Open Thread, 12/10/2018

Merry Christmas & Happy Holidays!

Just a heads up that DNA Geeks is running a holiday sale on the microscopes with free shipping (until stocks are sold out).

Also, updating a plugin broke the site, so I had to deactivate and reactive all the plugins. For whatever reason, the ‘related posts’ plugin also no longer works. Does anyone click those links? Might have to find a replacement.

Models of archaic admixture and recent history from two-locus statistics.

Incidence of Dementia over Three Decades in the Framingham Heart Study. Decreased incidence.

China Launches First-Ever Mission to the Moon’s Farside.

Fourth Brown Pundits podcast, “the Golden Age of Islam”. Here are the iTunes and Stitcher links. Would appreciate subscriptions+reviews.

America’s New Religions. I dislike overuse of the term “religion.” And I’m generally skeptical of the idea of “political religion” as a useful term, as opposed just mass movement. But I think I”m coming around.

When it comes to religion, I take for granted that you’ve read a book like In Gods We Trust. That being said, I do wonder about the psychological research used to support some of the conclusions in the field of the cognitive anthropology of religion in the wake of the “replication crisis.” Some of the stuff, like depictions of eyes making you more ethical don’t seem to be robust findings.

On The Insight this week we talked Game of Thrones. Yes, I do think meiotic drive is the best rational explanation for the persistence of Valyrian characteristics.

More data from the Estonian Biocentre. Also, the title of a paper, “Multiple deeply divergent Denisovan ancestries in Papuans” which is clearly in review.

The presence and impact of reference bias on population genomic studies of prehistoric human populations.

Genetically Modified People Are Walking Among Us.

Contingency in the convergent evolution of a regulatory network: Dosage compensation in Drosophila.

Criticizing Islam is turned into “hate speech” on Facebook. The problem is that the “big platforms” like Twitter and Facebook are so big and diverse that it’s not that hard to “game them” and engage in speech policing. Facebook is really about family photos now. And Twitter is best done non-ironically if you have more than a trivial following.

George R.R. Martin takes time off from not writing his book to laud New York pizza.

Why We Miss the WASPs. The reactions seem to be driven by people who were not clear what the narrow connotations of “WASP” originally was.

Anti-Zionism Isn’t the Same as Anti-Semitism. I pretty much agree, though operationally the lines between ‘anti-Zionism’ and ‘anti-Semitism’ bleed over pretty easily.

Models uncovering African population genetic history

In a deep sense, we know a lot more about the population genetic history of England at the fine-grain than we do about the whole continent of Africa. That’s going to change in the near future, as researchers now realize that the history and emergence of modern humans within the continent was a more complex, and perhaps more multi-regional, affair than had been understood.

Because of the relative dearth of ancient DNA, there has been a lot of deeply analytic work that draws from some pretty abstruse mathematical tools operating on extant empirical data. A series of preprints have come out which use different methods, and arrive at different particular details of results, but ultimately seem to be illuminating a reoccurring set of patterns. Dimly perceived, but sensed nonetheless.

Here’s the latest offering, Models of archaic admixture and recent history from two-locus statistics. I can’t pretend to have read the whole preprint (lots of math), but these empirical results jumped out at me:

We inferred an archaic population to have contributed measurably to Eurasian populations. This branch (putatively Eurasian Neanderthal) split from the branch leading to modern humans between ∼ 470 − 650 thousand years ago, and ∼ 1% of lineages in modern CEU and CHB populations were contributed by this archaic population after the out-of-Africa split. This range of divergence dates compares to previous estimates of the time of divergence between Neanderthals and human populations, estimated at ∼650 kya (Pr¨ufer et al., 2014). The “archaic African” branch split from the modern human branch roughly 460 − 540 kya and contributed ∼ 7.5% to modern YRI in the model (Table A2).

