…likely carries rs12913832 on her HERC2, and that’s fine by me….

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I was doing some snooping around due some questions about the HERC2 & eye color papers I mentioned yesterday. Guess what? Earlier this month a Danish group published a similar paper, Blue eye color in humans may be caused by a perfectly associated founder mutation in a regulatory element located within the HERC2 gene inhibiting OCA2 expression. It’s Open Access, so you can read it yourself. The language is a bit more stilted and hurried than the two papers I mentioned yesterday, but the basically independently confirmed the Australian group’s specific finding:

In conclusion, we have identified a conserved regulatory element within intron 86 of the HERC2 gene that is perfectly associated with the brown/blue eye color in studied individuals from Denmark, Turkey and Jordan. This element had an inhibitory effect on the OCA2 promoter activity in cell cultures, and the blue and the brown alleles were shown to bind non-identical subsets of nuclear extracts. In total, all these data strongly support a model where the blue eye color in humans is caused by homozygosity of the rs12913832*G allele.

Instead of just doing comparative analysis they actually tested the hypothesis in cell culture after preforming linkage & association, and seem to have come out with what you’d expect, the SNP on intron 86 of HERC2 regulates transcription at OCA2. Their Ns were a little small compared to the other two groups, but their inclusion of Middle Eastern individuals was interesting. They imply that it’s a common haplotype derived from a single mutational event, presumably recently driven up in frequency by selection. Their conjecture of location and rationale aren’t convincing, I’m sure commenters here could offer many more ingenious models based on historical & geographical particulars (I know the reasons proffered overlap with some of mine, but I’m a dude on a blog). I get the impression they haven’t heard of Haplotter (look at the references). All that being said, at the rate that papers are being pumped out the golden age of pigmentation genetics may not have a very long shelf life (granted, that’s a good thing). By the way, the gene they say has an association with hair color, RABGGTA, has been pegged as being under negative selection.

Update: ScienceDaily has a summary up with a most retarded title.

…Das Kapital! So says Bora:

Forget Dennett’s strawmen destruction – read Gould carefully for what GOULD is trying to say. The Big Book is ‘Das Kapitaal’ of the 21st century biology – someone now needs to write a shorter, simpler Manifesto for the masses to read and understand….and we can go from there.

Go from there? Jerry Coyne better watch out! Genetic roaders are going to be swept away by the vanguard of the scientific revolution!¹ Now, in all seriousness Das Kapital is an important book, a significant book. And there is truth in it as well; my understanding is that Karl Marx was one of the first to note what we would call the Industrial Revolution.² But there’s truth in the Bible too; it records verifiable history and archeology. That doesn’t mean that it’s a blue-print for science (unless you’re a Young Earth Creationist). Das Kapital was a failure in terms of giving rise to a science of economics in a positivistic sense; its predictions were falsified, whether into the future, or as a model of what the past was like.³ Of course that doesn’t matter to a True Believer. Das Kapital echoed through the centuries not because of its scientific value; rather, it became the scripture of a secular religion, a political movement which appealed to mass psychological predispositions toward utopianism and the normative preferences of intellectuals who wished to give their sentiments, values and interests the imprimatur of science.⁴
As for The Structure of Evolutionary Theory, I don’t think it has the same psychological resonance. An anti-reductionist manifesto is by its very nature resistant to compaction; it’s non-mathematical verbosity will evade economization. It is, thank gods, a relatively innocuous scripture because not only do the believers not read it (as is the norm), but the preacher’s message can only be wholly negative, because to rebut the parsimonious formulations of the opposition is an easier task than to tame the overgrown doctrine and present it without distortion. Amen! Selection at work among religions, just as that apostle of functionalism David Sloan Wilson would wish it.
1 – Right, I know that wasn’t Marx. I just couldn’t resist.
2 – Most economic historians don’t think that it was really a revolution from what I gather.
3 – I know there are Marxist economists and historians who aren’t total fruitcakes. That being said, my understanding is that it is a relatively marginalized faction or sect, not an ascendant wave of scholarship.
4 – I’m sure you know that Marx was a keen follower of Darwin’s theory (Update: John Lynch says not really. Fair enough).

