Ancient DNA Reveals Prehistoric Gene - Flow from Siberia in the Complex Human Population History of North East Europe 고대 의 DNA 가 북동 유럽 의 복잡 한 인류 역사 에서 시베리아 선사 시대 의 유전자 흐름 을 밝혀낸다 . Clio Der Sarkissian , Oleg Balanovsky , Guido Brandt , Valery Khartanovich , Alexandra Buzhilova , Sergey Koshel , Valery Zaporozhchenko , Detlef Gronenborn , Vyacheslav Moiseyev , Eugen Kolpakov , Vladimir Shumkin , Kurt W . Alt , Elena Balanovska , [ . .. ] , the Genographic Consortium [ view all ] Published : February 14 , 2013 https : / / doi . org / 10 . 1371 / journal . pgen . 1003296 출처 ; https : / / journals . plos . org / plosgenetics / article ? id = 10 . 1371 / journal . pgen . 1003296 AbstractNorth East Europe harbors a high diversity of cultures and languages , suggesting a complex genetic history . Archaeological , anthropological , and genetic research has revealed a series of influences from Western and Eastern Eurasia in the past . While genetic data from modern - day populations is commonly used to make inferences about their origins and past migrations , ancient DNA provides a powerful test of such hypotheses by giving a snapshot of the past genetic diversity . In order to better understand the dynamics that have shaped the gene pool of North East Europeans , we generated and analyzed 34 mitochondrial genotypes from the skeletal remains of three archaeological sites in northwest Russia . These sites were dated to the Mesolithic and the Early Metal Age ( 7 , 500 and 3 , 500 uncalibrated years Before Present ) . We applied a suite of population genetic analyses ( principal component analysis , genetic distance mapping , haplotype sharing analyses ) and compared past demographic models through coalescent simulations using Bayesian Serial SimCoal and Approximate Bayesian Computation . Comparisons of genetic data from ancient and modern - day populations revealed significant changes in the mitochondrial makeup of North East Europeans through time . Mesolithic foragers showed high frequencies and diversity of haplogroups U ( U 2 e , U 4 , U 5 a ) , a pattern observed previously in European hunter - gatherers from Iberia to Scandinavia . In contrast , the presence of mitochondrial DNA haplogroups C , D , and Z in Early Metal Age individuals suggested discontinuity with Mesolithic hunter - gatherers and genetic influx from central / eastern Siberia . We identified remarkable genetic dissimilarities between prehistoric and modern - day North East Europeans / Saami , which suggests an important role of post - Mesolithic migrations from Western Europe and subsequent population replacement / extinctions . This work demonstrates how ancient DNA can improve our understanding of human population movements across Eurasia . It contributes to the description of the spatio - temporal distribution of mitochondrial diversity and will be of significance for future reconstructions of the history of Europeans . Author SummaryThe history of human populations can be retraced by studying the archaeological and anthropological record , but also by examining the current distribution of genetic markers , such as the maternally inherited mitochondrial DNA . Ancient DNA research allows the retrieval of DNA from ancient skeletal remains and contributes to the reconstruction of the human population history through the comparison of ancient and present - day genetic data . Here , we analysed the mitochondrial DNA of prehistoric remains from archaeological sites dated to 7 , 500 and 3 , 500 years Before Present . These sites are located in North East Europe , a region that displays a significant cultural and linguistic diversity today but for which no ancient human DNA was available before . We show that prehistoric hunter - gatherers of North East Europe were genetically similar to other European foragers . We also detected a prehistoric genetic input from Siberia , followed by migrations from Western Europe into North East Europe . Our research contributes to the understanding of the origins and past dynamics of human population in Europe . Figures Citation : Der Sarkissian C , Balanovsky O , Brandt G , Khartanovich V , Buzhilova A , Koshel S , et al . ( 2013 ) Ancient DNA Reveals Prehistoric Gene - Flow from Siberia in the Complex Human Population History of North East Europe . PLoS Genet 9 ( 2 ) : e 1003296 . https : / / doi . org / 10 . 1371 / journal . pgen . 1003296 Editor : Scott M . Williams , Vanderbilt University , United States of AmericaReceived : September 11 , 2012 ; Accepted : December 18 , 2012 ; Published : February 14 , 2013 Copyright : © 2013 Der Sarkissian et al . This is an open - access article distributed under the terms of the Creative Commons Attribution License , which permits unrestricted use , distribution , and reproduction in any medium , provided the original author and source are credited . Funding : This research was supported by The Genographic Project , which is supported by funding from the National Geographic Society , IBM , and the Waitt Family Foundation . OB was funded my the RAS Programmes “ Molecular and cell biology ” and “ Gene pool dynamics . ” The funders had no role in study design , data collection and analysis , decision to publish , or preparation of the manuscript . Competing interests : The authors declare that no competing interests exist . IntroductionOur current knowledge of the origins of human populations and their migratory history relies on archaeological , anthropological , linguistic and genetic research . The study of genetic markers , especially the maternally inherited mitochondrial DNA ( mtDNA ) , has allowed important events in the genetic history of humans to be reconstructed [ 1 ] –[ 11 ] . However , reconstructions based solely on present - day genetic diversity can be biased by a variety of evolutionary mechanisms , such as genetic drift and / or past population events . The ability to accurately reconstruct recent human evolutionary events can be significantly improved through the direct analysis of ancient human remains from representative time periods . The mtDNA diversity of prehistoric populations has been previously described for Palaeolithic / Mesolithic hunter - gatherers from Central , Eastern and Scandinavian Europe [ 12 ] –[ 14 ] , and for Neolithic farmers from Southern and Central Europe ( CE ) [ 15 ] –[ 20 ] . These studies have uncovered an unexpected and substantial heterogeneity in the geographical , temporal and cultural distribution of the mtDNA diversity . However , little is known about past mtDNA diversity in North East Europe ( NEE ) , including the Baltic region , the Volga - Ural Basin ( VUB ) , and sub - Arctic Europe . It is likely that different demographic events have been involved in shaping the gene pools of the populations of Western / Central Europe and NEE , due to the geographical position and distinct climatic conditions of the latter . During the Upper Palaeolithic ( ∼ 30 , 000 – 40 , 000 years before present , yBP ) , the northernmost latitudes of Europe were covered by an ice sheet that prevented settlement by anatomically modern humans . With the glacial retreat at the end of the Ice Age ( ∼ 11 , 500 yBP ) [ 21 ] , small foraging groups progressed into NEE from southern periglacial refuges [ 22 ] –[ 23 ] . As climatic conditions improved in the early Holocene ( 8 , 000 – 10 , 000 yBP ) , the first human settlements appeared in the Kola Peninsula [ 24 ] , and foraging activities intensified in the steppe - forest zone of Northern Europe leading to the widespread establishment of complex Mesolithic societies of fishermen and hunter - gatherers [ 23 ] , [ 25 ] –[ 26 ] . At the same time , Western Europe and CE were undergoing the Neolithic transition , during which an agricultural lifestyle spread rapidly , largely due to favorable climatic and ecological conditions . The Neolithic transition is thought to have been slower and more gradual in NEE than in Western / Central Europe and to have involved little migration of early farmers from CE [ 27 ] . From the Neolithic onwards , contacts between populations of NEE and groups living in the South are evident in archaeological and historical records [ 24 ] . Around the Baltic , historical records describe numerous population movements that originated in Scandinavia ( e . g . , Viking incursions ∼ 800 Anno Domini , AD [ 28 ] ) , Western / Central Europe ( e . g . , the Slavic migrations ∼ 700 – 1 , 000 AD [ 29 ] ) or Central / East Siberia ( e . g . , the Mongol invasions ∼ 500 – 700 AD [ 30 ] ) . The geographical position of NEE makes it subject to influences from both Western and Eastern Eurasia , which could explain the linguistic and cultural diversity , observed in the area today . Two different linguistic families are spoken : Indo - European languages ( Slavic , Baltic and Germanic ) and Finno - Ugric languages ( e . g . , Estonian , Finnish , Mari , Saami [ 31 ] ) . Saami people of Fennoscandia ( northern Norway , Sweden , Finland and Russia ) are considered unique among Europeans in terms of their nomadic lifestyle and their livelihood , which is mainly based on fishing and reindeer herding . The ethnogenesis of the Saami remains unclear and two origins in Western and Eastern Europe were proposed [ 24 ] , [ 32 ] –[ 33 ] . The Saami differ from the rest of the European populations in their reduced genetic diversity [ 1 ] , [ 34 ] –[ 35 ] , and mtDNA lineages that are otherwise very rare in European populations ( haplogroups or hgs , U 5 b 1 b 1 a , V , Z 1 and D 5 ) . In particular , the Saami - specific U 5 b 1 b 1 a clade is defined by the so - called hypervariable region I ( HVR - I ) ‘ Saami motif ’ 16144 C - 16189 C - 16270 T ( numbering according [ 36 ] ) [ 37 ] . These lineages are also detected at low frequencies in adjacent NEE populations [ 32 ] , [ 38 ] –[ 40 ] , which on the other hand fall within the European mtDNA diversity and appear rather homogeneous irrespective of their languages [ 3 ] –[ 5 ] , [ 38 ] , [ 40 ] . Subtle mtDNA differences are however observed among them due to variable influences from genetically differentiated neighboring populations : central Europeans in the West , Saami in the North , and people from the VUB in the East . The absence of strong structure in the present - day mtDNA gene pool of NEE stands in contrast to the variety of languages and cultures , and to the complex history of how and when these were formed . Modern mtDNA data does not resolve the origins of the Saami either . Our aim was to provide answers to these questions and reconstruct events in the genetic history of NEE by generating and analyzing ancient DNA ( aDNA ) data from prehistoric human remains collected in northwest Russia ( Figure 1 ) . In particular , our objective was to characterize the genetic relationships between hunter - gatherer populations in NEE and Central / Northern Europe and to estimate the genetic legacy of ancient populations to present - day NEE and Saami . The oldest samples were collected in the Mesolithic graveyards of Yuzhnyy Oleni Ostrov ( aUz ; ‘ Southern Reindeer Island ’ in Russian ) and Popovo ( aPo ) , both dated around 7 , 000 – 7 , 500 uncalibrated . yBP , uncal . yBP . The sites of aUz and aPo are located along one of the proposed eastern routes for the introduction of Saami - specific mtDNA lineages [ 32 ] . Results from odontometric analyses suggested a direct genetic continuity between the Mesolithic population of Yuzhnyy Oleni Ostrov and present - day Saami [ 41 ] . We also analyzed human remains from 3 , 500 uncal . yBP site Bol ' shoy Oleni Ostrov ( aBOO ; ‘ Great Reindeer island ’ in Russian ) in the Kola Peninsula . This site is located within the area currently inhabited by the Saami . We compared the ancient mtDNA data from NEE with a large dataset of ancient and modern - day Eurasian populations to search for evidence of past demographic events and temporal patterns of genetic continuity and discontinuity in Europe . Download : PPTPowerPoint slidePNGlarger imageTIFForiginal imageFigure 1 . Map of Eurasia showing the approximate location of ancient ( uncalibrated dates ) and present - day Eurasian samples . Red dots represent the archaeological sites sampled for ancient mitochondrial DNA in this study : aUZ , Yuzhnyy Oleni Ostrov ; aPo , Popovo ; aBOO , Bol ' shoy Oleni Ostrov . Black circles represent ancient populations abbreviated as follows : aEG , Confederated nomads of the Xiongnu ( 2 , 200 – 2 , 300 yBP ) ; aKAZ , Nomads from Kazakhstan ( 2 , 100 – 3 , 400 yBP ) ; aKOS , Kostenski individual ( 30 , 000 yBP ) ; aKUR , Siberian Kurgans ( 1 , 600 – 3 , 800 yBP ) ; aLOK , Lokomotiv Kitoi Neolithic individuals ( 6 , 130 – 7 , 140 yBP ) ; aPWC , Scandinavian Pitted - Ware Culture foragers ( 4 , 500 – 5 , 300 yBP ) ; aUST , Ust ' Ida Neolithic population ( 4 , 000 – 5 , 800 yBP ) . Smaller black dots signify the location of Palaeolithic / Mesolithic sites sampled for ancient mitochondrial DNA in aHG ( 4 , 250 – 15 , 400 yBP ) . Present - day populations are abbreviated as follows : alt , Altaians ; BA , Bashkirs ; BU , Buryats ; CU , Chuvash ; EST , Estonians ; FIN , Finns ; ket , Kets ; kham , Khamnigans ; khan , Khants ; KK , Khakhassians ; KO , Komis ; KR , Karelians ; LTU , Lithuanians ; LVA , Latvians ; man , Mansi ; ME , Mari ; MO , Mordvinians ; MNG , Mongolians ; NEN , Nenets ; nga , Nganasans ; NOR , Norwegians ; tof , Tofalars ; tuv , Tuvinians ; UD , Udmurts ; SA , Yakuts ; saa , Saami ; sel , Selkups ; SWE , Swedes . The approximate location of the Volga - Ural Basin and of the different regions of Russian Siberia are also indicated . https : / / doi . org / 10 . 1371 / journal . pgen . 1003296 . g 001 ResultsAmplification success and authentication of the ancient DNA dataThe skeletal remains from aUz , aPo , and aBOO were genetically analysed by i ) direct sequencing of the mtDNA hyper - variable region I ( HVR - I , nucleotide positions , np 16056 – 16409 ) and ii ) typing of 22 haplogroup - diagnostic single nucleotide polymorphisms ( SNPs ) in the coding - region using the GenoCore 22 reaction [ 16 ] . Strict criteria were followed to authenticate aDNA data and detect contamination by exogenous DNA or artefactual mutations caused by post - mortem DNA damage ( see Materials and Methods ) . In total , 34 ancient genotypes were obtained that were considered unambiguous on the basis of these authenticity criteria ( Table 1 ) . Sequences have been deposited in Genbank ( http : / / www . ncbi . nlm . nih . gov / genbank / ; accession numbers KC 414891 - KC 414924 ) . Download : PPTPowerPoint slidePNGlarger imageTIFForiginal imageTable 1 . Results for mitochondrial DNA typing . https : / / doi . org / 10 . 1371 / journal . pgen . 1003296 . t 001 The success of DNA amplification reactions varied among archaeological sites as follows : 9 / 42 individuals ( 21 . 5 %) for aUz , 2 / 3 ( 66 . 7 %) for aPo , and 23 / 23 ( 100 . 0 %) for aBOO . The higher success rates ( 100 %) observed for samples from aBOO were consistent with their younger age and excellent macroscopic preservation , probably due to the cold climatic conditions of the Kola Peninsula ( Figure S 1 ) . The presence of naturally crushed marine shells in the burial grounds of aBOO has also been proposed to explain the exceptional preservation of the remains [ 42 ] . In contrast , and in accordance with their poorer macroscopic preservation , aDNA from the samples of aUz and aPo was more difficult to amplify , with a lower amplification success and some contaminated results that had to be excluded . Haplogroup distribution in modern - day populations of EurasiaIn order to identify the genetic affinities of the two ancient populations with other ancient and present - day Eurasian populations , mtDNA hg distributions were compared by Principal Component Analysis ( PCA ) . The PCA plot of the first two components ( 41 . 5 % of the total variance , Figure 2 ) showed that present - day populations largely segregate into three main clusters : Europeans ( in yellow ) , Middle Easterners ( in grey ) and Central / East Siberians ( in blue ) . The spread of extant populations of Europe and Central / East Siberia along the first component axis ( 28 . 5 % of the variance ) appeared to reflect their longitudinal position , whereas Europeans and Middle Easterners were separated along the second component axis ( 13 . 0 % of the variance ) . As shown previously , populations of the ‘ Central / East Siberian ’ cluster were predominantly composed of hgs A , B , C , D , F , G , Y , and Z , while in contrast populations of the ‘ European ’ cluster were characterized by higher frequencies of hgs H , HV , V , U , K , J , T , W , X , and I ( e . g . , [ 43 ] –[ 47 ] ) . The two ancient groups - aUzPo and aBOO - from two individual time periods appeared remarkably distinct on the basis of the PCA , suggesting a major genetic discontinuity in space and time . Download : PPTPowerPoint slidePNGlarger imageTIFForiginal imageFigure 2 . Principal Component Analysis of mitochondrial haplogroup frequencies . The first two dimensions account for 41 . 5 % of the total variance . Grey arrows represent haplogroup loading vectors , i . e . , the contribution of each haplogroup . Red dots represent ancient populations described in this study : aUzPo , Yuzhnyy Oleni Ostrov and Popovo ( 7 , 500 uncal . yBP ) ; aBOO , Bol ' shoy Oleni Ostrov ( 3 , 500 uncal . yBP ) . Other ancient populations were labeled as follows : aEG , Confederated nomads of the Xiongnu ( 4 , 250 - 2 , 300 yBP ) ; aHG , Palaeolithic / Mesolithic hunter - gatherers of Central / East Europe ( 4 , 250 - 30 , 000 yBP ) ; aKAZ , Nomads from Kazakhstan ( 2 , 100 – 3 , 400 yBP ) ; aKUR , Siberian Kurgans ( 1 , 600 – 3 , 800 yBP ) ; aLBK , Neolithic individuals from Germany ( 7 , 000 – 7 , 500 yBP ) ; aLOK , Lokomotiv Kitoi Neolithic individuals ( 6 , 130 – 7 , 140 yBP ) ; aSP , Neolithic individuals from Spain ( 5 , 000 – 5 , 500 yBP ) ; aPWC , Scandinavian Pitted - Ware Culture foragers ( 4 , 500 – 5 , 300 yBP ) ; aUST , Ust ' Ida Neolithic population ( 4 , 000 – 5 , 800 yBP ) . Extant populations were abbreviated as follows : ALB , Albanians ; ale , Aleuts ; alt , Altaians ; ARM , Armenians ; aro , Arorums ; AUT , Austrians ; AZE , Azerbaijani ; BA , Bashkirs ; bas , Basques ; BEL , Belarusians ; BGR , Bulgarians ; BIH , Bosnians ; BU , Buryats ; CHE , Swiss ; CHU , Chukchi ; CU , Chuvashes ; CYP , Cypriots ; CZE , Czechs ; DEU , Germans ; esk , Eskimos ; ESP , Spanish ; EST , Estonians ; eve , Evenks ; evn , Evens ; FIN , Finns ; FRA , French ; GBR , British ; GEO , Georgians ; GRC , Greeks ; HRV , Croatians ; HUN , Hungarians ; ing , Ingrians ; IRL , Irish ; IRN , Iranians ; IRQ , Iraqi ; ISL , Icelanders ; IT - 88 , Sardinians ; ITA , Italians ; JOR , Jordanians ; kab , Kabardians ; ket , Kets ; kham , Khamnigans ; khan , Khants ; KK , Khakhassians ; KO , Komi ; kor , Koryaks ; KR , Karelians ; kur , Kurds ; LTU , Lithuanians ; LVA , