ADMIXTURE across Eurasia: from Anatolia to Siberia

(Last Update: Oct 17)

Here is a result of an ADMIXTURE run of a few populations from Eurasia (left to right: Turks, Armenians, Georgians, followed by a mix of Uygur, Mongolians, Yakut, Hezhen in no order), combining the HGDP dataset with that of Behar et al. (2010).

It's more of a test, rather than a final result, as I've just finished integrating the two datasets, but it's a nice comparison of a wide assortment of linguistic families.

Notice Turks and Armenians being quite similar to each other, (green+blue), although Turks are differentiated by the presence of an east Eurasian component (5.5%). On the basis of uniparental markers, five years ago, I estimated this component as 6.2% which seems to be right on the money. In the combined Armenian/Georgian sample this admixture is only 0.14% and as can be seen is limited to a handful of Georgian individuals.

It is interesting that Georgians belong semi-uniquely to the green cluster. Turks' non-Mongoloid ancestors were Indo-European speaking like the Armenians still are. It would be tempting to see in the blue-green contrast an Indo-European/Caucasian one, especially as the Caucasoid component further east seems to be mainly blue, in agreement with the idea that it was Indo-Europeans (in particular mainly Iranic speakers) who brought Caucasoid genes to the heartland of Asia.

UPDATE I (Oct 17):

Moving to the north, we see (left-to-right) Han (red), Hungarian/Belorussian (blue), Chuvash (first red "step"), Uzbek (second red "step"). Unlike the Turks, the Hungarians, who also speak a language that came from the east, seem to lack a noticeable east Eurasian component.

Their linguistic conversion was one of elite dominance, where a handful of Mongoloid and quasi-Mongoloid upper echelons left their language but not their genes:

According to his observations, the “overlords” were characterized by Turanid, Uralian and Pamir race elements and also by certain long-headed components. The “middle layer” or “warriors’ layer”, however, showed an anthropological profile distinctly different from that of the overlords. It was essentially constituted by Mediterraneans, Nordoids (who might also have been tall robust Mediterraneans) and Pamir component while the absence of Turanid and Uralian race characteristics was remarkable. As regards the third layer, the so-called “common folk”, they were dominated, just as the middle layer was, by Mediterranean and Nordoid elements but, in addition, the Cromagnoid ones were also significant.

The Chuvash are Turkic and live in Europe, while the Uzbeks, closer to the Altaic homeland in Asia are also Turkic, and have a predictable higher percentage of east Eurasian genes.

Y chromosome and mtDNA of Louis XVI of France (?)

From the paper:

After the execution of Louis XVI in January 21st, 1793, eyewitnesses stated that many people from the crowd dipped their handkerchiefs in the king’s blood and kept these objects as mementos [8]. An Italian family has owned for more than a hundred years – as demonstrated by a letter addressed to the director of the Muse/ e Carnavalet in Paris, January 31st, 1900 – a dessicated gourd that presumably contained one of these handkerchiefs.

The mtDNA results:

the majority of the cloned sequences (87%) showed a rare N1b haplotype, with the substitutions 16093C-16145A-16176(G)-16223T. The same results were found in Bologna by direct sequencing, along with another substitution (16390G), not included in the amplicon generated in Barcelona. The haplotype found at the mtDNA HVR2(73G, 151T, 152C, 189G, 194T, 195C, 263G and 315.1C), is consistent with the N1b haplotype from the HVR1, although the substitutions 151T, 189G and 194T are not described in the current N1b dataset lineages. We interpret these three substitutions as additional, undescribed modifications of a N1b haplotype.

The Y-chromosome STR markers:

A ysearch query reveals a handful of distant (3 off in 9 markers) matches ranging from Anatolia to Scotland. Likewise yhrd turns up no matches using either the full or restricted panel, but a 1-off match with DYS389II-29 in the restricted panel in Marche, Italy.

Wikipedia tells me that Louis XVI's patrilineage goes all the way to Robert the Strong, and his matrilineage to Catherine of Mayenne.

One would think that a 1,000-year long line of kings and nobles would have left enough side branches and bastards along the way to register a few hits on the European map. Perhaps, that's a reason to stress the "presumed" in the paper's title. On the other hand, I find it interesting that the presumptive haplogroup of Louis XVI was G2a, the same as 2 of 5 warriors from Merovingian Bavaria (7th c. AD).

There is a way to authenticate the results, as the authors note:

At present it is not possible to prove genetically that the sample really belongs to the king Louis XVI. One possibility would be to extract a new sample from the dry heart attributed to the Dauphin Louis XVII, son of Louis XVI, preserved at the Basilique Saint-Denis in Paris, and compare both Y-chromosome profiles. Owing to the fact that the Y-chromosome profile found is not present in our current genetic databases such as YHRD, a potential match would directly authenticate the studied blood sample.

Forensic Sci Int Genet. 2010 Oct 10. [Epub ahead of print]

Genetic analysis of the presumptive blood from Louis XVI, king of France.

Lalueza-Fox C, Gigli E, Bini C, Calafell F, Luiselli D, Pelotti S, Pettener D.

Institut de Biologia Evolutiva, CSIC-UPF, Dr. Aiguader 88, 08003 Barcelona, Spain.

