Endings & beginnings

Update: Comments enabled now!

Until further notice this is my last post as a blogger at Discover Magazine. This shouldn’t impact regular readers. As always you can follow me by going to:

My feed, http://feeds.feedburner.com/RazibKhansTotalFeed

My Twitter, https://twitter.com/razibkhan

And of course, my website, http://www.razib.com

From December 1st, 2013, I will be blogging at Ron Unz’s new website, The Unz Review, at a familar subdomain http://www.unz.com/gnxp (feed, http://www.unz.com/gnxp/feed/).

I’m excited to explore this new opportunity. Ron is still nailing down the details of look, style, and functionality, so expect some changes on my Gene Expression sub-site. To make a long story short Ron wanted to beef up his science coverage, and I was amenable. At least when it comes to my particular bailiwick. Ron has merged my archives from the old Gene Expression website with the content generated at ScienceBlogs and Discover, so no matter where I go, or if I stop blogging due to other obligations, those archives will remain as a coherent whole.

I want to emphasize that my time at Discover was incredible. I want to give special thanks to Tasha Eichenseher, Amos Zeeberg, and Sheril Kirshenbaum. As it happens none of these individuals are associated with Discover at this point (Tasha is leaving as well), but they were instrumental in allowing me to either be here (in Sheril’s case) or focus on writing (in Tasha and Amos’ case). I assume you’ll be somewhat surprised that I mention Sheril, but I feel like I have to give special thanks to her because I’m 99% sure that it was her “good word” which allowed me to catch the eye of an outfit as respectable as Discover. Unlike a blogger as writerly as Ed Yong, or Sheril herself, I’ve always been more data nerd-cum-verbal pugilist. So this leads me to praise the great management skills of the two web editors I’ve had while being a blogger at Discover. They’ve let “Razib be Razib,” by and large letting me do my thing (though yes, in the interests of professionalism I’ve moved most of the more “direct” verbal volleys to Twitter). I really can’t thank anyone else at Discover because I barely knew they existed, which, in light of recent events, seems like a good thing. Overall I give Discover a good grade in terms of understanding how blogging should be run, with a light hand. This, despite the fact that I often put up posts which rubbed many “right-thinking-people” the wrong way, and scoured the comment threads acidly.

There’s really not much else to say. Aside from a new domain, don’t expect many changes.

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The total information world

Credit: Cryteria

Credit: Cryteria

Happy Thanksgiving (if you are an American)!

It’s been a busy few days in the world of personal genomics. By coincidence I have a coauthored comment in Genome Biology out, Rumors of the death of consumer genomics are greatly exaggerated (it was written and submitted a while back). If you haven’t, please read the FDA’s letter, and 23andMe’s response, as much as there is one right now. Since Slate ran my piece on Monday a lot of people have offered smart, and more well informed, takes. On the one hand you have someone like Alex Tabarrok, with “Our DNA, Our Selves”, which is close to a libertarian cri de coeur. Then you have cases like Christine Gorman, “FDA Was Right to Block 23andMe”. It will be no surprise that I am much closer to Tabarrok than I am to Gorman (she doesn’t even seem to be aware that 23andMe offers a genotyping, not sequencing, service, though fuzziness on the details doesn’t discourage strong opinions from her). An interesting aspect is that many who are not deeply in the technical weeds of the issue are exhibiting politicized responses. I’ve noticed this on Facebook, where some seem to think that 23andMe and the Tea Party have something to do with each other, and the Obama administration and the FDA are basically stand-ins. In other words, some liberals are seeing this dispute as one of those attempts to evade government regulation, something they support on prior grounds. Though Tabarrok is more well informed than the average person (his wife is a biologist), there are others from the right-wing who are taking 23andMe’s side on normative grounds as well. Ultimately I’m not interested in this this argument, because it’s not going to have any significant lasting power. No one will remember in 20 years. As I implied in my Slate piece 23andMe the company now is less interesting than personal genomics the industry sector in the future. Over the long term I’m optimistic that it will evolve into a field which impacts our lives broadly. Nothing the United States government can do will change that.

