## August 27, 2012

### 3-population test and east Eurasian-like admixture in Europe or The Isle of Refuge

The 3-population test (Reich et al. 2009) allows one to detect the presence of admixture in a population X from two other populations A and B. The value

f3(X; A, B)

is negative when X does not appear to form a simple tree with A and B but appears to be a mixture of A and B.

In a previous entry, I noted that continental European populations, and especially northern Europeans appear to have East Eurasian-like admixture on the basis of the 4-population test. The results of that test are more difficult to interpret, because the quantity f4(X, Y; A, B) can take significant negative or positive values depending on the relationships of populations X, Y with A, B. When A, B are East Eurasian and African populations respectively, and X, Y are West Eurasian ones, East Eurasian-like admixture in a northern European population will affect the f4 quantity similarly as African-like admixture in a southern Caucasoid one. This is not a problem with the f3 test, although caution is needed: a negative value indicates deviation from "treeness" and admixture, but a positive one does not reject admixture.

The f3 statistics were calculated with the threepop program of TreeMix with -k 500 over a set of 598,467 SNPs.

I have used 3 Asian/American reference populations (Karitiana from South America, CHB Chinese, and Papuans) and calculated the following:

f3(West Eurasian 1; West Eurasian 2, Asian/American)

As noted above, negative values of this indicate that West Eurasian 1 can be seen as an admixed population of West Eurasian 2 + Asian/American. The set of 14 West Eurasian populations used is:
CEU, TSI, Tuscan, Orcadian, French, French_Basque, North_Italian, Bedouin, Palestinian, Druze, Mozabite, Adygei, Russian, Sardinian
I thus report 2*(14 choose 2)*3 = 546 values of f3. Hence, I did not privilege Sardinians as a reference point, but instead tried all pairs of West Eurasian populations, and 3 different American/Asian references. There results can be found in the spreadsheet.

Out of the 546 triples, 64 show an f3 score less than Z less or equal to -3, and are thus significant.

The following populations have such a score in at least one pairwise comparison, when they are set as West Eurasian 1, and thus appear to have east Eurasian-like admixture

Note that east Eurasian-like admixture cannot be rejected for the other populations, but it can be confirmed for the above. Moreover, the mean strength of the observed effect for the significant comparisons was Z=-5.5 for Papuan reference, Z=-10.2 for CHB, and Z=-10.9 for Karitiana, again suggesting a northern origin of the east Eurasian-like admixture, albeit without so major a difference between Karitiana and CHB as in the 4-population test.

But, it is worth reading the raw data. For example, note above that of the Middle Eastern and North African populations, only Palestinians show a negative f3 score in any pairwise comparison. And actually they only do so for f3(Palestinian; Sardinian, Papuan) with a Z-score of -4.1. So, it appears that Palestinians have undergone admixture of a different sort than Europeans.

Significant differences were observed for Sardinians as West Eurasian 2 in 21 cases, for French Basque in 11 cases, for North_Italian and TSI in 6 cases, for CEU, OrcadianFrench, and Tuscan in 4 cases. So, it appears that other populations appear east Eurasian-liked admixed relative to Sardinians, and a couple of populations (Russian and Adygei) also appear so admixed relative to west Europeans.

Oetzi the Tyrolean Iceman

The fact that Europeans appear admixed with an east Eurasian-like element when compared with Sardinians does not mean that Sardinians may not also be admixed with this element. I used the genome of the Tyrolean Iceman (Keller et al. 2012) to test whether Sardinians appear east Eurasian-like admixed relative to the Iceman.

f3(Sardinian;Karitiana,Oetzi) = 5.36496e-06 (Z=0.00940612)

This might indicate no admixture, but f3 can detect admixture but can't prove non-admixture. The f4 is suggestive:

f4(Sardinian,Oetzi;Karitiana,San) = -0.00221783 (Z=-3.06251)

You should probably not take my word for the above. It may appear that, contrary to expectation, Oetzi was more east Eurasian-like than modern Sardinians. Indeed, in my initial analysis of him with ADMIXTURE, I found that he was 2.8% East_Asian, which would point to an East Eurasian shift of Oetzi relative to Sardinians, and which might be consistent with the f4 result. On the other hand, the negative f4 score could be related to African-like gene flow. On balance I would say that Sardinians appear quite similar to Oetzi.

Gok4 and Ajv52

Furthermore, I carried out the same analysis on Neolithic samples from Sweden (Skoglund et al. 2012). The number of SNPs here is much smaller. Results are:

Gok4 (TRB farmer): f4(Sardinian,Gok4;Karitiana,San) = -0.00167365 (Z=-1.23616)
Ajv52 (PWC hunter-gatherer): f4(Sardinian,Ajv52;Karitiana,San) = -0.004676 (Z=-3.76048)

While I would not bet the farm on these results (because of the small number of SNPs and the fact that they're based on a single individual), they do seem to suggest that these Neolithic Swedes were east Eurasian shifted relative to Sardinians. For example, for my Swedish_D sample, I get f4(Sardinian, Swedish_D; Karitiana, San) = -0.00372751 (Z=-22.8715). The Z-score is stronger (probably because of the much larger number of SNPs), but the f4 value of Ajv52 is lower (more east-Eurasian like). Modern Swedish_D appears intermediate between Gok4 and Ajv52, so this may suggest that Mesolithic Europeans may be, at least in part the source of this element.

(Comparison with Brana-1 Mesolithic Iberian indicates a negative non-significant f4 score, but with an even smaller number of SNPs).

In sum total, my experiments with ancient DNA samples from Europe suggest a little more east Eurasian-like shift relative to Sardinians (or conversely a little more African-like shift in Sardinians). Both Oetzi (who has the highest quality genome) appears to be so-shifted, but Ajv52 (a Neolithic northern hunter-gatherer) appears to be so as well. I am sure that if we get more high quality ancient DNA from Europe, some clear pattern may emerge, but I would not speculate further on the basis of these initial results.

Isle of Refuge

The above set of experiments has revealed once more that "there's something about Sardinians." There is perhaps a reason for the fact that the arrival of population elements from continental Europe seems to have bypassed them to some degree, or, at least affected them least. However it was that continental Europeans got their east Eurasian-like shift, the great tank of European genetic variation does not seem to have achieved equilibrium with the little cup of Sardinia. Something stood in the way.

Sardinia is the west-most of the large Mediterranean islands. It is more distant from mainland Europe/Asia than the other big islands (Cyprus, Crete, Sicily, and Corsica).

And, unlike islands much smaller than itself, its size has probably been instrumental in helping it afford it a certain autonomy and continuity of population. Only Sicily is largest, but one can practically swim across the Strait of Messina to reach it from the Italian peninsula.

Hence, a combination of large size, western geographical location, and distance from the mainland have contributed to the continuity of its population. But, geography may not have been sufficient if other events had not taken place. Through a combination of favorable geography and historical contingency, the Sardinians made it to the present largely unscathed, and, among their other graces, can now help scientists figure out what happened to the rest of us.

1. Thanks for spelling out the process. It was easy to follow.

2. That photograph is frightening, she looks seriously unhinged to me. :)

Basically I am reading that the Sardinians represent one group (probably Mediterranean coastal aborigines). Oetzi and AZT are this group and another admixed with Eurasian influence. Seems consistent.

3. There's something about Sardinian women, too... Is her name Mary, by the way? :-)

4. If there isn't "so major a difference between Karitiana and CHB as in the 4-population test", could this mean that African admixture in more southerly populations had some effect on the f4-based admixture estimates?

Amerindians are more distant from Africans than East Asians. This means that if African admixture is present in more southerly populations, estimates of East Eurasian admixture in populations less affected by African gene flow (North Europeans) would appear higher with an Amerindian reference.

5. The genetic pecularity found in Sardinia is not only due to the geographical isolation of the island, that in the reality is not so much elevated, being Corsica a sort of natural bridge between Sardinia and Italian Peninsula, but it is identifiable in the carachter of Sardinians, a population who has never submitted to invasors, still today the interior regions of Sardinia are called Barbagia, that means "land of Barbarians", as the ancient romans called it, because they had never conquered the region, in addition particular enviromental features like the presence of malaria on the coasts caused the migration of population on the mountains, where contacts with foreign populations were scarce.

6. Women are not a good comparation for me. Maybe because I am male? Hm.

I mean, when I checked "average faces" I found that I often couldnt find anything "exotic" in the look of the females, while the males of the same country looked strikingly exotic to me.

I was able to find countries in wich the average pictures of both sexes looked exotic, but I did not find a single one where the male looked familiar and the female looked exotic.

7. Pier Angeli was one of the most beautiful Italian women of her age, and she was slightly unhinged; one of those love things.

Sardinia was the home of people from North Africa for a very long time. The presence of those people must have shifted the genomes' of Sardinians slightly away from Europeans combined by periods of isolation and their own direction of genetic drift. Sardinians like most Europeans with a marine border are shifted towards Africans.

8. @Ponto,

IIRC, Polako/Davidski found minor African ancestry in Sardinians, using some Minor Allele Frequency (MAF) Software.

Now was this "African" admixture North African or Sub-Saharan African, that's the question - probably the former.

9. Re : Pierangeli

I don't think that she had 100% Sardinian ancestry.

View the distribution of her surname.

http://www.cognomix.it/mappe-dei-cognomi-italiani/PIERANGELI

Central Italy.

10. Apparently she was not Sardinian

http://www.mammalena.info/MY%20LP%20Records_VOCALS/PIER%20ANGELIS/ITALIA%20CON%20PIER%20ANGELI.htm

If anyone knows another famous Sardinian, feel free to drop me a line. I'm kinda tired of always using Caterina Murino, who is the only Sardinian I know ;-)

11. Mariangela Demurtas ;-)
http://www.last.fm/music/Mariangela+Demurtas

12. "Now was this "African" admixture North African or Sub-Saharan African, that's the question - probably the former."

it is surely Mechtoid North African ...
here is the portrait of Pietro Cocco

http://consiglio.regione.sardegna.it/XIVLegislatura/Immagini/Consiglieri/Cocco_Pietro.jpg

Southern Caucasoids may have colonised southern Europe and the Mediterranean Islands,way before LGM forced the ancestral Europeans to seek refuge in the south, absorbing the Southerners in the process ...

13. @aspromavro

http://www.cognomix.it/mappe-dei-cognomi-italiani/DEMURTAS

Hopefully, she is the real McCoy !

14. You could use the writer and Nobel prize winner Grazia Deledda.