Archive for January, 2008

Genome-wide associations, HERC2 and eye color

By Razib Khan | January 31, 2008 1:16 pm

ResearchBlogging.orgSound familiar? Well, good things come in pairs. A few days ago I posted on a paper which used a linkage analysis to come to the conclusion that an SNP on HERC2 was responsible for the variation in eye color in Europeans. Some background, a gene, OCA2, was implicated in the variation in eye color, and it turns out that a few haplotypes on this locus can be used to predict with reasonable accuracy the phenotype in question. The paper I blogged a few days ago was a extension of the work of this work; the same group found that one SNP on HERC2 could actually better explain the variation (though there was a locus of minor affect on OCA2), and that that variation was caused by the regulation of expression of OCA2 by HERC2. Case closed, right? No, it’s science, theoretically the case is always open; a continuing revelation so to speak. This paper covers the same topic, comes to similar conclusions, but explores some different methodology space:

…To date, the genetics of iris color is still not fully understood and is of interest, particularly in view of forensic applications. In three independent genome-wide association (GWA) studies of a total of 1406 persons and a genome-wide linkage study of 1292 relatives, all from the Netherlands, we found that the 15q13.1 region is the predominant region involved in human iris color. There were no other regions showing consistent genome-wide evidence for association and linkage to iris color. Single nucleotide polymorphisms (SNPs) in the HERC2 gene and, to a lesser extent, in the neighboring OCA2 gene were independently associated to iris color variation. OCA2 has been implicated in iris color previously. A replication study within two populations confirmed that the HERC2 gene is a new and significant determinant of human iris color variation, in addition to OCA2. Furthermore, HERC2 rs916977 showed a clinal allele distribution across 23 European populations, which was significantly correlated to iris color variation. We suggest that genetic variants regulating expression of the OCA2 gene exist in the HERC2 gene or, alternatively, within the 11.7 kb of sequence between OCA2 and HERC2, and that most iris color variation in Europeans is explained by those two genes….

Phew. That’s it? A chart from the paper can actually illuminate the dark weeds of this verbiage….

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CATEGORIZED UNDER: Genetics

Ethics & science

By Razib Khan | January 31, 2008 2:27 am

If science is a culture it needs a way to punish free-riders & cheaters. Otherwise the whole system will collapse. So check out Tetrapod Zoology; Darren has some details on shady goings-on.

CATEGORIZED UNDER: Science

The Structure of Evolutionary Theory blogging, chapter 3

By Razib Khan | January 31, 2008 12:51 am

GOUSTR.jpgChapters read:1, 2, 3, 4, 5, 6 and 7.
17% of the way through The Structure of Evolutionary Theory, can I get a w00t, w00t!?!?! Chapter 3 was a change. I am wondering if the verbal excesses on garish display in the first two chapters was just an extended fart that Stephen Jay Gould had to get out of his system so that he could be a bit more comfortable. Barely a mention of Shakespeare, medieval architecture or the Bible. An occasional gratuitous toss of Latin here and there, but a most definite improvement in that most nebulous character, readability. Though Gould won’t be accused of Hemingway-like prose economy, he’s definitely not in stylistic stasis anymore, and the substance on offer was more appetizing. Take Peter J. Bowler, mix with logorrhea and top it off with an ax-to-grind1, and you get chapter 3. Unfortunately, not a lot of up-to-date science or a detailed elucidation of Stephen Jay Gould’s majestic system of the world. Rather, he focuses on thinkers and controversies within the field of evolution which span the period between the French Revolution and the pre-Mendelian era (i.e., about 1900). But the survey of the history of the science during this period is not simply for the sake of understanding the precursors of modern theories; rather, Gould makes the argument that the structure of scientific revolutions, or lack of, can give us a sense of of the plausibility of various theories. As someone who has repeatedly made the case that science is a culture much more than a specific formal method I am not without total sympathy for this idea; that being said, I do think that science is temporally discriminatory so that ideas and intellectual dynamics of centuries past are discounted and not generally relevant to the issues at hand. The Structure of Evolutionary Theory obviously takes a different tack, and it is certainly consistent with Gould’s insistence on the importance of historical perspective in any evaluation of dynamics. I would though make the case that if Gould is right, that the minute details of intellectual history of the 19th century is extremely relevant to our understanding of the theoretical debates in the field today (the 21st century), then in many ways evolutionary biology is a very piss-poor excuse for a natural science. Perhaps we should resurrect the term natural philosophy and subsume it within that.

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CATEGORIZED UNDER: Evolution

'Blue-eyed Humans' do not 'Have A Single, Common Ancestor;

By Razib Khan | January 30, 2008 10:45 pm

ScienceDaily has a most-retarded title up for a report on some new research, Blue-eyed Humans Have A Single, Common Ancestor. I already blogged the paper at my other blog. The paper roughly confirms the previous finding that I blogged that an SNP on the gene HERC2 might regulate expression of OCA2 so that there is depigmentation; in particular in the iris. I have another post coming up tomorrow morning on another study on HERC2 (it’s in schedule).

