Razib Khan at the center of Eurasia

The Eurogenes blog is running a fundraiser. I chipped in mostly to support his continued blogging. I don’t agree with everything he posts, but the site is a good and valuable resource. “Genome blogging” hasn’t gotten as far as I’d have thought it would have in 2010, mostly because the initial burst of enthusiasm wasn’t followed up by a consistent producer community (in addition to the commentariat). But Eurogenes soldiers on….

0780e5c94be98d65256f715b26529e90In any case, as part of the donation I got an analysis of my genotype. I wasn’t super interested in this because I know a fair amount about my genotype, and the analysis isn’t too informative for someone like me who is >10% East Eurasian. But I thought I would post the PCA because it’s interesting. It’s hard to see in the image above (click it for a larger version), but you notice that I am almost equally positioned between the antipodes of Eurasia (Western Europeans vs. East Asians). Most South Asians occupy a position in between, but definitely skewed toward West Eurasians (the green). But you notice I’m nearly the most “eastern” of the main cluster of South Asians. Depending on how you calculate it I’m between 10% and 20% East Eurasian. This “pulls” me in that direction more than almost all other South Asians. Like a colossus I look east, and I look west, and stand athwart Eurasia bridging the gap.

In any case, if you have $12 to spare, think about donating to Eurogenes. Logistics are at the link.

Tad Williams’ revisits Osten Ard

heart_of_what_was_lost_tad_williamsTad Williams has a new book set in Osten Ard, The Heart of What Was Lost. At only 224 pages it seems more like a novella compared to what he produced for his original series. The last of that of that trilogy, Memory, Sorrow, and Thorn, To Green Angel Tower, weighed in at more than 1,000 pages in the original print hardcover edition (of course it was split in two for paper back).

People are talking about how Memory, Sorrow, and Thorn Book was an inspiration for series such as A Song of Ice and Fire. First, Williams finished the series in three books. So that’s a huge difference. Memory, Sorrow, and Thorn Book produced large narratives on a per publication basis, but the story was relatively spare compared to what people are attempting now (Brandon Sanderson’s The Stormlight Archive is already coming out with 1,000 pages books in a projected ten book series). Additionally, William’s world-building was relatively thin and superficial, while the ultimate resolution of the plot threads of Memory, Sorrow, and Thorn Book struck me as a bit cliche and pat.

This is not to denigrate what Tad Williams achieved with Memory, Sorrow, and Thorn Book. But to be honest I think the past generation has seen huge changes in epic fantasy. Whether for the worse or better, that is up to you….

Genomics is not magic, there is no magic

Screenshot 2016-11-28 02.43.45
MIT Technology Review has an article up, Do Your Family Members Have a Right to Your Genetic Code?, which is now part of the genomics-human-interest-piece genre you see regularly. Here you have the exemplar of this sort of narrative: what do you do when one twin gets a test and the other does not, and they disagree on how much they want to know? (obviously the twin being tested is a “I-want-to-know”) In this case though there is a twist: both of them are scientifically highly trained. And, it turns out that the twin who was worried/nervous about genetic results turned out to have ‘actionable’ results from the other twins’ decision.

There’s a major problem I have with this genre: genomics is not magic, genetics predates genomics by 100 years, and genetics predates DNA based molecular biology by 50 years. That means the basics of this dilemma have been present for over a century. Here are the conditions:

1) You have a condition
2) That condition is heritable
3) You have family members with varying degrees of relatedness to you

If it’s a highly penetrant variant, by which I mean that a very high proportion of individuals with the mutant allele will develop the condition, then the very fact of any individual being diagnosed has implications across the whole pedigree. Do you then keep it a family secret? Do you speak of it to friends? Do you avoid support groups based on the disease for reasons of genetic privacy?

Obviously sequencing an identical twin is a reductio ad absurdum. There’s very little uncertainty for highly penetrant alleles in this case. You know what the allele simply by inspecting the genome, even before diagnosis of any disease or condition (it may be a late in life disease). And, identical twins are almost perfect concordant in their genome. But qualitatively the same concerns have been present in some form for over a century.