Yet tunneling down to the level of 23andMe’s specific issues with the regulatory process, there is the reality that it has to deal with the US government and the FDA, no matter what the details of its science are. It’s a profit-making firm. Matt Herper has a judicious take on this, 23andStupid: Is 23andMe Self-Destructing? I don’t have any “inside” information, so I’m not going to offer the hypothesis that this is part of some grand master plan by Anne Wojcicki. I hope it is, but that’s because I want 23andMe to continue to subsidize genotyping services (I’ve heard that though 23andMe owns the machines, the typing is done by LabCorp. And last I checked the $99 upfront cost is a major loss leader; they’re paying you to get typed). I’m afraid that they goofed here, and miscalculated. As I said above, it won’t make a major difference in the long run, but I have many friends who were waiting until this Christmas to purchase kits from 23andMe.

Then there are “the scientists,” or perhaps more precisely the genoscenti. Matt Herper stated to the effect that the genoscenti have libertarian tendencies, and I objected. In part because I am someone who has conservative and/or libertarian tendencies, and I’m pretty well aware that I’m politically out of step with most individuals deeply involved in genetics, who are at most libertarian-leaning moderate liberals, and more often conventional liberal Democrats. Michael Eisen has a well thought out post, FDA vs. 23andMe: How do we want genetic testing to be regulated? Eisen doesn’t have a political ax to grind, and is probably representative of most working geneticists in the academy (he is on 23andMe’s board, but you should probably know that these things don’t mean that much). I may not know much about the FDA regulatory process, but like many immersed in genomics I’m well aware that many people talking about these issues don’t know much about the cutting edge of the modern science. Talk to any geneticist about conversations with medical doctors and genetic counselors, and they will usually express concern that these “professionals” and “gatekeepers” are often wrong, unclear, or confused, on many of the details. A concrete example, when a friend explained to a veteran genetic counselor how my wife used pedigree information combined with genomic data to infer that my daughter did not have an autosomally dominant condition, the counselor asserted that you can’t know if there were two recombination events within the gene, which might invalidate these inferences. Though my friend was suspicious, they did not say anything, because they were not a professional. As a matter of fact there just aren’t enough recombinations across the genome for an intra-genic event to be a likely occurrence (also, recombination likelihood is not uniformly distributed, and not necessarily independent, insofar as there may be suppression of very close events). And this was a very well informed genetic counselor.

Additionally, there are the two major objections to 23andMe’s service which some on Twitter have been pointing me to. First, they return results which are highly actionable. The FDA explicitly used the example of a woman who goes and gets a mastectomy due to a 23andMe result. I don’t think this is a very strong objection. No doctor would perform a mastectomy based on 23andMe results. So that’s not an issue. Then there are those who allude to psychological harm. This could be a problem, but 23andMe has multiple steps which make it so that you have to proactively find out information on these sorts of diseases. Call me a libertarian if you will, but I object on principle to the idea that medical professionals necessarily have to be involved in the dissemination of information about my own genome as a regulatory matter. Obviously when it comes to a course of treatment they will be consulted, and no doubt there will be replications of any actionable results. But I don’t trust the medical sector to be populated by angels. To illustrate why I don’t trust medical professionals to always behave out of the goodness of their hearts, consider that deaths from hospital infections started dropping sharply when Medicare stopped paying for treating these infections. Workers in the health care sector do care about patients, but even here incentives matter, and the human cognitive budget is such that they can shift the outcomes greatly by reminding nurses and doctors that washing hands is going to impact the bottom line (the reality is that hospitals probably instituted much stricter measures). What does this have to do with personal genomics? You are our own best advocate, and one of the major reasons that those in higher socioeconomic strata have better health outcomes is that they are so much less passive as patients. The more detailed the information you have on your own health, the better you can advocate and be involved in the decision-making process. And the reality is that with dropping prices in sequencing, and the ability to design software to do interpretation, without draconian measures there’s almost nothing the United States government will be able to do to prevent anyone with a moderate amount of motivation from getting this sort of information.