We chose a separate population trio to validate our inference and compare levels of archaic admixture with different representative populations. This second trio consisted of the Luhya in Webuye, Kenya (LWK), Kinh in Ho Chi Minh City, Vietnam (KHV), and British in England and Scotland (GBR). We inferred the KHV and GBR populations to have experienced comparable levels of migration from the putatively Neanderthal branch. However, the LWK population exhibited lower levels of archaic admixture (∼ 6%) in comparison to YRI, suggesting population differences in archaic introgression events within the African continent (Table A3).

To be frank I’m not sure as to the utility of the term “archaic” anymore. I sometimes wish that we’d rename “modern human” to “modal human.” That is, the dominant lineage that was around ~200,000 years ago in relation to modern population ancestry.

Skull from Iwo Eleru, Nigeria. Photo credit: Katerina Harvati and colleagues CC-BY

But, these results are aligned with other work from different research groups which indicate that something basal to all other modern humans, but within a clade of modern humans in relation to Neanderthal-Denisovans, admixed with a modern human lineage expanding out of eastern Africa. The LWK sample is Bantu, and has a minority Nilotic component that has West Eurasian ancestry. This probably accounts for the dilution of the basal lineage from 7.5% to 6%.

I wouldn’t be surprised if the final proportions differ. And other research groups have found deep lineages with African hunter-gatherers. My own view is that it does seem likely that one of the African human populations that flourished ~200, 000 years ago expanded and assimilated many of the other lineages. The “Out of Africa” stream is one branch of this ancient population. But it seems possible that the expansion was incomplete, and that other human lineages persisted elsewhere until a relatively late date.

A genetic history of the human race is not controversial science nor is it fraught

Recently I was talking to a journalist about genetic genealogy, and we both agreed that soon Christine Kenneally’s The Invisible History of the Human Race: How DNA and History Shape Our Identities and Our Futures will need an update. Though published in 2015, much of the research in The Invisible History of the Human Race dates to much earlier.  In the last few years, personal genomics has gone from a sector of millions to tens of millions. In years after 2020 it will go to hundreds of millions.

And yet I’m not sure the educated public is ready to understand what a genomic future is going to look like.

This is why I think that the Elizabeth Warren DNA story is important to get right. The reality is that this isn’t really about Elizabeth Warren’s ancestry, it’s a story at the intersection of high politics and culture wars, and genetics is getting caught in the undertow. Recently I heard Ben Shapiro comment that Warren likely had “maybe 1/1024th Native American.” Actually, I think it’s very likely she has 0.5 to 1% Native American ancestry (read this Elizabeth Warren DNA post for why I say that) Not to be trite, but facts don’t care about Ben Shapiro’s feelings. I know he’s not a fan of Warren, but he shouldn’t be laundering misrepresentations.

Even in the comments of this website motivated reasoning cropped up when the original Warren story became a national sensation. Many on the Right side of the spectrum laughed at the results and interpreted them in the least generous terms. The falsehoods and misunderstandings promoted by the media, often inadvertently because most journalists don’t have the skills to navigate the science, were injected into the conservative memesphere.  Shapiro has admitted, to his own chagrin, his lack of science background, and I suspect if I explained it to him he wouldn’t use “maybe 1/1024th Native American” line. He doesn’t need to. If you are a conservative there are many reasons to be critical of Elizabeth Warren.

But I can’t blame Shapiro too much. He was reacting to this story in The New York Times, Elizabeth Warren Stands by DNA Test. But Around Her, Worries Abound. In this piece, the attacks on Warren are coming from the Left and Native American activists. There is a real story here. The Boston Globe has published an editorial warning her not to run. The air has changed around her.

From the piece in The Times:

Warren’s presidential ambitions, she has yet to allay criticism from grass-roots progressive groups, liberal political operatives and other potential 2020 allies who complain that she put too much emphasis on the controversial field of racial science — and, in doing so, played into Mr. Trump’s hands.

Ms. Warren’s allies also say she unintentionally made a bigger mistake in treading too far into the fraught area of racial science — a field that has, at times, been used to justify the subjugation of racial minorities and Native Americans.

