July 4, 2013

HERC2 haplotypes worldwide study at Kurdish DNA

I must congratulate again Palisto of Kurdish DNA blog for his excellent work on the description of HERC2 haplotypes and their frequency across world populations. It is not a peer-reviewed academic paper but it could well be, and within the high quality sector.

Palisto, The color of the eyes: at least 17 HERC2 variants in Human gene pool. Kurdish DNA 2013. Freely accessible blog articleLINK

After initially detecting seven haplotypes in the Kurdish genetic pool (which were named ht1-7) and then studying these in the Eurasian gene pool, he decided to study the African haplotypes, largely in the "other" category, as well as comparing them all with the known Neanderthal and Denisovan sequences, at the very least to infer a root. The main result is this tree:

So the ancestral haplotype is ht13, found not just among Neanderthals and Denisovans, but also among scattered populations of H. sapiens both in Africa as in Eurasia-plus. 

From it hang ht8 (Homo sapiens, found in and outside Africa) and ht18 (Neanderthal-exclusive).

This main branch has two major sub-haplogroups, which I will label D and E for convenience (A would be ht13, B ht8, and C Neanderthal-only ht18). Haplogroup D (hts 11, 16 and 17) seems to have remained in Africa (only ht 11 was detected at low frequencies in Lebanon), while haplogroup E (all the rest) massively participated in the migration out of Africa (OoA).

However it must have done already in highly diversified form, as most named haplotypes are found at significant frequencies both outside and inside Africa. There are four exceptions only:
  1. Ht9 is only found in Africa (with a minor Arabian exception), so this haplotype did not took part in the OoA.
  2. Ht15 has not been found in Africa instead, so it is possible that it evolved already in Eurasia.
  3. Ht2 and its descendant ht1 (both of which cause blue eyes, albeit in recessive manner) don't seem to exist in Africa either (with the exception of the HGDP San sample, which seems notably admixed with Europeans, at levels of almost 20%, not your typical Bushmen really), so again they probably arose already in Eurasia. 
These are the wider regional frequencies:

However at the original article there is a much more detailed list, which is probably more interesting to use when pondering each haplotype. For example the overall data for America is pretty much irrelevant, as it groups native peoples with mixed creole ones.

For example we can see that "blue eyes" ancestral haplotype ht2 looks like originated in West Asia, and it may also be the case of its descendant ht1. 

Ht 15 in turn may well have coalesced in Altai, from where it spread to mostly Native American peoples (represented by Mestizo Colombians). A similar pattern can be seen in ht14, however this must be original from Africa (the Biaka have it, as do Mozabites) and therefore it is found also in some other scattered populations like Cambodians, Sindhi, etc.

Something I wonder about is the low diversity displayed by East Asians in this haplotype. Or inversely, why did West Eurasians evolve so all non-African novel variants? While there is still some left to analyze in the ND box, it is very small in East Asia. I wonder if it has some relation with skin pigmentation pathways indirectly influencing this change somehow.


  1. This comment has been removed by the author.

  2. Some remarks :

    1) I see Maju has just asked Palisto for explanation about the column labeled "N with ht3-18 data". I have been the same request.

    2) in the tree, ht9, ht10, ht15 and ht14 are separate and parallel branche(s) from "West Eurasian" branch ht6 -> ht7 -> ht5 -> ht4 -> ht3 -> ht2,ht1.

    3) A lot of results testing ht1 and ht2 only are certainly wrong, except maybe, the results with a dark bar (Swedes, Danes, German, Austrian Swiss, Galician) which seems me acceptable. I don't know Switzerland enough to know if it is acceptable that ht1+ht2=94% which gives 88,36% of the 16 sampled Swisses have clear eyes, according to the rule given by Palisto. Maybe also, this depend of the region(s) of the 16 Swisses.

    But for me, the results for other samples with no determination of ht3-ht18
    are not acceptable for ht1 andht2, specially for:
    Kent 33%, 14% clear eyes, it is aberrant, at least for the local natives.
    Utah-USA 51%, 25%, seems very weak for American WASP.
    Tuscan is the most absurd : inacceptable partial test n=80 11%, 1% clear eyes; acceptable full test although weak number n=8 44%, 19,36% clear eyes.
    The partial Spanish results (except Galician) are absurd, even if Spaniards have the brown eyes generally, clear eyes are not rare. For Spanish Basques 25% 3,75 clear eyes compared to French Basques 40% 16% clear eyes, I leave the response to Maju.

    For me, this shows the other laboratories have a better technic (it are able to test ht3-ht18 haplotypes) and also that tested all haplotypes, allows a cross-check and tested again if problem.

    1. !) In the summary table I merged two data sets, the first data set is just focusing on ht1 and ht2 and is directly extracted from http://alfred.med.yale.edu/; the second data set is the one that I fully analyzed (based on HERC2 HGDP data Davidski provided).
      This is why I gave two N's, "N total" and "N with ht3-18 data". Frequency of Ht1 and ht2 were calculated using "N total" (N of both data sets), for all other haplotypes I had to use the number of the second data set alone.
      The table is basically a merged version of two tables.

