Razib Khan’s raw genotype data on 23andMe, Family Tree DNA, Geno 2.0 and Ancestry

It has been a while since I posted an update on my genotype. Since then I’ve been tested on most of the major platforms. I don’t see any harm in releasing this to the public or researchers who want to look at it (though I don’t know why anyone would).

You can download all the files here.

Having my genotypes public is pretty useful for me. If I inquire about someone’s genetics oftentimes people get weirdly defense and ask “what about you?” I Just invite them to look at my raw data and analyze it for themselves! I’m not a hypocrite about this.

Over the years I’ve had researchers inquire about my ethnicity when they stumble upon my genotype on platforms such as openSNP. So in full disclosure, most of my ancestry is pretty standard eastern Bengali. I’m more East Asian shifted than most Bangladeshi samples in the 1000 Genomes project, but then my family is from Comilla, in the far east of eastern Bengal (anyone who cares, my Y is of course R1a1a-Z93 and my mtDNA U2b).

As before I’ll put the genotype under a Creative Commons license:Creative Commons License

Understanding prehistory through genetic inference and ancient DNA

Before David Reich’s book, , I highly recommend a new preprint from Pontus Skoglund and Iain Mathieson*, Ancient genomics: a new view into human prehistory and evolution.

It’s basically at the sweet spot for a lot of readers: doesn’t overemphasize methods or archaeological minutiae that’s hard to follow. That being said I do think you would benefit if you read two things which would complement in those directions, , and Ancient Admixture in Human History.

* I have to say, I consider Iain a friend, but am I the only one a bit perplexed by how a British person can have such a difficult to spell version of his name? I always have to look it up!

Most popular GNXP post of all time?

Was talking to a friend and mentioned offhand that the most popular GNXP post of all time was written in 2010 very casually and because of a question on Twitter posed by Jason Goldman. At 700,000 Google Analytics sessions it periodically still gets bumped up by places like Reddit.

The book to the right is a pretty big clue. Can you guess the post? I’m posting the link in the comments below….

Neanderthal vs us: for wont of a SNP?

Recently at a human evolution conference in England Svante Paabo (or someone in his group) was alluding to discovering how modern humans and Neanderthals differed by looking at the ~30,000 genetic positions (bases) where modern humans and Neanderthals exhibit fixed differences. That is, Neanderthals and modern humans exhibit totally disjoint frequencies.

I’ve been saying this for years, but I’ll say it again: this is probably a fool’s errand. I do think there are major differences at loci which we know about, such as at FOXP2. But, it isn’t clear that even at FOX2 Neanderthals and modern humans exhibited complete lineage sorting. That is, there’s evidence that the Altai Neanderthal had introgression from modern (or modern-related) human populations, and that those variants were sweeping. And there is still variation in modern human populations at FOXP2.

All Homo exhibit encephalization, credit Luke Jostins

It looks like Soft Sweeps Are the Dominant Mode of Adaptation in the Human Genome (also see Detecting polygenic adaptation in admixture graphs). But it may be that soft selections and recurring gene flow are common features of the broader Homo lineage for several million years.

In other words, looking for silver bullet variants which can explain why we are so special may always fail, because there are no silver bullets (for several years at ASHG I note that there were presentations which attempted to determine the locus of humanity by looking at the loci of functional interest where Neanderthals and modern humans differed). Rather, human exceptionalism is no exceptionalism, and human populations explore a wide space of phenotypes defined by a huge range of allelic variance which spans many of our extant lineages.

Open Thread, 11/26/2017

A few days ago there was a Twitter thing about top five books that have influenced you. It’s hard for me to name five, but I put three books down for three different reasons:

  • , because it gives you a model for how to analyze and understand evolutionary processes. There are other books out there besides . But if you buy this book you don’t need to buy another (at SMBE this year I confused Andy Clark with Mike Lynch for a second when introducing myself. #awkward)
  • . A lot of historical writing can be tendentious. I’ve also noticed an unfortunate tendency of historians dropping into contemporary arguments and pretty much lying through omission or elision to support their political side (it usually goes “actually, I’m a specialist in this topic and my side is 100% correct because of obscure-stuff where I’m shading the facts”).  illustrates the solidity that an archaeological and materialist take can give the field. This sort of materialism isn’t the final word, but it needs to be the start of the conversation.
  • . To know things is important in and of itself. My own personal experience is that the returns to knowing things in a particular domain or area do not exhibit a linear return. Rather, it exhibits a logistic curve. Initially, it’s hard to make sense of anything from the facts, but at some point comprehension and insight increase rapidly, until you reach the plateau of diminishing marginal returns.