A second objection is that the SNPs returned are of small and very probabilistic effect. This is embedded in issues regarding the “missing heritability” and the reality that most complex diseases are due to many factors. Because of the small effect size, and until recently, small sample sizes, this literature has been littered with false positives, which passed arbitrary statistical thresholds. The argument then boils down to the reality that 23andMe in many cases is not really adding any informative value. If that’s the case though then why the urgency to regulate it? Horoscopes and diet books do not add informative value either. This problem with small effect SNPs is widely known, so bringing it up as if it is revelatory is rather strange to me. Additionally, as Eric Lander and others have pointed out the locus which helped us discover statins is of very small effect. As long as they’re not false positives, small-effect SNPs are likely a good way to go in understanding biological pathways for pharmaceutical products. But that doesn’t speak to the risk prediction models. I think there the possibilities are murkier even in the long run because complex traits are complex. Even if we have massive GWAS with sample sizes in the millions and 100x whole-genome coverage (this will happen), the environmental factors may still be significant enough that researchers may balk at definitive risk predictions.

Ultimately where I think personal genomics is going is alluded to in the Genome Biology piece: as part of a broader suite of information services, probably centralized, filtered, and curated, by a helper artificial intelligence. What cognitive science and behavioral economics are telling us is that individuals operate under mental budget constraints. Dan MacArthur is probably right that personal genomics enthusiasts overestimated how involved the average person on the street was going to want to get in terms of their own interpretations of returned results. The reality is that even genetic counselors can barely keep up. Someday the field will stabilize, but this is not that day. But overall the information overload is going to get worse and worse, not better, and where the real upside, and game-changer, will be is in the domain of computational tools which helps us make decisions with a minimum of effort. A cartoon model of this might be an artificial intelligence which talks to you through an ear-bud all day, and takes your genomic, epigenomic, and biomarker status into account when advising you on whether you should pass on the dessert. But to get from here to there is going to require innovation. The end point is inevitable, barring a collapse of post-industrial civilization. The question is where it is going to happen. Here in the United States we have the technology, but we also have cultural and institutional road-blocks to this sort of future. If those road-blocks are onerous enough it doesn’t take a genius to predict that high-tech lifestyle advisement firms, whose aims are to replace the whole gamut of self-help sectors with rationally designed applications and appliances, will simply decamp to Singapore or Dubai.

Personal genomics is a small piece of that. And 23andMe is a small piece of personal genomics. But they are not trivial pieces.

The post The total information world appeared first on Gene Expression.

The FDA and 23andMe

napFirst, download your 23andMe raw results now if you have them. If you don’t know what’s going on, the FDA has finally started to move aggressively against the firm. Unfortunately this is not surprising, as this was foreshadowed years ago. And, 23andMe has been moving aggressively to emphasize its medical, as opposed to genealogical, services over the past year. But this isn’t the story of one firm. This is the story of government response to very important structural shifts occurring in the medical delivery system of the United States. The government could potentially bankrupt 23andMe, but taking a step back that would still be like the RIAA managing to take down Napster. The information is coming, and if there’s one thing that can overpower state planning it is consumer demand. Unless the US government wants to ban their citizens from receiving their own genetic data they’re just putting off the inevitable outsourcing of various interpretation services. Engagement would probably be the better long term bet, but I don’t see that happening.

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Open Thread, 11/24/13


One of the stranger call-ins on my interview with Kathleen Dunn last month was when a woman who proudly declared that she was a math major in college asserted that 23andMe had told her she wasn’t at risk for many diseases which now in her 60s she had developed. I didn’t want to be too pointed about it, but if you are in your 60s you are at risk for developing many illnesses no matter what your “genetic risk.” This is clear from 23andMe’s statistics, which display high baseline risks for many common diseases. From reading comments on 23andMe discussion forums it seems that perceived false negatives are going to be a much bigger issue than false positives over the long run. If the tests are “wrong” in a direction which leaves you in a better state than predicted you might feel like you’ve dodged a bullet. On other hand if the tests are “wrong” in a direction which gave you false comfort, or add insult to injury when you’ve developed a debilitating disease, then you feel much more burned.

