concise Guide will surely suffice to follow anything on this blog.

Or, barring that, please review the online resources which you have available. Two examples:

Graham Coop’s Notes on Population Genetics or Joe Felsenstein’s unpublished textbook Theoretical Evolutionary Genetics.

April 24, 2017

The civilization before history

Filed under: History,Sumeria,Uruk — Razib Khan @ 10:36 pm

A forgotten civilization?

No, I am not talking about Atlantis or Hyperborea or Lemuria. Nothing made up here. Nor am I talking about the real Neolithic cultures highlighted in War Before Civilization. I alluding to the period between 3500 and 3100 BCE in the Near East when the city of Uruk was the nexus for and a source of a massive cultural and mercantile expansion. I’ll quote Wikipedia:

Around 3600 BC, during the Middle Uruk period, Uruk trade networks started to expand to other parts of Mesopotamia, and as far as North Caucasus. According to archaeologist Konstantine Pitskhelauri, this expansion started even earlier, at the end of the 5th millennium BC, and continued in the 4th millennium.

Large masses of Uruk migrants settled in the South, and later in the North Caucasus. The sites in this general area include Habuba Kabira in Syria, and Arslantepe in Turkey. Uruk expansion to the northeast included sites like Godin Tepe in Iran. Tepe Gawra, in northwest Iraq, is another important site with deep stratigraphy that includes the Uruk period in later layers. Hamoukar is a large site in northeastern Syria that has been recently excavated; it includes Uruk and pre-Uruk layers.

Uruk enclaves have also been identified at Tell Brak and Nineveh in northern Mesopotamia, and on the Syrian Euphrates at Qrayya, and Jebel Aruda. On the Euphrates in Anatolia, Uruk enclaves were found at Hassek Hoyuk, Samsat, and Tepecik (Elazığ Province, near Keban Dam).

Sargon of Akkad is usually asserted to have been the first empire-builder in history, in that his rulership extended across many ethnicities, from the Mediterranean to the Persian Gulf. The Four Corners of the World he claimed. But the Sargonid system lasted for but a century, and successor Mesopotamian hegemonies did not extend beyond the land of two rivers until the rise of the Neo-Assyrian Empire over 1,000 years later.

In contrast, the Uruk culture persisted for hundreds of years, far longer than successor polities in that area in the 3rd millennium. It was also more expansive than even than Sargon’s empire.

There has long been a debate about the nature of the Uruk expansion. What is ideology? Was it trade? Was it migration? Was it conquest?

Empire of power, empire of ideas

Since we do not have writing to tell us a narrative we can never know definitively, at least until ancient DNA clears up the demographic questions. In Babylon: Mesopotamia and the Birth of Civilization the author points out that Communism spread across many societies without invasion (though in some cases there was external invasion; ask the Germans). Similarly, many religions have also spread without external invasion. Christianity’s spread to Armenia, Ethiopia, Georgia, and Ireland, occurred relatively gradually and synthesized without indigenous cultural forms due to broad-based diffusion as well as elite adoption so as to integrate into the Christian world system. But there is something very distinct about the Uruk expansion in contrast to the above examples: some of the cities seem to be replica copies of Uruk in toto.

If it was an ideological movement of emulation by local elites only there should have been at least some synthesis even these narrow regions of Uruk-outside-of-Sumeria. In fact there seem to have been small pieces of Uruk society scattered across the Fertile Crescent (and beyond!) during this period, embedded in wholly culturally alien territory. Additionally, there is some circumstantial evidence for fighting and conquest.

Now that we know there were massive migrations during the Neolithic and Bronze ages across the Near East and Europe, I think we should update our estimations of the alternative hypotheses. In light of radically decreasing genetic distance between the eastern and western portions of the Fertile Crescent since the rise of agriculture it seems implausible to think that the Uruk expansion might not have at least been partly mediated by the movement of people. People moved. So did ideas.

That being said, as observed in Babylon: Mesopotamia and the Birth of Civilization, the recession of the Uruk hegemony after ~3100 BCE was extreme in its totality and rapidity. Heretofore longstanding zones of Uruk civilization outside of southern Mesopotamia disappear immedlately. Peasant ways of life which had flourished in the local regions during earlier periods reappear as the city-states disappear. Not only does the way of life defined by the Uruk period retreat, but the sole overarching preeminence of Uruk in what became Sumeria disappears, to be replaced by a millennium of jostling between rival city-states, Uruk (Erech in the Bible), Ur, Kish, and Lagash.

Later analogs to the Uruk collapse

Does this remind you of something? The Late Bronze Age was characterized by a collapse of civilization as well, with a regress to old centers such as Babylonia, Assyria, and Egypt. Smaller polities on the Levantine coast emerged in the wake of the decline of the earlier empires, while Greece and Anatolia went into “Dark Ages,” as the Mycenaean citadel society descended into barbarism and the Hittite domains totally collapsed.

The city-states of Classical Greece were fundamentally different from the Mycenaean citadel-culture that had preceded them centuries earlier. The Greek civilization of the Bronze Age had adopted many of the forms of the Minoan society based in Crete and extending around the Aegean. Aesthetically, and in terms of their writing system. Mycenaean civilization was fundamentally one of rough hewn barbarians grafted onto a beautiful well developed canopy of Minoan motifs. And the Minoans themselves were clearly influenced by the broader constellation of Near Eastern civilizations, from the Hittites to the kingdom of Cyprus and down to Egypt.

Classical Greece was very different, mostly doing away with the autocratic kingships of the Bronze Age, as well as adopting a different form of writing from the Phoenicians. Linear B was impenetrable to them. All the scribes had died without passing their knowledge.

Though Homer and the broader corpus of Greek mythology clearly preserves elements of the Bronze Age society (translation of Mycenaean Linear B tablets makes it clear that many of the Classical gods had roots in the the pantheon of the Bronze Age), the Classical Greeks had forgotten their Mycenaean past (before Linear B was translated it was assumed by most that it was not Greek, but rather a mainland extension of Minoan civilization). The cyclopean masonry typical of Mycenaean citadels were believed by Greeks of the later period to have been constructed by…cyclops.  This method had been forgotten in the several hundred year Greek Dark Age. The battles depicted in the Iliad are clearly those between petty Dark Age warlords, not the kings of old (though the prominence of Mycenaean cities such as Pylos and Mycenae were recalled).

The point here is that Mycenaean Greek civilization, which was created to a great extent by imitating a non-Greek prototype, collapsed, after which there was total regression to peasant barbarism. The Greek civilization that emerged later was much more distinctive, and less imitative, than the initial incarnation.

The Sumerian Dark Age and its aftermath

Unlike the case with the Mycenaeans, I believe that Uruk expansion to the west, north, and east, was mediated by migration and conquest from the source. Mycenaean civilization was modeled upon, and strongly inflected by, Minoan civilization, which was modeled upon Near Eastern polities. But they were never total replicas of each other. Though there were certainly mercantile connections and colonies of Near Easterners in the Aegean, it seems likely that these later cases of influence were genuine instances of cultural diffusion. We have writing to back-up our presuppositions.

In contrast, the nature of the Uruk expansion indicates transplantation in totality and exact replication of the original society. To me this reminds me of Roman colonies. Unlike cultural diffusion, the colonies of Latin speaking Roman citizens in regions of southern Gaul, Iberia, and North Africa, served as entry-points for Romanitas. But this Romanization could be reversed. This was certainly the case in southern Britain, which had a fully developed Latin Roman urban society, but collapsed back to barbarism with the retreat of the legions. Arguably it was also the case in the hinterlands of the Balkans, with modern Vlachs and Romanians being the descendants of the Latin peasants.

It is not difficult then to assume that if there was some exogenous shock to the Uruk system ~3100 BCE, the isolated colonies would quickly whither. Just as the urban centers of southern Britain were replaced by fortresses of semi-barbaric British elites, so the subjugated hinterland cultures, which had persisted, quickly filled the vacuum left by the collapse of the Uruk polity. Eventually, just as Classical Greece developed its own distinct indigenous civilization in the broader commonwealth of eastern Mediterranean polities, so Ugarit, Ebla, Mari, the city-states of Hatti, and Urartu, came into the light of history in the 3rd millennium organically.

Forgotten Antediluvian Sumeria

In Babylon the author suggests that the flood legend allows them to partition their own literate civilization, which developed after 2900 BCE, from the fallow two century period after the collapse of the Uruk ascendancy. Could the the Sumerians have forgotten the greatness of the 4th millennium in a few centuries? I believe that they might have.
The Uruk ascendancy of the 4th millennium, if it took political form, would have have exhibited none of the totality and dominion of a modern nation-state. Rather, like the Maurya Empire, and many antique polities, it would have been defined by numerous strongpoints extending out from a dense and well networked core. In the outer zones of control the dominion would have consisted primarily of close supervision of the interstices between territories occupied by indigenous tribal chiefdoms, who may have given nominal fealty to the local governor appointed from Uruk. A collapse would have consisted proximately of the destruction or abandonment of the strongpoints, and ultimately the forgetting of the period of alien hegemony by the local populations.

At that time core Sumeria was an oral society, and in the centuries after the Uruk expansion there were major changes to many aspects of its physical superstructure, and therefore one presumes the ideologies underpinning the control of the population by the elite. Without written records the quasi-imperial past might have become muddied very quickly if there was a transition of elites. The peasants would have had no great incentive to remember the Uruk hegemony, while the nouveau elites may have wanted to created their own legends, rather than be haunted by the earlier greatness.

The many civilizations before writing

My forebears?

The Uruk ascendancy should not be a surprising idea when we think about it in the context of world “history.” The civilization of the Indus valley was certainly a civilization, but its script remains undeciphered. Though they were likely symbolic in some manner, it is quite possible that they were not a fully fleshed representation of language in the way cuneiform was. Most of the examples of the script are exceedingly short.

But we know something about the Indus people in part because we know that they traded with Sumeria, and there were people from this culture who were resident in Sumerian towns. Clearly Sumer viewed these people as peers, albeit aliens.

Another example would be the Inca. Before the Spanish overthrew their empire, it stretched from Columbia to central Chile. Because we have Spanish records, and memories of the Inca nobility who were assimilated into the post-conquest order, we know that this was not simply an ideological expansion. It was a military one. And one of demographic transplantation and imposition. Though there still debates, it seems most likely that the Inca did not have true literacy.

The ultimate point is that ancient people were far more organized and cohesive across large territories than we likely give them credit for. Let me finish with this article from last year in Science, Slaughter at the bridge: Uncovering a colossal Bronze Age battle:

About 3200 years ago, two armies clashed at a river crossing near the Baltic Sea. The confrontation can’t be found in any history books—the written word didn’t become common in these parts for another 2000 years—but this was no skirmish between local clans. Thousands of warriors came together in a brutal struggle, perhaps fought on a single day, using weapons crafted from wood, flint, and bronze, a metal that was then the height of military technology.

And yet chemical tracers in the remains suggest that most of the Tollense warriors came from hundreds of kilometers away. The isotopes in your teeth reflect those in the food and water you ingest during childhood, which in turn mirror the surrounding geology—a marker of where you grew up…Just a few showed values typical of the northern European plain, which sprawls from Holland to Poland….

Further clues come from isotopes of another element, nitrogen, which reflect diet. Nitrogen isotopes in teeth from some of the men suggest they ate a diet heavy in millet, a crop more common at the time in southern than northern Europe.

Ancient DNA could potentially reveal much more: When compared to other Bronze Age samples from around Europe at this time, it could point to the homelands of the warriors as well as such traits as eye and hair color. Genetic analysis is just beginning, but so far it supports the notion of far-flung origins. DNA from teeth suggests some warriors are related to modern southern Europeans and others to people living in modern-day Poland and Scandinavia. “This is not a bunch of local idiots,” says University of Mainz geneticist Joachim Burger. “It’s a highly diverse population.”

As University of Aarhus’s Vandkilde puts it: “It’s an army like the one described in Homeric epics, made up of smaller war bands that gathered to sack Troy”—an event thought to have happened fewer than 100 years later, in 1184 B.C.E. That suggests an unexpectedly widespread social organization, Jantzen says. “To organize a battle like this over tremendous distances and gather all these people in one place was a tremendous accomplishment,” he says.

Standardized metal weaponry and the remains of the horses, which were found intermingled with the human bones at one spot, suggest that at least some of the combatants were well-equipped and well-trained. “They weren’t farmer-soldiers who went out every few years to brawl,” Terberger says. “These are professional fighters.”

Curiouser and curiouser….

April 23, 2017

LaTeX notes

Filed under: Blog,LaTeX — Razib Khan @ 11:40 pm

I recently installed a plugin that will allow me to render LaTeX. Mostly this is because I’ve long avoided writing out equations because it’s awkward in HTML, and it gets unintelligible quickly. This will allow me to explore population genetics in its “natural language” a little easier.

But I just noticed on my RSS feed view the LaTeX is not rendering for whatever reason. Where there should be equations or LaTeX rendered text there is a blank space. This is unfortunate, but I don’t know what to do about it. So just click through if you want the equations. If you are willing to “hum through” those portions it shouldn’t matter. The equations aren’t going to take up much of any post.

Also, Donald Knuth is a god. Probably he’ll think that’s blasphemous because he’s a Lutheran and all, but The Art of Computer Programming beats the Bible in my book!

Why the rate of evolution may only depend on mutation

Filed under: Evolutionary Genetics,Genetics,Population genetics — Razib Khan @ 10:07 pm

Sometimes people think evolution is about dinosaurs.

It is true that natural history plays an important role in inspiring and directing our understanding of evolutionary process. Charles Darwin was a natural historian, and evolutionary biologists often have strong affinities with the natural world and its history. Though many people exhibit a fascination with the flora and fauna around us during childhood, often the greatest biologists retain this wonderment well into adulthood (if you read W. D. Hamilton’s collections of papers, Narrow Roads of Gene Land, which have autobiographical sketches, this is very evidently true of him).

But another aspect of evolutionary biology, which began in the early 20th century, is the emergence of formal mathematical systems of analysis. So you have fields such as phylogenetics, which have gone from intuitive and aesthetic trees of life, to inferences made using the most new-fangled Bayesian techniques. And, as told in The Origins of Theoretical Population Genetics, in the 1920s and 1930s a few mathematically oriented biologists constructed much of the formal scaffold upon which the Neo-Darwinian Synthesis was constructed.

The product of evolution

At the highest level of analysis evolutionary process can be described beautifully. Evolution is beautiful, in that its end product generates the diversity of life around us. But a formal mathematical framework is often needed to clearly and precisely model evolution, and so allow us to make predictions. R. A. Fisher’s aim when he wrote The Genetical Theory Natural Selection was to create for evolutionary biology something equivalent to the laws of thermodynamics. I don’t really think he succeeded in that, though there are plenty of debates around something like Fisher’s fundamental theorem of natural selection.

But the revolution of thought that Fisher, Sewall Wright, and J. B. S. Haldane unleashed has had real yields. As geneticists they helped us reconceptualize evolutionary process as more than simply heritable morphological change, but an analysis of the units of heritability themselves, genetic variation. That is, evolution can be imagined as the study of the forces which shape changes in allele frequencies over time. This reduces a big domain down to a much simpler one.

Genetic variation is concrete currency with which one can track evolutionary process. Initially this was done via inferred correlations between marker traits and particular genes in breeding experiments. Ergo, the origins of the “the fly room”.

But with the discovery of DNA as the physical substrate of genetic inheritance in the 1950s the scene was set for the revolution in molecular biology, which also touched evolutionary studies with the explosion of more powerful assays. Lewontin & Hubby’s 1966 paper triggered a order of magnitude increase in our understanding of molecular evolution through both theory and results.

The theoretical side occurred in the form of the development of the neutral theory of molecular evolution, which also gave birth to the nearly neutral theory. Both of these theories hold that most of the variation with and between species on polymorphisms are due to random processes. In particular, genetic drift. As a null hypothesis neutrality was very dominant for the past generation, though in recent years some researchers are suggesting that selection has been undervalued as a parameter for various reasons.

Setting the live scientific debate, which continue to this day, one of the predictions of neutral theory is that the rate of evolution will depend only on the rate of mutation. More precisely, the rate of substitution of new mutations (where the allele goes from a single copy to fixation of ~100%) is proportional to the rate of mutation of new alleles. Population size doesn’t matter.

The algebra behind this is straightforward.

First, remember that the frequency of the a new mutation within a population is \frac{1}{2N}, where N is the population size (the 2 is because we’re assuming diploid organisms with two gene copies). This is also the probability of fixation of a new mutation in a neutral scenario; it’s probability is just proportional to its initial frequency (it’s a random walk process between 0 and 1.0 proportions). The rate of mutations is defined by \mu, the number of expected mutations at a given site per generation (this is a pretty small value, for humans it’s on the order of 10^{-8}). Again, there are 2N individuals, so you have 2N\mu to count the number of new mutations.

The probability of fixation of a new mutations multiplied by the number of new mutations is:

    \[ \( \frac{1}{2N} \) \times 2N\mu = \mu \]

So there you have it. The rate of fixation of these new mutations is just a function of the rate of mutation.

Simple formalisms like this have a lot more gnarly math that extend them and from which they derive. But they’re often pretty useful to gain a general intuition of evolutionary processes. If you are genuinely curious, I would recommend Elements of Evolutionary Genetics. It’s not quite a core dump, but it is a way you can borrow the brains of two of the best evolutionary geneticists of their generation.

Also, you will be able to answer the questions on my survey better the next time!

The logic of human destiny was inevitable 1 million years ago

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

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

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

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

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

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

Luke Jostins’ figure showing across board encephalization

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

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

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

The case against nutrition “science”

Filed under: cholesterol,Nutrition — Razib Khan @ 12:11 pm

My attitude toward nutrition science is to be skeptical of everything. I am of the generation that lived through the SnackWells fat-free cookie craze (demand was so high at one point that there was a problem with continuous understocking). A friend who is a professor of biology once admitted to me that part of him feels somewhat bad for anti-vaccination believers, because when it comes to nutrition he and many of his colleagues take a very jaundiced view of any orthodoxy. The surfeit of observational studies combined with the huge revenues at stake mean that skepticism is warranted.

This puts the public, and those who serve them in a peculiar position. Last year I recall going to a restaurant where some of the menu items were labeled as “low cholesterol, heart healthy.” I told our server that there is no evidence that dietary cholesterol has any effect on serum levels in your body. But the overhang of nutritional orthodoxy persists, and the American Heart Associations prominence and tendency to be a lagging indictor of the science is going to cast a pall over “public awareness” for decades.

Now researchers are going back to the original studies which supported modern orthodoxy, and finding results that are surprising. Re-evaluation of the traditional diet-heart hypothesis: analysis of recovered data from Minnesota Coronary Experiment (1968-73). Here is the conclusion:

Available evidence from randomized controlled trials shows that replacement of saturated fat in the diet with linoleic acid effectively lowers serum cholesterol but does not support the hypothesis that this translates to a lower risk of death from coronary heart disease or all causes. Findings from the Minnesota Coronary Experiment add to growing evidence that incomplete publication has contributed to overestimation of the benefits of replacing saturated fat with vegetable oils rich in linoleic acid.

The whole story is told over at Scientific American.

Open Thread, 3/23/2017

Filed under: Blog,Open Thread — Razib Khan @ 10:48 am


The reader survey now N > 300. I assume it will stabilize in the next few weeks in the 400s.

So far the biggest surprise that I’ve noticed is the ratio of married to divorced; 14o to 9. But, this aligns with research that college educated people do not get divorced at a high rate, and more than 50% of my readership has completed graduate educations, so the sample is probably even more biased.

In France it is Marcon vs. Le Pen for the second round it seems. It seems likely Marcon will win the second round…but I do wonder if some far Left voters will refuse to vote for a candidate is a pretty transparent avatar of the globalist elite.

I love California, but, In costly Bay Area, even six-figure salaries are considered ‘low income’:

San Francisco and San Mateo counties have the highest limits in the Bay Area — and among the highest such numbers in the country. A family of four with an income of $105,350 per year is considered “low income.” A $65,800 annual income is considered “very low” for a family the same size, and $39,500 is “extremely low.” The median income for those areas is $115,300.

The problem many, but not all, Lefties in this part of the country have is their rhetoric is always about making housing affordable, not making more housing (which would naturally lead to more affordability).

Stanford CS department updates introductory courses: Java is Gone.

I was a bit surprised how few readers had read Matt Ridley’s Genome: The Autobiography of a Species in 23 Chapters. I’d highly recommend it.

A new wave of GSS data is out. Might start some GSS blogging again.

Maybe moderate drinking isn’t so good for you after all:

But our latest research challenges this view. We found while moderate drinkers are healthier than relatively heavy drinkers or non-drinkers, they are also wealthier. When we control for the influence of wealth, then alcohol’s apparent health benefit is much reduced in women aged 50 years or older, and disappears completely in men of similar age.

People I know had long warned these were observational studies. But perhaps I run with a strange crowd….

Why the Menace of Mosquitoes Will Only Get Worse: Climate change is altering the environment in ways that increase the potential for viruses like Zika.

April 22, 2017

America’s great Saudi foreign policy sin

Filed under: International Affairs,Saudi Arabia — Razib Khan @ 9:24 pm
The future past

Periodically on my Twitter feed there is mention of the new series, The Handmaid’s Tale. The New York Times has a typical positive review. The author attempts to assert its contemporary relevance, ending with ‘the new “Handmaid’s Tale” enters the culture as its own kind of Offred-like resistance, pushing back against a reality that somehow got ahead of the show’s own imagination.’

This is not the 1980s. Or the early 2000s. The President of the United States is a nominal Christian at best. Maggie Haberman, who covers Trump for The New York States had this to say about his relationship to Mike Pence:

…When Trump and Pence were first getting to know each other, the one thing that Trump had relayed to people, according to several advisers I spoke to at the time, was that he was a little uncomfortable with how frequently Pence prayed. And Pence is fairly devout about his praying. Trump is not a serious churchgoer and in an anomaly for a presidential candidate, very rarely went to church services when he was running….

We live in an age of massive secularization, even on the conservative Right. Ergo, the rise of a post-religious Right predicated on ethnic identity, whether implicitly or explicitly. Though Donald Trump and the Republicans in Congress are going to rollback a few of the victories of the cultural Left, there is no likelihood of turning back the clock on the biggest win of the last generation for that camp, gay marriage.

Also, don’t watch the series, read the book. Books are usually better. While I’m recommending reading, while Atwood’s work gets a lot of attention (it’s already been made into a film back in 1990), I want to suggest Pamela Sargent’s The Shore of Women for those curious about a different take on broadly similar themes. Flipping the framework of The Handmaid’s Tale on its head Sargent depicts a far future gynocracy, as opposed to a near future patriarchy. Additionally, The Shore of Women  has echoes of the bizarre 1970s film Zardoz.

I’ve always felt the Sargent is an underrated writer (also see Ruler of the Sky, a novelization of the life of Genghis Khan). Her output is not high volume, but it is high quality.

But this post is not about The Handmaid’s Tale, and the specter of an anti-feminist dystopia. Rather, it will be on the reality of an anti-feminist dystopia which exists in our world, which also happens to be religiously totalitarian and oligarchic. I am talking about the great ally of the United States of America in the Middle East, the kingdom of Saudi Arabia.

In its broadest sketches you know exactly what I’m alluding to. The kingdom run by and for the House of Saud is a bizarre construction, juxtaposing material modernity with an ideological empire of medieval repression and control.

If there is one regime in the world which resembles ISIS in its fidelity to brutal and anti-modern norms, and the application of violence as a method to keep a population in check, it is the kingdom of Saudi Arabia.

The legend of Saudi Arabia’s repression and infantilization of women is so well known that I need not repeat it here. Rather than view a depiction of the Republic of Gilead, I would suggest that one watch a documentary on the lives of Saudi women.

Many are aware that Saudi Arabia is complicit in de facto slavery. But did you know that Saudi Arabia officially outlawed slavery in 1962? An article from 1967, Saudi Arabian Slavery Persists Despite Ban by Faisal in 1962.

Saudi Arabia’s racism against Asian workers, especially, non-Muslims, has been extensively documented in the press. It’s a problem it shares with its neighbors. But Saudi Arabia is also a racist society toward its own citizens. An article in Foreign Policy mentions this in passing:

…Judges must all espouse the government-approved Salafi version of Islam. Blacks, who make up around 10 percent of the population, are banned from judgeships — as are women and Muslims who observe a different version of the faith — because the monarchy’s religious tradition still views blacks as slaves, other Muslims as heretics, and women as half human….

The concept of kufu or equality of status in Muslim marriages is apparently used to prevent marriages of Saudis with African (ergo, slave) ancestry with those of pure tribal ancestry.

Saudi Arabia has a very large Shia population in the eastern provinces near the Persian Gulf. The religious persecution of these Shia is arguably without parallel even in the Middle East, as they live under a constant state of siege and marginalization.

Modernity over Mecca

The crimes that the Saudi state commits against its subjects are legion. But Saudi Arabia has been waging a decades long cultural war against the rest of Islamic civilization. The government and the Salafi clerical hierarchy has encouraged active destruction of Islamic holy sites, because they consider these places as possible temptations for idolatry and veneration. Not only is that part of the cultural heritage of Muslims, but it is part of the cultural heritage of the world.

And the kingdom does not just commit crimes against its own. The vast majority of 9/11 hijackers were Saudi. The Saudi intervention in Yemen has turned out to be a humanitarian disaster. Saudis were present in the top leadership of Al-Qaeda, and they are reportedly prominent as part of the foreign fighter contingents in ISIS. They were instrumental in the suppression of the protest movement in Bahrain.

This litany is to reiterate that one of the closest allies of the United States is a very nasty regime. Women are second class citizens. Non-Muslims can not even become citizens. Shia are second class citizens. The state is run by, and for, an oligarchy of Saudi princes. It engages in acts of destruction against the collective heritage of the human race. It bankrolls military assaults on neighboring countries, and its citizens in their private capacities have been the financiers of terror international for a generation.

And yet this is America’s great ally. This bond goes back to 1945, when FDR and the king of Saudi Arabia met. During the Cold War the Saudis were a pro-Western regime in the great game of powers, despite the fact that the values which they held to be true and right were the antithesis of everything the West had become and aspired to. The Saudi-American connection remained despite disagreements over Israel and the 1970s oil crisis.

The Saudi state is not a conventional nation-state, it is a family owned corporation. Operationally the king is not an absolute monarch because the oligarchy needs to have buy-in. There are thousands of princes, though power is not equitably distributed. The personal nature of Saudi rule extends to its relationship to the United States: the Saudis have clearly ingratiated themselves with the American power elite through their financial generosity and business opportunities which are possible.

But it is not just the ruling caste, but the courtiers as well who have been captured, How Saudi Arabia captured Washington:

This contributes, they said, to a practice in Washington whereby the bad behavior of other Middle East states — particularly US adversaries such as Iran — receive heavy attention and debate. But bad behavior by Gulf allies — human rights abuses, opposition to democracy movements, foreign policy actions that often undercut US interests — while far from ignored are discussed with less frequency and vigor.

In other words, one explanation for the robustness of the American-Saudi relationship may not simply be geopolitical alignment of interests, but the powerful personal incentives that the American ruling class and intelligensia have been given by the Saudi ruling elite. This is a business opportunity that the American ruling class can’t overlook.

Public execution in Saudi Arabia

My own attitude is that there are cases and instances where the United States must ally with unpalatable regimes. I am not a neoconservative or liberal internationalist. Humanitarian regimes emerge through an organic process; imposition by fiat usually causes more problems than they solve. But the American rhetorical stance against their adversaries as ‘dictatorial’ or ‘illiberal’ or ‘undemocratic’ is shown to be hypocritical by the fastness of close ties to Saudi Arabia. Between “friends” some religious oppression, sexual apartheid, and familial oligarchy are clearly acceptable, they have been for over 70 years. The friendship is strong enough to withstand the reality that Saudi nationals by and large were behind the 9/11 terrorist attacks, and that Saudi Arabia has been funding radicalism across the world for decades.

When American politicians and public thinkers take high-toned moralistic line they seem ludicrous and absurd to well informed non-American observers. Total consistency is impossible, but when Americans inveigh as the “totalitarian mullahs” in Iran, many non-Americans just shake their heads when they observe that across the Persian Gulf is a regime of a far nastier bent in relation to what it puts its people through. And that regime is our close ally.

Unpalatable alliances do not entail one to abandon all principles, and even humanitarian rhetoric. But, they do enjoin upon one a bit more self-awareness in one’s self-righteous condemnation of the behavior of adversaries.

April 21, 2017

2017 Gene Expression reader survey

Filed under: 2017 Reader Survey,Blog — Razib Khan @ 6:22 am


Since I’m finally getting settled in here, I thought it was a good time to do a reader survey: https://www.surveymonkey.com/r/MW3YFZH.

So it’s open. You can only take it once, but it shouldn’t take more than a few minutes. There are 30 questions but the first 20 are mostly demographic and should go very quickly (e.g., your age, your sex, your race), and the last 10 are not difficult either (if you don’t know if you are a deontologist or consequentalist on ethics, don’t answer). Many are now of the form where you can answer more than one option.

I basically took the template of last year’s survey, made several changes, removing some questions and adding some. Also, I stole a few from Slate Star Codex.

You can read the non-text answers of the 2016 survey here.

In the middle of May I will the raw data (no-IP) and post it here so others can analyze if they want.

Addendum: Since I don’t know where else to put this, I have noticed an increase in referrals through my Amazon links. So that’s much appreciated. Obviously I’m not really getting paid much for blogging or doing the sysadmin activities, but it’s definitely going to covering overages from VPS traffic or anything like that. Remember, even if you don’t buy directly through the link I still get a referral if you are on Amazon during a session and buy something different.

Addendum 2: Forgot to mention. I’ve been doing reader surveys since 2004. The final tally of the number of people who fill the survey is always between 300 and 500, invariant of how much traffic I received (my traffic has varied about an order of magnitude over the years). It is curious to me that this “core readership” (as I perceive it) is about the same size as a Roman cohort.

April 20, 2017

Aryan marauders from the steppe came to India, yes they did!

Filed under: Genetics,Genomics,History,India — Razib Khan @ 10:21 pm

Its seems every post on Indian genetics elicits dissents from loquacious commenters who are woolly on the details of the science, but convinced in their opinions (yes, they operate through uncertainty and obfuscation in their rhetoric, but you know where the axe is lodged). This post is an attempt to answer some questions so I don’t have to address this in the near future, as ancient DNA papers will finally start to come out soon, I hope (at least earlier than Winds of Winter).

In 2001’s The Eurasian Heartland: A continental perspective on Y-chromosome diversity Wells et al. wrote:

The current distribution of the M17 haplotype is likely to represent traces of an ancient population migration originating in southern Russia/Ukraine, where M17 is found at high frequency (>50%). It is possible that the domestication of the horse in this region around 3,000 B.C. may have driven the migration (27). The distribution and age of M17 in Europe (17) and Central/Southern Asia is consistent with the inferred movements of these people, who left a clear pattern of archaeological remains known as the Kurgan culture, and are thought to have spoken an early Indo-European language (27, 28, 29). The decrease in frequency eastward across Siberia to the Altai-Sayan mountains (represented by the Tuvinian population) and Mongolia, and southward into India, overlaps exactly with the inferred migrations of the Indo-Iranians during the period 3,000 to 1,000 B.C. (27). It is worth noting that the Indo-European-speaking Sourashtrans, a population from Tamil Nadu in southern India, have a much higher frequency of M17 than their Dravidian-speaking neighbors, the Yadhavas and Kallars (39% vs. 13% and 4%, respectively), adding to the evidence that M17 is a diagnostic Indo-Iranian marker. The exceptionally high frequencies of this marker in the Kyrgyz, Tajik/Khojant, and Ishkashim populations are likely to be due to drift, as these populations are less diverse, and are characterized by relatively small numbers of individuals living in isolated mountain valleys.

In a 2002 interview with the India site Rediff, the first author was more explicit:

Some people say Aryans are the original inhabitants of India. What is your view on this theory?

The Aryans came from outside India. We actually have genetic evidence for that. Very clear genetic evidence from a marker that arose on the southern steppes of Russia and the Ukraine around 5,000 to 10,000 years ago. And it subsequently spread to the east and south through Central Asia reaching India. It is on the higher frequency in the Indo-European speakers, the people who claim they are descendants of the Aryans, the Hindi speakers, the Bengalis, the other groups. Then it is at a lower frequency in the Dravidians. But there is clear evidence that there was a heavy migration from the steppes down towards India.

But some people claim that the Aryans were the original inhabitants of India. What do you have to say about this?

I don’t agree with them. The Aryans came later, after the Dravidians.

Over the past few years I’ve gotten to know the above first author Spencer Wells as a personal friend, and I think he would be OK with me relaying that to some extent he was under strong pressure to downplay these conclusions. Not only were, and are, these views not popular in India, but the idea of mass migration was in bad odor in much of the academy during this period. Additionally, there was later work which was less clear, and perhaps supported an Indian origin for R1a1a. Spencer himself told me that it was not impossible for R1a to have originated in India, but a branch eventually back-migrated to southern Asia.

But even researchers from the group at Stanford where he had done his postdoc did not support this model by the middle 2000s, Polarity and Temporality of High-Resolution Y-Chromosome Distributions in India Identify Both Indigenous and Exogenous Expansions and Reveal Minor Genetic Influence of Central Asian Pastoralists. In 2009 a paper out of an Indian group was even stronger in its conclusion for a South Asian origin of R1a1a, The Indian origin of paternal haplogroup R1a1* substantiates the autochthonous origin of Brahmins and the caste system.

By 2009 one might have admitted that perhaps Spencer was wrong. I was certainly open to that possibility. There was very persuasive evidence that the mtDNA lineages of South Asia had little to do with Europe or the Middle East.

Yet a closer look at the above papers reveals two major systematic problems.

First, ancient DNA has made it clear that there has been major population turnover during the Holocene, but this was not the null hypothesis in the 2000s. Looking at extant distributions of lineages can give one a distorted view of the past. Frankly, the 2009 Indian paper was egregious in this way because they included Turkic groups in their Central Asian data set. Even in 2009 there was a whole lot of evidence that Central Asian Turkic groups were likely very different from Indo-European Turanian populations which would have been the putative ancestors of Indo-Aryans. Honestly the authors either consciously loaded the die to reduce the evidence for gene flow from Central Asia, or they were ignorant (the nature of the samples is much clearer in the supplements than the  primary text for what it’s worth).

Second, Y chromosomal marker sets in the 2000s were constrained to fast mutating microsatellite regions or less than 100 variant SNPs on the Y. Because it is so repetitive the Y chromosome is hard to sequence, and it really took the technologies of the last ten years to get it done. Both the above papers estimate the coalescence of extant R1a1a lineages to be 10-15,000 years before the present. In particular, they suggest that European and South Asian lineages date back to this period, pushing back any possible connection between the groups, and making it possible that European R1a1a descended from a South Asian founder group which was expanding after the retreat of the ice sheets. The conclusions were not unreasonable based on the methods they had.  But now we have better methods.*

Whole genome sequencing of the Y, as well as ancient DNA, seems to falsify the above dates. Though microsatellites are good for very coarse grain phyolgenetic inferences, one has to be very careful about them when looking at more fine grain population relationships (they are still useful in forensics to cheaply differentiate between individuals, since they accumulate variation very quickly). They mutate fast, and their clock may be erratic.

Additionally, diversity estimates were based on a subset of SNP that were clearly not robust. R1a1a is not diverse anywhere, though basal lineages seem to be present in ancient DNA on the Pontic steppe in some cases.

To show how lacking in diversity R1a1a is, here are the results of a 2016 paper which performed whole genome sequencing on the Y. Instead of relying on the order of 10 to 100 SNPs, this paper discover over 65,000 Y variants worldwide. Notice how little difference there is between different South Asian groups below, indicative of a massive population expansion relatively recently in time which didn’t even have time to exhibit regional population variation. They note that “The most striking are expansions within R1a-Z93 [the South Asian clade], ~4.0–4.5 kya. This time predates by a few centuries the collapse of the Indus Valley Civilization, associated by some with the historical migration of Indo-European speakers from the western steppes into the Indian sub-continent.

(BEB = Bengali, GIH = Gujarati, PJL = Punjabi, STU = Sri Lanka Tamil, ITU = Indian Telugu)

The spatial distribution of Z93 lineages of R1a is as you can see to the left. There are branches in South Asia, Central Asia, and in the Altai region. Ancient DNA from the Bronze Age Mongolia has found Z93. Modern Mongolians clearly have a small, but appreciable, fraction of West Eurasian ancestry. Some also carry R1a1a. Z93 has also been found in North-Central Asian steppe samples that date to ~4,500 years before the present.

Today with ancient DNA we’re discovering individuals who lived around the time of the massive  expansion alluded to above. What are these individuals like? They are a mix of European, Central Eurasian, Near Eastern, and Siberian. Many of them share quite a bit of ancestry with South Asian populations, in particular those from the northwest of subcontinent, as well as upper castes more generally.

A new paper using ancient DNA from Scythians (Iranian speakers) also shows that they carried Z93. Some of them had East Asian admixture. These were the ones from the eastern steppe. So not entirely surprising. In the supplements of the paper they have an admixture plot with many populations. At K = 15 in supplementary figure 14 you see many ancient Central Eurasian populations run against modern groups. At this K there is a South Asian modal cluster which is found in South Asians as well as nearby Iranian groups from Afghanistan.

It is not light green or dark blue. You see see that this salmon color is modal in tribal South Indian populations, or non-Brahmin South Indians. It drops in frequency as you move north and west, and as you move up the caste ladder. Observe that is present even among the relatively isolated Kalash people of Chitral.

Outside of South Asia-Afghanistan, this salmon component is found among Thai and Cambodians. From talking to various researchers, and recent published findings, it seems clear that this signature is not spurious, but is indicative of some migration from South Asia to Southeast Asia in the historical period, as one might infer based on cultural affinities. It is also found at lower frequencies among the Uyghur of Xinjiang. This is not entirely surprising either. This region of the Tarim basin was connected to Kashmir across the Pamirs. The 4th century Buddhist monk from the Tarim basin city of Kucha, who was instrumental in the translation of texts into Chinese, Kumārajīva, may have had a Kashmiri father.

Even before Islam much of Northwest India and Central Asia were under the rule of the same polity, and after Islam there is extensive record of the enslavement of many Indians in the cities of the eastern Islamic world, as well as the travel of some Indian merchants and intellectuals into these regions.

And yet this South Asia cluster is not present in the ancient steppe samples carrying R1a1a-Z93. None of them to my knowledge. Many ancient samples share ancestry with South Asians. For example it seems that many ancient West Asian samples from Iran share common history as evident in genetic drift patterns with many South Asians. And, there is good evidence that a subset of South Asians, skewed toward northwest and upper caste groups, share drift with steppe Yamna samples. But South Asians are often clearly composites of these exogenous populations and an indigenous component with affinities with Andaman Islanders, and more distantly Southeast Asians and other eastern non-Africans.

How can you reconcile this with migration out of South Asia? The path is found in publications such as Genetic Evidence for Recent Population Mixture in India. Here you have a paper which models mixing between Ancestral North Indians (ANI) and Ancestral South Indians (ASI). The ANI would be the source population for the ancestry shared with West Eurasians. And, they would lack ASI ancestry because the mixing had not occurred. The admixture dates the paper are between two and four thousand years before the present.

There is a problem though. These methods detect the last admixture events. Therefore, they are a lower bound on major mixing events, not a record of when there was no mixing. Secondarily, but not less importantly, recent work indicates that because of the pulse admixture simplification these methods likely underestimate the time period of admixture.

Another issue for me is the idea that ANI and ASI could be so separate within India. If ANI is the source of gene flow into other parts of Eurasia from South Asia, then I believe that ASI is intrusive to the subcontinent. I don’t think that ASI being intrusive is so implausible. Southeast Asia has undergone massive genetic changes over the Holocene, and it may be that there was much more ASI ancestry in placers like Burma before the arrival of Austro-Asiatic rice farmers. The presence of Austro-Asiatic languages in northeast India and central India shows a precedent of migration from Southeast Asia into the subcontinent.

In sum, the balance of evidence suggests male mediated migration into South Asia from Central Asia on the order of ~4-5,000 years ago. There are lots of details to be worked out, and this is not an assured model in terms of data, but it is the most likely. In the near future ancient DNA will clear up confusions. Writing very long but confused comments just won’t change this state of affairs. New data will.

Addendum: Indian populations have finally been relatively well sampled, thanks to Mait Mepsalu’s group in Estonia, David Reich’s lab and, the Indian collaborators of both, and the 1000 Genomes (HGDP gave us Pakistanis). Additionally, Zack Ajmal’s Harappa website did some work filling in some holes in the early 2010s.

* A Facebook argument broke out about one of my posts where one interlocutor asserted that he leaned on papers from the late 2000s, not all the new stuff. That’s obviously because the new stuff did not support his preferred position, while the old stuff did. I would prefer that faster-than-light travel were possible, so I’ll just stick to physics before 1910?

The Sounds of Sumer

Filed under: Epic of Gilgamesh in Sumerian,History,Sumer — Razib Khan @ 7:25 pm

Oxford Nanopore finally giving hope to biologist’s dreams

Filed under: Genomics,Oxford Nanopore,Sequencing — Razib Khan @ 5:48 pm

I don’t talk too much about genomic technology because it changes so fast. Being up-to-date on the latest machines and tools often requires regular deep-dives right now, though I believe at some point technological improvements will plateau as the data returned will be cheap and high quality enough that there won’t be much to gain on the margin.

Of course we’ve already come a long way. Fifteen years ago a “whole human genome” cost on the order of billions of dollars. Today a high quality whole human genome will run you on the order of $1,000. This is fundamentally a technology driven change, with big metal machines automatically generating reads and powerful computers to process them. One couldn’t imagine such a scenario 30 years ago because the technology wasn’t there.

I’ve stated before that I don’t think genomics fundamentally alters what we know and understand about evolution. At least so far. But it is a huge change in the domain of medicine. Cleary the human genomicists, especially Francis Collins, overhyped the yield of the technology in relation to healthcare in the 2000s. But with cheap and ubiquitous sequencing we may see the end of Mendelian diseases in our lifetime (through screening and possibly at some point CRISPR therapy).

This has been driven by technological innovation in the private sector around a few firms. The famous chart showing the massive decline in the cost of genomic sequencing over the past 15 years is due in large part to the successes of Illumina. But, Illumina has also had a quasi-monopoly on the field over the past five years (or more), and that shows with the leveling off of the decline in cost. Until the past year….

What gives? Many people believe that Illumina is moving again in part because a genuine challenger is emerging, or at least the flicker of a challenge, in the form of Oxford Nanopore. Oxford Nanopore has been around since 2005, but it really came into the public eye around 2010 or so. But like many tech companies it overpromised in the early years. I remember skeptically listening to a friend in the fall of 2011 talk about how quickly Nanopore was going to change the game…. I didn’t put too much stock into these sorts of presentations to hopeful researchers because I remember Pacific Biosciences making the same sort of pitch to amazed biologists in 2008. Pac Bio is still around, but has turned out to be a bit player, rather than a challenger to Illumina.

But I have to admit that Nanopore has really started to step up its game of late. Probably one of the major things it has accomplished is that it’s made us reimagine what sequencing technology should look like. Rather than refrigerators of various sizes, Oxford Nanopore allows us to imagine sequencing technology which exhibits a form factor more analogous to a USB thumb drive. The first time I saw a Nanopore machine in the flesh I knew intellectually what I was going to see…but because of my deep intuitions I still overlooked the two Nanopore machines laying on the workbench in front of me.

Despite their amazing form factor, these early Nanopore machines had limited application. They didn’t generate much data, and so were utilized by researchers who worked with smaller genomes. Scientists who worked with bacteria seem to have been using them a lot, for example. Additionally the machines were error prone and people were working out their kinks in real time in laboratories (one tech told me early on they were so small that he swore they were affected by ambient vibrations so he found ways to dampen that source of error).

A new preprint suggests we may be turning the corner though, Nanopore sequencing and assembly of a human genome with ultra-long reads:

Nanopore sequencing is a promising technique for genome sequencing due to its portability, ability to sequence long reads from single molecules, and to simultaneously assay DNA methylation. However until recently nanopore sequencing has been mainly applied to small genomes, due to the limited output attainable. We present nanopore sequencing and assembly of the GM12878 Utah/Ceph human reference genome generated using the Oxford Nanopore MinION and R9.4 version chemistry. We generated 91.2 Gb of sequence data (~30x theoretical coverage) from 39 flowcells. De novo assembly yielded a highly complete and contiguous assembly (NG50 ~3Mb). We observed considerable variability in homopolymeric tract resolution between different basecallers. The data permitted sensitive detection of both large structural variants and epigenetic modifications. Further we developed a new approach exploiting the long-read capability of this system and found that adding an additional 5x-coverage of “ultra-long” reads (read N50 of 99.7kb) more than doubled the assembly contiguity. Modelling the repeat structure of the human genome predicts extraordinarily contiguous assemblies may be possible using nanopore reads alone. Portable de novo sequencing of human genomes may be important for rapid point-of-care diagnosis of rare genetic diseases and cancer, and monitoring of cancer progression. The complete dataset including raw signal is available as an Amazon Web Services Open Dataset at: https://github.com/nanopore-wgs-consortium/NA12878.

30x just means that you’re getting bases sampled typically 30 times, so that you have a very accurate and precise read on its state. 30x has become the default standard in medical genomics. If Nanopore can do 30x on human genomes at reasonable cost it won’t be a niche player much longer.

The read length is important because last I checked the human genome still had large holes in it. The typical Illumina machine produces average read lengths in the low hundreds of base pairs. If you have large repetitive regions of the human genome (and you do have these), you’re never going to span them with such short yardsticks. Additionally, these short reads have to be tiled together when you assemble a genome from raw results, and this is a computationally really intensive task. It’s good when you have a reference genome you can align to as a scaffold. But researchers who don’t work on humans or model organisms may not have a good reference genome, or in many cases a reference genome at all.

Pac Bio occupies a space where it provide really long reads for a high price point. Most of the time this isn’t necessary, but imagine you work on a disease which is caused by large repetitive regions. You are likely willing to pay the price that is asked. And because Pac Bio generates very long reads it makes de novo assembly much easier, as your algorithm has to tile together far fewer contiguous sequences, and long sequences are less likely to have lots of repetitive matches in the genome.

But Pac Bio machines are expensive and huge. In the abstract above it alludes to “Portable de novo sequencing of human genomes.” This is a huge deal. The dream, as whispered by some genomicists I have known, is that at a point in the future biologists would carry portable sequencers which would produce very long reads that so that they could de novo assemble sequences on the spot. A concrete example might be a health inspector checking on the sorts of microbes found on the counter of a restaurant, or a field ecologist who might be sample various fungi to discover cryptic species.

Obviously this is still a dream. The preprint above makes it clear that to do what they did required a lot of novel techniques and development of new tools. This isn’t beta technology, it’s early alpha. But because it’s 2017 the outlines of the dream are coming into public view.

Citation: Nanopore sequencing and assembly of a human genome with ultra-long reads
Miten Jain, Sergey Koren, Josh Quick, Arthur C Rand, Thomas A Sasani, John R Tyson, Andrew D Beggs, Alexander T Dilthey, Ian T Fiddes, Sunir Malla, Hannah Marriott, Karen H Miga, Tom Nieto, Justin O’Grady, Hugh E Olsen, Brent S Pedersen, Arang Rhie, Hollian Richardson, Aaron Quinlan, Terrance P Snutch, Louise Tee, Benedict Paten, Adam M. Phillippy, Jared T Simpson, Nicholas James Loman, Matthew Loose
bioRxiv 128835; doi: https://doi.org/10.1101/128835

10 Things About Ancient History You Should Really Know

Filed under: Ancient History,History — Razib Khan @ 3:07 pm

For this “10 things” I am going to constraint the historical period to the period before 1000 BCE. Basically all that came before Greece and Rome (from a Western perspective).

1) The Bronze Age Near East had its own equivalent of a Westphalian system. See The Brotherhood of Kings.

2) Even in the 3rd Millennium BCE the world was quite international. There are references in Sumerian tablets to expatriate communities of merchants from Meluhha. Meluhha almost certainly referring to what we call the Indus Valley civilization.

3) The relationship between Sumerians and Akkadians prefigures the relationship between the Greeks and Romans. Mesopotamia had long had Semitic speaking groups like Akkadians, as evidenced by their prominence in lists of rulers to an early date, but in the most antique period Sumerians were dominant. Over time though Sumerians disappeared as a distinct ethnicity, and the language was preserved as one of liturgy for thousands of years after their extinction.

4) The longstanding antagonists of Sumer, the nation of Elam in southwest Iran, persisted for 1,500 years after the Sumerians left the scene. They were finally absorbed by the Medes and Persians in the 6th century BCE.

5) Because cuneiform tablets can be baked and preserved our documentary evidence from some earlier periods in Near Eastern history is much better than more epochs, simply due to preservational differences.

6) The Hittite polity, which lasted for nearly 1,000 years as the dominant rival of many other Near Eastern powers, was analogous in some ways to the Hungarian kingdom, with a very distinct ruling class. The Hittites called themselves the Nesa, and ruled over various non-Indo-European popualtions, in particular the Hatti.

7) Sumeria likely had a larger population than the same area after the Mongol sack of Baghdad (there may also be an issue with salinization of lower Mesopotamia over time).

8) The Biblical Philistines may in part have been Bronze Age Greeks (bonus: the political units of Bronze Age Greece may have been larger than during the Classical period because bronze forging requires more mobilization of resources than iron).

9) Pleistocene “megafauna” survived into the Bronze Age.

10) Indo-Europeans of an Indo-Aryan variant called the Mittani were the ruling class in much of the territory ruled by ISIS for the past few years. They even worshipped Indo-Aryan gods.

Addendum: I invite readers to give me better suggestions. I’m not an ancient historian, just an enthusiast!

April 19, 2017

Mouse fidelity comes down to the genes

Filed under: Genetics,Genomics,Human Genetics — Razib Khan @ 10:02 pm

While birds tend to be at least nominally monogamous, this is not the case with mammals. This strikes some people as strange because humans seem to be monogamous, at least socially, and often we take ourselves to be typically mammalian. But of course we’re not. Like many primates we’re visual creatures, rather than relying in smell and hearing. Obviously we’re also bipedal, which is not typical for mammals. And, our sociality scales up to massive agglomerations of individuals.

How monogamous we are is up for debate. Desmond Morris, who is well known to many from his roles in television documentaries, has been a major promoter of the idea that humans are monogamous, with a focus on pair-bonds. In contrast, other researchers have highlighted our polygamous tendencies. In The Mating Mind Geoffrey Miller argues for polygamy, and suggests that pair-bonds in a pre-modern environment were often temporary, rather than lifetime (Miller is now writing a book on polyamory).

The fact that in many societies high status males seem to engage in polygamy, despite monogamy being more common, is one phenomenon which confounds attempts to quickly generalize about the disposition of our species. What is preferred may not always be what is practiced, and the external social adherence to norms may be quite violated in private.

Adducing behavior is simpler in many other organisms, because their range of behavior is more delimited. When it comes to studying mating patterns in mammals voles have long been of interest as a model. There are vole species which are monogamous, and others which are not. Comparing the diverged lineages could presumably give insight as to the evolutionary genetic pathways relevant to the differences.

But North American deer mice, Peromyscus, may turn to be an even better bet: there are two lineages which exhibit different mating patterns which are phylogenetically close enough to the point where they can interbreed. That is crucial, because it allows one to generate crosses and see how the characteristics distribute themselves across subsequent generations. Basically, it allows for genetic analysis.

And that’s what a new paper in Nature does, The genetic basis of parental care evolution in monogamous mice. In figure 3 you can see the distribution of behaviors in parental generations, F1 hybrids, and the F2, which is a cross of F1 individuals. The widespread distribution of F2 individuals is likely indicative of a polygenic architecture of the traits. Additionally, they found that some traits are correlated with each other in the F2 generation (probably due to pleiotropy, the same gene having multiple effects), while others were independent.

With the F2 generation they ran a genetic analysis which looked for associations between traits and regions of the genome. They found 12 quantitative trait loci (QTLs), basically zones of the genome associated with variation on one or more of the six traits. From this analysis they immediately realized there was sexual dimorphism in terms of the genetic architecture; the same locus might have a different effect in the opposite sex. This is evolutionarily interesting.

Because the QTLs are rather large in terms of physical genomic units the authors looked to see which were plausible candidates in terms of function. One of their hits was vasopressin, which should be familiar to many from vole work, as well as some human studies. Though the QTL work as well as their pup-switching experiment (which I did not describe) is persuasive, the fact that a gene you’d expect shows up as a candidate really makes it an open and shut case.

The extent of the variation explained by any given QTL seems modest. In the extended figures you can see it’s mostly in the 1 to 5 percent range. In Carl Zimmer’s excellent write up he ends:

But Dr. Bendesky cautioned that the vasopressin gene would probably turn out to be just one of many that influence oldfield mice. Though it is strongly linked to parental behavior, the vasopressin gene accounts for 6.7 percent of the variation in nest building among males, and only 2.9 percent among females.

The genetic landscape of human parenting will turn out to be even more rugged, Dr. Bendesky predicted.

“You cannot do a 23andMe test and find out if your partner is going to be a good father,” he said.

Sort of. The genetic architecture above is polygenic…but not incredibly diffuse. The proportion of variation explained by the largest effect allele is more than for height, and far more than for education. If human research follows up on this, I wouldn’t be surprised if you could develop a polygenic risk score.

But I don’t have a good intuition on how much variation in humans there really is for these sorts of traits that are heritable. I assume some. But I don’t know how much. And how much of the variance in behavior might be explained by human QTLs? Humans don’t lick or build nests, or retrieve pups. Also, as one knows from Genetics and Analysis of Quantitative Traits sexually dimorphic traits take a long time to evolve. These are two deer mice species. Within humans there may not have been enough time for this sort of heritable complexity of behavior to evolve.

There are a lot of philosophical issues here about translating to a human context.

Nevertheless, this research shows that ingenious animal models can powerfully elucidate the biological basis of behavior.

Citation: The genetic basis of parental care evolution in monogamous mice. Nature (2017) doi:10.1038/nature22074

Older Posts »

Powered by WordPress