Yunusbaev_The Caucasus as an Asymmetric Semipermeable Barrier to Ancient Human Migrations

5/26/2018 Yunusbaev_The Caucasus as an Asymmetric Semipermeable Barrier to Ancient Human Migrations

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The Caucasus as an Asymmetric Semipermeable Barrier to Ancient Human Migrations

Bayazit Yunusbaev1,2,3*, Mait Metspalu1*, Mari Jrve1*, Ildus Kutuev1,2, Siiri Rootsi1, Ene

Metspalu1, Doron M. Behar1, Krt Varendi1, Hovhannes Sahakyan1,4, Rita Khusainova2,3,

Levon Yeppiskoposyan4, Elza K. Khusnutdinova2,3, Peter A. Underhill5, Toomas Kivisild1,6,

Richard Villems1

1Department of Evolutionary Biology, University of Tartu and the Estonian Biocentre, Tartu, Estonia

2Institute of Biochemistry and Genetics, Ufa Research Center, Russian Academy of Sciences, Ufa, Russia

3Department of Genetics and Fundamental Medicine, Bashkir State University, Ufa, Russia

4

Institute of Molecular Biology of the Academy of Sciences of Armenia, Yerevan, Armenia

5Department of Psychiatry and Behavioral Sciences, Stanford University School of Medicine, Stanford, USA

6Leverhulme Centre for Human Evolutionary Studies, University of Cambridge, Cambridge, UK

*These authors contributed equally to this work


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eastern from western North Caucasians. Variation within the autosomal genome is

consistent with predominantly Near/Middle Eastern origin of Caucasians, with minor

external impacts. Genetic discontinuity between North Caucasus and the East European

Plain contrasts with continuity through Anatolia and Balkans, suggesting major routes

of ancient gene flows and admixture.

The Caucasus is a mountainous region between the Black and Caspian Seas, divided by the

High Caucasus Mountain Range into the North and South Caucasus. The earliest evidence of

the dispersal of the genusHomooutside Africa comes from the Caucasus (1, 2); anatomically

modern humans appeared there at least 42,000 years ago (3). The linguistic diversity in the

Caucasus is remarkably high (4). The Abkhazian-Adyghe (Northwest (NW) Caucasian),

Nakh-Dagestanian (Northeast (NE) Caucasian) and Kartvelian (South Caucasian) language


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Irrespective of their languages, in our heatmap plot of pairwise FST, the Caucasus populations

show the lowest genetic distances to one another (7), followed closely by their distance to the

populations of the Near/Middle East, Turks in particular (Figure 2A). Meanwhile, a sharp

increase of genetic distance progressing from the Caucasus to the East Europe Plain is evident

(Figure 2A). The Indo-European-speaking Armenians and Ossetians follow the same pattern

and do not show higher genetic similarity to Indo-European-speaking populations from

Europe or the Near/Middle East. Similarly, the populations of the Caucasus cluster together

between their neighbors according to geography on the two-dimensional plots of the principal

components (PC) of autosomal variation (Figure 2B; Figure S1). Importantly, in contrast to

the continuous transition from the Near/Middle East to the Caucasus, there is a noticeable gap

between the Caucasus and the East European Plain (Figure 2B). Geography rather than

language based clustering can also be observed in the PC analysis of Y chromosome data

(Fi S2) I d d l t i f G i h b l t K t li f il f


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We analyzed the autosomal data of the Caucasus and reference populations (5, 6) using a

structure-like (9) clustering approach (10). At K=7, the major ancestry component of the

Caucasus populations (shown in blue) has comparable presence in the Near/Middle East, but

is almost absent among the immediate northern neighbors of the Caucasus the populations

of the East European Plain (Figure 3; Figure S4). Similarly to the blue ancestry component,

the green component is also ubiquitously present among the Caucasus populations,

irrespective of their linguistic affinities, but at much lower frequencies than blue. The green

component is most frequent in the Indus basin (Pakistan), extending to Central Asia and the

Near/Middle East, while fading away in Europe. Although structure-like clustering cannot be

readily interpreted into (human) migrations, this pattern might suggest a gene flow from

South Asia to the west and northwest. We cannot point to any well documented evidence of

such events during the historic period. However, the noticeable presence in NE Caucasus of

th Y h h l L3 f f d l i P ki t (11) d N th I (12)


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Hurrians-Urartians, the gene flow postulated here may equally well antedate the arrival of the

Armenian language to the area.

The mountain range that divides the Caucasus into the North and South Caucasus has

apparently not been an impenetrable barrier for gene flows. This is illustrated by the relative

similarity of the ancestry component patterns of the Caucasus populations on either side of the

High Caucasus Mountain Range (Figure 3). However, the dark blue ancestry component,

dominant among the Slavic-, Turkic-, and Finnic-speaking East European Plain populations,

reaches the North Caucasus (10-20%), but just barely (~5%) crosses the High Caucasus to the

three linguistically distinct South Caucasus populations Armenians, Georgians and

Abkhazians (Figure 3). Remarkably, the decrease of Y chromosome haplogroup G and J1

frequencies towards the Eastern European populations inhabiting the area adjacent to the

N th C h th R i d Uk i i (14 15) f b t


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on distance matrices (18, 19) to analyze our whole genome data in order to test whether

factors other than geographic distance can explain the observed variation in genetic distances

between populations. Considering pairwise FSTdistances between populations, we tested

independent variables which are expected to increase genetic differentiation and thus impact

the linear relationship between geographic and genetic distance, defining them as putative

barriers (7, Table S4, supporting online text). Three of the putative barriers we tested first

were geographic the Caucasus barrier between North Caucasus and Eastern Europe, the

Balkans barrier between Anatolia and Europe, and the South Asian barrier between South

Asia and the Near/Middle East. The other barriers tested separated populations that are known

isolates/outliers due to religion, language, or different origin the Jewish groups, Kuban

Nogays, French Basques, Druze, and Burusho from their respective surrounding

populations. Geographic distance by itself explained only 43% (coefficient of determination r2

0 43) f th i ti i ti di t b t l ti d b F Th


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Black and Caspian Seas dated 1214,000 years BP (20, 21) which may have served as a

natural barrier (supporting online text).