Every disease you manifest and every trait you show on your face is a reflection on the genetics of your extended pedigree. Any information you divulge as a matter of course or happenstance then becomes a “bioethical dilemma.” The choices you make will smoke out values. For example, I weight the interests and privacy of the nuclear family far more than even the nearest circle of relations. I would without much thought sacrifice the diluted expectation of privacy (diluted because of diminished relatedness) for my extended kin (siblings, parents, cousins) if I needed information to help my children. In contrast, if I lived in a Hindu joint family my calculus might be different.

Hipster video gaming

Screenshot 2016-11-27 23.50.40
Screenshot 2016-11-27 23.53.36I began playing video games as a child after the crash of 1983. At the time I wasn’t aware of the tumult in the culture and the technology scene that that had caused. Video games were just fun, not the it thing I suppose. Perhaps as an analogy it would be like getting online in the early 2000s, after the dot-com crash of 2000. The internet by then was a normal part of everyday life, but the excitement and cultural omnipresence abated.

In that context the original NES took center stage rather slowly and organically in the mid-1980s, eventually triggering the competition between Sega, TurboGrafx, Nintendo, and later Sony. I got off that particular train when I was about seventeen, seeing the amount of time that the hobby swallowed. But I couldn’t help but be amused by this article in The New York Times, Nintendo’s New Console May Feed Your Nostalgia, if You Can Get One:

When she heard that Nintendo was planning to reproduce its iconic Nintendo Entertainment System video game console for the holiday season, Emily Bradbury put a note on her calendar and set an alarm on her phone.

She was not interested in buying it for her children. She wanted it for her husband.

“He’s 40 years old and grew up with a Nintendo,” Ms. Bradbury said. “It’s a nostalgia thing.”

Top books purchased through this site

51OftfuYlSL._SX316_BO1,204,203,200_So I have an Amazon referrer account. I’ve had one since 2003. Pretty much I use it to get money when people buy books (or other items) through links here. It’s a non-trivial, though not princely, sum of money. Especially since it’s passive. These are books I’ve read and want to talk about anyhow (usually around Christmas someone follows a book link, and ends up purchasing a computer or two, which is a way of “supporting my work” that I can get behind).

But one of the more interesting side effects is that I can see what my readers are buying (or if they are). For example, it heartens me when I see someone purchase Principles of Population Genetics. That means “I’m making a difference,” as I doubt that these are advanced undergraduates or graduate students. An interesting aspect is that I can see what interests people in terms of “clickbait”, before clickbait was a thing. Bobbi S. Low’s Why Sex Matters routinely gets a lot of clicks because of the title, despite the fact that I don’t flog it. In contrast, In Gods We Trust gets a lot of clicks because I tell people to read it to understand my thinking on religious phenomena.

51gYdVvOoQL._SX379_BO1,204,203,200_As the year ends I like to tally books people have ordered. It turns out that the most purchased book through this website for the year leading into December is The Monkey’s Voyage: How Improbable Journeys Shaped the History of Life. For Kindle, it’s Congo: The Epic History of a People.

Another category is conversion rate. In relation to number of clicks what proportion purchase. Tops for the books in that category is Bioinformatics Data Skills: Reproducible and Robust Research with Open Source Tools. My personal experience is that for technical books many people still prefer print for physicality and rendering of figures and graphs. For Kindle the highest conversion was Intelligence: All That Matters and Longitude: The True Story of a Lone Genius Who Solved the Greatest Scientific Problem of His Time. I think there was a “daily deal” or something at one point, and that prompted many purchases of the latter.