Chapters read:1, 2, 3, 4, 5, 6 and 7.
Booyah! Over 10% of the way through The Structure of Evolutionary Theory. Unfortunately, I’m still in heavily exegetical territory. Personally I much prefer Richard Elliott Friedman when it comes to textual interpretation of ancient works, but I knew what I was getting into. In any case, in chapter 2 Stephen Jay Gould mentions the Bible and Shakespeare considerably less, though his verbosity keeps on a truckin’. Instead of an exposition of Gould’s own view of evolutionary theory he recapitulates and interprets Charles Darwin’s argument in Origin of Species. Now, I read Origin of Species when I was a wee lad, so honestly I don’t remember it too well. It seems that all you need from it are the general insights; I don’t see the point of pouring over the welter of specific arguments that Darwin marshaled to convince a still partially Creationist intellectual class as to the correctness of evolution as a fact and the primacy of natural selection as the process which drove that fact.¹ Gould is correct that many evolutionary thinkers tend to view Darwin as a saint, and that it can be a bit much. That being said, I’m not sure if it really happens that much in a field such as evolutionary genetics, where the genuflection is notional and symbolic. In The Mating Mind evolutionary psychologist Geoffrey Miller does go back to Darwin’s original work in The Descent Of Man And Selection In Relation To Sex to help shape his argument that sexual selection was a primary driver of the our own species’ development over time (e.g., the gradual increase in brain size between 2 million years BP and 200,000 years BP). But I think this is an exception to the rule, evolutionary biology is of course a science, and venerable works of one age are simply the bricks buried and forgotten deep in the structure of scientific knowledge. Darwin’s looms large because of his cultural significance; to some extent he was a sign of the overthrow of the old religious dispensation. Like Nietzsche or Marx he will remain in the spotlight for centuries because of his historical importance above and beyond what his scientific accomplishments. In The Structure of Evolutionary Theory Stephen Jay Gould in is proposing an alternative path from that of the “orthodox Darwinism” which reaches back to the original founder, and so he must grapple with Darwin as a launching off point. Below, my general impressions….

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Two interesting articles out in the PNAS early release feed.

Molecular insights into human daily behavior:

Human beings exhibit wide variation in their timing of daily behavior. We and others have suggested previously that such differences might arise because of alterations in the period length of the endogenous human circadian oscillator. Using dermal fibroblast cells from skin biopsies of 28 subjects of early and late chronotype (11 “larks” and 17 “owls”), we have studied the circadian period lengths of these two groups, as well as their ability to phase-shift and entrain to environmental and chemical signals. We find not only period length differences between the two classes, but also significant changes in the amplitude and phase-shifting properties of the circadian oscillator among individuals with identical “normal” period lengths. Mathematical modeling shows that these alterations could also account for the extreme behavioral phenotypes of these subjects. We conclude that human chronotype may be influenced not only by the period length of the circadian oscillator, but also by cellular components that affect its amplitude and phase. In many instances, these changes can be studied at the molecular level in primary dermal cells.

Weird. ScienceNow notes some implications:

…raises the possibility of an inexpensive and objective test of a person’s “owlness” or “larkness.” Such a test would be no small matter, given the prevalence of sleep disorders and the fact that many drugs, including cholesterol medications and chemotherapy, work more effectively if administered at certain points in a person’s sleep/wake cycle. Pinpointing individual clock cycles could pave the way for personalized sleep and drug therapies, says Achim Kramer, a Free University chronobiologist who helped design the study.

Selectivity of Black Death mortality with respect to preexisting health:

Was the mortality associated with the deadliest known epidemic in human history, the Black Death of 1347-1351, selective with respect to preexisting health conditions (“frailty”)? Many researchers have assumed that the Black Death was so virulent, and the European population so immunologically naive, that the epidemic killed indiscriminately, irrespective of age, sex, or frailty. If this were true, Black Death cemeteries would provide unbiased cross-sections of demographic and epidemiological conditions in 14th-century Europe. Using skeletal remains from medieval England and Denmark, new methods of paleodemographic age estimation, and a recent multistate model of selective mortality, we test the assumption that the mid-14th-century Black Death killed indiscriminately. Skeletons from the East Smithfield Black Death cemetery in London are compared with normal, nonepidemic cemetery samples from two medieval Danish towns (Viborg and Odense). The results suggest that the Black Death did not kill indiscriminately-that it was, in fact, selective with respect to frailty, although probably not as strongly selective as normal mortality.

We’ve all read Farewell to Alms, so we know the argument that quick die offs can be good for standards of living by relieving some of the Malthusian pressure. Though if you ever took a normal medieval history course you’d probably be told about the premium on labor which emerged after the Black Death due to shortages and its affect on the collapse of the old manorial system (I was). But this data is interesting because it confirms that the most economically productive proportion a society where muscle power might was of essence have increased as a proportion of the population after these sorts of epidemics swept through. Perhaps these are the sorts of shocks that social systems need to shift toward another equilibrium? (I know, morbid)

Last year a group out of Australia published a paper which purported to explain eye color variation based upon a polymorphism around the OCA2 locus. The paper was A Three-Single-Nucleotide Polymorphism Haplotype in Intron 1 of OCA2 Explains Most Human Eye-Color Variation, and I blogged it here. Basically the paper showed that three SNPs arranged on several haplotypes could be plugged into a function to generate a relatively good prediction of eye color. Why does this matter? First, because eye color is one of the first things you learn about “genetics” in high school, but we’re still stuck in the theoretical Mendelian land where we have to infer from inheritance patterns of putative loci instead of knowing where they are empirically in reality. I remember one girl in high school being taken a back learning that blue eyed parents could not have brown eyed children, ever, she being a brown eyed daughter of blue eyed parents and with no knowledge of adoption. Second, there are forensic uses that might be made of knowledge of the genes which control physical appearance. Finally, there are some interesting evolutionary questions which emerge out of examining salient phenotypic characteristics which vary between populations. As most of you probably know, light eye color is predominantly a European trait. I have argued before that it emerged because of its affect on skin color, with eye color being a secondary byproduct, in the recent evolutionary past (i.e., last 10,000 years).