I don’t really recommend blogs too much anymore. But please check out The Stage and Social Evolution Forum.

The post Open Thread, 11/24/13 appeared first on Gene Expression.

Open Thread, 11/24/13


One of the stranger call-ins on my interview with Kathleen Dunn last month was when a woman who proudly declared that she was a math major in college asserted that 23andMe had told her she wasn’t at risk for many diseases which now in her 60s she had developed. I didn’t want to be too pointed about it, but if you are in your 60s you are at risk for developing many illnesses no matter what your “genetic risk.” This is clear from 23andMe’s statistics, which display high baseline risks for many common diseases. From reading comments on 23andMe discussion forums it seems that perceived false negatives are going to be a much bigger issue than false positives over the long run. If the tests are “wrong” in a direction which leaves you in a better state than predicted you might feel like you’ve dodged a bullet. On other hand if the tests are “wrong” in a direction which gave you false comfort, or add insult to injury when you’ve developed a debilitating disease, then you feel much more burned.

I don’t really recommend blogs too much anymore. But please check out The Stage and Social Evolution Forum.

The post Open Thread, 11/24/13 appeared first on Gene Expression.

Our ancestors are part us…or the other way around?

Keeping a close watch on media representations of the new Nature paper on the ancient Siberian genome. Here’s The New York Times, 24,000-Year-Old Body Is Kin to Both Europeans and American Indians. I don’t have a problem with the title, but the roll-out isn’t totally accurate in what it will connote to the audience in my opinion:

he genome of a young boy buried at Mal’ta near Lake Baikal in eastern Siberia some 24,000 years ago has turned Tout to hold two surprises for anthropologists.

The first is that the boy’s DNA matches that of Western Europeans, showing that during the last Ice Age people from Europe had reached farther east across Eurasia than previously supposed. Though none of the Mal’ta boy’s skin or hair survive, his genes suggest he would have had brown hair, brown eyes and freckled skin.

The second surprise is that his DNA also matches a large proportion — some 25 percent — of the DNA of living Native Americans. The first people to arrive in the Americas have long been assumed to have descended from Siberian populations related to East Asians. It now seems that they may be a mixture between the Western Europeans who had reached Siberia and an East Asian population.

The Mal’ta boy was aged 3 to 4 and was buried under a stone slab wearing an ivory diadem, a bead necklace and a bird-shaped pendant. Elsewhere at the same site some 30 Venus figurines were found of the kind produced by the Upper Paleolithic cultures of Europe. The remains were excavated by Russian archaeologists over a 20-year period ending in 1958 and stored in museums in St. Petersburg.

The issue I have is that modern Europeans are a new population which emerged through admixture processes over the past ~10,000 years. And one of those populations which contributed to their ancestry are the descendants of the Siberian boy! Talking about “Western Europeans” ~20,000 years ago is geographic convenience. They wouldn’t be “Western Europeans” as we understand them genetically. Even if there wasn’t any recent admixture, ~1,000 generations of drift is not trivial. Though the archaeology may clarify, I also don’t think it is definite that the ancient Siberians were from Europe as we’d understand it. Perhaps they all come from a common Central Eurasian stock which diversified?

Not that I have a better solution for terminology.

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The long First Age of mankind


“What it begins to suggest is that we’re looking at a ‘Lord of the Rings’-type world – that there were many hominid populations,” says Mark Thomas, an evolutionary geneticist at University College London who was at the meeting but was not involved in the work.

Mark Thomas, as reported by Nature

This is in reference to the ancient DNA meeting where David Reich reported that the Denisovans, an exotic archaic population which contributed ~5-10 percent of the ancestry of Papuans, was itself a synthesis of Neandertals and a mysterious group currently unknown. This is not surprising, as the broad outlines of these results were presented at ASHG 2012, though no doubt they’re moving closer to publication. But for this post I want to shift the focus to a different time and place, after the ancient admixture with archaic lineages, and to the reticulation present within our own.