1846077Finally, there are books I see which I didn’t recommend, and didn’t know about. An intriguing one off this list is Barry Cunliffe’s By Steppe, Desert, and Ocean: The Birth of Eurasia. The main issue I’ve had with Cunliffe’s work of late is that he doesn’t seem to be reading enough of the Reich/Willerslev duopoly’s papers. Not that everyone has time to engage in such primary literature diving, but at this point you’re remiss if you write about archaeology and don’t include genetics. Unfortunately a search inside doesn’t indicate that By Steppe, Desert, and Ocean is DNA-heavy, but sometimes you take history and archaeology on its own terms and integrate them into your overall model of the world, rather than having someone else do that for you….

Open Thread, 11/27/2016

510bcY7t15LI spruced up my personal website recently. It was getting sort of cluttered. Also, the new theme should look better on mobile.

Not sure how long Twitter will be around, but as long as it’s around, make sure to follow me.

Screenshot 2016-11-27 00.59.01Got my copy of The Atheist Muslim: A Journey from Religion to Reason. I’m personally opposed to a term like “atheist Muslim,” because a Muslim by definition to me is not atheist. But the author, Ali Rizvi, is an interesting fellow.

Going to try and get to Land of Promise: An Economic History of the United States before Christmas. Don’t know if I’ll get to it, but it’s been on my “to-read” list for a while.

Has anyone ever thought that the novel Musashi was somewhat reminiscent of Cúchulainn? No idea why I think this, but it’s always been on my mind…

I think someone keeps asking about South Asian genetic signatures in Southeast Asia, and I keep forgetting to respond to them. I think there was old (say Iron Age) gene flow from South Asia to various parts of Southeast Asia (basically the cores of Hindu-Buddhist archaic semi-historical polities such as Angkor era Cambodia), and, also more recent gene flow due to colonialism era migration mediated by Europeans. Also, I suspect there was more gene flow from early Holocene Southeast Asia into South Asia than we currently comprehend.

2978777Ten years after first reading it I appreciate Adam K Webb’s Beyond the Global Culture War more. Why? Probably because universal liberal democracy seems less assured as the final stationary state of society in all places now than it did then. It’s an interesting book in part because it attacks the global cultural element with which it is probably easiest to identify me with.

Afro-Asiatic and Eurasian backflow

300px-Hamito-Semitic_languagesIf you follow Y genealogy you know that the distribution of R1ba2 exhibits a peculiar pattern. R1b is the most common haplgroup in Western Eurasia, and shares a deep common ancestry with R1a. It seems to have risen to high frequencies in Europe only during the Bronze Age, though has been found in earlier periods. But within Africa R1b is found in very high concentrations around Lake Chad. This particular R1b lineage seems to have diverged from other Eurasian branches in the latter portion of the Pleistocene, so one possible consideration is that this was an instance of Eurasian backflow during the Ice Age.

One reason I have been somewhat skeptical of this model is that the Sahara desert was much more extensive and arid during much of the Pleistocene than today. And during this period humans had less cultural technology to endure the rigors of the deep desert. Or, if they did, their population densities were likely much lower, which probably served as an impediment to gene flow.

A new paper in The American Journal of Human Genetics sheds light on what might have been going on here. Chad Genetic Diversity Reveals an African History Marked by Multiple Holocene Eurasian Migrations. The major findings are straightforward. First, much greater sampling of populations, and a better depth/density of marker coverage, allowed the researchers to detect low levels, on the order of ~1%, Eurasian admixture in some Central African groups. This admixture seems to date to the Holocene, ~5,000 to ~7,000 years before the present (they used LD based methods on the autosome). Interestingly, the R1b lineage common in Central Africa also seems to coalesce during this time. Finally, the admixture seems to be closest to Sardinians among extant populations.

The Sardinian affinity of much of African Eurasian admixture may seem peculiar, but it makes more sense when one considers that Sardianians are probably the best modern proxies for the earliest Neolithic farmers from the Eastern Mediterranean. Modern Middle Eastern populations are very different from those which flourished in the prehistory between the rise of agriculture and complex civilizations because of admixture within Middle Eastern groups. The initial push into Africa by the agriculturalists dates to a period before we have a good understanding of the ethnographic balance.