Abstract
A text on a pyrographically decorated gourd dated to 1793 explains that it contains a handkerchief dipped with the blood of Louis XVI, king of France, after his execution. Biochemical analyses confirmed that the material contained within the gourd was blood. The mitochondrial DNA (mtDNA) hypervariable region 1 (HVR1) and 2 (HVR2), the Y-chromosome STR profile, some autosomal STR markers and a SNP in HERC2 gene associated to blue eyes, were retrieved, and some results independently replicated in two different laboratories. The uncommon mtDNA sequence retrieved can be attributed to a N1b haplotype, while the novel Y-chromosome haplotype belongs to haplogroup G2a. The HERC2 gene showed that the subject analyzed was a heterozygote, which is compatible with a blue-eyed person, as king Louis XVI was. To confirm the identity of the subject, an analysis of the dried heart of his son, Louis XVII, could be undertaken.

Link

African admixture in the Near East: where from?

Here is the result of running ADMIXTURE for K=5 using 275K SNPs on the combined HGDP + HapMap African and West Asian populations, also including Adygei and Tuscans. The populations are in order: Luhya, Maasai, Tuscans, Yoruba, Adygei, Bedouins, Druze, Mozabites, Palestinians.

At this level of detail, Africans are divided into three clusters which can be labeled Sub-Saharan (red), East African (blue), and "Mozabite" or North African (purple). Europeans and West Asians form the green cluster, while the Arab samples have a substantial contribution of the yellow cluster.

Here are the admixture proportions:

African admixture in the two European populations is probably in the limits of statistical noise and consists of "Mozabite" (0.4%) for Tuscans and "E African" for Adygei (0.6%).

Druze, an Arab population that was religiously isolated from Arab Muslims for about a thousand years seems to have correspondingly missed most African admixture, registering 0.6% "Mozabite" and 1.1% "E African".

Non-Druze Arabs have clear traces of African admixture both in the form of "Mozabite" North African (4.5% for Palestinians, 4.9% for Bedouins), E African (6% for Palestinians and 5.7% for Bedouins) and a little Sub-Saharan (1.3% for Palestinians and 2.1% for Bedouins).

I had pointed the mainly eastern African admixture in Near Eastern Arabs a year ago in my review of HAPMIX. Clearly Maasai are a better stand-in than the Yoruba for whatever African ancestry Arabs have.

It is quite interesting to note the genetic distance (expressed in Fst) between the five inferred clusters:

We can plainly see that proximity to Eurasians increases in the order of Sub-Saharan, East African, "Mozabite". I have little doubt that Somalis and Ethiopians from East Africa would occupy an intermediate position between Maasai from Kenya and "Mozabites" in that order.

An interesting observation is that the "Arab" cluster is slightly more distant to all African clusters than the European/W Asian cluster is. This might seem perplexing as geography might dictate that it should be closer to the African clusters.

However, this is not very surprising to me, as there was gene flow between West Asia and Europe and Africa in old times, evidenced by such things as the presence of Eurasian Y-haplogroup R-V88 in Africa and African haplogroup E1b in Europe and West Asia.

The original Arab ancestors, were probably haplogroup J1e-bearing Semites exploiting arid environments of West Asia. Present-day Levantine Arabs (especially Bedouins, in the available samples) maintain a strong signal of this component of their ancestry, admixed, however, principally with the original Tuscan- and Adygei- like West Asians, and secondarily with E and N Africans.

Revisiting GenomesUnzipped "Ashkenazi Jewish" admixture

There were two individuals in my recent post who showed some evidence of "Ashkenazi Jewish" admixture (DBV001: 100% and VXP001: 32%). I list in the comments of that post some possible explanatios for why VXP001 (who has no knowledge of Jewish ancestry) might get such a result. Naturally, using 275K SNPs is better than the 192 of EURO-DNA-CALC, so I did a separate run that included these two individuals.

The results are:

DBV001: 85.1% European/W Asian, 10.5% "Arab", 0.5% "E African", and 3.8% "Mozabite". This is entirely consistent with full known Jewish ancestry. The closest population to the Middle Eastern component of Jews are presumably the Druze, who have about 16.9% of the "Arab" (which should probably be relabeled "Semitic") cluster. Ashkenazi Jews are known to be intermediate between Levantine and European populations, and DBV001's result is entirely consistent with this.

As I've mentioned before, the exact percentage of Middle Eastern ancestry in modern European Jews is difficult to estimate, as this would depend on determining the exact percentage of "European/W Asian" and "Semitic" components was present in their gene pool before they settled in Europe. If, for example, they were 100% in the "Semitic" cluster, then DBV001 would be about 10% of Middle Eastern ancestry, but if they were like modern Druze, then this percentage would be 100*10.5/16.9 = 62.1%. The truth is probably somewhere in between.

VXP001: A shorter story, as VXP001 comes out 100% "European/W Asian". Thus, I am inclined to believe that VXP001's AJ score is either due to the small number of markers, or to a European-origin component in the composite Ashkenazi Jewish gene pool that he happens to share.

UPDATE (Oct 23): A much more detailed analysis of Genomes Unzipped individuals.

Clustering European Populations with ADMIXTURE

Here is the result of running ADMIXTURE for K=6 using 275K SNPs on the combined HGDP+HapMap European populations + the CHB Chinese sample from HapMap. (Only the larger HapMap Tuscan sample was included, rather than the smaller HGDP one).

Using a large number of K in closely related populations makes convergence quite harder, but the end result does correspond to several identifiable clusters.

yellow: Northern European

green: "Adygei"

red: "Sardinian"

purple: "Basque"

light and dark blue: Chinese

It's interesting that the Chinese split before some Europeans do. Interestingly, one of the two Chinese components (light blue) is the one represented in Russians, so this split probably reflects some type of northern/southern differentiation in Chinese, as the east Eurasian component in Russians was introduced from northern Finno-Ugric speakers.

Here are the admixture proportions:

It would be interesting to add the Xing et al. dataset into the mix, however, there is little overlap between all three datasets, rendering the aggregate quite useless for such fine-level work.