But first we need to backtrack a bit. Let’s think about what we knew in the early 2000s. If you want a refresher, you might check our Spencer Wells’ The Journey of Man or Stephen Oppeneheimer’s Out of Eden, which focused on Y and mtDNA lineages respectively. These books were capstones to the era of uniparental phylogeographic analysis of the spread and diversification of anatomically modern African hominids ~50-100,000 years ago. Rather than looking at the whole genome (the technology was not there yet) these researchers focused on pieces of DNA passed down via direct maternal or paternal lineages, and reconstructed clean phylogenetic trees using a coalescent framework. Broadly speaking these trees were concordant, and told us that our lineage, all extant humans, derived from a small African population which flourished ~100,000 years ago. These insights suffused the thought of human evolutionary thinkers in other disciplines (see The Dawn of Human Culture). H. sapiens sapiens, veni, vidi, vici.

After that initial “Out of Africa” migration a series of bottlenecks and founder events led to the expansion of our lineage, as it replaced all predecessors. By the Last Glacial Maximum, ~20-25,000 years ago, the rough outlines of human genetic variation were established (with the exception of the expansion into the New World). We know now that this picture is very incomplete at the most innocuous, and highly misleading given the least charitable interpretation.

Reticulation. Graphs. Admixture. These words all point to the reality that rather than being the culmination of deep rooted regional populations which date back to the depths of the Pleistocene, most modern humans are recombinations of ancient lineages. On the grandest scale this is illustrated by the evidence of ‘archaic’ ancestry in modern humans. But even more pervasively we see evidence of widespread admixture between distinct lineages which are major world populations which we think of as archetypes. This is true for Amerindians, South Asians, and Europeans. This is also the case for Ethiopians, and Australian populations. A major problem crops up when we talk about extinct ancient populations which were the founding substituent elements of modern ones: it doesn’t make sense to use modern referents when they are simply recombinations of what they are describing. But language and history being what they weare we can’t change the awkwardness of talking about “Ancestral North Eurasians,” anodyne and somewhat incoherent at the same time (Eurasia is a modern construct with contemporary historical salience).

Into the mix comes another ancient DNA paper which reconstructs the genome of a boy who lived in Siberia, near Lake Baikal, somewhat over 20,000 years ago. It’s titled Upper Palaeolithic Siberian genome reveals dual ancestry of Native Americans. Here’s the topline finding: a substantial minority of the ancestry of modern Native Americans derives from a North Eurasian population which has closer affinities to West Eurasians than East Eurasians. And, this is an old admixture event. In the paper itself they observe that all “First American” populations seem to exhibit the same admixture distance to the Siberian genome. These results are also broadly consistent with the admixture of this population in Western Eurasia, especially northeast Europe. As among Amerindian populations it seems that this element is at substantial minority across Europe as a whole, and perhaps at parity in some populations, such as Finns.

Fig1To the left you see the geographical affinities of the MA-1 Siberian sample. It is shifted toward West Eurasians in the PCA. But on the map with circles representing populations, the definite evidence of admixture between Amerindians and MA-1 is clear in the shading. The statistic used, f-3, looks for complex population history between and outgroup (X) and a putative clade. From this test it is evident Amerindians had some admixture related to MA-1. Because of the dating of Siberian remains it does not seem likely that admixture was from Amerindians to West Eurasian and related populations. Rather, the reverse seems more plausible. You can also see from the map the close affinities with particular European and Central Asian populations of MA-1. This is intriguing, and requires further follow up. Though MA-1 and its kin were closer to West Eurasians than East Eurasians, it still seems likely that there was an early divergence between the populations of north-northeast Eurasia, and those of the southwest. Eventually they came back together in various proportions to produce modern Europeans, but it seems likely that during the Pleistocene these two groups went their own way.

treemixThere are hints of this in the TreeMix plot to the right. Note now drifted MA-1 is in relation to other West Eurasians (the branch is long). I suspect some of this is due to the fact that this individual is nearly 1,000 generations in the past. Not only is it difficult to name ancient populations with those of moderns, I suspect that some of the variation in the ancient populations has been lost, and so they seem exotic and difficult to fit into a broader phylogenetic framework (they had hundreds of thousands of SNPs though). And yet MA-1 can be fitted into the broader framework of populations which went north or west after leaving Africa because of mtDNA and Y chromosome results. Both of these indicate that MA-1 was basal to West Eurasians, with haplogroup U for mtDNA, and R for the Y lineage.

