There are two new papers out in AJHG about eye color variation and genomics. Three Genome-wide Association Studies and a Linkage Analysis Identify HERC2 as a Human Iris Color Gene and A Single SNP in an Evolutionary Conserved Region within Intron 86 of the HERC2 Gene Determines Human Blue-Brown Eye Color. The second paper is an extension of the work of the Australian group which has been elucidating pigmentation relationships around OCA2 for several years now. The first paper is more interesting (to my mind) because it’s the first genome-wide association study to focus on this region. I’ve extracted figure 6a out of the paper, you might recognize the map. I’m not surprised; go to Haplotter and enter in HERC2, it pops out as a region of selection near OCA2 (I first noticed it when checking for OCA2). As for the map, pretty cool huh? As the authors note there’s a pretty good correlation between the frequency of the trait and the SNP of interest. The authors point to the north-south cline, but I am curious about the east-west one. Additionally, look at Bulgaria. I’ve been looking at Slavicization of the Balkans, and this is an interesting data point….

Related: Dienekes has a high res map up.

Note: Please be careful about taking the phenotypic clines too literally, I am to understand that there was a little extrapolation going on here and there. And of course, standard caveats on representativeness of the samples from each region and all.

(Via Assman)

Over at Greg’s place, Brian Switek notes:

Thanks for the link Greg (and thanks for the compliment, Steve). I’ve generally been unimpressed with Coyne’s popular articles, especially given that he seems to go out of his way to attack Gould and evo-devo whenever it seems fit to do so (which is just about anytime, apparently). Criticism and controversy is fine (even expected), but the way Coyne reacted to Judson’s post was a bit too harsh and condescending. Part of the problem, I think, is that there doesn’t seem to be a good definition of what a hopeful monster is or is not, what a saltation is or is not, etc. When I had a look through the literature there have been confirmations and refutations of these concepts but everyone defines them differently, so it the confusion seems to create a lot of problems. Still, from what I can tell Coyne’s view of evolution is awfully narrow, and it’s a view that many of us don’t seem to share.

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In The Hopeless Monster? Not so fast! Bora says:

In a back-and-forth with a commenter, Coyne defends himself that he is talking about the changes in genes, not evolution. This just shows his bias – he truly believes that evolution – all of it – can be explained entirely by genetics, particularly population genetics. His preferred definition of evolution is probably the genocentric nonsense like “evolution is a change of gene frequencies in a population over time”. I prefer to think of it as “evolution is change in development due to ecology” (a softening of Van Valen’s overly-strong definition “evolution is control of development by ecology”). Population genetics is based on the Hardy-Weinberg equilibrium – pretty much all of it is a build-on and embellishment of it. Population geneticists tend to forget, once they get into complex derivations of HW, that HW has about a dozen completely unrealistic assumptions underlying it. Now, in a case-to-case basis, some of those assumptions can be safely ignored, some can be mathematically taken care of, but some are outside of the scope of mathematics (or at least the kind of math that can be integrated into the development of HW). Those are ignored or dismissed and, if this is pointed out by those working on evolution from a Bigger Picture perspective, met with anger.

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Long time readers of this weblog will know I have an interest in Vitamin D. It has been hypothesized to be one of the major causal factors in generating human skin color variation, and we know from evolutionary genomics that the genes which underly skin color have been under very recent & powerful selection pressures. There is also data that Vitamin D levels may have a relationship to endemic diseases such as flu, and chronic ones such as arthritis. And then we find out nuggets such as the fact that most non-whites in Canada are Vitamin D deficient.
But what if we’re putting the cart before the horse? Vitamin D Deficiency Study Raises New Questions About Disease And Supplements:

“Our disease model has shown us why low levels of vitamin D are observed in association with major and chronic illness,” Marshall added. “Vitamin D is a secosteroid hormone, and the body regulates the production of all it needs. In fact, the use of supplements can be harmful, because they suppress the immune system so that the body cannot fight disease and infection effectively.”
Marshall’s research has demonstrated how ingested vitamin D can actually block VDR activation, the opposite effect to that of Sunshine….
…
Vitamin D deficiency, long interpreted as a cause of disease, is more likely the result of the disease process, and increasing intake of vitamin D often makes the disease worse. “Dysregulation of vitamin D has been observed in many chronic diseases, including many thought to be autoimmune,” said J.C. Waterhouse, Ph.D., lead author of a book chapter on vitamin D and chronic disease.
“We have found that vitamin D supplementation, even at levels many consider desirable, interferes with recovery in these patients.”
“We need to discard the notion that vitamin D affects a disease state in a simple way,” Marshall said. “Vitamin D affects the expression of over 1,000 genes, so we should not expect a simplistic cause and effect between vitamin D supplementation and disease. The comprehensive studies are just not showing that supplementary vitamin D makes people healthier.”

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From Geographic distribution of environmental factors influencing human skin coloration:

…The UVR [ultraviolet radiation] data recorded by satellite were combined with environmental variables and data on human skin reflectance in a geographic information system (GIS). These were then analyzed visually and statistically through exploratory data analysis, correlation analysis, principal components analysis, least-squares regression analysis, and nonlinear techniques. The main finding of this study was that the evolution of skin reflectance could be almost fully modeled as a linear effect of UVR in the autumn alone. This linear model needs only minor modification, by the introduction of terms for the maximum amount of UVR, and for summer precipitation and winter precipitation, to account for almost all the variation in skin reflectance…..

The map above was generated from the regression analysis. Apparently it has been updated as of 2007 (received the link from a friend). It does look much better than it did in the original paper (which I have read and have a PDF copy of). Do note that the selection of peoples whose reflectance values were plugged into the model obviously matters. But I still think it’s interesting the sort of predictions this map produces and how it fits with our intuitions of what the distributions should be, and the knowledge of what they are. Note the equivalent latitudes in Europe and North America, or Australia.

Was checking out the exit poll data. Two things that jumped out at me….
Here are the votes for Obama from non-blacks in the South Carolina primary by age:
18-29 – 52%
30-44 – 25%
45-59 – 23%
60+ – 15%
Here are the votes by income for Edwards:
Under $15,000 – 14%
$15,000-$30,000 – 15%
$30,000-$50,000 – 16%
$50,000-$75,000 – 22%
$75,000-$100,000 – 26%
$100,000-$150,000 – 24%
$150,000-$200,000 – not enough data
$200,000 or more – 29%
Update: Andrew Sullivan says:

Then this: Obama won every demographic among the religiously observant. And the more devout they are – judging by their church attendance – the better he did. His narrowest margins against Clinton and Edwards were among those who never attend church services.

In New Hampshire and Nevada we have data which suggests Obama is stronger among the more secular (no data from Iowa that I can see). But I think the most plausible explanation is that what you’re seeing in South Carolina is the impact of the black vote; blacks are more religious than whites. Just as younger whites (there aren’t many Latino or Asian American voters in South Carolina from what I can tell from the exit polls) were more favorable toward Obama than older whites, I would be willing to bet that wealthier and more educated whites would also lean in his direction compared to poorer and less educated whites. Whatever you might say about it, but Obama does have a diverse coalition, and not just in terms of race. (though to be fair, one can say that about the Democratic party as a whole of late, with a coalition of racial and ethnic minorities, the remaining white working class vote as well as social issue driven professionals).

The New York Times Magazine has a long piece about replacement of Uganda’s native Ankole breed with Holsteins:

“You know, in Uganda, we have to look for survival of the fittest,” Mugira said once he finished sorting out the confusion. “These ones, they are the fittest,” he went on to say, gesturing toward his Holsteins. In physical terms, there was really no contest between the tough Ankoles and the fussy foreign cattle, which were always hungry and often sick. But the foreigners possessed arguably the single most important adaptive trait for livestock: they made money. Holsteins are lactating behemoths. In an African setting, a good one can produce 20 or 30 times as much milk as an Ankole.

Who could complain about over an order of magnitude increase in productivity? Well:

If the Ankole cattle are able to mount a comeback, it will be because circumstances have endowed them with a unique set of defenses, both evolutionary and political. Members of President Museveni’s ethnic group populate the upper ranks of Uganda’s government. Some prominent Bahima have started an organization devoted to preserving Ankoles, under the patronage of a one-eyed army general who spends his free time painting rapturous portraits of cows. One afternoon, at a pricey restaurant in Kampala, I had lunch with the organization’s chairman, Samuel Mugasi. Dressed in a dapper gray suit and a French-cuffed pale blue shirt, he told me he was a civil servant and part-time rancher.