If you haven’t, I recommend you subscribe to Patrick Wyman’s Tides of History podcast. I pretty much wait now for every new episode.

The big Washington food fight. GMO labeling is coming.

In Our Time has two very good episodes recently I recommend on the Picts and Thebes.

The Unexamined Brutality of the Male Libido. When I read the title I assumed that the piece was somehow informed by evolutionary psychology. No. It’s larded with Freudianism.

Evolutionary psychology has taken its hits over the last 15 years, and rightly so when it’s basically re-warmed social psychology, but the stuff informed by primatology is 21st century science (you can agree to disagree, but there’s something to grab onto there). Freudianism sometimes gets a bad rap even though its origins were not nearly as woolly as we might think, but cutting-edge early 20th century psychology is really beyond its sell-by date today.

This is the stuff that makes me pessimistic that the “replication crisis” is going to have any impact on the media or the public. For example, At Yale, we conducted an experiment to turn conservatives into liberals. The results say a lot about our political divisions in The Washington Post. The author of the op-ed is a major person in the center of the controversy around replication. In particular, “ego depletion.” This op-ed is based on studies with p-values of 0.034 and such.

That being said, Radiolab has an episode on Stereotype Threat which acknowledges worries about its replication. Really all that matters to me is the funnel plot.

Detecting past and ongoing natural selection among ethnically Tibetan women at high altitude in Nepal. It’s polygenic and we don’t understand the architecture of the trait that well it seems. Basically, early selection sweep analysis detected some major loci, but it’s not the whole story. Reminds me of pigmentation.

An endogenous retroviral envelope syncytin and its cognate receptor identified in the viviparous placental Mabuya lizard. This is pretty cool, the same process seems to be occurring over and over.

Rethinking phylogenetic comparative methods. I think this is will be an impactful paper once it gets published.

Meanwhile, this looks interesting: The role of chromosomal inversions in speciation.

I posted some Taylor Swift memes to Twitter as a joke. They seem quite popular, especially the ones related to string theory and evolution, though the one related to Arminian and orthodox Calvinist soteriology took off in a different sector of Twitter.

The funny thing is several people were angry because they thought I was putting down Taylor Swift. I was just making fun of the media fixation on famous people and their stupid thoughts.

My friend D. Allan Drummond has gone “full artiste.” He’s now selling some of his incredible biologically-themed 3-D printing. You can read about his work in this profile at Nerdist (by day he’s a biochemist who used to be an evolutionary geneticist who used to be an engineer).

One month of DNAGeeks & Cyber Monday sale

For a while, one of the weird things about DNAGeeks sales in quantities has been that people who look at haplogroup I1‘s page have not been buying the shirts. This is in contrast to haplogroup R1b. The geographically the two groups overlap a fair amount. It’s not totally implausible to guess that 75% of the humans who have stepped foot on the moon have been paternal haplogroup’s R1b and I1. And the two have had about the same number of page-views.

I began to make gross generalizations about the type of man who carries I1. Well, the joke’s on us: turns out that the previous font made it look like “I1” was lowercase L, as in “l1.” Well we’ve fixed that problem, so let’s see how that works out!

When my friends and I started DNAGeeks over a weekend we didn’t have a precise idea where it was going to go and what was going to be popular. People keep asking “so what it’s about about?” Well DNA obviously, but the journey is just starting.

We knew genetics and genomics and have a wide diversity of other skills (I can write, others handle the code and business sides), but “DNA-themed products” was not something which I saw a lot of market testing on. So as they say in the start-up world we’re trying to iterate and figure out what works and doesn’t. The goal is make more people passionate about genetics, and also target people who are already passionate about genetics.

One thing we have learned is that the DNA helix symbol is very popular (thanks Joel!). We’re putting it on shirts, mugs, and now cellphone cases (iPhone only, since only iPhone owners spend money). Also, I’m happy to report a fair number of Gene Expression t-shirts have sold.

Until tomorrow if you used DNAEXPLAINED17 as a coupon code on checkout you get 15% off. Viva la consumerism!

The question should be “Who Are Salafi Muslims and Why Are Many So Extreme?”