      2) This was not my interpretation of the tree.

      3)The Swiss data is based on data at ALFRED. Here is the list of ht1 + ht2 (=rs12913832=G)
      Swiss have 93.8% rs12913832=G

    2. "2) in the tree, ht9, ht10, ht15 and ht14 are separate and parallel branche(s) from "West Eurasian" branch ht6 -> ht7 -> ht5 -> ht4 -> ht3 -> ht2,ht1."

      There is no such "West Eurasian branch" in the tree: how can you interpret the tree that way?! I'm flippant. If we call the main Eurasian branch E, as suggested bay me in the blogpost, then it goes as follows:
      → E1 (ht12)
      → E2 → E2a (ht6)
      → E2 → E2b → E2b1 (ht9 - Africa only)
      → E2 → E2b → E2b2 → E2b2a (ht7)
      → E2 → E2b → E2b2 → E2b2b → E2b2b1 (ht10)
      ... etc.

      What you call "West Eurasian" and the rest are totally alternating in their phylogenetic positions, and also all them (with the above mentioned exceptions) are common in Africa (or at least common enough in isolated African populations like the Biaka) and must have therefore an African origin. The only West Eurasian specific branch seems to be ht2 (and its offshoot ht1), although the Altai-American ht15 branch can also be considered that way by origin surely. All the rest are global or Africa-only.

      "But for me, the results for other samples with no determination of ht3-ht18
      are not acceptable for ht1 andht2, specially for:
      Kent 33%, 14% clear eyes, it is aberrant".

      It is indeed a strange result but I would not dare to challenge it without parsing the data. It may be caused by a fluke in sampling, or it may be that we have the wrong impression about commonality of blue eyes in Kent, or it may be that there are other haplotypes causing blue eyes. I did not comment but the data of 0% ht1+2 in many parts of Iberia is even more shocking. Granted that blue eyes are much less common than in the North but Andalusians and Galicians definitely have blue eyes with much higher frequency than 0%.

      Rather than challenging the data without personally reviewing it, I'd suspect other alleles being behind blue eyes in such populations, maybe even downstream of ht2-1 or maybe in other genes.

      "Utah-USA 51%, 25%, seems very weak for American WASP."

      They are not WASP: they are WADM: White Anglo-Danish Mormons.

      Anyhow, according to this map, Kent (and other parts of South and West Britain) has <50% of blue eyes (less than North French for example). Britain overall is probably not much above 50% on this trait. The center of "blue-eyeness" is an irregular oval around the Eastern Baltic, where frequencies peak to >80%.

      (More maps: another map but less useful: includes an "undefined" category but less data points in Europe; another map of pigmentation allele frequencies in Europe; a color version of Coon's "light eyes", not the same as blue, map).

      Notice that grey, green and amber eyes, which may be considered "light" are not blue, also some blue eye phenotypes are generated by other alleles.


    3. ...

      "For Spanish Basques 25% 3,75 clear eyes compared to French Basques 40% 16% clear eyes, I leave the response to Maju".

      It can well be, maybe depending on where exactly you sample. I'd use the terms Southern and Northern Basques however, otherwise people may get offended, as calling someone "Spanish" or "French" is considered almost insulting over here, at least by many people. Blue eyes are not too common over here: green, amber and grey eyes are at least as common (probably more) and then of course brown eyes tend to dominate. As blue eye alleles behave recessively, even if both my grandfathers had blue eyes (my grandmothers had them brown), among my siblings and parents nobody has blue eyes: brown, amber and amber-green only. Among my cousins there are a few with blue eyes but I would have to consider their other ancestors and I do not know them in many cases. I think these traits (blue eyes, blond hair, etc.) are more common in Spaniards overall. Probably Northern Basques too have them more commonly. So, yes, the data for Basques does fit (but not for Iberia).

      "For me, this shows the other laboratories have a better technic"...

      Can you mention any specific papers or other kind of reports?

    4. PS- Reconsidering your comment:

      "Kent 33%, 14% clear eyes, it is aberrant, at least for the local natives".

      That 14% is not "clear eyes" but blue eyes exclusively, and only those caused by HERC2 (and maybe Palisto has missed some downstream ht2-derived variant, which would also cause blue eyes within the HERC2 mechanism).

      But whatever the case, that 14% does not include "clear eyes" that are not blue. These have other origins which are not well understood as of now, including possibly the presence of HERC2 blue color trigger in recessive state.

  3. 3) Check out the column ND (Not determined) for Kent, Utah, etc. I could not determine the ht for those, this is why frequencies for ht1 and ht2 might be low...

  4. Can an individual check what his/her HERC2 haplotype is with our 23andme data?

    1. Ask 23&Me. I guess so but I do not know with any detail what tests they make.

    2. "Can an individual check what his/her HERC2 haplotype is with our 23andme data?"

      In order to get your SNP results, do the following:
      1. Go to "Account" (top right corner)
      2. Go to "Browse Raw Data
      3. Go to "Jump to a gene", type in "HERC2", click "Go".
      4. Find your results in one of the columns of the spreadsheet below.



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