Is Girls’ Generation the outcome of the Pleistocene mind?

There’s an excellent paper up at Cell right now, Modeling Recent Human Evolution in Mice by Expression of a Selected EDAR Variant. It synthesizes genomics, computational modeling, as well as the effective execution of mouse models to explore non-pathological phenotypic variation in humans. It was likely due the last element that this paper, which pushes the boundary on human evolutionary genomics, found its way to Cell (and the “impact factor” of course).

The focus here is on EDAR, a locus you may have heard of before. By fiddling with the EDAR locus researchers had earlier created “Asian mice.” More specifically, mice which exhibit a set of phenotypes which are known to distinguish East Asians from other populations, specifically around hair form and skin gland development. More generally EDAR is implicated in development of ectodermal tissues. That’s a very broad purview, so it isn’t surprising that modifying this locus results in a host of phenotypic changes. The figure above illustrates the modern distribution of the mutation which is found in East Asians in HGDP populations.

One thing to note is that the derived East Asian form of EDAR is found in Amerindian populations which certainly diverged from East Asians > 10,000 years before the present (more likely 15-20,000 years before the present). The two populations in West Eurasia where you find the derived East Asian EDAR variant are Hazaras and Uyghurs, both likely the products of recent admixture between East and West Eurasian populations. In Melanesia the EDAR frequency is correlated with Austronesian admixture. Not on the map, but also known, is that the Munda (Austro-Asiatic) tribal populations of South Asia also have low, but non-trivial, frequencies of East Asian EDAR. In this they are exceptional among South Asian groups without recent East Asian admixture. This lends credence to the idea that the Munda are descendants in part of Austro-Asiatic peoples intrusive from Southeast Asia, where most Austro-Asiatic languages are present.

And yet one thing that jumps out at me is that there is no East Asian EDAR in European populations, even in Russians. I am a bit confused by this result, because of the possibility of Siberian-affiliated population admixture with Europeans within the last 10,000 years, as adduced by several researchers (this is not an obscure result, it manifests in TreeMix repeatedly). The second figure shows the inferred region from which the East Asian EDAR haplotype expanded over the past 30,000 years. The authors utilized millions of forward simulations with a host of parameters to model the expansion of EDAR, so that it fit the distribution pattern that is realized (see the supplements here for the parmeters). To make a long story short they infer that there was one mutation on the order of ~30,000 years before the present, and that it swept up in frequency driven by selection coefficients on the order of ~0.10 (10% increase relative fitness, which is incredibly powerful!). This is on on the extreme end of selective sweeps, and likely of the same class as the haplotype blocks which characterize SLC24A5 and LCT (the block is shorter, though that makes sense because of the deeper time depth). Again, I am perplexed why such an ancient allele, which is found in Amerindians, or Munda populations, is absent in Europeans who have putative East Eurasian admixture. The whole does not cohere for me. There is a weak point in one or more of my assumptions.

Then there’s the section on the mouse model. To me this aspect was ingenious, though I’m not particularly able to assess it on its technicalities. The earlier usage of mouse models to test the effects of mutations on EDAR was in the context of coarse copy number changes which resulted in massive dosage changes of protein. The phenotypic outcomes were rather extreme in that case. Here they used a “knockin” model where they recreated the specific EDAR point mutation. Instead of extreme phenotypes they found that the mice were much more normal in their range of traits, though the hair form shifts were well aligned with what occurred in humans. Additionally there were some changes in the number of eccrine glands, with a larger number in the derived East Asian EDAR carriers (with additive effect). Finally they noticed that there were differences in mammary gland pad area and branching. None of this is that surprising, EDAR is a significant regulatory gene which shapes the peripheries and exterior of an organism.

To double check the human relevance of what they found in the mouse model they performed a genome-wide association in a large cohort of Han Chinese. The correlations of particular traits were in the directions that they expected; those individuals with East Asian EDAR variants had thicker hair, shovel-shaped incisors, and a greater density of eccrine glands. It is perhaps important to note that the frequency of the derived variant is so high in Han populations that they didn’t have enough homozygote ancestral genotypes to perform statistics, so their comparisons involved heterozygotes with the derived mutant and also a copy of the ancestral state. This is like SLC24A5 in Europeans, where it is difficult to find individuals of European heritage who have double copies of the non-European modal variant.

Let’s review all the awesome things they did in this study. They dug deeply into the evolutionary genomics of the region around the EDAR, concluding that this haplotype was driven up in frequency from on ancestral variant ~30,000 years ago in a hard selective sweep. And a sweep of notable strength in terms of selection coefficient. This may be one of the largest effect targets of natural selection in the genome of non-Africans over the past 50,000 years. Second, they used a humanized mouse model to explore the range of phenotypes correlated with this mutational change in East Asians. So you have a strong selection coefficient on a locus, and, a range of traits associated with changes on that locus. Third, they confirmed the correlation between the traits and the mutation in humans, despite there being prior research in this area (i.e., they reproduced). This is all great science, and shows the power of collaboration between the groups.

Much of the elegance and power of the paper applies to the discussion section as well, but to be frank this is where things start falling apart for me. You can get a sense of it in The New York Times piece, East Asian Physical Traits Linked to 35,000-Year-Old Mutation. The headline here points to a legitimately important point from this line of research, many salient physical characteristics of the human races seem to be due to strong selection events at a few loci. In addition to EDAR I’m thinking of the pigmentation loci, such as SLC24A5. I wouldn’t be surprised if there was something similar for the epicanthic fold. If it is visible, and defines between populations differences, it is generally not genomically trivial. There’s usually a story underneath that difference.

In the broad scale of human natural history the problem that arises for me is that we have traits, we have genes under selection, but we have very weak stories to explain the mechanism and context of natural selection. Here there is a strong contrast with the loci around lactase persistence and malaria resistance. In those situations the causal mechanism for the selection seems relatively clear. Critics of evolutionary psychology are wont to accuse the field of ‘Just So’ storytelling, but the same problem crops up in the more intellectually insulated domain of evolutionary genomics (in part because the field is very new, and also mathematically and computationally abstruse). To illustrate what I’m talking about I’m going to quote from the discussion of the above paper:

A high density of eccrine glands is a key hominin adaptation that enables efficient evapotraspiration during vigorous activities such as long-distance walking and running (Carrier et al., 1984; Bramble and Lieberman, 2004). An increased density of eccrine glands in 370A carriers might have been advantageous for East Asian hunter=gatherers during warm and humid seasons, which hinder evapo-transpiration.

Geological records indicate that China was relatively warm and humid between 40,000 and 32,000 years ago, but between32,000 and 15,000 years ago the climate became cooler and drier before warming again at the onset of the Holocene (Wang et al., 2001; Yuan et al., 2004). Throughout this time period, however, China may have remained relatively humid due to varying contribution from summer and winter monsoons.

High humidity, especially in the summers, may have provided a seasonally selective advantage for individuals better able to functionally activate more eccrine glands and thus sweat more effectively (Kuno, 1956). To explore this hypothesis, greater precision on when and where the allele was under selection—perhaps using ancient DNA sources—in conjunction with more detailed archaeological and climatic data are needed.

A climate adaptation is always a good bet. The problem I have with this hypothesis is that modern day gradients in the distribution of this allele are exactly the reverse of what one might expect in terms of adaptation to heat and humidity. Additionally, is there no cost to this adaptation? After the initial sweep upward, the populations where the derived EDAR mutant is found in high frequencies went through the incredible cold of the Last Glacial Maximum, and groups like the Yakuts are known to have cold adaptations today. Not only that, but the Amerindians from the arctic to the tropics all exhibit a cold adapted body morphology, the historical consequence of the long sojourn in Berengia.

Granted, the authors are not so simplistic, and the somewhat disjointed discussion alludes to the fact that EDAR has numerous phenotypic effects, and it may be subject to numerous positive selection pressures. This seems plausible on the surface, but this complexity of mechanism seems ill-fitted to the fact that the signal of selection around this locus is so clean and crisp. It seems that this is not going to be an easy story to unpack, and there’s a good deal of implicit acknowledgement of that fact in this paper. But tacked right at the end of the main text is this whopper:

It is worth noting that largely invisible structural changes resulting from the 370A allele that might confer functional advantage, such as increased eccrine gland number, are directly linked to visually obvious traits such as hair phenotypes and breast size. This creates conditions in which biases in mate preference could rapidly evolve and reinforce more direct competitive advantages. Consequently, the cumulative selective force acting over time on diverse traits caused by a single pleiotropic mutation could have driven the rise and spread of 370A.

A simple takeaway is that the initial climatic adaptation may have given way to a cultural/sexual selective adaptation, whereby there was a preference for “good hair” as exemplified by pre-Western East Asian canons (black and lustrous), as well as a bias toward small breasts. This aspect gets picked up in The New York Times piece of course. I’ll quote again:

But Joshua Akey, a geneticist at the University of Washington in Seattle, said he thought the more likely cause of the gene’s spread among East Asians was sexual selection. Thick hair and small breasts are visible sexual signals which, if preferred by men, could quickly become more common as the carriers had more children. The genes underlying conspicuous traits, like blue eyes and blond hair in Europeans, have very strong signals of selection, Dr. Akey said, and the sexually visible effects of EDAR are likely to have been stronger drivers of natural selection than sweat glands.

The passage here is ambiguous because the author of the article, Nick Wade, doesn’t use quotes, and I don’t know what is Akey and what is Wade’s gloss on Akey. For example, for theoretical reasons of reproductive skew (a few men can have many children) in general sexual selection is considered to be driven most often by female preference for male phenotypes. I assume Akey knows this, so I suspect that that section is Wade’s gloss (albeit, a reasonable one given the proposition of preference for smaller breasts). The main question on my mind is how seriously prominent population geneticists such as Joshua Akey actually take sexual selection to be as a force driving variation and selection in human populations. It seems that quite often sexual selection is presented as a deus ex machina. A phenomenon which can rescue our confusion as to the origins of a particular suite of traits. But our assessment of the likelihood of sexual selection presumably has to be premised on prior expectations informed by a balance of different forces one can gauge from the literature, and here my knowledge of the current sexual selection literature is weak. Perhaps my skepticism is premised on my ignorance, and the population geneticists who proffer up this explanation are more informed as to the state of the literature.

All this brings me back to the farcical title. When this paper first made news last week I was having dinner with a friend of Japanese heritage (who spent his elementary school years in Japan). I asked him point blank, “Do you like small breasts?” His initial response was “WTF!?! Razib,” but as a mouse geneticist he understood the thrust of my question after I outlined the above results to him. From personal communication with many East Asian American males I am not convinced that there is a overwhelmingly strong preference for small breasts within this subset of the population. But the key here is American. These are individuals immersed in American culture. The norms no doubt differ in East Asia. The typical visual representation of celebrity East Asian females that we see in the American media depict individuals who are slimmer and more understated in their secondary sexual characteristics than is the norm among Western female celebrities (e.g., Gong Li, the new crop of Korean pop stars, even taking into account the plastc surgery of the latter). Part of this is no doubt the reality that the normal range of variation across the population differs, and part of it may be the nature of aesthetic preferences.

But the possibility of deep rooted psychological reasons driving sexual selection (to my knowledge there was no culture which spanned South China and Siberia) brings us back to old ideas about the Pleistocene mind. And, it brings us back to evolutionary psychology, a field which is the whipping boy of both skeptics of the utility of evolutionary science in understanding human nature, and rigorous practitioners of evolutionary biology. And yet here it is not the evolutionary psychologists, but rock-ribbed statistical geneticists who I often see being quoted in the media invoking sexual selection. But do we know it is sexual selection, or is it just our best guess? Because more often than not best guesses are wrong (though best guesses are much more likely to be right than worst guesses!).

Evolutionary genomics has come a long way in the past 10 years. We know, for example, the genetic architecture and some aspects of the natural history of many traits. But, there are still shortcomings. Lactase persistence is the exception to the rule. Even a phenotype as straightforward as human pigmentation has no undisputed answer as to why it has been the repeated target of selection across Eurasia over the past 40,000 years. Oftentimes the right answer is simply that we just don’t know.

Citation: http://dx.doi.org/10.1016/j.cell.2013.01.016

Source: Discover Magazine – Gene Expression