Because of the horrible massacre at a mosque with Sufi tendencies in Egypt, there are a lot of “explainers” out there about sectarian divisions in Islam. The one in The New York Times, Who Are Sufi Muslims and Why Do Some Extremists Hate Them? could be worse. This portion especially gets at the major issue:

For a time, beginning in the 12th century, Sufism was a mainstay of the social order for Islamic civilization, and since that time it has spread throughout the Muslim world, and to China, West Africa and the United States. As Sufism spread, it adapted elements of local culture and belief, making it a popular practice.

Alexander D. Knysh, a professor of Islamic studies at the University of Michigan and expert in modern Sufism, describes it as a “very wide, amorphous movement” practiced within both the Sunni and Shiite traditions.

Specific claims about Sufism beyond the most general fail because vast swaths of Islamic history and Muslim peoples and practice are Sufi. In the modern western media, there is an unfortunate tendency to dichotomize Islam into a harsh and fundamentalist form and a moderate and mystical Sufi variety. Though a small minority of Sufis have drifted toward very heterodox beliefs, the vast majority are orthodox Muslims who also adhere to a school of Islamic law.

And Sufis are not all pacific saints. In the 19th century Libya the Sensussi Sufi movement was critical in the continuation of the trans-Saharan slave trade, and later served as a major focal point for violent resistance against the Italian colonial project. The great anti-philosopher of the medieval period, Al-Ghazali, who is generally agreed to have ushered in the decline of philosophical thinking within orthodox Sunni Islam, was a Sufi.

The question should not be about Sufis. Sufis are not moderate or mystical Muslims, they are simply Muslims. That is, they’re the mainstream. Rather, the crux of the issue is that violent radicals have emerged from the soil of Salafism. Not all Salafis are violent. But violent Salafis are the ones who regularly target other Muslims and their holiest of sites.

Salafism is a modern movement of the past few centuries. Like Protestant Fundamentalism, it is a product of the engagement of traditional religion with the modern world. Self-consciously Salafist Muslims have never known a world where the West was not dominant. Therefore it is no surprise that they look to the accrued tradition of Islamic civilization and see in it failure and decay.

Like some Radical Protestants, the Salafists imagine that they are creating a community of Muslims who are true to the path of the religion in its earliest years before it became tainted with monarchy. Basically, Salafists wish to transform Islam from a religion of history to one of pure axiomatic abstractions.

Why do Salafi radicals attack Sufis? Their tendency to engage in takfir against other Muslims goes back to the proto-Salafi Wahhabists. And Sufi Islam, with a venerable history going back more than 1,000 years, is naturally going to be the target of Salafi rage because it was the Islam that failed to stem the tide of Western ascendancy, the Islam that witnessed the slow and gradual decline from the greatness of the 8th and 9th centuries. The children shall eat their own parents.

Cultural and religious relics as clues to cultural process

Much of the public is given the impression that Christianity became the official religion of the Roman Empire under the reign of Constantine. Though it is hard to deny that it was the favored religion, especially by the end of his rule, modern ideas of the “official” religion of a given state are somewhat anachronistic for this period and place. In Alan Cameron argues that the true death-blow to non-Christian religions in the Roman Empire occurred during the reign of Gratian, 50 years after Constantine, with the cessation of subsidies to the traditional religion (a contrasting view is that elite paganism was vital as a public force up until Theodosius the Great’s conquest of the Western Empire).

In the author reviews the almost imperceptible change that occurred in the lives of the Roman elite, who looked back to a continuous cultural lineage that drew from the late republic. These elite men and women exhibited passivity and complacency, as the norms which had come before would presumably obtain until the end of time. What they did not understand is that there are periods when societies go through rapid changes, so that a rupture occurs between the past and the future in the span of a lifetime.

Whether you think elite public paganism lost its vitality in the last decades of the 4th century or sometime in the 5th, the reality is that it was a spent force by the time Justinian began his the marginalization of the last of the Neoplatonic philosophers around 500.

Of course, this does not mean that sub-pagan practices did not persist among the European peasantry for centuries. But the reality is that they were at least nominally Christian, and a coherent sense of traditional religious identity apart from that outward affiliation did not exist (at least after Christianization).

Which brings me to the people of the Mani peninsula, in the southern Peloponnese. This isolated region was reputed to retain the practices of Greek paganism as late as the year 1000 A.D. Let me quote Constantine VII, Byzantine emperor from 913 to 959:

Be it known that the inhabitants of Castle Maina are not from the race of aforesaid Slavs (Melingoi and Ezeritai dwelling on the Taygetus) but from the older Romaioi, who up to the present time are termed Hellenes by the local inhabitants on account of their being in olden times idolaters and worshippers of idols like the ancient Greeks, and who were baptized and became Christians in the reign of the glorious Basil. The place in which they live is waterless and inaccessible but has olives from which they gain some consolation.