Running EURO-DNA-CALC on GenomesUnzipped

(Last Update Oct 23)

genomesunzipped is a new initiative to put data of personal genomics customers online. It's a great idea, and the data will be quite useful to many people.

I downloaded the available data and ran EURO-DNA-CALC on them. Of course it is meant to be used for European or West Eurasian people, which all of them seem to be.

Here are the results for the 12 people whose data were online as of this writing. In bold are components whose confidence intervals do not intersect 0.

Most of them seem to be of NW European descent as their names suggest, and a couple seem to be partly or significantly of Jewish descent.

If you are one of these people, feel free to write to me or leave a comment to tell me if I'm right or dead wrong!

UPDATE (Oct 14): A more detailed analysis of DBV001 and VXP001 in this post.

UPDATE (Oct 23): A much more detailed analysis of all Genomes Unzipped individuals in the context of western Eurasia.

UPDATE (Nov 1): Joe Pickrell discovers Jewish great-grandparent

Deep ancestors of human DNA compatible with structured African population

(Last Update Oct 13)

This is a wonderful paper as it directly deals with the old coalescence times of human autosomal DNA and their presumed incompatibility with the Out of Africa model:

A genome-wide frequency distribution of the TMRCAs has been reported by curating
the literature (Garrigan and Hammer 2006) but no systematic and consistent analysis has been performed in a single genome-wide data set. We report the fi rst genomewide estimation of the TMRCAs of anatomically modern humans, and we investigate if diff erent scenarios of human evolutionary history are supported by this estimate.

The four scenarios considered by the authors are seen schematically in the following figure from the paper:

The Recent out of Africa: Single Origin Population model is the simple model that has found support in the shallow coalescence times of human Y-chromosomes and mtDNA and has made the jump to popular culture. In this model, humans are a young species that underwent a bottleneck, and Eurasians are descended from a group of Africans that left the continent. This model has been criticized for its perceived inability to explain deep divergence times in autosomal DNA.

The Recent out of Africa: Multiple Archaic Populations is the model I have advocated over the years (check out the "Palaeoafrican" label of the post for my past writings on the subject). It agrees with the previous model in the recent African origin of modern Homo sapiens but it states that the African population was structured and not panmictic: divided into fairly isolated long-standing subpopulations, and that Eurasians are descended from a single one of these African subpopulations (which I have termed "Afrasians").

The existence of a structured African population makes easy work of deep divergence times, as the variants that have such deep origins are presumed to have evolved separately in different African subpopulations, and then to have found themselves in the modern gene pool after the breakdown of this structure.

The Multi-Regional: Recent Admixture model is the one advocated by those seeing Neandertal and/or Homo erectus introgression in Eurasia. Like the previous two models, it agrees on the recent African origin of modern humans, but it sees a place for long isolated pre-existing Eurasian hominids, who contributed some of their mtDNA to modern humans.

Like the previous model, deep divergence times are no problem, as two variants with deep common ancestry are presumed to stem from the separated Eurasian and African Homo. This model has found recent support by analysis of the Neandertal genome but as the authors of that study and myself have stressed, the evidence for 1-4% Neandertal introgression into Eurasians has an alternative explanation consistent with the previous (Multple Archaic Populations in Africa) model.

Finally, the Multi-Regional: Long Standing Admixture model sees no special place for Africa, except as the point of origin of human Y chromosomes and mtDNA. Humans are descended from Homo populations from around the world that have always maintained gene flow between them. This model obviously explains deep divergence times, but has a difficult time explaining the African origin of the uniparental markers, the palaeoanthropological evidence for an emergence of anatomical modernity in East Africa and the genetic evidence for a diminution of genetic variation in Eurasia with increasing distance from East Africa.

The authors seem to propose a fifth model, Ancestral Bottleneck which is noted as a bottleneck 150,000 years ago in a possibly ancestral structured population. This model doesn't get its own figure, but can be seen in the Single Origin Population model as "Potential bottleneck 150,000 years ago".

This model seems to combine elements of the first two ones: it is an essentially single origin model for extant humans, but it keeps the possibility of structure in Africa prior to the bottleneck, and pushes the breakdown of this structure before the bottleneck.

Here is what the distribution of TMRCAs for autosomal DNA, mtDNA, and Y-chromosomes:

The authors observe that really old most recent common ancestors are predicted by all four models, so they are no reason to discount the Single Origin Population model. However, it is plain that the variance of TMRCAs observed for actual human autosomal DNA is great (the black curve is "flat"). Here is what they write:

The variance of the empirical TMRCAs is larger than the variance predicted by three of the four different models of human evolution (see Figure 2 and Supplementary Table 3), and this large variance has been interpreted as the result of archaic sub-structure in Africa (Harding and McVean 2004). Indeed, the Multiple Archaic Populations' (scenario 2) shows similar variance of TMRCAs as the empirical data, but the inflated variance of the empirical TMRCA estimates can also be due to variation in mutation or recombination rate across the 40 sequence-regions (McVean et al. 2004).

In other words, the variance is great (more young and old TMRCAs than expected), either because of variation in mutation and recombination rates (i.e., different genomic regions evolve at different paces), or because of the multiple archaic populations idea. Unfortunately, the paper does not attempt to show how e.g., a variable genome-wide mutation rate might serve to flatten the TMRCA variance of the three models that fail to reproduce the data.