There is “racial science” like there is “evolution science” or “Creation science.” The term is not used by any scientist that I know of, but comes up by critics and polemicists. The New York Times, whether consciously or not, is going to convince a lot of scientifically illiterate people who don’t read their science pages that there is a field of “racial science” (using the term “race science” liberally is a thing on the Left…reminds me of social conservatives who used to call everyone who was not an evangelical Protestant a “non-Christian”)

Here’s what went on in the Warren case is:

  1. Not scientifically controversial
  2. But scientifically new

Here is a review, A comprehensive survey of models for dissecting local ancestry deconvolution in human genome which looks at “20 methods or tools to deconvolve local ancestry.” There may be disagreement on the best method for various reasons, but there is no disagreement that local ancestry deconvolution is possible. It is not controversial. In fact, it is rather important in areas such as admixture mapping for diseases.

The science isn’t that hard to explain at a high level. The figure to the left is from a new paper that recently came on the genetics of the New World (using ancient DNA). What you see is that some human populations are isolated from other human populations. For example, the last common substantial ancestry of Native American populations before 1492 and Northern Europeans dates to the period between 20,000 to 40,000 years ago.

Tens of thousands of years of genetic separation result in genetic distinctiveness. This is a standard old population genetic model. When populations come back together and mix, that daughter population is clearly going to be genetically a mix between the two parent populations. But the human genome is a sequence of three billion distinct base pairs, and the mixing exhibits discrete patterns within the genome.

Humans are diploid, which means we have two copies of each gene. These genes are aligned along homologous chromosomes. One homolog you inherit from the father and one homolog you inherit from the mother. These two homologs are the basis for Mendel’s Law of Segregation.

When sex cells, sperm and eggs, are formed they carry only one of the homologs. They are haploid, with single gene copies. If they weren’t, you’d end up tetraploid instead of diploid. You get one gene copy from the mother and one gene copy from the father.

But, before the formation of sex cells, during meoisis, the homologs undergo recombination. In humans that means that there is swapping between stretches of homologous chromosomes. The average human has between 20 and 40 recombination events across the genome. A concrete way to think about it is that the individual who is producing sperm or egg is taking the chromosomes they inherited from their parents, and mixing them together, so the final set of chromosomes are a synthetic combination of the chromosomes of grandparents.

Purple segments half-identical to paternal grandfather

To make this concrete, to the left is a partial depiction of one of my children’s chromosomes, and the relatedness to my father. The purple regions are genomic stretches where the child is half-identical to the paternal grandfather. The light gray sections have no genetic descent from my father. The reason is that one of the homologs is from the maternal side. The other homolog is from me, and could be from either my father or my mother. Where the purple alternates with light gray, you see clearly where recombination events happened, as maternal and paternal homologs broke and paired together to produce sperm with novel chromosomes (e.g., my contributed chromosome 11 is 90% my father, 10% my mother…while chromosome 19 is more balanced.

But that’s not the only way to look at recombinations. To the right is an ancestry painting for 23andMe from a friend of mine who is ~25% East Asian and ~75% Northern European. On their chromosome you see two homologs. The blue segments are Northern European. The dark brown segments are East Asian. Notice the alternation between European and East Asian on one of the homologs: this chromosome is almost certainly from the parent who is 50% East Asian and 50% European. There was a recombination event where an “East Asian” homolog, inherited from the parent of East Asian origin, recombined with the “European” homolog, inherited from the parent of European origin.

The resultant chromosome is something new in a physical sequence, with alternating segments of East Asian and European ancestry. Just as the whole genome has an imprint of the genetic history of a population, so sequences of the genome also exhibit distinctiveness due to their origins. Because each generation introduces recombination events, the lengths of these distinct ancestry blocks can tell you how many generations in the past the admixture may have happened.

That’s the theory. The new aspect is that genomic technology has allowed science to assess patterns of local ancestry to a much greater extent than was possible even 15 years ago. With hundreds of thousands of genomic positions, variants, scientists are now able to map regions of the genome to an incredible level of granularity, deploying theoretical understanding of Mendelian and population genetics that dates back to the 20th century.