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CATEGORIZED UNDER: Genetics

Four Stone Hearth 33

By Razib Khan | January 30, 2008 2:55 pm

Is up at Greg’s.

CATEGORIZED UNDER: Blog

Structure of Evolutionary Theory link round up

By Razib Khan | January 30, 2008 2:33 pm

Over at Laelaps. Too busy wrestling the 5-pound monster as I tread water attempting to process the copious verbal excreta, so I appreciate the effort!

CATEGORIZED UNDER: Blog

Olivia Judson on sticklebacks

By Razib Khan | January 30, 2008 12:19 pm

Give the lady her due, Olivia Judson can lay down some serious exposition when she’s on:

There are a couple of interesting things about this discovery. The first is that the molecular basis of the change from pelvis to no pelvis does not involve a mutation to the protein-coding region of the Pitx1 gene itself. In other words, the protein made from the gene hasn’t changed. What has changed is the way the gene is expressed. This is in contrast to the sorts of mutations one often reads about as being involved in evolution, which typically involve changes to the protein itself.
A second interesting feature of the stickleback pelvis is that — unlike the armor plates — the loss is probably due to mutations having occurred independently in the different populations. What’s more, changes to the use of Pitx1 are also implicated in pelvic loss in nine-spine sticklebacks (Pungitius pungitius) — yet nine-spine and three-spine sticklebacks have been going their own evolutionary ways for at least 10 million years. Mice that have been genetically engineered to lack Pitx1 have a suite of abnormalities, including crushed faces and abnormal pituitaries, that cause them to die young. Intriguingly, they also have a reduced pelvis and hind limbs, and as with the sticklebacks, the reduction is lopsided and shows a greater loss on the right than on the left.

Recall my post about HERC2, a mutation on an intron on this gene might have resulted in a change in regulation of OCA2, which induces depigmentation. Speaking of which, human skin color seems to have gotten light independently at least three times, in Europe, East Asia and among the Neandertals (that we know of). Remember, loss of function is a lot easier than gain of function. Dark-skinned peoples tend to exhibit a consensus sequence which is relatively similar no matter their phylogenetic relationship (e.g., the residents of the Solomon Islands are closer to East Asians than Africans in terms of ancestry, but on the loci which control skin color they are nearly identical by state with Africans). Why model organisms? Because we have faith that Nature is One.

CATEGORIZED UNDER: Genetics

Just Science 2008 announcement

By Razib Khan | January 30, 2008 6:39 am

Since Just Science starts next week I’m going to have to take a break from Stephen Jay Gould blogging due to the constraints that I’m going to have to adhere to when it comes to posts (i.e., it has to be science). Expect blogging to focus on chapters from W. D. Hamilton Narrow Roads of Gene Land, Volume 1: Evolution of Social Behaviour. You know about kin selection, but do you know kin selection?

CATEGORIZED UNDER: Blog

Barbie girl….

By Razib Khan | January 30, 2008 6:39 am

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

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CATEGORIZED UNDER: Blog

The Structure of Evolutionary Theory is like….

By Razib Khan | January 30, 2008 2:01 am

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).

CATEGORIZED UNDER: philosophy

The Structure of Evolutionary Theory blogging, chapter 2

By Razib Khan | January 29, 2008 8:55 pm

GOUSTR.jpgChapters 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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CATEGORIZED UNDER: Evolution

1 SNP to rule them & in the darkness bind them?

By Razib Khan | January 29, 2008 6:00 am

ResearchBlogging.orgLast 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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CATEGORIZED UNDER: Genetics

The Structure of Evolutionary Theory blogging, chapter 1

By Razib Khan | January 28, 2008 10:21 pm

GOUSTR.jpgChapters 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!

CATEGORIZED UNDER: Genetics

I'm politics dumb

By Razib Khan | January 28, 2008 10:16 pm

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

CATEGORIZED UNDER: Blog

Geneticists are narrow a**holes?!?!

By Razib Khan | January 28, 2008 10:09 am

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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CATEGORIZED UNDER: Genetics

Bonus Katz

By Razib Khan | January 27, 2008 7:14 pm

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CATEGORIZED UNDER: Blog

Evolution is not the change in allele frequencies?

By Razib Khan | January 27, 2008 4:20 pm

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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CATEGORIZED UNDER: Genetics

Vitamin D not so good for health?

By Razib Khan | January 27, 2008 11:30 am

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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CATEGORIZED UNDER: Biology

Age & income: South Carolina exit polls

By Razib Khan | January 26, 2008 9:51 pm

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).

CATEGORIZED UNDER: Politics

Pygmy & Bantu ethnogenesis in Central Africa

By Razib Khan | January 26, 2008 10:16 am

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.

CATEGORIZED UNDER: History
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