Very high frequencies of R1b in modern Central Africa groups may indicate drift. But another possibility is that the migration was male-mediated. This seems to have been the case in much of Eurasia, so it would not be surprising in this context. The status of these males was such that despite their diminishing genetic impact on overall ancestry, their Y chromosomes, and possibly their language, with varied forms of Afro-Asiatic, persisting down to the present.

Finally, here’s the last paragraph of the discussion:

Our study has shown that human genetic diversity in Africa is still incompletely understood and that ancient admixture adds to its complexity. This work highlights the importance of exploring underrepresented populations, such as those from Chad, in genetic studies to improve our understanding of the demographic processes that shaped genetic variation in Africa and globally.

The species barriers between Neanderthals and anatomically modern humans

gr2A new paper in The American Journal of Humans Genetics, The Divergence of Neandertal and Modern Human Y Chromosomes, reports on possible reasons why we don’t see Y chromosomes in modern humans from this archaic lineage, despite exhibiting detectable levels of autosomal admixture. As you might recall the clear lack of deep branching Y and mtDNA lineages was long one of the major genetic rationales for why gene flow between Neanderthals and modern humans was presumably not very significant. This, despite suggestive evidence from morphological analysis as well as inferences from autosomal data. The problem is that it is harder to do the sort of clean phylogenetic reconstruction via a coalescent model utilizing autosomal data (which recombines, as opposed to the Y and mtDNA, which do not for the regions of interest), so ancient genome sequences were really what was needed to convince most people with these sorts of markers.

This makes us ask: why are Neanderthal Y and mtDNA lineages not found in modern humans which exhibit indications of gene flow from other hominin lineages? After all, the lack of these really led many people off on the wrong track for years. I recall in 2008 going to a talk by Svante Paabo who reported that the Neanderthal mtDNA he had sequenced was definitely very different from anything in the current databases for our species, which confirmed his assumption that there was no admixture into modern populations (Paabo changed his tune very soon after due to the whole genome sequencing obviously). One simple explanation is that because effective population sizes of Y and mtDNA are smaller than autosomal regions of the genome they’ll be more strongly subject to drift, and exhibit higher extinction rates. In other words, it wouldn’t be that surprising of all Neanderthal Y and mtDNA went extinct after admixture because they were a small minority, and most lineages went extinct in any case. Researchers who work in non-human phylogeography who relied on mtDNA in particular can tell of many stories of being led astray by looking at one informative locus.

But chance may not be what is at work here. Buried in the discussion of the paper:

…polypeptides from several Y-chromosome genes act as male-specific minor histocompatibility (H-Y) antigens that can elicit a maternal immune response during gestation. Such effects could be important drivers of secondary recurrent miscarriages30 and might play a role in the fraternal birth order effect of male sexual orientation.31 Interestingly, all three genes with potentially functional missense differences between the Neandertal and modern humans sequences are H-Y genes, including KDM5D, the first H-Y gene characterized…It is tempting to speculate that some of these mutations might have led to genetic incompatibilities between modern humans and Neandertals and to the consequent loss of Neandertal Y chromosomes in modern human populations. Indeed, reduced fertility or viability of hybrid offspring with Neandertal Y chromosomes is fully consistent with Haldane’s rule, which states that “when in the [first generation] offspring of two different animal races one sex is absent, rare, or sterile, that sex is the [heterogametic] sex.”

The origin of species is obviously one of the founding questions which arose with the emergence of evolutionary biology. Haldane’s rule dates to the 1920s. In mammals the heterogametic sex are males, so these the hybrids which will be selected against (or, they may be sterile). There’s been a lot of research of late on why Neanderthals went extinct, and whether there were speciation barriers in keeping with the biological species concept between our two lineages. This result suggests that there is going to be interesting stuffed coming out of the population genomics of ancient hominins in the near future….