“They have tasted the money,” Mugasi said of the farmers who switched to Holsteins. “They are excited about having these big earnings, and they are forgetting the cultural aspect.”

A lot of people talk as if white tourists in Third World countries are special in the way that they bemoan the passing of quaint “traditions” which they had enjoyed “experiencing,” but which the “natives” were happy to get rid of. But this sort of patronizing and instrumental attitude toward the unwashed is universal, it seems to be an attitude correlated with leisured status. Indian Americans and Irish Americans who visit their ancestral “homelands” over the years complain about the destruction of the cultural traditions, i.e, poverty, which made their earlier experiences more “authentic: (luckily for Indian Americans who want to get in touch with their “roots” most of India is still living in authentic squalor and deprivation!).

But there’s a serious case to be made for preservation of extant genetic variation. The question I have is this: how many individuals of various breeds do you really need to keep around so that diversity is preserved for future utilization? In other words, I understand the logic of adaptive acceleration where large Ne is critical to the production of rare positive mutations; but don’t we get to a point of diminishing returns for populations where we’re more interested in modal alleles which might be disjoint across breeds? That is, the genetic traits from breed A you want to preserve in case they come in handy are common in breed A, so you don’t need that many of breed A around to serve as a reservoir. I just don’t see why we need maximal diversity, it seems the sort of variation which is encapsulated by species richness is more important here than proportionally weighted diversity indexes.

In any case, as alluded to in the article, maintaining relict populations of dying breeds like this seems like a public good which any prudent government can provide. But another issue with the article is that it doesn’t seem like the author is a science writer, so he engages in the fallacy of blending genetics. For example:

…And something else is being obliterated: genes. Each time a farmer crossbreeds his Ankoles, a little of the country’s stockpile of adaptive traits disappears. It isn’t easy to measure genetic “dilution.” What is evident, however, is that the Ankoles possess much worth saving. For instance, their horns, often seen as ornaments, actually disperse excess body heat.

I guess it’s nice that he put quotes around dilution, but the rest of the article suggests to me that the author hasn’t internalized that genetics is discrete, and that information isn’t destroyed through cross-breeding. Rather, it seems that a good program of cross-breeding could result in a superior breeds of Holstein optimally suited to the local climate. That’s what happened with indigenous African lineages as they hybridized with introduced South Asian ones 2,000 years ago to produce the Ankole according to the article! This sort of piece in a widely circulated publication such as The New York Times Magazine could have been a serious examination of agricultural and quantitative genetics, and just how much we depend on these unsexy sciences to feed the world. As it is, there’s a lot of hand-waving scare-mongering….

A few weeks ago, I posted some stuff about what genetics an tell us about the Slavic expansion into the lands of Finno-Ugric tribes. Obviously, I don’t think this is a line of inquiry is specific to that situation; and used judiciously it can add a lot of value toward answering many questions. From PNAS, Maternal traces of deep common ancestry and asymmetric gene flow between Pygmy hunter-gatherers and Bantu-speaking farmers (Open Access). Here’s the conclusion:

The mtDNA data presented here suggest that the ancestral population in CA [Central Africa] that eventually gave rise to modern-day AGR [Bantu Agricultural] and PHG [Pygmy Hunter-Gather] populations, consisted principally of L1c clades that have survived to give the diverse forms observed among AGR, and essentially a single lineage among western PHG. The maternal gene pool composition of modern western PHG suggests a small number of ancestors that started to diverge from an ancestral Central African population no more than ~70,000 YBP. After a period of isolation, accounting for current phenotypic differences between AGR and PHG, gene flow between the ancestors of the two groups began to occur no more than ~40,000 YBP. Our data are consistent with continuous maternal gene flow from PHG-to-(proto)AGR over a long period. Unlike that of PHG, the proto-AGR maternal gene pool was enriched by the more recent arrival of L0a, L2, and L3 carriers, coinciding with the introduction of Late Stone Age technologies in the region and paving the way for the most important demographic, linguistic, and technological event in subSaharan Africa: the Bantu expansions.

I actually think that this is a good analogy with the Slavic case in some ways. The Bantu Expansion to the east and south seems to resemble the Slavic expansion (which doesn’t have a specific name) to the north and east. In both cases you have pre-literate groups of farmers who seem to be pushing into new territory in an ad hoc manner, and absorb local group which only remain extant as residua. And like the Slavic language, the Bantu languages are also broadly intelligible, suggesting a recent origin and rapid radiation. That being said, the relationship of the Finnic peoples is strongly supported by linguistics and to a lesser extent by genetics. The Pygmies can be though plausibly argued to be distinct instances of adaptation of disparate peoples to life in the deep forest (note the well known genetic differences between eastern and western Pygmy groups and their tendency to speak the language of the surrounding agricultural populations), so the analogy is not perfect. But that’s why you do the research.
Update: Greg Laden, who has lived amongst the Pygmies, comments:

Eastern Pygmies live along side non-Bantu (Sudanic) people. Western-central pygmies do.
In all cases, pygmy women marry into villager households, and their children are then always considered as villagers (bantu or sudanic) thereafter. There is no other gene flow between the populations that is known.
Western central pygmies and their non-pygmy neibhors often overlap to a considerable degree physically, and the best way to tell them apart, I am told by my colleagues who work there, is by their dress and other cultural fixtures. Eastern Pygmies and their Sudanic neighbors look as different as any two groups of people I’ve ever observed.
I believe that the sudanic/pygmy contact in the eastern region is less than 1,000 years old, and the bantu/pygmy contact in the western region is several thousand years old.
So, you’ve gotta figure all this in.

In classic heritability studies, the variance of some phenotype Y is decomposed (in the simplest model) into the variance attributable to genetic effects, G, and the variance attributable to environment, E, such that Var(Y) = G+E. As the majority of heritability studies are done by geneticists, who are in general more interested in G than in E, the environmental variance is, to them, largely an error term. When thought of this way, it is clear that “environmental variance” can contain effects that, though not genetic, are certainly not “environmental” in any traditional sense.

In particular, the error term must includes simple stochastic noise on any part of the complex mapping from genotype to phenotype. Even at the early points in this map–the genome sequence and gene expression–there is considerable opportunity for random events to greatly affect phenotype. For lack of a better term, I’m going to call noise introduced at this level “genomic noise“; some examples follow:

1. While the genome is sometimes thought of as a constant in all cells from a given individual, that is not the case. Besides mutations, the genomes in some cell types undergo extensive remodeling during development. For example, consider the T and B cells of the immune system. During development, the genes in the immunoglobulin cluster are recombined to create the receptors presented by the cell. This recombination is stochastic– even from an identical starting spot, the precise combination of genes obtained in independent recombinations can vary greatly. It stands to reason that this genomic noise could, in turn, propogate up to phenotypic variation, and indeed, that is the case– if you look at identical twins who are discordant for multiple sclerosis (an autoimmune disease), you find that those early recombination events have made them less than identical.

2. Genomic noise is introduced in brain cells, as well, by the random movement of transposable elements and their effects on gene expression. The important studies (or perhaps study, singular; I can’t seem to find anything other than the linked paper) here have been done in the mouse, and any phenotypic effect is highly speculative, but as the costs of sequencing drop, it will be possible to study these sorts of somatic changes on a large scale.

3. Moving up a level from genomes to gene expression, it’s clear that some variation in levels of gene expression is simply stochastic. But interestingly, recent work has suggested that, though most everyone has two copies of all autosomal genes, a rather large fraction of genes (excluding imprinted ones) are only expressed from one copy, and the choice of copy to express varies from cell to cell. This opens up the possibility of cells or even entire tissues ending up effectively haploid for a given gene. So if you were to have two individuals heterozygous for some phenotypically relevant variant, they could end up with quite different phenotypes depending on the random choice of allele to express (see also G’s post on the topic here).

I find these sorts of speculations entertaining, and I imagine some of these postulated effects will soon be tested. Until then, just something to keep in mind.