Genome-wide associations, HERC2 and eye color

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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Skin color is a deceptive character

The figure to the left is from Signatures of Positive Selection in Genes Associated with Human Skin Pigmentation as Revealed from Analyses of Single Nucleotide Polymorphisms. I thought of this chart when considering the idea that the phenotypic races that we see around us might be relatively new; perhaps an artifact of recent human evolution. Look at “Oceania,” those are Bougainville Islanders, from off the coast of Papua New Guinea. In the CEPH-HGDP populations the “South Asians” are from the much lighter skinned northwest fringe of the subcontinent; otherwise, I suspect you would be seeing the South Asian group moving toward the location of the Bougainville Islanders. This is not a surprising finding, earlier studies implied that very dark-skinned populations tended to exhibit a “consensus sequence” due to functional constraint; there’s a reason humans are dark-skinned around the equator, and there’s only one way to do it. But here’s an important point: Bougainville Islanders are closer to East Eurasians than they are to other world populations in terms of ancestry. In other words, the dark-skin and the genes which confer that trait that results in an affinity between Melanesians and Africans in appearance is not a function of relatively recent common descent, but of local adaptation. Similarly, extreme dark-skinned South Asian groups are generally closer to Europeans in terms of ancestry than light-skinned East Asians.

This is all pretty common sense when you think about it. But with that said skin color is a very salient trait. The skin is our biggest organ, it’s a large part of what others see. Therefore, there is a natural human tendency to classify in colors. If you read the reports from Chinese delegations who were sent to investigate Cambodia they describe the natives as “black.” Similarly, according to Mary Lefkowitz the ancient Greeks observed that there were the blacks of Ethiopia and those of Southern India. They also noted that both the Egyptians and North Indians were brown-skinned people (“wheat colored”). But, perhaps importantly, they often distinguished the various peoples by other characteristics (e.g., Ethiopians and Indian hair form). So on the one hand you have an nod to the importance of skin color as a criterion of perception & categorization, and on the other hand an acknowledgment that populations differ in more than color. But in the United States there are peculiar social conditions which result in problematic conflations.

As everyone knows, to be very dark-skinned in the United States was identical to being of one race for a greater part of our history. Certainly there was a small Native American population, but they could be discarded from the shaping of social norms because of their low numbers. To have dark-skin was to be of African ancestry. Though there were certainly other distinguishing characteristics between those of African and European ancestry, skin color was the most visible and noticeable. It was used as the main discriminatory trait because that was all that necessary. This still persists in our folk culture when people talk about individuals “being discriminated against because of the color of their skin.” Skin color connotes a racial identity. And yet you have groups like South Asians, who overlap with African Americans in complexion, but are not really”black” as we understand it. Steve Sailer has been noting for years the implicit value system highlighted by the reality that the very dark-skinned Vijay Singh is not identified as a black golfer, while the lighter-skinned (and only 1/4 African in ancestry) Tiger Woods is. Of course it doesn’t work this way all the time, and South Asians are often identified as black, at least upon first impression. But the more confusing situations can also occur because of the nature of American categorizations. So tight is the correlation of non-white and “black” in the minds of some people that really peculiar characterizations can ensue. For example, in high school I had an acquaintance who would refer to myself & a Cambodian girl as black. That was understandable, we both had brown-skin. But, one day he referred to a Chinese friend of mine as black. This friend was not a dark-skinned, she had a brunette white complexion (not olive). When I queried my acquaintance about the fact that this “black” individual was probably lighter skinned than at least 1/3 of our other classmates (all of whom were white), he simply insisted that she was a “Chinese black.” That was about as far as I got, obviously he couldn’t express the inchoate associations within his mind between racial identity and skin color. In his world, there were whites and blacks. If someone wasn’t white, that entailed that they were black.

As is rather clear from the content on this weblog we are getting a good fix on the genetics of pigmentation. Not only do we know the patterns of inheritance via classical pedigree analysis, but we now have a good grasp on which regions of the genome control world-wide variation in melanin content of the skin, eye and hair. We are even beginning to understand when selection began to occur on the loci which control this variation. We have some working hypotheses of why skin color is under functional constraint, and what sort of changes might drive adaptive evolution. But all this is sometimes harder to discuss because the typical American has so many social and psychological associations between skin color and group identity. It isn’t just another trait, like bristles on the back of a Drosophila, no, it is the token of one of the most significant sociological phenomena which characterize American society today. Steve will have quite a bit to blog about into the foreseeable future.

Note: I suspect that the transposition of genomic knowledge to folk wisdom is easier in societies such as Brazil or India where extant phenotypic variation on this trait exhibits a larger range, much of it within families. Race and color are still very important issues, but the joints around which the perceptions are carved are more flexible and numerous.

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The Structure of Evolutionary Theory blogging, chapter 3

Chapters read:1, 2, 3, 4, 5, 6 and 7.
17% of the way through , 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. 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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‘Blue-eyed Humans’ do not ‘Have A Single, Common Ancestor;

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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Olivia Judson on sticklebacks

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.