Another day, and another genome-wide association study. Genetic determinants of hair, eye and skin pigmentation in Europeans:
...We carried out a genome-wide association scan for variants associated with hair and eye pigmentation, skin sensitivity to sun and freckling among 2,986 Icelanders. We then tested the most closely associated SNPs from six regions--four not previously implicated in the normal variation of human pigmentation--and replicated their association in a second sample of 2,718 Icelanders and a sample of 1,214 Dutch. The SNPs from all six regions met the criteria for genome-wide significance. A variant in SLC24A4 is associated with eye and hair color, a variant near KITLG is associated with hair color, two coding variants in TYR are associated with eye color and freckles, and a variant on 6p25.3 is associated with freckles. The fifth region provided refinements to a previously reported association in OCA2, and the sixth encompasses previously described variants in MC1R.
A methodological point which they acknowledge: their assessments of phenotype were rather subjective and contingent upon self-reporting. When it comes to eye, and to a lesser extent hair, color think this is not that big of a deal, but I think that there are probably going to be serious issues in subjective self-reporting of skin color in an already fair complected population. I would bet that that is one reason they didn't find an association with skin color on some of the SNPs.
They basically confirmed the OCA2 finding in regards to it being the main determinant of blue vs. brown eyes. Additionally, there are other loci of smaller effect, primarily TYR. I was surprised that they noted that several SNPs seem to distinguish more strongly between blue and green eye colors than between either and brown. I now think binning phenotypes into blue vs. non-blue or light vs. dark might miss some serious genetic action.
While the association of eye color with a few large loci of major effect seems supported by this study, the results for hair color seem are complicated and equivocal. Not when it comes to red hair of course, MC1R loss-of-function mutations which turn off brown pigment production & up-regulate red-yellow pigment have long been known. But I was more curious about the blonde vs. brown hair color variation. The signals they picked up in this study were numerous and I haven't really teased them apart in my head yet, but, it seems to highlight why an equivalent of the OCA2 findings haven't popped up for explaining the prevalence of blond hair. Just not that simple.
Finally, another story here is pleiotropy. The association of the red hair associated SNPs on MC1R with freckles, very fair skin and UV sensitivity has long been known, but this paper points to multiple other SNPs which have multi-pronged affects. Interestingly, one SNP, A allele of rs1540771, is reported to be associated with UV skin sensitivity and brown hair! This might be a spurious finding, but suggests that a SNP doesn't have to have the same direction of effect globally in terms of pigmentation (i.e., the implication is that the SNP might increase or maintain hair pigmentation and decrease skin pigmentation). As some of you might know I'm fascinated by the phenomenon of very dark skinned blondes in Melanesia; so this sort of genetic process whereby a SNP can have countervailing tendencies in different regions of the body might explain some of that. In any case, I do suspect that a substantial, though not all, of the eye and hair color variation might have a link to selection for fair skin.
Addendum: So what's up with all the moderate minor allele frequencies? If selection is at work how come it hasn't fixed? A form of balancing selection? Or perhaps the selective sweep is still running through the population....
So you think blonde hair is exotic :-) I'm partial to exotic dark eyes...
While visiting the South Seas I noticed that the Polynesians have very dark eyes. Even in Tahiti, where the skin colour isn't that dark, and hair isn't always black. Also the "demis" have inherited dark eyes, whatever their other parentage may be. There seems to be a dark-eye gene that isn't tightly coupled to skin or hair colour.
The source of the evolutionary pressure is obvious: in the South Seas there is a lot of ultraviolet radiation, either directly from the Sun, or indirectly as a reflection from the ever-present sea. UV overload will eventually lead to cataracts. Dark eyes protect against it. So there is a mechanism that favours dark eyes, and is not connected to production of vitamins, like skin colour is.
So why do we Northern Europeans have blue eyes? Maybe our long and dark winter protects us, or the short but furious summer doesn't have enough UV. Or that gene got dropped when the ancestors weren't living close to water.
There seems to be a dark-eye gene that isn't tightly coupled to skin or hair colour.
the gene which controls most (3/4) of eye color variation in europeans is OCA2. that variation has some, though not total, control over skin color variation as well (on the order of 10%).
I now think binning phenotypes into blue vs. non-blue or light vs. dark might miss some serious genetic action.
Man, where were you when I said this at the Academy of Natural Sciences 20 years ago!
It's not hard to find hazel-eyed children of blue eyed parents. Now that it's possible to test DNA, perhaps the usual dismissal of such data with sniggering comments about mailmen and absent husbands can finally be replaced with actual research.
Red hair is a funny thing, it recesses for awhile and suddenly it is there. My uncle had bright red hair, my mother auburn and yet my grandmother and grandfather had dark brunette hair.I believe that we may have inherited our red hair from my Scottish and Irish ancestors, but we do have ancestors way back from Holland, also.
Even though none of us have red hair, per say, if we are not careful when we dye our hair it end up one type of red or another. It appears that red hair is with us to stay. We also have the red freckles on our skin, but red hair is not just to be associated with light skinned Caucasian persons because working in a grocery store I have plenty of chances to talk with the customers and some really complained that their existence was ignored because they had red hair, red toned dark skin colors and even have been accused of dying their skin red. This is a hidden discrimination that most people do not think about.The way I figure it, if our skin color has come about naturally, than it is supposed to be that way. I always tell my children to accept their red hair and their red freckles with pride. No one should be ashamed of their skin color.