The Basil in question reigned from 867 to 886.

Of course, we don’t know if Constantine and his contemporaries were correct in all the details of the people of Mani. It seems unlikely that he would have misidentified them as Greek as opposed to Slavs (whose paganism was more recent), but perhaps they practiced a debased form of folk Christianity mixed with old superstitions? But, if they did continue to practice the religion of ancient Greece it illustrates how persistent traditional beliefs than be in a world where the state and cultural elites have more limited purview than one might have thought. It seems unlikely that the people of Mani would have been unfamiliar with Christianity (there are ruins of churches going back to the 4th century in the area), but they may have been socially isolated enough that the incentives to convert to the new religion did not exist.

The Tengerrese people of East Java, who remain Hindu, maybe a modern analogy. The worshippers of the gods of the old Norse were by chance the Sami, who did not become fully Christian until after the Reformation. And up until the Islamic period, the city of Harran remained predominantly pagan (the Persians were close enough that the East Roman authorities respected the religious liberties of these people lest they defect).

Soft selection for gentleness in Puerto Rican African Honeybees

When I was a kid “killer bees” were a major pop culture thing. There were movies about the bees, and we would get updates about their march northward in the news. They were a cautionary tale of our species’ hubris.

Today we have a little bit more perspective. These bees were actually just African honeybees, the ancestral population to European honeybees, which were introduced to the New World with Europeans centuries earlier than the African honeybees. African honeybees were not that different from European honeybees, but they were more aggressive and tended to outcompete European honeybee colonies. They are a major problem for the beekeeping industry, but not a major threat to human life.

Today the African and European populations in the United States seem to have stabilized in their ranges, with a hybrid zone between them. African bee’s migratory behavior makes them less competitive with European bees in colder climates.

A friend of mine once mentioned to me that if he had to do it all over again he would do research on the evolutionary genomics of Hymenoptera, and in particular bees. People care about bees. So it ‘s no surprise that I noticed this paper out in Nature Communications, A soft selective sweep during rapid evolution of gentle behavior in an Africanized honeybee:

Highly aggressive Africanized honeybees (AHB) invaded Puerto Rico (PR) in 1994, displacing gentle European honeybees (EHB) in many locations. Gentle AHB (gAHB), unknown anywhere else in the world, subsequently evolved on the island within a few generations. Here we sequence whole genomes from gAHB and EHB populations, as well as a North American AHB population, a likely source of the founder AHB on PR. We show that gAHB retains high levels of genetic diversity after evolution of gentle behaviour, despite selection on standing variation. We observe multiple genomic loci with significant signatures of selection. Rapid evolution during colonization of novel habitats can generate major changes to characteristics such as morphological or colouration traits, usually controlled by one or more major genetic loci. Here we describe a soft selective sweep, acting at multiple loci across the genome, that occurred during, and may have mediated, the rapid evolution of a behavioural trait.

Come for the bees, but stay for the soft selection! If you talk to anyone in evolutionary and population genomics you know that the future is in understanding patterns of soft selection and polygenic selection from standing variation. Though these are related phenomena which are associated with each other, all are all distinct.

Standing variation just refers to the diversity which is segregating in the population at any given time. At any given moment many loci exhibit polymorphism. This polymorphism can be a target of natural selection if it is correlated with heritable variation and differentials in fitness. Though soft selection can be quite wooly it’s inverse, hard selection, is clear: in genetic terms hard selection can be seen in allele frequency changes at a single variant in a locus, going from the point where it is a novel mutation to nearly fixed in the population. In Haldane’s original conception hard selection involved excess deaths, and imposed a limit on the rate of evolution as well as the amount variation you could expect within a given population. This model was convenient in the pre-genomic and early genomic era because empirical selection tests had to focus on large allele frequency changes around singular loci. Researchers didn’t have large numbers of whole-genome samples available (nor the computational ability to analyze them).

Today this is not a limitation. In the analysis above the authors had 30 individuals of the 3 populations sequenced at high quality (20x). They ended up with millions of genetic variants they could analyze.

The plot to the left shows that “gentle African honeybees” (gAHB) tend to be closer to the African honeybee populations (AHB) overall (though with some hybridization with European honeybees, EHB). This is not surprising.

But the key observation was that over 12 generations the African honeybees of Puerto Rico became progressively less aggressive, despite maintaining overall morphological similarities to the mainland Mexican African bees from which they likely derive. Though buried in the discussion, there is a rationale for why this morphological change may have occurred: the Puerto Rican bees are subject to a lot of negative selection against aggression because of the density of the island, as well as the reality that aside from humans there aren’t other many species where their aggressive tendencies are beneficial. Basically, if you are an aggressive colony, it’s harder to make a go in densely settled areas (the implication here then is that there are probably “gentle” African honeybee populations across Latin America, they just are never disaggregated from the broader meta-population).

Credit: Phillip Messer and Nandita Garud

It’s the genomics where the real evolutionary insight comes in: they found that there were multiple soft sweep events around genetic regions implicated in behavior. In their overall genome the gAHB of Puerto Rico resembled mainland AHB, but in this subset of genetic loci they resembled EHB. Many of these loci had also been known to be targets of selection when the original European bee population diverged from the ancestral African population. Basically this is a genomic illustration of convergent evolution.

Regular readers of this blog will recognize the ways they detected selection. They used a modified form of EHH, which is reasonable since the selection event was recent enough to have been associated with distinct haplotype blocks. Also, standard Fst analysis showed that these were outliers in relation to the broader genetic pattern of relatedness (these loci were more like EHB than AHB, while most loci were more like AHB than EHB).

So this a form of polygenic selection. Remember, natural selection only knows genes through the phenotype (with intra-genomic selection being an exception). A behavior like aggression is probably subject to the fourth law of behavior genetics. That is, variation won’t be defined around a single genetic locus. Rather, variation across the genome will be correlated with variation in the phenotype. As selection favors a particular value of the phenotype across the distribution the allele frequencies across many genetic loci will shift, but they will not necessarily fix. Polygenic selection operates on the dispersed standing genetic variation which explains much of the variation of the phenotype in question. Instead of total sweeps to fixation due to large fitness differences between a given allele and its alternative form, the selection impact is distributed and diffused across the genome.

Though most of the genetic variants seem to recapitulate the evolution of the less aggressive phenotype that occurred with the original migration north of African honeybees, some of the selection signatures were novel. This points to the reality that when you have soft selection on standing variation you may have similar phenotypes which evolve via different means. Additionally, the authors noted that these results were in contrast to controlled breeding experiments in mammals where selection for gentility (“domestication”) often targeted a few loci and exhibited strong pleiotropic effects (due to the genetic correlation). These results point to the limitations of inferences made from human-directed selection.

Soft selection is probably ubiquitous. Consider the evolution of skin color in humans. There are lots of variants and lots of variation, and most of the variation seems to be ancestral. Only at the locus SLC24A5 do you have a perfect illustration of a hard selective sweep, probably from a de novo mutation that emerged around the Last Glacial Maximum.

From a geneticists’ perspective evolution is basically conceived of as changes in allele frequencies over time. Much of this is due to natural selection. Now that the world of soft selection is opening up, I suspect that we’ll understand a lot more of what we see around us, at least in the generality.

Citation: A soft selective sweep during rapid evolution of gentle behaviour in an Africanized honeybee.

Dodging the Apple Premium (still)

Because of what I have been provided by my employers over the last few years I’ve been working on a . These are fine machines, but they have not converted me to being a convert to all things Apple. I have two machines with Ubuntu at home that I have no problem with using (one of them has a dual-boot where I have a copy of Windows which I use every six months or so to make sure that security updates are installed).

In any case, my current phone has been acting erratically over the past few weeks. Up until now I had been resisting getting a new phone because it wasn’t as if I really needed one…but when there is a jeopardy that your phone will decide to not boot up, one has to act.

So I was agonizing over the or . I’ve had multiple Samsung’s before. And the  seemed fine. The flip side is that everyone in my office uses an , and I get crap for staying with Android. This is not a major issue…but I can’t lie, I’m curious about the iPhone.

In the end, I probably stayed with Android for one primary reason: people in the Apple ecosystem seem totally hostage to Apple. Upgrades are a total pain, and there are minor things I need to get fixed in regards to my ‘s OS which is going to require a “Genius.” The whole situation strikes me as farcical and not futuristic. I’d rather tinker with my Ubuntu distribution than wait in line at a crowded Mac store.

So pass for now….