HERC2 and eye color

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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)

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19 Comments

  1. Does the bump in incidence of light eyes in the Israeli/Palestinian region relative to the rest of the Middle East reflect the post-WWII wave of Ashkenazi immigration? Or is the indigenous population only being considered?

  2. What’s really neat about the Kayser et al paper is that none of the alleles at sites that previously showed itty-bitty effects amounted to anything when the genome-wide association was done. Only at HERC2 and OCA2, with the first much more important than the second. 
     
    If we believe H.A. Orr’s model of adaptation, whereby effect size of adaptive alleles falls off exponentially as a new one is chosen, does this suggest that selection for light eyes in Europe is much more recent than we thought, since Europeans have apparently taken only 2 steps in an adaptive climb? If the trait were under adaptive evolution for longer, wouldn’t we detect at least some of the myriad other alleles of smaller effect?

  3. Marc, 
     
    I don’t know, but would imagine yes – though I have known blue eyed Syrians? 
     
    It’s a pity that Western Anatolia (Turkey) seemingly has no data?! 
     
    Also, I’m a little surprised that Greece shows up with more blue eyes than most of Italy – I guess there is more Slavic admixture than I supposed? 
     
    Does the Eastern Spain area represent Neolithic farmers or Carthaginians spreading out from Barcelona I wonder? 
     
    Does Southern England represent Neolithic farmers, the legacy of the Romans, or South Asian immigration to London and surrounds?

  4. does this suggest that selection for light eyes in Europe is much more recent than we thought, since Europeans have apparently taken only 2 steps in an adaptive climb? 
     
    remember, i don’t think that light eyes are the primary adaptation. i think the HERC2/OCA2 system is one of the large QTLs which affect skin color. the tissue specific down regulation would be byproduct.

  5.  
    Does Southern England represent Neolithic farmers, the legacy of the Romans, or South Asian immigration to London and surrounds?
     
     
    the purpose of this study was to assay native europeans. i’d bet they excluded those with obvious non-european ancestry.

  6. also, assman that is predicated on there really being no other loci of small effect. do you really believe that? one association study is a lot to depend on….

  7. Raz, 
     
    WRT the Bulgarians, in the Eastern Balkans, that shade might represent the Thracians who came before them, whereas the Western Balkans are knows to have had Slavic settlement, like Croats/Hrovats and Serbs/Srpski, in some quantity – not to mention the Ostrogoths before that, both groups which I would suppose to be lighter than the Thracians?? 
     
    I’ve also know a good few Romanians – some who have been quite olive in complexion.

  8.  
    I’ve also know a good few Romanians – some who have been quite olive in complexion.
     
     
    right, but biggest gypsy pop in the balkans. gypsies are genetically around half south asian usually. 
     
    yeah, good point about thracians. i think aristotle or herodotus mentioned them as quite rufus? 
     
    assman, btw, it isn’t just orr. fisher’s adaptive analogy uses the same model, though it isn’t as formally rigorous as orr’s.

  9. Pretty much. Fisher was talking about phenotypic evolution, while Orr is talking about genetic evolution. 
     
    I feel pretty safe, maybe not sure, about the no small effect finding. With two big samples, they should’ve picked up something. If effect sizes show diminishing returns, and if we’re only really sure about 2 alleles — both with rather pronounced effects — that means we can predict the effect size of a putative 3rd-place allele. Just take the ratio between effect sizes of HERC2 and OCA2, and then apply that to the size of OCA2. 
     
    I’m not a bioinformatics person, so I have no intuition about whether such an allele would or would not be detected in an association study of this size, but it seems like a 3rd-place effect should be big enough to show up.

  10. With two big samples, they should’ve picked up something. 
     
    but one of the assocations picked up a small signal on chrom. 1. they dismissed it cuz it wasn’t in the others. but like i said, i think that it’s a byproduct of tissue specific expression.

  11. Although right, if eye color is just part of some larger suite of traits that’s adapting Europeans to agricultural Europe, the new alleles at HERC2 and OCA2 may be the large pleiotropic ones, and the smaller effect ones are involved in other traits in the suite.

  12. the new alleles at HERC2 and OCA2 may be the large pleiotropic ones, and the smaller effect ones are involved in other traits in the suite. 
     
    SLC24A5 is as recent, and of larger affect. SLC45A2 isn’t that much older according to the one number i’ve found. don’t know about TYR & KITLG. but that’s 5 loci right there. the pedigree analysis predicted about that many large effect loci controlling skin color, and then lots of smaller affect ones making up the balance.

  13. I wish the shading was more detailed, with more nuances.  
     
    Having grown up in Ireland, I can say that Ireland has at least 75% Blue Eyes – based on observation estimates…  
     
    The extreme South West of the Country, however should show more brown eyes than blue 
     
    Maybe there are other genes which have an influence on blue eyes, which are more prevalent in Ireland, and hence don’t show in this data??

  14. bryan sykes in ‘blood of the isles’ mentions old data that confirms what you are saying. the index of ‘nigrecense.’

  15. Finland and surroundings are in the centre, also if you include the same map for hair colour… It is a bit surprising that Baltic states and western Russia are “lighter” than some areas of Scandinavia. So blonde Russians can’t be explained by viking influence. 
     
    Southern England has probably a strong celtic influence.

  16. don’t take the map that literally for russia ;-) scandinavia, well, there’s a lot of good conscription data from there, so i’d believe that….

  17. “don’t take the map that literally for russia ;-)” 
     
    Why not…? :) There are loads of non-artificial blonde people in St. Petersburg and Carelia areas… There have been big “artificial” population movements in that area so I don’t know which point of time this data refers to…

  18. Just saw this – via Dienekes blog – an Eye & Hair Color article from Wiki Italy, which has a good high resolution image… supposedly it’s from Coon?? 
     
    The Legend says: 
    Dark Red 
    - Brown predominant 
     
    Red 
    - Brown > Light + Mixed 
     
    Orange 
    - Brown = Light & Mixed 
     
    Dark Yellow 
    - Light & Mixed > Brown 
     
    Yellow 
    - Light predominant 
     
    It shows that South West Irish people (Co Kerry) are darker than the Irish average for example. Contrary to the eye color alone, it shows most of Greece to be darker than most of Italy – which is what I’d expect.

  19. Has anyone thought about northern dogbreeds which have blue eyes in this discussion? The contrast to “normal” dog eye colour is remarkable.

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