When we look at uniparental markers (mtDNA and Y-chromosomes), all four models predict older ancestors than observed. Here is what they write:

The models of human evolution typically predict older TMRCAs compared to the estimated 170,000 years for mtDNA (Ingman et al. 2000) and the upper estimate of 100,000 years for the Y-chromosome (Tang et al. 2002; Wilder et al. 2004; Shi et al. 2010). For mtDNA, a TMRCA of 170,000 years is within the range of values predicted by the `Multiple Archaic Populations' scenario (P(TMRCA less than 170,000) = 0.21), but the mitochondrial TMRCA estimate is diffi cult to reconcile with the remaining three scenarios (P less than 4x10<sup>-2</sup>). For the Y-chromosome, a TMRCA of 100,000 years is clearly at odds with three of the models (P less than 6x10-4), but for the `Multiple Archaic Populations' scenario with archaic African admixture, the proportion of simulated gene trees with TMRCAs younger than 100,000 years is larger than for the other three models, albeit quite small (P = 1.5x10^-2).

Thus, while all four models can perhaps account for old autosomal TMRCAs (The "multiple archaics" on its own, the other three with help from variable genome-wide evolution), none of them can account for the young ages of human Y-chromsomes and mtDNA, with "multiple archaics" again coming on top, being consistent with "mitochondrial Eve", and coming closer (but not quite) to consistency with "Y-chromosome Adam".

There are ways to reconcile all four models with the uniparental markers, however. For the Multiple Archaic Populations model, they acknowledge that the Y-chromosome problem would go away if they increased the number of these populations from their current 3, while for the rest they invoke selection to account for the recency of human mtDNA and Y-chromosomes.

The effective population size tug of war

Parenthetically, it is important to note here the problem of the effective population size, as it has fueled quite a lot of sensationalistic media stories and documentaries (of the "humans were at the brink of extinction, and then a small band of them survived and went on to conquer the world" kind).

Here are some useful observations:

High effective population size => old TMRCAs

Low effective population size => young TMRCAs

Directional selection => young TMRCAs

Balancing selection => old TMRCAs

Structured population => old TMRCAs

In order to account for the recency of human Y-chromosomes and mtDNA, scientists came up with very low population sizes for our ancestors ("the endangered tribe" meme).

Unfortunately, this has the side-effect of predicting very low ages for autosomal DNA, lower than observed! To fix one problem, another one is created.

Can we have our cake and eat it too? An idea is to invoke balancing selection in autosomal DNA, i.e., the persistence of two variants at a given locus because they confer different advantages/disadvantages and an equilibrium between them exists, not allowing one or the other to reach its destiny of fixation.

Another idea is to invoke directional selection in Y-chromosomes and mtDNA. In directional selection, competing alleles are weeded out not by the winds of fortune, but by the supremacy of the successful alleles (Adam and Eve in our case) which push them to the side.

A different idea is to invoke ancient population structure. This immediately adds time to the TMRCA (since the different sub-populations became separated), and can thus explain old divergence times.

A fourth idea is to invoke "technical" things like variable mutation rate across the genome, or see problems in the standard age estimations for Adam and Eve. That way you can explain why there are more old autosomal TMRCAs than your model predicts, or why Adam and Eve are younger.

No wonder that there is no consensus among experts!

Conclusion

This paper certainly shows that the multiple archaic African populations model that I have advocated is a strong contender for being close to what actually happened. A priori, I think that the ecological and climatic variation in Africa -especially due to its north-south geometrical orientation-, and the long-established presence of Homo in the continent, make it unlikely that a single population of Homo survived there at the expense of all others.

In short, I think that: humans were never endangered in Africa, never dwindled to small numbers (inferred ancestral effective population sizes in the paper are 8k for Multiple Archaic Populations and 14k for Ancestral Bottleneck), and were not a single panmictic population spanning ecological niches and climate zones.

Rather, there were always separate populations in Africa, and climatic change (and more lately behavioral/subsistence change) has resulted in an ever-present process of population fusions and fissions. One of these sub-populations, living somewhere in East Africa, accumulated enough biological advantages to become extremely successful, populating Eurasia on the one hand where some admixture with archaic Eurasians may have taken place, but, also, successfully populating the rest of Africa, where it absorbed other subpopulations of Homo in the continent itself.

UPDATE (Oct 13): Some discussion of the paper and my own theories in Gene Expression, wherein Chris Stringer, a leading proponent of the "Recent out of Africa: Single Origin Population" says that:

My new book covers all this, and your recent work, but I do agree with Dienekes on the importance of deep African population substructure to the story..

While Gregory Cochran thinks I'm wrong:

Dienekes is wrong about the Neanderthal interbreeding results being explained by African population substructure, , but there are a lot of indications that there was significant substructure. A lot of this involves work that is not yet published: I look forward to seeing the details. Some of what I hear is remarkable.

For myself, I'm waiting to see data on native east Africans on segments of "Neandertal" ancestry. Let's look at native groups from Somalia, Kenya, Ethiopia, Tanzania with limited Caucasoid admixture and let's see how much "Neandertal" ancestry they have. If they don't have any, then "Neandertal" genes must have a Eurasian admixture explanation. If they have too little, then it can be explained by Caucasoid admixture in more recent times. But, if they have much more "Neandertal" admixture than Caucasoid admixture can explain, then the obvious solution is African population substructure.

