4-population test and East Eurasian-like ancestry in Northern Europe

Update: This is the first part of my discussion on the topic. For part 2 go here; for part 3 here.

I decided to follow up on a hint in the recent Reich et al. (2012) paper on Native Americans to the effect that:

... east/central Asian admixture has affected northern Europeans to a greater extent than Sardinians (in our separate manuscript in submission, we show that this is a result of the different amounts of central/east Asian-related gene flow into these groups).

 I used the implementation of the 4-population test of Reich et al. (2009) in the fourpop program of  TreeMix. 255,020 SNPs common in the various datasets were used throughout, and blocks of 200 SNPs for standard error estimation.

I used HGDP Sardinian, X, Han, San, with X being one of the following:

Armenian_D, Turkish_D, Russian_D, Polish_D, German_D, Irish_D, Greek_D, Finnish_D, Sicilian_D, Swedish_D, Portuguese_D, Lithuanian_D, Somali_D, AMHARA_Pa, Dai, Japanese, Kyrgyz_Bishkek_Ho, Mozabite, Bedouin, North_Italian, French_Basque, Tuscan, Russian, Orkney_1KG, Kent_1KG, Cornwall_1KG, Yoruba, Mbuti_Pygmies

As always, you can find a list of population sources at the bottom of the Dodecad blog.

As I have noted in my review of Moorjani et al., this test shows a superposition of a set of populations on the African-East Asian axis, so populations occupy different positions depending on whether they have African or East Asian admixture. It's a palimpsest. That paper ignored the Eastern ancestry in North Europeans, and used the CEU (a population of mainly North European origin) instead of Sardinians, hence generating inflated estimates of African ancestry in Southern Europeans.

Now that the Central/East Asian ancestry in northern Europeans seems to be recognized by some of the co-authors of the earlier paper, and using the Reich et al. (2012) framework, the different processes superimposed on the African-East Asian axis can probably be disentangled. Hopefully, we won't have to wait too long for the full treatment. Maybe it can go to the arXiv too!

In any case, here are the f4(Sardinian, X; Han, San) values for the different populations:

It is quite clear that North European populations are shifted towards East Asians, with the exception of the Turkish_D sample which is also so shifted, due to its Central Asian Turkic admixture. There are also a few cases of substantial African shift, such as the Bedouin and Mozabite Berbers.

I have also rescaled the f4 statistics on a 0: Sardinian to 100: Japanese scale, including only West Eurasian populations that are East Asian-shifted relative to Sardinians:

I have calculated the correlation coefficient between the f4 statistics for this set of West_Eurasian populations and the sum of the Siberian+East Asian components of my K7b calculator on the same set of populations. This is +0.85, highly significant, and consistent with the idea that ADMIXTURE software and formal tests of admixture capture the same phenomenon. I also calculated the correlation coefficient with the Atlantic_Baltic component that is modal in Europeans, which is equal to +0.56 and confirms the higher East Eurasian shift in  European populations.

(I have also repeated the above with the K12b calculator; the correlation between the f4 statistics and the Siberian+East Asian+Southeast Asian components is +0.76, and the North_European +0.84. The latter is higher than with the Atlantic_Baltic component (+0.56) which combines North and West European ancestry. It thus appears that the East Eurasian admixture in Europe is not a general feature of the oldest Europeans, but reflects a more recent phenomenon.)

Furthermore, I have carried out f4 regression ancestry estimation (Reich et al. 2009) using the f4(Sardinian, San; X, Han), in the horizontal axis, and f4(Sardinian, X; San, Han) statistics, in the vertical. An initial plot shows that while northern Europeans fall precisely on a line in this space, Turks and Armenians deviate substantially, while Greeks, Tuscans, and Basques less noticeably so:

The regression analysis shows a weak correlation (R^2=0.149). The southern Caucasoid populations from Armenia to Iberia appear roughly perpendicular to the north European cline, suggesting that they do not significantly partake in the same phenomenon as the northern groups.

I thus limited myself to the European populations falling on the Russian to North_Italian cline, which form a near-perfect cline (R^2= 0.9783)

Admixture estimation was performed on the triangle whose three corners were (from the regression equation):

LOW: (0.0151411, 0.0000000)
HIGH: (0.00000, 0.02049)

and

TEST: the f4 statistics for each test population

Inferred admixture proportions using this method can be seen below:

I have repeated the above experiment using French_Basque instead of Sardinian, Mbuti instead of San, and Dai instead of Han:

Now, North_Italian shows no East-Eurasian-like admixture relative to French Basque, so there is one less row. The Basques appear to be Asian-shifted relative to Sardinians, so, overall, I would trust the former results more than the latter, but, in any case, the overall pattern seems fairly solid across a choice of reference populations.

While I would not take these results very literally in the absolute sense, I think they show quite well the relative ordering of populations, and are consistent with both my initial observation...

With respect to the Asian- and African- shift of West Eurasian populations, I note that northern Europeans (and Basques) are less African-shifted than southern Europeans, and, at the same time they are more Asian-shifted: the 16 least Asian-shifted populations have a coastline in the Mediterranean (excluding the Portuguese), while the 16 least African-shifted populations do not (excluding the French).

... as well as the remark in passim in the Reich et al. (2012) supplementary material mentioned above.

The prominent position that Sardinians have assumed in the genetic history of Europe puts the discovery of Veeramah et al. that Sardinians tend to be monomorphic in sites where mainland Europeans are polymorphic into new light. It now appears that the reduced genetic polymorphism of Sardinians vis a vis mainland Europeans may not be due to them having undergone a "bottleneck" relative to mainland Europeans, but rather, at least in part, a consequence of admixture in the latter. Admixture matters.

Hopefully, geneticists will become more willing to interpret patterns of decrasing genetic diversity not only as a consequence of diversity-reducing "bottlenecks", but also of admixture in populations that are especially diverse.

In the case of Sardinians and Europeans we have been lucky in that East Asians continue to exist, helping us untangle their (or their relatives') contribution to the population history of Europe. But, in other cases (such as the introgression of archaic DNA into the modern human gene pool), latent population admixture between divergent populations may lead to misinterpretations of the direction of gene flow.

 The raw dump of fourpop output can be obtained from here (for Sardinian-Han-San) and here (for Basque-Mbuti-Dai).