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Yanked out of google analytics, below the fold….

10 – Why is porn legal but prostitution illegal?
9 – IQ comparison site.
8 – Converting between IQ and SAT scores .
7 – Genetics of Hair Color (again).
6 – German penises ‘too small for EU condoms’.
5 – Porno Arabica (this is due to Assman over-utilizing our search boxes!)
4 – Pigmentation variation in Europe.
3 – James Watson Tells the Inconvenient Truth: Faces the Consequences.
2 – 10 Questions for Heather Mac Donald.
1 – Intercourse and Intelligence.

Hm….

Chapters read:1, 2, 3, 4, 5, 6 and 7.
So I’m reading Stephen Jay Gould’s magnum opus, The Structure of Evolutionary Theory. I figure if I read this I won’t have to read anything else by the guy; if he couldn’t squeeze it into 1,464 pages, it really wasn’t worth mentioning I’m assuming. Here are impressions from the 90 page first chapter, which is a general overview of his ideas and biography….
1) There is the fact of evolution (descent with modification), and the mechanism of evolution promoted by Charles Darwin (gradual phyletic change operating through natural selection at the level of the individual). Gould accepts the former wholeheartedly, but he has serious reservations about the details of the latter.
2) This book is an exposition of his ideas as to how the second must be modified and elaborated to more fully describe the process of evolution. His thousand-page rejoinder is squarely aimed at correcting the overly simple narrative promoted by the putative heirs of Charles Darwin, culminating in the work of ultra-Darwinians such as Richard Dawkins. His brief is pluralistic; Gould emphasizes multiple levels of selection operating above the level of the individual, as well as non-selective parameters which are also major determinants in the shaping of the tree of life.
3) Gould has evolved quite a bit in his own views, from a sparely dogmatic naive pan-selectionist to a pluralist of baroque latitudinarian sensibilities. He considers himself part-time historian of science, and believes his scientific training as a paleontologist gives him particular insights which a pure humanist might not have. Gould also seems to fancy that he is less touched by the philistinism which is part & parcel of the outlook of most empirical scientists.
4) This last part shows, Stephen Jay Gould is well versed in the Bible, Shakespeare, and many polysyllabic & obscure words (confute?). He is also an connoisseur of high art & architecture. He likes baseball too (but you knew that!).
5) Periods are less important than commas.
Update: I’m an inspiration yo!

Didn’t know there was a State of the Union today until I got home and turned on NPR.

A few weeks ago Kambiz of Anthropology.net was mentioning how there’s very little mention of gene expression on this weblog. Fair enough, but hey, what about this? And this paper just popped into my RSS today, so check it out, Differential Allelic Expression in the Human Genome: A Robust Approach to Identify Genetic and Epigenetic Cis-Acting Mechanisms Regulating Gene Expression:

We describe a new methodology to identify individual differences in the expression of the two copies of one gene. This is achieved by comparing the mRNA level of the two alleles using a heterozygous polymorphism in the transcript as marker. We show that this approach allows an exhaustive survey of cis-acting regulation in the genome: we can identify allelic expression differences due to epigenetic mechanisms of gene regulation (e.g. imprinting or X-inactivation) as well as differences due to the presence of polymorphisms in regulatory elements. The direct comparison of the expression of both alleles nullifies possible trans-acting regulatory effects (that influence equally both alleles) and thus complements the findings from gene expression association studies. Our approach can be easily applied to any cohort of interest for a wide range of studies. It notably allows following-up association signals and testing whether a gene sitting on a particular haplotype is over- or under-expressed; or can be used for screening cancer tissues for aberrant gene expression due to newly arisen mutations or alteration of the methylation patterns.

This is a provisional paper, so one assumes there will be some revisions. In any case, cancer is important & all, but this is the kind of stuff I’m interested in (see Discussion):

…We tested 56 genes for association of differential allelic expression patterns observed with a cis-acting regulatory polymorphism using genotypes generated by the HapMap project…For 23 of these genes we identified a region statistically associated with differences in allele expression that could indicate the existence of a regulatory haplotype (i.e., a region of one chromosome likely containing the polymorphism(s) causing the differential cis-regulation). These regions are often tens of kb long, consistent with previous descriptions of the linkage disequilibrium patterns in humans….

Related: Kambiz has a post up on this with a lot more commentary, Identifying Cis-Acting Elements that regulate Human Gene Expression. Also, in Nature, Genome-wide analysis of transcript isoform variation in humans.