The Kuban Nogays and the Kara Nogays (Figure 1) have a special status among the

Caucasian populations due to their recent, late 18th early 19thcentury arrival from the

Pontocaspian steppes (22), evident from both Y chromosome and autosomal PC plots (Figure

S2; Figure 2B) as well as ADMIXTURE analysis (Figure 3) (only the Kuban Nogays were

included in the autosomal analyses). It has been shown that the Nogays possess 40% of East

Eurasian mtDNA lineages (23). Comparing the two subpopulations with respect to

proportions of typical western Eurasian (G, J, R1a1) and eastern Y chromosome lineages (C,

D, N, O), it becomes apparent that the Kara Nogays have more (~35%) typical eastern Y

chromosome lineages, while among the Kuban Nogays the percentage is around 17% (Table

S2) P h i t ti l h f d th t b th th K b N d th K


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levels of between-population differentiation, with an average FSTof 0.113, a value which is

almost as large as the FSTof 0.157 for worldwide populations (25). Our results, based on

genome-wide data, reveal instead that the populations of the Caucasus region show between

population differentiation (average FST= 0.004) that is slightly lower than that of the Near

East (0.006) and of Europe (0.006), and are thus more consistent with the results of Bulayeva

et al.(26). Whereas the Y chromosome haploid system reveals some cases of high

differentiation between regions and/or individual populations in the Caucasus, such as the

separation of the Dagestanian-speaking NE Caucasian populations from the rest of the region

(Figure S2), the autosomal variation in the Caucasus matches geography rather than linguistic

divisions. While the variation of all three genetic systems analyzed here autosomal, Y

chromosome, and mtDNA shows a genetic continuity between the Caucasus and the

Near/Middle East, there is a clear discontinuity, supported by principal component,

ADMIXTURE d lti l i l b t th N th C d th E t


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Semitic speakers of the Near East and the Arabian Peninsula (Figure 3), having been carried

to the Caucasian populations by route or routes unknown at present.

We conclude that irrespective of the Early Upper Paleolithic presence of anatomically modern

humans both south and north of the Caucasus, the combined high-resolution autosomal and

gender-specific genetic variation of the Caucasian populations testifies to their predominantly

southern, Near/Middle Eastern descent. Y chromosomal variants under strong founder events,

seen in particular among populations inhabiting the northern flank of the High Caucasus

Mountain Range, appear to never have expanded to the East European Plain, while the

nomadic people of the latter, once settled down predominantly on the northern slopes of the

Caucasus, have preserved, to different extent, some of their earlier genetic heritage. In sum,

though the Caucasus may well have served as a corridor for invasive expeditions in the past,

thi h h d l i i fl th l l d t l ti f th i


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Figure legends

Figure 1. Geographical map of the populations of the Caucasus included in this study.

The language family affiliation of each population is given. Adapted from Wikipedia.

Figure 2. Pairwise FSTdistances and principal component analysis of the Caucasus and

neighboring populations.

APairwise FSTdistances between populations, ranging from red (low) to blue (high), based

on autosomal data. The populations [data from this study and the literature (5, 6)] are divided

into regional groups. BPlot of the first and second components of the principal component

analysis (27) of the Caucasus and neighboring populations based on autosomal data, with the

clustering of populations approximating geography. The thick lines denote probable directions

f t f l i t t d b t th N th C d E t E


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References

1. D. Lordkipanidze et al., Postcranial evidence from early Homo from Dmanisi, Georgia.Nature449, 305-310 (2007).

2. D. E. Lieberman, Palaeoanthropology: homing in on early Homo.Nature449, 291-292(2007).

3. D. S. Adler et al., Dating the demise: neandertal extinction and the establishment ofmodern humans in the southern Caucasus.J. Hum. Evol.55, 817-833 (2008).

4. B. Comrie, Linguistic Diversity in the Caucasus.Annu. Rev. Anthropol.37, 131-143(2008).

5. J. Z. Li et al., Worldwide human relationships inferred from genome-wide patterns ofvariation. Science319, 1100-1104 (2008).

6. D. M. Behar et al., The genome-wide structure of the Jewish people.Nature466, 238-242(2010).

7. Materials and methods are available as supporting material on ScienceOnline.8. E. E. Marchani, W. S. Watkins, K. Bulayeva, H. C. Harpending, L. B. Jorde, Culturecreates genetic structure in the Caucasus: autosomal, mitochondrial, and Y-chromosomal

variation in Daghestan.BMC Genet.9, 47 (2008).

9. J. K. Pritchard, M. Stephens, P. Donnelly, Inference of population structure usingmultilocus genotype data. Genetics155, 945-959 (2000).

10.D. H. Alexander, J. Novembre, K. Lange, Fast model-based estimation of ancestry inunrelated individuals. Genome Res.19, 1655-1664 (2009).

11 S S t t l P l it d t lit f hi h l ti h di t ib ti


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21.A. A. Svitoch, Khvalynian transgression of the Caspian Sea was not a result of wateroverflow from the Siberian Proglacial lakes, nor a prototype of the Noachian flood.

Quatern. Int.197, 115-125 (2009).22.M. Kolga, I. Tnurist, L. Vaba, J. Viikberg, The Red Book of the Peoples of the Russian

Empire. (NGO Red Book, Tallinn, ed. 2, 2001).

23.M. A. Bermisheva et al., Phylogeografic analysis of mitochondrial DNA in the Nogays:the high level of mixture of maternal lineages from Eastern and Western Eurasia. Mol.

Biol. (Mosk.)38, 617-624 (2004).

24.T. Zerjal et al., The genetic legacy of the Mongols.Am. J. Hum. Genet.72, 717-721(2003).

25.I. Nasidze et al., Alu insertion polymorphisms and the genetic structure of humanpopulations from the Caucasus.Eur. J. Hum. Genet.9, 267-272 (2001).

26.K. Bulayeva et al., Genetics and population history of Caucasus populations.Hum. Biol.75, 837-853 (2003).

27.N. Patterson, A. L. Price, D. Reich, Population structure and eigenanalysis. PLoS Genet.2, 2074-2093 (2006).

28.We thank the individuals who provided DNA samples for this study, and Mari Nelis,Georgi Hudjashov and Viljo Soo for conducting the autosomal genotyping. R.V. andD.M.B. thank the European Commission, Directorate-General for Research for FP7

Ecogene grant 205419. R.V. thanks the European Union Regional Development Fund for

support through the Centre of Excellence in Genomics, the Estonian Ministry of

Education and Research for the Basic Research grant SF 0270177As08, and the Swedish

Collegium for Advanced Studies for support during the initial stage of this work. S.R.

thanks the Estonian Science Foundation for grant 7445. E.M. thanks the Estonian Ministry

f Ed ti d R h f th B i R h t SF 0270177B 08 d th


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Tuscans

N Italians

Romanians

Bulgarians

Lithuanians

Belorussians

Ukrainians

Chuvashes

Mordvins

Russians

Kuban Nogays

N Ossetians

Kumyks

Balkars

Lezgins

Chechens

Adyghe

Abkhazians

GeorgiansArmenians

Iranians

Turks

Syrians

Lebanese

Jordanians

Palestinians

Druze

Bedouins

Saudis

Fig 2

A Near/Middle East Caucasus East Europe

West & South

Europe


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Ba

ntuSA

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Yo

rubans

Mandenkas

Ethiopians

Egyptans

Saudis

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Druze

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anians

Lebanese

Syrians

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French

FrenchB

asques

North

Italians

T

uscans

Rom

anians

Bulgarians

Ukr

ainians

Belorussians

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anians

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Chu

vashes

Arm

enians

Georgians

Abkhazians

Balkars

A

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setans

Chechens

Lezgins

Kuban

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Africa Near East & Europe

South North

The Caucasus Cen. Asia South Asia East Asia

IE KV AA IE ND TUK = 7

Fig 3


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Supporting Online Material

Materials and Methods

DNA samples from all the subregions and major language groups of the Caucasus were

analyzed, using whole genome, Y chromosome and mtDNA markers. The geographic

locations and language affiliations of the Caucasus populations studied are presented in

Figure 1. DNA samples were obtained from unrelated male volunteers after getting informed

consent in accordance with the guidelines of the ethical committees of the institutions

involved. DNA was purified from blood by the phenol/chloroform extraction method. DNA

concentrations were determined by spectrometry (NanoDrop products, Wilmington, DE,


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We used PLINK software 1.05 (5) to filter the combined dataset to include only SNPs on the

22 autosomal chromosomes with minor allele frequency >1% and genotyping success >97%.

Because background linkage disequilibrium (LD) can affect both principal component and

structure-like analysis, we thinned the marker set by excluding SNPs in strong LD (pairwise

genotypic correlation r2>0.4) in a window of 200 SNPs (sliding the window by 25 SNPs at a

time). The final data set consisted of 210,575 SNPs and 1119 individuals that were used in

subsequent analyses.

We explored the population structure at K=3 to K=10. To monitor convergence between

individual runs at each K we ran ADMIXTURE one hundred times and examined the

loglikelihood (LL) values of a ten percent fraction of runs with the highest LL yield at each K.

We assumed that the global maximum had been reached if the maximum difference between

those LL values was negligible (less than one LL unit) (2, 6). Since this was the case for all

t t d l f K d d th lt t b bl d l tt d lt f i th


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virtually identical values, converged at respective global maxima, and are thus usable

representations of genetic structure at different levels (Figure S4).

Principal component analysis and FST

Since the principal component analysis (PCA) method assumes that markers are unlinked, we

thinned our marker set for this analysis with PLINK software 1.05 (5) according to the same

parameters used for genetic clustering analysis in order to mitigate background LD. However,

LD pruning was carried out after the exclusion of the populations from Africa (except

Egyptians), East Asia and Siberia, and also Hazaras, Kurds, Uygurs and Altaians, resulting in

a final data set of 189,747 markers and 838 individuals. PCA was carried out in the smartpca

program (8) using outlier removal procedure (18 outliers were removed, leaving 820

individuals). Pairwise genetic differentiation indices (FSTvalues) were also estimated using

t ft b d th thi d k t


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Multiple regression on distance matrices

We used multiple regression on distance matrices (MRM) (11, 12) to explore various

explanatory variables (genetic distance, barriers to gene flow) predicting the genetic distances

between populations. In this method a single dependent distance matrix Yis considered as a

function of multiple independent distance matrices Xi(independent variables), and the

statistical significance of regression coefficients for each independent variable Xiis tested

based on matrix permutations (13). The corresponding permutation procedure is described in

Legendre et al.(13) and implemented in the ecodist R package (14).

In order to test whether factors other than geographic distance can explain the observed

variation in genetic distances between populations and whether the contribution of each

variable is statistically significant, we considered a matrix of pairwise FSTdistances between

populations as a response matrix and included explanatory variables into the regression model

ith t l i bi ti A i t f i d d t i bl h t ti


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X3: Putative barrier separating South Asia from the Near/Middle East.

X4: Zero distances between the isolated Jewish communities and distances of 1 between the

Jews and the populations surrounding them.

X5: Putative barrier separating the Kuban Nogays and the French Basques from other

populations.

X6: Putative barrier separating the Druze from other populations.

X7: Putative barrier separating the Burusho from other populations.

Y chromosome analyses

A total of 1952 samples from 24 populations from the Caucasus were analyzed for Y

chromosome markers. The samples were typed for 51 Y chromosome SNP markers, 2 of

which [M81 and M128 (15)] were found to have the ancestral state in all of the samples. The

t f th k 12f2 (16) YAP (17) SRY (18) T t (19) 92R7 (20) M9 M12


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DYS388 (29, 30) and DYS461 (31). The phylogenetic network of the data obtained was

constructed with the program Network 4.5.0.0 (Fluxus-Engineering), using the median joining

algorithm. Spatial frequency maps were drawn with the program Surfer 8 (Golden Software

Inc., Cold Spring Harbor, NY, USA). Coalescence ages were calculated according to the

ASD0method (32).

mtDNA analyses

The haplogroups of 2262 mtDNA samples from 24 Caucasus populations were determined by

typing HVSI and coding region markers according to the nomenclature presented in Richards

et al.(33) (Table S4). The data obtained were used to generate a PC plot of the Caucasus

populations in the context of populations from neighboring regions, using the POPSTR

software (http://harpending.humanevo.utah.edu/popstr/).


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languages of the NE Caucasus cluster apart from the rest of the Caucasus peoples who are

genetically similar despite language family barriers, whereas the Nakh-speaking NE

Caucasian Chechens and Ingushes do not fall into either group, being set apart by a high

frequency of haplogroup J2a2* (Figure S2; Table S2). But this single example of concordance

of genetic and linguistic data in NE Caucasus is only observable in case of the Y

chromosome; neither autosomal nor mtDNA data support the distinctness of the Dagestanian

language group populations (Figure 2B; Figure S1; Figure S3). NE Caucasian Y

chromosomes (n=640) mostly belong to haplogroups J1* (35.3%), J2a2* (27.8%), and

R1b1b2 (9.8%); while those from NW Caucasus (n=844) mostly belong to haplogroups G2a

(45.4%), R1a1* (14.9%), and J2a* (9.1%), and those from S Caucasus (n=305) also mostly to

haplogroups G2a (41.3%), J2a* (12.1%), and R1a1* (7.9%) (Table S2). In summary, the NE

Caucasian populations are distinguished mainly by a high frequency of haplogroup J1, more

ifi ll J1* hi h i di ti t f th J1 * li i th N /Middl E t


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P58 mutation first arose, since the coalescence ages of the J1e* clade are highest in the

Near/Middle East, the estimate for the whole region being 12 000 2 600 years (Table S5).

The J1e* subclade has spread to the Caucasus relatively lately, as evidenced by a low

coalescence age, the limited divergence of Caucasian J1e* STR haplotypes both from

Near/Middle Eastern STR haplotypes and from each other (Figure S7), and the generally low

frequency of this subhaplogroup in the Caucasus. The J1e* coalescence age of 5 600 1 400

years, considerably lower than the estimates for other J subhaplogroups in the Caucasus,

possibly reflects a migration of Neolithic farmers from the Near East and is consistent with

the scenario proposed by Tofanelli et al.(39). The J1* clade is not uniform, but divided into

two clusters according to the number of repeats of the STR marker DYS388 (10-14 versus 15-

17 repeats), clearly distinct on median joining networks (Figure S7). The long DYS388

group is the older of the two, apparently having risen in the Near/Middle East, where it has a

l f 21 400 8 900 A di t l ti t th


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The lineages of the J1 sister haplogroup J2 have spread from their Near/Middle Eastern

homeland in both the eastern and western direction, and, with some exceptions, also to the

Caucasus in the north. The haplogroup J2 subclades J2a* and J2a2* have both spread

throughout the Caucasus, although remaining at lower frequencies in NE Caucasus, with the

exception of the Chechens and the Ingush, who have a high frequency of J2a2* (Figure S8).

On the other hand, the subclades J2a2a and J2b, the latter otherwise spread from southern

Europe to India (23, 37), are practically absent in the Caucasus. Our coalescence age

estimates, probably strongly influenced by the high frequency and diversity of subclade J2a2*

among the Chechens and the Ingush, set the time of the expansion of J2a2* to the Caucasus

into the distant past, at about 1214,000 years (Table S5).

Both the J1*(xP58) short DYS388 group and J2a2* exhibit founder effects about 12,000

i th NE C ibl l t d t th Kh l i t i ti


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presence of this lineage in the Caucasus was shown by Nasidze et al.(42), it was intriguing to

find it to be present so widely and with such a high frequency. Similarly to Anatolia (21), the

absolute majority of haplogroup G samples in the Caucasus belong to subhaplogroup G2, with

only a few (mostly Armenian) samples falling into G1. The major subclade G2 is unevenly

distributed, being very frequent in NW Caucasus and S Caucasus (covering about 45% of the

paternal lineages in both regions, with the highest incidence detected in North Ossetians, at

70%), while present in NE Caucasus with an average frequency of only 5%, ranging from 19

to 0%.

Interestingly, the decrease of both haplogroup J1 and G frequencies (the two major lineages in

the Caucasus) towards the eastern European populations inhabiting the area adjacent to NW

Caucasus, such as southern Russians and Ukrainians (43, 44), is very rapid and the borderline

h (Fi S5 Fi S6) i di ti th t fl f th C i th th


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In addition to physical barriers like mountains and rivers, factors such as linguistic, ethnic and

religious restrictions should be considered as potential barriers to gene flows when analyzing

human populations. Deviations from panmixia, such as assortative mating between members

of specific social groups, or admixture with highly divergent immigrant populations, can also

lead to higher genetic distances between neighboring human populations. Because all these

forces lead to higher differentiation between neighboring populations, they can be considered

as barriers to gene flow. In terms of multiple regression analysis, not considering such factors

can lead to decreased explanatory power of the simpler model if that includes only geographic

distance as a predictor.

Multiple regression analysis on distance matrices provides a convenient framework to

consider multiple, independently acting factors. Whenever such factors can be formulated as

di t t i th lti l i th d (MRM) b d t t t th i l


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FSTanalysis

The heatmap plot (Figure 2A) reveals three clusters of low genetic distance, encompassing

geographically nearby populations: the Near/Middle East, the Caucasus, and Europe.

However, Europe is not as homogeneous as the other clusters. French Basques and Volga

Basin Turkic-speaking Chuvashes are clearly more distant from their immediate neighbor

populations, while geographically somewhat southern populations, from the Atlantic to the

Black Sea (French, Italians, Bulgarians and Romanians), exhibit particularly low inter-

population genetic distances. As already mentioned, the smooth transition from the Caucasus

to Anatolia (Turks) and Iran, and from the latter to Syrians, Lebanese, Jordanians and further


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Figure legends

Figure S1

Plots of the first and the second, the first and the third, and the second and the third

components of the principal component analysis of the Caucasus and neighboring populations

based on autosomal data [data from this study and the literature (1, 2)]. For population

abbreviations see Table S1.

Figure S2

Plot of the first and second principal components of Y chromosome variation in the Caucasus

and neighboring regions. Populations [data from this study and the literature (21, 23, 34, 36,

43, 45-49)] are colored according to their language group affiliations. Populations of the


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proportions shown in color from K=3 to K=10. Populations introduced for the first time in

this study and analyzed together with data from Li et al.(1) and Behar et al.(2) are labeled in

color.

Figure S5

Spatial frequency distribution of the Y chromosome haplogroup G. Frequency data from this

study and the literature (21, 23, 36, 43, 45-49, 62-76) were converted into a spatial frequency

map using the Surfer software (version 8, Golden Software Inc., Cold Spring Harbor, NY,

USA), applying the kriging algorithm.

Figure S6

Spatial frequency distribution of the Y chromosome haplogroup J1 and its subclades: Aall of

J1 B J1 * d C J1*( P58) F d t f thi t d d th lit t (21 23 34 36


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Figure S8

Spatial frequency distribution of the Y chromosome haplogroup J2 and its subclades:A

all of

J2, BJ2a*, and CJ2a2*. Frequency data from this study and the literature (21-23, 36, 37, 43,

45, 46, 48, 68, 78-80, 84) were converted into spatial frequency maps using the Surfer

software (version 8, Golden Software Inc., Cold Spring Harbor, NY, USA), applying the

kriging algorithm.


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References

1. J. Z. Liet al., Worldwide human relationships inferred from genome-wide patterns ofvariation. Science319, 1100-1104 (2008).

2. D. M. Beharet al., The genome-wide structure of the Jewish people.Nature466, 238-242(2010).

3. D. H. Alexander, J. Novembre, K. Lange, Fast model-based estimation of ancestry inunrelated individuals. Genome Res.19, 1655-1664 (2009).

4. J. K. Pritchard, M. Stephens, P. Donnelly, Inference of population structure usingmultilocus genotype data. Genetics155, 945-959 (2000).5. S. Purcellet al., PLINK: A tool set for whole-genome association and population-based

linkage analyses.Am. J. Hum. Genet.81, 559-575 (2007).

6. M. Rasmussenet al., Ancient human genome sequence of an extinct Palaeo-Eskimo.Nature463, 757-762 (2010).

7. D. H. Alexander, J. Novembre, K. Lange, ADMIXTURE 1.04 Software Manual (2010;http://www.genetics.ucla.edu/software/admixture/admixture-manual.pdf).

8. N. Patterson, A. L. Price, D. Reich, Population structure and eigenanalysis. PLoS Genet.2, 2074-2093 (2006).

9. S. Banerjee, On geodetic distance computations in spatial modeling.Biometrics61, 617-625 (2005).

10.H. M. Cannet al., A human genome diversity cell line panel. Science296, 261-262(2002).

11 B F M l R d i ti d i th d f t ti f i ti ith


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23.S. Senguptaet al., Polarity and temporality of high-resolution y-chromosome distributionsin India identify both indigenous and exogenous expansions and reveal minor genetic

influence of Central Asian pastoralists.Am. J. Hum. Genet.78, 202-221 (2006).

24.P. A. Underhillet al., inRethinking the Human Revolution: New Behavioural andBiological Perspectives on the Origin and Dispersal of Modern Humans (Mcdonald

Institute Monographs) P. Mellars, K. Boyle, O. Bar-Yosef, C. Stringer, Eds. (McDonald

Institute for Archaeological Research, Cambridge, 2007), pp. 33-42.

25.P. A. Underhillet al., Separating the post-Glacial coancestry of European and Asian Ychromosomes within haplogroup R1a.Eur. J. Hum. Genet.18, 479-484 (2010).

26.M. F. Hammeret al., Jewish and Middle Eastern non-Jewish populations share a commonpool of Y-chromosome biallelic haplotypes. Proc. Natl. Acad. Sci. U. S. A.97, 6769-6774(2000).

27.N. Elliset al., A nomenclature system for the tree of human Y-chromosomal binaryhaplogroups. Genome Res.12, 339-348 (2002).

28.T. M. Karafetet al., New binary polymorphisms reshape and increase resolution of thehuman Y chromosomal haplogroup tree. Genome Res.18, 830-838 (2008).

29.P. de Knijffet al., Chromosome Y microsatellites: population genetic and evolutionaryaspects.Int. J. Legal Med.110, 134-149 (1997).

30.M. Kayseret al., Evaluation of Y-chromosomal STRs: a multicenter study.Int. J. LegalMed.110, 125-133 (1997).

31.P. S. White, O. L. Tatum, L. L. Deaven, J. L. Longmire, New, male-specific microsatellitemarkers from the human Y chromosome. Genomics57, 433-437 (1999).

32.L. A. Zhivotovskyet al., The effective mutation rate at Y chromosome short tandemrepeats, with application to human population-divergence time.Am. J. Hum. Genet.74,

50 61 (2004)


33/48

44.V. N. Kharkovet al., Gene pool structure of Eastern Ukrainians as inferred from the Y-chromosome haplogroups.Russ. J. Genet.40, 326-331 (2004).

45.A. M. Cadenas, L. A. Zhivotovsky, L. L. Cavalli-Sforza, P. A. Underhill, R. J. Herrera, Y-chromosome diversity characterizes the Gulf of Oman.Eur. J. Hum. Genet.16, 374-386

(2008).

46.C. Floreset al., Isolates in a corridor of migrations: a high-resolution analysis of Y-chromosome variation in Jordan.J. Hum. Genet.50, 435-441 (2005).

47.J. R. Luis et al., The Levant versus the Horn of Africa: Evidence for bidirectionalcorridors of human migrations.Am. J. Hum. Genet.74, 532-544 (2004).

48.M. Pericic, L. B. Lauc, I. M. Klaric, B. Janicijevic, P. Rudan, Review of croatian geneticheritage as revealed by mitochondrial DNA and Y chromosomal lineages. Croat. Med. J.46, 502-513 (2005).

49.P. A. Zallouaet al., Y-chromosomal diversity in Lebanon is structured by recent historicalevents.Am. J. Hum. Genet.82, 873-882 (2008).

50.N. Al-Zaheryet al., Y-chromosome and mtDNA polymorphisms in Iraq, a crossroad ofthe early human dispersal and of post-Neolithic migrations.Mol. Phylogenet. Evol.28,

458-472 (2003).

51.D. M. Beharet al., Counting the founders: the matrilineal genetic ancestry of the JewishDiaspora. PLoS One3, e2062 (2008).

52.M. Bermisheva, K. Tambets, R. Villems, E. Khusnutdinova, Diversity of mitochondrialDNA haplotypes in ethnic populations of the Volga-Ural region of Russia.Mol. Biol.

(Mosk.)36, 990-1001 (2002).

53.S. Cvjetanet al., Frequencies of mtDNA haplogroups in southeastern Europe--Croatians,Bosnians and Herzegovinians, Serbians, Macedonians and Macedonian Romani. Coll.

A t l 28 193 198 (2004)


34/48

64.C. Di Gaetanoet al., Differential Greek and northern African migrations to Sicily aresupported by genetic evidence from the Y chromosome.Eur. J. Hum. Genet.17, 91-99

(2009).

65.F. Di Giacomoet al., Clinal patterns of human Y chromosomal diversity in continentalItaly and Greece are dominated by drift and founder effects.Mol. Phylogenet. Evol.28,

387-395 (2003).

66.R. Goncalveset al., Y-chromosome lineages from Portugal, Madeira and Acores recordelements of Sephardim and Berber ancestry.Ann. Hum. Genet.69, 443-454 (2005).

67.M. F. Hammeret al., Dual origins of the Japanese: common ground for hunter-gathererand farmer Y chromosomes.J. Hum. Genet.51, 47-58 (2006).

68.T. M. Karafetet al., High levels of Y-chromosome differentiation among native Siberianpopulations and the genetic signature of a boreal hunter-gatherer way of life.Hum. Biol.74, 761-789 (2002).

69.A. O. Karlsson, T. Wallerstrom, A. Gotherstrom, G. Holmlund, Y-chromosome diversityin Sweden - A long-time perspective.Eur. J. Hum. Genet.14, 963-970 (2006).

70.R. J. Kinget al., Differential Y-chromosome Anatolian influences on the Greek andCretan Neolithic.Ann. Hum. Genet.72, 205-214 (2008).

71.I. Nasidzeet al., Genetic evidence concerning the origins of South and North Ossetians.Ann. Hum. Genet.68, 588-599 (2004).

72.I. Nasidze, T. Sarkisian, A. Kerimov, M. Stoneking, Testing hypotheses of languagereplacement in the Caucasus: evidence from the Y-chromosome.Hum. Genet.112, 255-

261 (2003).

73.V. N. Pimenoffet al., Northwest Siberian Khanty and Mansi in the junction of West andEast Eurasian gene pools as revealed by uniparental markers.Eur. J. Hum. Genet.16,

1254 1264 (2008)


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Table S1.Samples used for whole genome analysis.

Geographic

region

Population Abbreviation Li et

al.(1)

Behar et

al.(2)

This

study

Total

Africa NE Bantu BN 11 11

S Bantu BS 8 8

Mandenka Mnd 22 22

Yoruba Yor 21 21

North Africa Egypt Egy 12 12Ethiopians Eth 19 19

Near/Middle

East

SaudisSdi 20 20

Bedouin Bdn 45 45

Druze Drz 42 42

Jordanians Jor 20 20

Lebanese Leb 7 7

Palestinian Pal 46 46

Syrians Syr 16 16

Iranians Irn 20 20

Turks Tur 19 19

Europe French Fre 28 28

French Basques FrB 24 24


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Kurds (sampled in

Kazakhstan)Krd 6 6

Uzbeks Uzb 15 15

Uygur Uyg 10 10

Altaians Alt 13 13

South Asia Hazara Haz 22 22

Pathan Ptn 22 22

Burusho Bur 25 25

Balochi Blo 24 24

Brahui Brh 25 25

Makrani Mak 25 25Sindhi Sin 24 24

Siberia Yakuts Yak 25 25

East Asia Cambodians Cam 10 10

Dai Dai 10 10

Lahu Lah 8 8

Han Han 44 44

Daur Dau 9 9

Oroqen Oro 9 9

Mongolas Mng 10 10

Japanese Jap 28 28

Total 639 267 214

Grand Total 1120


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M20

M436

NE Caucasus N

94sidnA

24sravA

82slalavgaB

72slalamahC

561snehcehC

76snigraD

501hsugnI

37skymuK

13snigzeL

34snarasabaT

Mountain Jews 10

NEC 046latoT

Kuban Nogays 87

Kara Nogays 76

Nogays & Kara Nogays Total 163

NW Caucasus

88snizabA

00226 5 19 178 4 0

22 2 3 9 1362 2

1

1

810213 2 5 0 0 0 10 0 0 0 347191

10 3 1

13 0

1127121

277 1

5 2 1

218 4

30 0

10

01 2 0 4 10 35 0143 0 0 0 9 1

1 23 4

1 213

2 183 12

2610 1714 2

9

2

865

61

2

22

332 77 2604111

1 1815

6

428 2 23

1 7281213

N 1 b

1

L3

N*

J2a

*

J2a

2*

J1e

*

L1

L2

I2*

1

J1*

K*

TE1b1b1c

G1

J2a

2a

J2b*

G2a

H1

I1 I2a

C C3c

D E E1b1b1a

4P29M322M2.73P

M357

M 7 M

07M

M231M76 M317

M52 M9

M438

12f2M170

M253

M

85P321M87M

M130 YAP

M267

M48 M174

M172

M40 M201

M168

M35 M285 P15

0000

I2b

F*

0

0

2

2

0

M89

Table S2.Y chromosome data of the Caucasus populations and the phylogenetic relationships

of the 51 Y chromosome markers typed.


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NE Caucasus N A B C D E F G H HV* HV0 HV1 HV2 I J K L M M

585426sidnA

8111441316sravA

74133slalavgaB

13243slalamahC

2016823422671snehcehC

3121728621011snigraD

543819232301hsugnI

1396227231211skymuK

56211264snigzeL

3719225snarasabaT

Mountain 311132sweJ

NEC 8006426143305220271001430218latoT

Kuban Nogays 131 12156521482625216

Kara 32126275318157031syagoN

Nogays & Kara Nogays Total 261 13 6 20 18 0 7 13 54 6 0 1 3 7 6 5 1 5 1

NW Caucasus

3543192155501snizabA

1312531275121551ehgydA

8112353142041sraklaB

4193114321571321snaissekrehC

11921243121501051nidrabaK

146417251601syahcaraK

N 42171462521112831snaitessO

NWC 4120065551131851712910236213719latoT

South Caucasus

152322231481631snaizahkbA

121132163snainemrA

346111267snaigroeG

S 1411112142snaitessO

SC 272latoT 1 0 8 7 0 1 0 57 6 0 4 1 11 9 13 0 0 2

NE Caucasus N N1d N2a N9 R R0a T*(xT1) T1 U U1 U2 U3 U4 U5 U6 U7 U8 U9 V

2422281326sidnA

3845116sravA

126233slalavgaB

1113243slalamahC

313341671snehcehC 13518862

221011snigraD 1517242

5301hsugnI 11413922224

21111211skymuK 1567735

6332464snigzeL

25snarasabaT 154441122

Mountain 21532sweJ

Table S3.mtDNA data of the Caucasus populations.


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Table S4. The power of various models to predict the observed genetic distances (pairwise

FSTdistances) between the populations studied. The coefficient of determination r2, its

increase relative to the default model of only geographic distance explaining genetic distance,

the marginal regression coefficient, and p-value are given. Statistically significant predictors

printed in bold.

Predictors (putative

barriers)

r2 Increment in

r2

Marginal regression

coefficient

p-

value

only geographic distance 0.4316 * 0.0347 0.0001Caucasus barrier 0.5522 0.1206 0.0055 0.0001

Balkans barrier 0.5058 0.0742 -0.0048 0.0001

Mountain Jews 0.4751 0.0435 0.0063 0.0030

Iranian Jews 0.4693 0.0377 0.0058 0.0247

Burusho 0.4523 0.0207 0.0044 0.0596

Georgian Jews 0.4481 0.0165 0.0039 0.0959

Iraqi Jews 0.4467 0.0151 0.0037 0.1247

Druze 0.4376 0.0059 0.0023 0.4500

French Basque 0.4341 0.0025 0.0016 0.7090

South Asian barrier 0.4328 0.0012 0.0006 0.6570

Kuban Nogays 0.4318 0.0002 -0.0004 0.9531

All predictors 0.7695 0.3378 * *

T bl S5 C l i i h d d f h h h l 1 ( d bh l )


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Table S5.Coalescence times with standard errors for the Y chromosome haplogroups J1 (and subhaplogroups) a

regions/populations. Median haplotypes of the 10 Y chromosome STR markers based on which the coalescence t

(32)] are also given.

Haplogroup Region/population N TC

(ky)

SE

(ky)

DYS19 DYS388 DYS389I DYS389II DYS390

J1* All J1* (Caucasus, Near/Middle East, Central Asia) 121 18.6 4.4 14 13 13 16 23

J1* Caucasus 72 14.6 4.2 14 13 13 16 23

J1* Near/Middle East 33 22.8 6.0 14 13 14 17 23

J1*,DYS388


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PC2

PC1

Bdn

Sdi

Egy

Bdn

Pal Jor

Drz

Cyp

Syr

Leb

IqJInJ

Armenians

MountainJewsGeorgianJews

GeorgiansAbkhazians

Adyghe

Chechens

Balkars

Lezgins

Nogais

Chv

Rus

Mrd

Lit

Blr

Ukr

Fre

FrB

Rmn

Bul

NIt

Tus

Uzb

TjkTrmIrn

Ptn

Blo

Mak

Brh

Sin

Bur

Tur

Pal Jor

DrzCyp

Syr

Leb

IqJ

InJ

Armenians

MountainJews

GeorgianJews

Georgians Abkhazians

AdygheChechens

Balkars

Lezgins

Nogais

Fre

Rmn

Bul

NIt

Tus

Trm

Irn

Ptn

Blo

Mak

Brh

Sin

Tur

Fig S2


42/48

Chv

Dar

Aba

Abh

Ady

CrkKab

Bag

Cha

Tab

Avr

And

Lzg

Che

Ing

UAE

EgyIrq

Jor

Leb

Pal

Syr

Grg

Blr

Rus

SSv

Ukr

Pak

Irn

Krd

MnJ

Arm

NOs

SOs

Bsh

Ttr KNo

Nog

BlkKar

KumTur

PC2(19%)

LANGUAGE GROUPS

Nakh-Dagestanian

Abkhaz-Adyghe

Turkic

Indo-European

Afro-Asiatic

Kartvelian

Caucasus populations

Other populations

g

Fig S3


43/48

AbaQtr

Bsh

KNo

MnJ

Abh

Ady

Crk Kab

UAE

IrqJorLeb

PalSyrEgy

Irn

Krd

Arm

NOs

SOs

SSv

RusBlr

Ukr

And

Avr

Bag

ChaCheDar

IngLzg

Tab Blk

Chv

KarKum

Nog

Ttr

Tur Grg

Pak

PC2(12.5

%)

LANGUAGE GROUPS

Nakh-Dagestanian

Abkhaz-Adyghe

Turkic

Indo-European

Afro-Asiatic

Kartvelian

Caucasus populations

Other populations

g S3

3

Fig S4


44/48

3

4

5

6

7

8

9

10

BantuSA

BantuNE

Yorubans

Mandenkas

Ethiopians

Egyptans

Saudis

Bedouins

Palestnians

Druze

Jordanians

Lebanese

Syrians

Turks

French

FrenchBasques

NorthItalians

Tuscans

Romanians

Bulgarians

Ukrainians

Belorussians

Lithuanians

Russians

Chuvashes

Armenians

Georgians

Abkhazians

Balkars

Adyghe

N.

Ossetans

Chechens

Lezgins

KubanNogays

Kumyks

GeorgianJews

MountainJews

IraqiJews

IranianJews

Iranians

Tajiks

Turkmens

Uzbeks

Uygurs

Altaians

Hazaras

Pathans

Burusho

Balochis

Brahui

Makranis

Sindhi

Yakuts

Cambodians

Dai

Lahu

Han

Daur

Oroqens

Mongols

Japanese

Mordvins

Kurds

Africa Near East & Europe

South North

The Caucasus Cen. Asia South Asia East Asia

Fig S5


45/48

Fig S6


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g

Fig S7


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g

Fig S8


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Fig S8

Documents

Yunusbaev_The Caucasus as an Asymmetric Semipermeable Barrier to Ancient Human Migrations