Mol Biol Evol (2010) doi: 10.1093/molbev/msq265

Deep divergences of human gene trees and models of human origins

Michael GB Blum and Mattias Jakobsson

Two competing hypotheses are at the forefront of the debate on modern human origins. In the first scenario, known as the recent Out-of-Africa hypothesis, modern humans arose in Africa about 100,000-200,000 years ago, and spread throughout the world by replacing the local archaic human populations. By contrast, the second hypothesis posits substantial gene flow between archaic and emerging modern humans. In the last two decades, the young time estimates – between 100,000 and 200,000 years – of the most recent common ancestors for the mitochondrion and the Y-chromosome provided evidence in favor of a recent African origin of modern humans. However, the presence of very old lineages for autosomal and X-linked genes has often been claimed to be incompatible with a simple, single origin of modern humans. Through the analysis of a public DNA sequence database, we find, similar to previous estimates, that the common ancestors of autosomal and X-linked genes are indeed very old, living, on average, respectively 1,500,000 and 1,000,000 years ago. However, contrary to previous conclusions, we find that these deep gene genealogies are consistent with the Out-of-Africa scenario provided that the ancestral effective population size was approximately 14,000 individuals. We show that an ancient bottleneck in the Middle Pleistocene, possibly arising from an ancestral structured population, can reconcile the contradictory findings from the mitochondrion on the one hand, with the autosomes and the X-chromosome on the other hand.

Link

ADMIXTURE on African HapMap populations

Here is the result of running ADMIXTURE on the three African HapMap-3 populations, using about 440K SNPs, including Tuscans as a non-African group.

The Tuscans are in purple and show no trace of African admixture. All the other populations are separated: red: Luhya (Bantu); green: Maasai (Nilotes); Yoruba (Niger-Congo).

The two east African groups show asymmetrical affinities: the Maasai have some Luhya red, while the Luhya have little Maasai green, while they have substantial West African turqoise, consistent with the origin of their Bantu language.

Related: ADMIXTURE on HapMap-3 populations

Utah Whites vs. Tuscans with 1.5 millions SNPs

This time I took the full ~1.5M SNPs and ran ADMIXTURE on two HapMap-3 European populations, CEU Utah Whites and Tuscan Italians. I sorted the individuals based on their ancestral proportions, but still the cutoff is quite obvious, and the separation is perfect.

CEU belong to the blue cluster with 93.7%, and TSI in the red one with 94.9%.

The most red Utah White has 31.4% "southern" ancestry, while the most blue Tuscan has 21.2% "northern" ancestry. Thus, the cutoff "jump" between the two populations, at the middle of the figure, is 47.4%.

The standard deviation of the "southern" component among CEU individuals is 6.9%, and the standard deviation of the "northern" component among Tuscans is 5.7%.

How real is this "admixture"?

As I have mentioned before in the blog, apparent "mixedness" between populations decreases as the number of markers increases. Thus, the question arises: is the apparent "admixture" between Tuscans and Utahns a real effect of individuals diverging toward a population other than their own, or an artefact of a limited number of markers?

We should note that increasing the number of markers has diminishing returns: most new markers are in linkage disequilibrium with existing markers, and hence provide little additional information: going from 10 to 110 markers has a huge effect, but going from 1000 to 1100 a trivial one.

To study this question I took a 1/5 random sample of the markers, or about 300K SNPs and repeated the ADMIXTURE run:

Now, CEU are 93.9% in the blue cluster (vs. 93.7% in the 1.5M run) and the variance of the red component in CEU individuals is 6.8% (vs. 6.9% in the 1.5M run).

Tuscans are 94.0% in the red cluster (vs. 94.9% in the 1.5M run) and the variance of the blue component in TSI individuals is 6.5% (vs. 5.7% in the 1.5M run).

The conclusion is obvious that the 5-fold increase in markers from 300K to 1.5M had no noticeable effect in the apparent mixedness of populations and individuals.

ADMIXTURE in the New World

Here is the result of running ADMIXTURE on ~450K markers on six HapMap-3 populations; left-to-right: African Americans from the Southwest (ASW), Utah Whites (CEU), Beijing Chinese (CHB), Mexicans from Los Angeles (MEX), Toscans (TSI), and Yoruban from Nigeria (YRI).

Here are the admixture proportions (in %):

It is obvious, however, from the ADMIXTURE plot above, and the triangle plots below (for ASW and MEX), that the admixture is not uniformly distributed.

Notice the two African American individuals with substantial Amerindian admixture (14 and 29%), while the rest are a simple 2-way mix of Europeans and Sub-Saharans with minor Amerindian admixture in some of them. The standard deviation of European admixture is 8.3%, lower than in Mexicans.

Mexicans are variable in terms of their European-Amerindian mix, but with less variable tiny Sub-Saharan component (0.6% with a standard deviation of 1.2%). This is probably due to the fact that blacks were absorbed earlier in Mexico, while European-Amerindian social stratification and continued European immigration has fueled the retention of considerable variation. European admixture in Mexicans is 27.7% on average, but with a standard deviation of 24.0% and minimum/maximum value of 0.0 to 90.5% in the sample I am considering.

Eva Longoria, for example, who recently learned that she is 70% European in "Faces of America" belongs to the top-5% of Mexican American "European-ness", although there is probably considerable variation of Mexican Americans within the country.

ADMIXTURE on HapMap 3 populations

Here is the result of running ADMIXTURE on about ~50K markers from the HapMap 3 populations. I'll annotate the final K=9 run; the rest are given at the end:

I list the distinctive colors for the populations, Left-to-Right. The minor components are easy enough to pick up and as expected:

ASW (A): African ancestry in Southwest USA [Sub-Saharan blue]

CEU (C): Utah residents with Northern and Western European ancestry from the CEPH collection [European yellow]

CHB (H): Han Chinese in Beijing, China [East Asian orange]
CHD (D): Chinese in Metropolitan Denver, Colorado [East Asian orange]

GIH (G): Gujarati Indians in Houston, Texas [South Asian purple]

JPT (J): Japanese in Tokyo, Japan [East Asian light green]

LWK (L): Luhya in Webuye, Kenya [East African bright green]

MEX (M): Mexican ancestry in Los Angeles, California [Amerindian pink]

MKK (K): Maasai in Kinyawa, Kenya [East African light blue]

TSI (T): Tuscan in Italy [European yellow]

YRI (Y): Yoruban in Ibadan, Nigeria (West Africa) [Sub-Saharan blue]

The rest of the runs for K=3 to K=8 are below:

K=3: Notice: Asian red+Caucasoid blue on Gujarati Indians and Mexicans. At this level of resolution, these two populations look similar. Notice presence of blue in East Africans but not Yorubans (green at the end).

