America’s great Saudi foreign policy sin

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.

2017 Gene Expression reader survey


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 1: 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.

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

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?

Oxford Nanopore finally giving hope to biologist’s dreams

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

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!

Mouse fidelity comes down to the genes

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

Women hate going to India


For some reason women do not seem to migrate much into South Asia. In the late 2000s I, along with others, noticed a strange discrepancy in the Y and mtDNA lineages which trace one’s direct male and female lines: in South Asia the male lineages were likely to cluster with populations to the north an west, while the females lines did not. South Asia’s females lines in fact had a closer relationship to the mtDNA lineages of Southeast and East Asia, albeit distantly.

One solution which presented itself was to contend there was no paradox at all. That the Y chromosomal lineages found in South Asia were basal to those to the west and north. In particular, there were some papers suggesting that perhaps R1a1a originated in South Asia at the end of the last Pleistocene. Whole genome sequencing of Y chromosomes does not bear this out though. R1a1a went through rapid expansion recently, and ancient DNA has found it in Russia first. But in 2009 David Reich came out with Reconstructing Indian population history, which offered up somewhat of a possible solution.

What Reich and his coworkers found that South Asia seems to be characterized by the mixture of two very different types of populations. One set, ANI (Ancestral North Indian), are basically another western or northwestern Eurasian group. ASI (Ancestral South Indian), are indigenous, and exhibit distant affinities to the Andaman Islanders. The India-specific mtDNA then were from ASI, while the Y chromosomes with affinities to people to the north and west were from ANI. In other words, the ANI mixture into South Asia was probably through a mass migration of males.

But it’s not just Y and mtDNA in this case only. A minority of South Asians speak Austro-Asiatic languages. The most interesting of these populations are the Munda, who tend to occupy uplands in east-central India. Older books on India history often suggest that the Munda are the earliest aboriginals of the subcontinent, but that has to confront the fact that most Austro-Asiatic language are spoken in Southeast Asia. There was no true consensus where they were present first.

Genetics seems to have solved this question. The evidence is building up that Austro-Asiatic languages arrived with rice farmers from Southeast Asia. Though most of the ancestry of the Munda is of ANI-ASI mix, a small fraction is clearly East Asian. And interestingly, though they carry no East Asian mtDNA, they do carry East Asian Y. Again, gene flow mediated by males.

The same is true of India’s Bene Israel Jewish community.

A new preprint on biorxiv confirms that the Parsis are another instance of the same dynamic: The genetic legacy of Zoroastrianism in Iran and India: Insights into population structure, gene flow and selection:

Zoroastrianism is one of the oldest extant religions in the world, originating in Persia (present-day Iran) during the second millennium BCE. Historical records indicate that migrants from Persia brought Zoroastrianism to India, but there is debate over the timing of these migrations. Here we present novel genome-wide autosomal, Y-chromosome and mitochondrial data from Iranian and Indian Zoroastrians and neighbouring modern-day Indian and Iranian populations to conduct the first genome-wide genetic analysis in these groups. Using powerful haplotype-based techniques, we show that Zoroastrians in Iran and India show increased genetic homogeneity relative to other sampled groups in their respective countries, consistent with their current practices of endogamy. Despite this, we show that Indian Zoroastrians (Parsis) intermixed with local groups sometime after their arrival in India, dating this mixture to 690-1390 CE and providing strong evidence that the migrating group was largely comprised of Zoroastrian males. By exploiting the rich information in DNA from ancient human remains, we also highlight admixture in the ancestors of Iranian Zoroastrians dated to 570 BCE-746 CE, older than admixture seen in any other sampled Iranian group, consistent with a long-standing isolation of Zoroastrians from outside groups. Finally, we report genomic regions showing signatures of positive selection in present-day Zoroastrians that might correlate to the prevalence of particular diseases amongst these communities.

The paper uses lots of fancy ChromoPainter methodologies which look at the distributions of haplotypes across populations. But some of the primary results are obvious using much simpler methods.

1) About 2/3 of the ancestry of Indian Parsis derives from an Iranian population
2) About 1/3 of the ancestry of Indian Parsis derives from an Indian popuation
3) Almost all the Y chromosomes of Indian Parsis can be accounted for by Iranian ancestry
4) Almost all the mtDNA haplogroups of Indian Parsis can be accounted for by Indian ancestry
5) Iranian Zoroastrians are mostly endogamous
6) Genetic isolation has resulted in drift and selection on Zoroastrians

The fact that the ancestry proportion is clearly more than 50% Iranian for Parsis indicates that there was more than one generation of males who migrated. They did not contribute mtDNA, but they did contribute genome-wide to Iranian ancestry. There are wide intervals on the dating of this admixture event, but they are consonant oral history that was later written down by the Parsis.

So there you have it. Another example of a population formed from admixture because women hate going to India.

Citation: The genetic legacy of Zoroastrianism in Iran and India: Insights into population structure, gene flow and selection.
Saioa Lopez, Mark G Thomas, Lucy van Dorp, Naser Ansari-Pour, Sarah Stewart, Abigail L Jones, Erik Jelinek, Lounes Chikhi, Tudor Parfitt, Neil Bradman, Michael E Weale, Garrett Hellenthal
bioRxiv 128272; doi: https://doi.org/10.1101/128272

Only half of the traffic on this website is from a personal ‘computer’

I spend way too much time semi-competently managing the VPS this site is hosted on. But at least now I can look at Google Analytics. I’ve found some interesting things.

For example, 35% of the traffic on this site comes from phones, and 10% from tablets. That means that conventional computers are only somewhat more than half of the views. Additionally, 50% more of the Facebook shares are via the mobile Facebook app than the normal desktop version (I tend to get the most referrals from Twitter since I have a bigger Twitter following, but at some point I expect Facebook to surpass that as people realize I’m blogging again).

Probably going to make a few changes to make the site more mobile friendly since so many of you tend to read it on that device….

Evolutionary game theory and international relations

The North Korea Paradox: Why There Are No Good Options:

Denny Roy, a political scientist who studies Asian security issues, told me last fall that North Korea “intentionally employs a posture of seemingly hyper-risk acceptance and willingness to go to war as a means of trying to intimidate its adversaries.”

This puts the world in a quandary: How could any outside threat possibly exceed the risk that North Korea already takes on itself? How could any concession remove the North Korean weakness that drives its behavior?

Basically North Korea is a weak state. Its only leverage is to hold the world hostage and act crazy. Unfortunate, but true.

But this piece reminded me a lot of stuff that John Maynard Smith described in Animal Signals. Sometimes it is the weaker and more vulnerable animals which have to engage in high risk agonistic competition, so that they can show more fit individuals that there is going to be a significant cost in initiating hostilities.

It also reminds me of high school. If you are smaller than average, it is best to make it clear to larger bullies that you won’t be passive. You may lose the fight, but by escalating rapidly you can dissuade a bully from targeting you, as opposed to someone who is more likely to be an easier victim.

Of course, bullies need to be “rational” actors here….