To look at Elizabeth Warren’s genome, and discover that a small segment of a particular length derives from a Native American population, is not a “controversial field of racial science.” This sort of analysis is now becoming de rigueur in much of medical genetics in larger part because population history has a major impact on disease risk susceptibility. To be fair, doing a local ancestry deconvolution on populations which are much, much, closer genetically due to recent shared history is difficult. But Warren’s is not one of those cases!

Honestly, I don’t know what the outcome of The New York Times calling this “racial science” is going to be, seeing as how it seems likely in the next few years >100 million Americans will have likely done ancestry tests. Many scientists, fairly, do criticize of the interpretations of these tests, and how the public perceives them. But the underlying models and methods are workaday.

It is the interpretation, and how they interact with social and political values, is fraught. The link in the phrase “controversial field of racial scienceactually goes to an article where social and political commentators and activists react to Warren’s decision to take the DNA test. There is no discussion of the science at all. It’s controversial because of what they believe the implications are, not because the science is faulty or unsound.

For example, many (though not all) Native Americans object to the idea of using genetic science to shed light on the status of particular individuals as Native American or not. The decision to take this DNA test, in an environment where many already privately grumbled about Warren’s claims, was obviously clearly a political and public relations misstep. But that does not speak to whether the science itself is sound or unsound.

Conservatives will be highly skeptical of Warren because of her policy positions. And, if the above article is correct, it seems that some of the Left is now against her on the grounds of her impolitic foray into Native American identity. That is all fine, and not much of a concern of mine. But when non-science journalists get their hands on a science story, they tend to mess it up, and that is a problem in the long-term. The sands of politics and society are protean, and always shifting. Science is something more solid, and we should not try to muddy the waters.

Of Plagues and Prehistory

The Fate of Rome: Climate, Disease, and the End of an Empire is an excellent book. I highly recommend it! But one of its assertions, which I accepted at face value at the time I read it, now seems to be less certain (likely wrong). The author contends that the network of trade and interaction facilitated by the emergence of the Pax Romana was instrumental in the rise of periodic pandemics. There was the Antonine Plague, the Plague of Cyprian, and the Plague of Justinian. In contrast, Neolithic Europe, and earlier civilizations may have been subject to endemic diseases. But not pandemics.

A new paper in Cell seems to falsify this view. Emergence and Spread of Basal Lineages of Yersinia pestis during the Neolithic Decline:

Between 5,000 and 6,000 years ago, many Neolithic societies declined throughout western Eurasia due to a combination of factors that are still largely debated. Here, we report the discovery and genome reconstruction of Yersinia pestis, the etiological agent of plague, in Neolithic farmers in Sweden, pre-dating and basal to all modern and ancient known strains of this pathogen. We investigated the history of this strain by combining phylogenetic and molecular clock analyses of the bacterial genome, detailed archaeological information, and genomic analyses from infected individuals and hundreds of ancient human samples across Eurasia. These analyses revealed that multiple and independent lineages of Y. pestis branched and expanded across Eurasia during the Neolithic decline, spreading most likely through early trade networks rather than massive human migrations. Our results are consistent with the existence of a prehistoric plague pandemic that likely contributed to the decay of Neolithic populations in Europe.

The plot to the right shows that Yersinia pestis in Swedish Neolithic farmers, who are genetically similar to modern Sardinians, is basal to the Yersinia pestis in Bronze Age steppe pastoralists, which is basal to later outbreak strains. The point here is that Yersinia pestis seems to a dynamic part of the broader Eurasian pathogenic landscape. The Plague of Justinian was not something new, but the latest manifestation of a reoccurring phenomena. The conditions for its flourishing existed before the rise of Rome.

What was probably different in the case of the Roman Empire was a matter of frequency and rapidity. As the paper, and David of the Eurogenes blog note, there was a massive demographic and social regression in late Neolithic Europe. It is hard to disentangle the variables though because they are all connected. When you read the impact that plague had in the New World on native societies, one of the key elements is that societies on the Malthusian margin often collapse when mortalities go above expectation. Crops go unharvested, and people have to tie up their labor in taking care of the ill. This leads to malnutrition and further susceptibility to the plague.

Or, you can imagine a system where a warm and rainy climatic regime increases primary productivity (e.g., medieval climatic optimum), which leads to greater population density and therefore specialization and economic activity and trade. Then, you might be subject to a climatic shift, in which case productivity drops, and famine ensues. This famine results in increased susceptibility to disease, and plague spreads through the preexistent trade networks established during times of plenty.

The decline is partially endogenous to the system of human societies. External climatic shocks are going to happen now and then. But there are internal dynamics, such as population density, which are going to impact how resilient a society is to an external shock.

It seems likely that the first dense agglomerations of humans were likely going to run up against the limits scale no matter what. Disease serves as a natural Malthusian check, and it was likely inevitable due to the vicissitudes of the circumstances that there would be spikes in mortality so that the population was reduced back to its carrying capacity.

This is a general point. Early societies were subject to random shocks, and those shocks knocked them down a peg for quite some time. But eventually social systems became less fragile, and total collapse and cultural amnesia was generally avoided. The socio-economic complexity of the Roman Empire declined precipitously in the 5th century, with the post-Roman world having to slowly wind itself back up during the “High Middle Ages” (in Western Europe at least). But the ideological superstructure of the Roman world, Christianity and such, maintained an intellectual and cultural continuity, so that Roman institutions and forms could be resurrected when social and economic complexity necessitated it (e.g., Roman civil law). The post-Roman Europeans were primitive in many ways compared to Rome, but their society had not be totally obliterated, so they did not have to reinvent the wheel, so to speak.

More specifically in this instance, it seems that the arrival of the Eurasian agro-pastoralists in the third millennium BC into Northern Europe was not due to their inadvertent biological weaponry. The diseases they brought. The Neolithic societies descended from those who introduced farming were already in collapse, and likely very vulnerable to the predations of agro-pastoralists. This is almost certainly a common event in prehistory, which we will become much more aware of in the near future due to science. For example, I predict pestilence will be associated with the end of the Uruk Period in the Near East.

How paternity testing is like international trade

Nonpaternity rate % N
Switzerland 0.83 1607
USA, Michigan, white 1.49 1417
USA, California, white 2.1 6960
USA, Hawaii 2.3 2839
UK, West London 3.7 2596
Paternity Testing Laboratories
UK 16.6 1702
USA, Los Angeles, white 24.9 1393
Sweden 38.7 5018
South Africa, Cape Coloured 40 1156

The results above are from Kermyt Anderson’s How Well Does Paternity Confidence Match Actual Paternity? This is still one of the best surveys of the field, despite being 12 years ago. A more recent paper, Cuckolded Fathers Rare in Human Populations, uses more powerful genetic genealogy methods to come to the same conclusion as Anderson’s survey: extrapair paternity, or nonpaternity events, are rare in Western societies. I don’t think it is limited to Western societies. I suspect that when high throughput sequencing is applied to Chinese clan lineages and Hindu gotras, you will found that nonpaternity events are similar to those in the West.*

On the other hand, in some small-scale societies, the rates are much higher.

I won’t delve into the evolutionary anthropology here. Rather, I want to point to a new paper, Growth of ancestry DNA testing risks huge increase in paternity issues. Ancestry testing is huge. Within the next year, it is almost certain that 10% of the American population when having some sort of high-density genomic testing done.

As the author of the paper pointed out to me on Twitter, 1% of 16 million people is still a lot. Yes, in absolute terms. But we need to look at the other side of the equation.

In Anderson’s original data one of the interesting results is that in most datasets drawn from paternity testing laboratories, where there is a very high suspicion of nonpaternity events, most of the fathers nevertheless were biological fathers! In a nonpaternity testing context, nonpaternity events will be much closer to ~1%. But, I think it is reasonable to suppose that some of the 99% of the fathers who turn out to be biological fathers also have suspicions…which are unfounded.

Like free trade, you tend to see one side of the equation much more than the other. In free trade scenarios, a minority of workers may lose their jobs or have to work under reduced wages, but the vast majority of consumers will get cheaper or better products. The former is much more salient than the latter.

Similarly, the small minority of fathers and families who are going to be “surprised” in a negative way, is balanced out by the likely larger number who have low-grade suspicions, but in fact, are confirmed in their biological relatedness.

Addendum: Needless to say, if you are part of the “cuckold community”, you should probably not getting this sort of testing.

* The necessity of good quality whole-genome sequencing is due to the fact that male relatives are excellent candidates for nonpaternity events. To get a certain estimate one would want to count unique mutations across the pedigree.

Open Thread, 10/2/2018

I’m reading Ramesh Menon’s The Mahabharata: A Modern Reading before I go to sleep. If you are ignorant, the Mahabharata is about an epic poem that’s an order of magnitude longer than the Iliad or The Odyssey combined. Menon’s prose rendering seems to get some good marks, so I that’s not why I chose it. It’s not the most artful writing, but that’s not what I was looking for, nor would I appreciate it in any case.

My rationale for reading this two-fold. First, as someone who was raised on Bulfinch’s Mythology and has read Genesis in dozens of translations, I thought it was behoove me to become a bit more culturally fluent about brown stuff. Especially in light of the fact that I’m “tagged” on a “Hindu Twitter” thread every few weeks now (12+ hard science disciplines apparently prove the Mahabharata happened 25,000 years ago!).

Second, the age of Indian historical population genetics is coming to an end. Perhaps ten years from now people will be doing temporal transects of eastern Maharashtra, but the bigger framework will be nailed down soon enough. And real intellectual understanding is going to have to synthesize archaeology and mythology with the demographic inferences.

The Urbane Cowboys podcast now has had three Bengali American conservatives on. #representation You should subscribe (I might be on again to talk about CRISPR soon).

Browncast #3. I talk about Indian genetics.

Does DNA Make Us Who We Are? A reader of this weblog shouldn’t find anything new in this book. There are some technical issues in this book you might pick up, as well as airbrushing out of Eric Turkheimer citation. But I left that stuff out of the review since regular people won’t care or understand.

Plomin is definitely an enthusiast on some counts. But most of the book covers his career and views on behavior genetics.

Why There Will Not Be a Beige Future: Skin Color, Genetics, Race and Racism. Written for an audience less familiar with genetics. You shouldn’t need to read this. But some of you still don’t know what the breeder’s equation is.

The New Evolution Deniers. I haven’t read this piece, but people keep asking me about it. Plenty of biologists have these sorts of views from what I can tell, but they’re never going to say a word.

So that’s why this battle is lost in my opinion. I don’t really care. American culture is now a battle between different groups of propagandists who manipulate the levers of power. The rest is commentary, and positivism and critical-rationalism are dead in the broader culture. They only persist in the “inner party” of the elect. Truth is the real conspiracy….

The Harlot by the Side of the Road: Forbidden Tales of the Bible. Good book.

I’ve been defending Marc Lamont Hill’s right to speak and express his views, and retain his professional positions. Mostly because “free speech” really doesn’t matter unless you kind of detest the views you are defending…. So I guess I’ m still delusional and not a realist. I contain multitudes.

Inside the chaos and corruption of Tripoli, where militias rule the streets. We violated the “Pottery Barn rule.”

Mountain lion genomes provide insights into genetic rescue of inbred populations.

Ancient Yersinia pestis genomes from across Western Europe reveal early diversification during the First Pandemic (541-750). Last author “Krause.” You’ll be seeing that a lot related to historical genomics from this group in the near future. Ancient DNA is cheap enough that it can be used to resolve historical questions as opposed to shedding light on prehistory.

Simulation of Karyotype Evolution and Biodiversity in Asexual and Sexual Reproduction.

Sex differences in gene expression in the human fetal brain.