K=4: East Africans get their own (yellow) cluster. Notice the diminution of the Sub-Saharan (purple) element, relative to the previous figure. This is due to the fact that the East African element is intermediate between Caucasoids and Sub-Saharans and "eats up" the other two elements, although residual Caucasoid red and Sub-Saharan purple remains. The tripartite origin of Mexicans is especially visible in this plot, with components being in order of European, East Eurasian, Sub-Saharan.
K=5: Gujarati Indians now get their own (purple) cluster. Here the difference between Luhya (mostly Sub-Saharan blue + East African yellow) and Maasai (the reverse) is quite striking. The former are Bantu speakers and thus not indigenous to east Africa.
K=6: Mexicans get their own cluster (blue) reflecting their Amerindian, rather than East Asian ancestry which could not be resolved in the previous figures.
K=7: the Luhya get their own cluster, splitting off from the Maasai. There are now 3 components in Africa centered on Yorubans (light blue), Luhya (very light green) and Maasai (red).
K=8: A low-frequency element appears in Maasai that is hard to interpret; it is preserved in the next and final K=9 run (shown at the beginning of the post), in which the Japanese and Chinese are split off.

Eurasian ADMIXTURE (a precursor to Eurasian-DNA-Calc?)

(Last Update: Oct 8; K=7 added)

I took the 540,814 markers from the HGDP dataset that are also included in the 23andMe personal genomics test, and that have less than 1% no-call rate.

I ran ADMIXTURE on all the West- (and some mainly Caucasoid Central-) Eurasian populations, including Yoruba and Han Chinese to account for non-Caucasoid admixture in parts of Eurasia.

The populations are (left-to-right): Tuscan, North Italian, Sardinian, French, French Basque, Orcadian, Russian, Adygei, Palestinian, Bedouin, Druze, Mozabite, Pathan, Sindhi, Balochi, Brahui, Burusho, Yoruba, Han Chinese.

Here are the admixture proportions corresponding to this experiment:

This seems like a good starting point for the new EURASIAN-DNA-CALC I have in the works.

Relative to the existing EURO-DNA-CALC, doubling the number of ancestral populations (from 3 to 6), and increasing the number of SNPs (by 3 orders of magnitude) introduces some obvious computational problems. I have some ideas on how to resolve them, so stay tuned.

APPENDIX

For the sake of completeness here are the ADMIXTURE runs for K=3 to K=5.

At K=3, the three major races (Caucasoid: green, Mongoloid: red, Negroid: blue) emerge.

At K=4, the Caucasoids are split into West Eurasians (red) and Central Asians (purple)
At K=5, the West Eurasians are split into Europeans (yellow) and West Asians (blue)

PS: I will probably do some ADMIXTURE runs for K=7 and higher in the next few days; the results will be posted in this blog post as an update.

UPDATE (K=7)

The Druze get their own cluster (pink) with an average membership of 65.4% of Druze individuals

Y chromosomes of Vlax Roma

From the paper:

The Gypsies arrived in Europe 900–1100 years ago, when they first appeared in the Balkans. The present-day Gypsy population groups in Europe are the compound product of the early migrations from the Balkans into Europe [1]. The Gypsies came to Hungary from the Balkans in two large migrations. The Carpathian Romanies arrived in the 15th century and the Vlax Romanies came in the 19th century. The Carpathian Gypsies speak Hungarian and the Vlax Romanies speak Hungarian and Romani languages.

Interesting:

A median-joining (MJ) network of haplogroup H1a-M82 has demonstrated the sharing of identical Indian specific Y-chromosomal lineages between all Romani populations including Malaysian Indians as well as the Vlax Romanies (Fig. 2A and B). This common lineage of haplogroup H1a-M82 represents a common descent from a single ancestor providing a strong genetic link to the ancestral geographical origin of the proto-Gypsies [1]. According to Sengupta et al. [24] the age of microsatellite variation within haplogroup H1 in Indian populations is more than 9.7 +/- 4.4 ky. This time was estimated to be 992 years (95%CI 425–3472) in the Romani populations investigated by Gresham et al. [1] suggesting the Indian H1 haplogroup is the ancestral one.

Gresham et al. (pdf) used the genealogical mutation rate. Hence, the discrepancy between the Sengupta et al. age estimates and their own is partly due to the choice of mutation rate. Nonetheless, it's obvious that the Balkan H1 is still 3 times younger than the Indian one, and obviously of South Asian origin. Notice also how the Gresham et al. paper gives a large confidence interval for its estimate, in agreement with my observations about the inadequacy of a limited number of Y-STRs, and Y-STRs in general to couple tightly with historical events.

Nonetheless, if one uses an order-of-magnitude approach, the Gresham et al. estimate is quite compatible with historical knowledge about the arrival of Gypsy founders to the Balkans, just as was the case for Serbian Roma.

The ~1ky estimate for Balkan Gypsy H1 is similar to the ~1ky estimate for the updated J1 Cohen Modal Haplotype. For reasons explained in that post, this is probably an overestimate, and I can envision a scenario according to which the tribal descendants of an H1-man who lived in the 1st millennium AD made their way to Europe at the turn of the millennium, proliferating into the Gypsy communities of today.

Related:

• Y-chromosome study of Serbian Roma
• Y chromosomes of Iberian Gypsies
• Y chromosomes of Bayash Romani
• Y-chromosomes of Albanian populations (Ferri et al. 2010)

Forensic Science International: Genetics doi:10.1016/j.fsigen.2010.08.017

Paternal genetic history of the Vlax Roma

Andrea Zalán et al.

Romanies constitute the largest minority group belonging to different subgroups in Hungary. Vlax Romanies are one of these Romani subgroups. The Gypsies came to Hungary from the Balkans in two large migrations. The Carpathian Romanies arrived in the 15th century and the Vlax Romanies came in the 19th century. The Carpathian Gypsies speak Hungarian and the Vlax Romanies speak Hungarian and Romani languages.
Only a limited number of genetic studies of Y-chromosomal haplotypes/haplogroups have been done before, moreover most studies did not contain information regarding the investigated Roma populations which subgroups belong to.
In the present study, we analyzed a wide set of Y-chromosomal markers to do comparable studies of the Vlax Roma in eastern Hungarian regions. The results can be compared in the context of previously published data on other Romani groups, Indian and Hungarian reference populations.
Haplogroups H1a-M82 and J2a2-M67 were most common in the investigated population groups. A median-joining network of haplogroup H1a-M82 has demonstrated the sharing of identical Indian specific Y-chromosomal lineages between all Romani populations including Malaysian Indians as well as the Vlax Romanies. This common lineage of haplogroup H1a-M82 represents a common descent from a single ancestor provides a strong genetic link to the ancestral geographical origin of the proto-Gypsies.
The detected haplogroups in the Vlax Romani population groups can be classified into two different Y-chromosomal lineages based on their putative origin. These lineages include ancestral Indian (H1a-M82), present-day Eurasian (J2a2-M67, J2*-M172, E1b1b1a-M78, I1-M253, R1a1-M198 and R1b1-P25) Y-chromosome lineages. Presence of these lineages in the paternal gene pool of the Roma people is illustrative of the Gypsy migration route from India through the Balkan to the Carpathian Basin.

PopAffiliator: estimating origin with forensic autosomal STRs

Anders Pålsen alerts me to PopAffiliator, a neat little tool that guesses the origin of a sample from one of several major population groups:

The STR collection database used to train and evaluate the machine learning model encompasses data gathered from more than 40 different studies and contains a total of 56,222 individuals, distributed by 7 major geographical locations: East Asia, Eurasia, sub-Saharan Africa, North Africa, Near East, Central-South America and North America. The data is available here.

The tool uses 17 forensic autosomal STR markers. This may seem like too little in this day and age, but it is sufficient for the purpose at hand.

A few years ago someone had posted at the dna-forums site -I can't seem to find the topic today- a STRUCTURE-based calculator on mostly the same markers. That calculator contained 500 German/500 Chinese/500 African individuals:

• Group 3=Africans
• Group 2=Chinese
• Group 1=Germans

Back then, I ran STRUCTURE on the data yielding the following results:

1: 0.041 0.025 0.934 500
2: 0.949 0.012 0.039 500
3: 0.019 0.955 0.026 500

If we look at the 1,500 individuals, it turns out that correct "guess" of a person's origin (i.e., his maximum inferred cluster membership coefficient corresponding to the real one) occurred in 497/500 Africans, 491/500 Chinese, and 490/500 Germans.

Pretty good! Typing hundreds of thousands of SNPs to guess if someone is East Asian, European, or Sub-Saharan African is overkill, and there is already widespread forensic profiling of numerous human populations, so why not amortize all this data?

The problem with using so few numbers isn't that they are insufficient to guess one's origin, but that they are insufficient to estimate admixture, if present. Here is the triangle plot from my aforementioned mini-experiment:

If hundreds of thousands of SNPs had been used, the red, green, and blue dots would be gathered in tight clusters in the three corners, with the occasional individual deviating in a different direction. Nonetheless it's also clear that very few individuals deviate beyond the 50% cutoff from their true origin, which might fool one into assigning them to the wrong population.

Since I have some autosomal test data of my own, I decided to give PopAffiliator a try.

The link to PopAffiliator will go to the right sidebar of the blog.

INTERNATIONAL JOURNAL OF LEGAL MEDICINE
DOI: 10.1007/s00414-010-0472-2

PopAffiliator: online calculator for individual affiliation to a major population group based on 17 autosomal short tandem repeat genotype profile

Luísa Pereira et al.

Because of their sensitivity and high level of discrimination, short tandem repeat (STR) maker systems are currently the method of choice in routine forensic casework and data banking, usually in multiplexes up to 15–17 loci. Constraints related to sample amount and quality, frequently encountered in forensic casework, will not allow to change this picture in the near future, notwithstanding the technological developments. In this study, we present a free online calculator named PopAffiliator (http://cracs.fc.up.pt/popaffiliator) for individual population affiliation in the three main population groups, Eurasian, East Asian and sub-Saharan African, based on genotype profiles for the common set of STRs used in forensics. This calculator performs affiliation based on a model constructed using machine learning techniques. The model was constructed using a data set of approximately fifteen thousand individuals collected for this work. The accuracy of individual population affiliation is approximately 86%, showing that the common set of STRs routinely used in forensics provide a considerable amount of information for population assignment, in addition to being excellent for individual identification.

Link

French cattle in global genomic context

The congruence of cattle breeds with inferred clusters is remarkable. K=47 frappe analysis is probably testing the limits of human visual perception...

PLoS ONE 5(9): e13038. doi:10.1371/journal.pone.0013038

Insights into the Genetic History of French Cattle from Dense SNP Data on 47 Worldwide Breeds

Mathieu Gautier et al.

Abstract
Background
Modern cattle originate from populations of the wild extinct aurochs through a few domestication events which occurred about 8,000 years ago. Newly domesticated populations subsequently spread worldwide following breeder migration routes. The resulting complex historical origins associated with both natural and artificial selection have led to the differentiation of numerous different cattle breeds displaying a broad phenotypic variety over a short period of time.

Methodology/Principal Findings
This study gives a detailed assessment of cattle genetic diversity based on 1,121 individuals sampled in 47 populations from different parts of the world (with a special focus on French cattle) genotyped for 44,706 autosomal SNPs. The analyzed data set consisted of new genotypes for 296 individuals representing 14 French cattle breeds which were combined to those available from three previously published studies. After characterizing SNP polymorphism in the different populations, we performed a detailed analysis of genetic structure at both the individual and population levels. We further searched for spatial patterns of genetic diversity among 23 European populations, most of them being of French origin, under the recently developed spatial Principal Component analysis framework.

Conclusions/Significance
Overall, such high throughput genotyping data confirmed a clear partitioning of the cattle genetic diversity into distinct breeds. In addition, patterns of differentiation among the three main groups of populations—the African taurine, the European taurine and zebus—may provide some additional support for three distinct domestication centres. Finally, among the European cattle breeds investigated, spatial patterns of genetic diversity were found in good agreement with the two main migration routes towards France, initially postulated based on archeological evidence.

Link

Turks to destroy the archaeological site of Allianoi

Ancient Roman spa awaits flooding in Turkey

By Nicolas Cheviron (AFP) – 15 hours ago

ALLIANOI, Turkey [correct: occupied Asia Minor] — Under a mild autumn sun, workers bustle about like bees at a Roman bath complex sprawling over a green plain in western Turkey in what looks like a regular excavation site.

But the fate awaiting the impressive ancient spa of Allianoi is dark: the workers here are tasked with burying the site and not digging it out to reveal its secrets.

Much to the consternation of archaeologists and civic bodies, the Turkish government has said it will go ahead with flooding the valley the site sits in to serve as a dam reservoir with a capacity to irrigate 8,000 hectares (19,760 acres) of farmland.

The work now underway is an effort to preserve the complex for future generations, before officials allow water to accumulate in the reservoir for the Yorganli dam before the end of the year.

As archaeologists -- denied entry to the site -- mourn the loss of a significant treasure, workers dump wheelbarrows of sand over the foundations of the hospital of Galen, a prominent Roman physician born in the 2nd century AD in the nearby city of Pergamon, or modern-day Bergama.

Soon the thermal bath -- with its five metre-high (17 feet-high) walls and a pool still powered by a hot spring -- will disappear under the sand, after being covered with a pinkish protective coating, along with buildings looking out over a columned courtyard, rooms covered with mosaics and paved walkways.

It is a sad sight for Professor Ahmet Yaras who excavated Allianoi for nine years and who says 80 percent of the site has yet to see the daylight.

"Normally, cultural treasures need to be examined and registered before any action is taken on a site. Here, flooding the site before the excavation is complete is a massacre," lamented the archaeologist.

"There is no other warm bath, health center in the world as well preserved as this... Unfortunately, all this will be abandoned forever," he said.

Furthermore, Yasar expressed doubt that the sand will be enough to preserve the site under 30 metres of water.

"Even if the site were protected, the sedimentation brought by the dam will reach 15 or 16 meters in 50 years time. It would be crazy to try to excavate the complex again at such a depth," he added.

But the fate of the site is not much of a concern for the farmers at the nearby village, who see the Yorganli dam -- completed in 2007 -- as the answer to their irrigation problems.

"They exaggerate, I do not think there is much of the ancient there. It is just a hot spring," said Mehmet Aydin, 52, who grows cotton, tomatoes and corn on his plot.

His remarks almost echo the views of Environment Minister Veysel Eroglu who said in late August: "Allianoi does not exist, it is an invention... There is just a hot spring like many others across Turkey."

His remarks were roundly criticized while the International Council on Monuments and Sites (ICOMOS), the European non-governmental preservation organization Europa Nostra and archaeologists from the European Union urged the Turkish government in a letter to preserve the "common [correct: Greco-Roman] heritage" at Allianoi.

But the game seems to be over: Culture Minister Ertugrul Gunay quashed hope of saving Allianoi last week when he dismissed the idea of questioning the local archaeological commission's decision in late August to bury the site for preservation.

"After all, Allianoi remained underground for a long time and it surfaced only during drilling works," he said.

Some ADMIXURE estimates on Eurafricans

Here is an ADMIXTURE run on the Xing et al. (2010) dataset using markers with less than 1% genotyping no-calls. Populations (left-to-right) are: Alur, Hema, Luhya (from Africa), and CEU, Tuscan, Slovenian, Urkarah, and Kurdish (from Western Eurasia).

Most West Eurasians have no trace of Sub-Saharan ancestry, except Kurds (estimated here at 2.3% overall, range: 1-3.6%), and a couple of Slovenians (4.5% and 1.6%, overall 0.2%). The fairly uniform distribution in Kurds suggests to me that this is an ancient phenomenon reflecting gene flow between the Near East and Africa and not a recent phenomenon.

The Hema are an African population exhibiting West Eurasian affinities (11.0%, range: 4.2-15.2%). Consult my comments on the original Xing et al. article on some information on these Nilo-Saharan pastoralists from the Democratic Republic of Congo.