To really understand what’s going on here is going to take a while. A later subfossil, circa ~15,000 years before the present, yielded some genetic material, and exhibited continuity with MA-1. This suggests that Siberia may have had massive population replacement relatively recently. We know this was likely the case elsewhere. Reading Jean Manco’s Ancestral Journeys one possible scenario is that Pleistocene Europeans were MA-1 like, but were replaced by Middle Eastern farmers in the early Neolithic. But later eruptions from Central Asia brought mixed populations (Indo-Europeans?) with substantial MA-1 affinities to the center of European history.

Finally, one must make a note of phenotype. The authors looked at 124 pigmentation related SNPs (see supplemental). The conclusion seems to be that MA-1 was not highly de-pigmented, as is the case with most modern Northern Europeans. This stands to some reason, as substantial ancestry of this sort in Amerindians would result in phenotypic variation which does not seem to be present. Though the authors do suggest that coarse morphological variation among early First Americans (e.g., Kennewick Man) might be due to this population, which had West Eurasian affinities.

Where does this leave us? More questions of course. Though I’m confident the befuddlement will clear up in a few years….

Citation: doi:10.1038/nature12736

Addendum: Please read the supplements. They’re rich enough that you don’t need to read the letter if you don’t have access. Also, can we now finally bury the debate when east and west Eurasians diverged? Obviously it can’t have been that recent if a >20,000 year old individual had closer affinity to western populations.

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The color of life as a coincidence

Credit: Eric Hunt

Credit: Eric Hunt

I do love me some sprouts! Greens, bitters, strong flavors of all sorts. I’ve always been like this. Some of this is surely environment. My family comes from a part of South Asia known for its love of bracing and bold sensation. But perhaps I was born this way? There’s a fair amount of evidence that taste has a substantial genetic component. This does not mean genes determine what one tastes, but it certainly opens the door for passive gene-environment correlations. If you do not find a flavor offensive, you are much more likely to explore it depths, and cultivate your palette.


Dost thou dare?
Credit: W.A. Djatmiko

And of course I’m not the only one with a deep interest in such questions. With the marginal income available to us many Americans have become “foodies,” searching for flavor bursts and novelties which their ancestors might never have been able to comprehend. More deeply in a philosophical sense the question of qualia reemerges if there is a predictable degree of inter-subjectivity in taste perception (OK, qualia is always there, though scientific sorts tend to view it as intractable in a fundamental sense).

But there’s heritability, and then there’s genes. We know that perception in some ways is heritable, but what is perhaps more interesting is if you can peg a specific genomic location to it. Then the evolutionary story becomes all the richer. And so it is with the locus TAS2R16, where a nonsynonymous mutation at location 516 seems to result in heightened sensitivity to bitter tastes. More specifically, it’s rs846664, and the derived T allele is fixed outside of Africa, while the ancestral G allele still segregates at appreciable fractions within African populations. A new paper in Molecular Biology and Evolution puts this locus under a microscope, though it does not come up with any clear conclusions. Origin and Differential Selection of Allelic Variation at TAS2R16 Associated with Salicin Bitter Taste Sensitivity in Africa presents some interesting findings. First, let’s look at the distribution of the variation in their sample populations at the SNP of most particular interest:

Region Population T516G
Outside of Africa Non-Africans 0.000
Ethiopia Semitic 0.059
Tanzania Sandawe 0.083
Ethiopia Omotic 0.093
Ethiopia Cushitic 0.095
Tanzania Iraqw 0.111
West Central Africa Fulani 0.114
Kenya Niger-Kordofanian 0.133
Ethiopia Nilo-Saharan 0.156
Kenya Afroasiatic 0.162
West Central Africa Niger-Kordofanian 0.214
Kenya Nilo-Saharan 0.225
Kenya Luo 0.250
Central Africa Niger-Kordofanian 0.329
Tanzania Hadza 0.333
Central Africa Bulala 0.361
Central Africa Nilo-Saharan 0.367
West Central Africa Afroasiatic 0.462
West Central Africa Nilo-Saharan 0.500

As you can see T is fixed outside of Africa, and varies across many African populations  Previous work implied this, though coverage within Africa was not good. One thing to observe though is that the frequency of A within Africa can not be explained by recent Eurasian admixture. The frequency is way too high for that to be the sole explanation, and in any case there is no evidence that ~33% of the Hadza’s ancestry is of Eurasian provenance (the Hadza being one of the three major groups of African hunter-gatherers, along with the Bushmen and Pygmies).

Within the paper the authors resequenced ~1,000 base pairs across diverse African populations in an exonic region of this gene (the stuff that codes for amino acids). What they discovered is that of the SNPs segregating, 516 in particular was critical toward effecting phenotyping change. Not only did individuals with the T variant notably exhibit stronger bitter sensitivity, but in vitro expression with a reporter was elevated. Because they had such a dense genomic region they could perform various nucleotide based tests to detect natural selection, and, attempt coalescent models to infer genealogical history.

I’m going to spare you some of the gory details at this point. Here’s what they found. First, it does look like the region is under natural selection in many African populations, in particular, the derived haplotype with T at 516 at the center. But this result is not reproduced across all tests. The coalescent simulations make clear why: the mutation is an old variant with deep roots in the hominin lineage. In other words this variation pre-dates H. sapiens. It looks like the T allele has rapidly increased in frequency relatively recently, though more on the order of ~50,000 years, rather than ~10,000.* Basically around the time of the “Out of Africa” event. Additionally, there’s a tell-tale sign that this is being subject to selection within Africa: the genetic differences across populations at TAS2R16 far exceed the genome-wide values (the Fst at this locus is in the top 1% of loci within the African genome). Finally, one should note that the G allele haplotypes seem to be much more strongly constrained, as if they’re under purifying selection. This means that the switch to T is not all gain.

At this point you may be ready for a story about how some African populations, like Eurasians, underwent a lifestyle change, and diet changes resulted in a shift in sensory perception. That does not seem to be the story. Rather, the authors did not seem to be able to agree upon a neat explanation for what is driving these recent sweeps up from ancient standing genetic variation. They do observe that the variation does tend to cluster geographically, more so than the genome-wide results would imply. There’s likely some adaptation going on, they simply don’t know what. In the introduction and elsewhere you can see that variation at TAS2R16 does correlate with other traits. Not too surprising due to the relatively ubiquity of pleiotropy; one gene with many effects.

Stepping outside of the implications of this specific result, let’s think about what might be a takeaway: something as essential as taste perception might be a side effect of other aspects of evolutionary processes. In other words, we don’t know what the phenotypic target of selection is in this case, but we do have a good handle one of the major side effects, which is sensory perception. How one taste seems like a big deal.** Andthere have been many theories propounded that variation in bitter sensitivity is due to adaptation to poisonous plants and such, but really no one knew, and that was just the most plausible of low hanging fruit. With these results from Africa, where there is more variation in the trait and genes, and good geographic coverage, that seems to be an implausible model to adhere to (one would think the hunter-gatherer Hadza would exhibit the most sensitivity, no?). Many of the traits and tendencies which we humans see as fundamental, essential, and of great import, many actually be side effects of powerful evolutionary forces hammering at the genetic-correlation matrices which define the hidden network of co-dependencies within the genome. So there, I said it. Life is an accident. Enjoy it.

Citation: Campbell, Michael C., et al. “Origin and Differential Selection of Allelic Variation at TAS2R16 Associated with Salicin Bitter Taste Sensitivity in Africa.” Molecular biology and evolution (2013): mst211.

* If it was closer to ~10,000 I think haplotype based tests would come back with something, but they do not.

** Some Epicureans might be accused of reducing the good to taste!

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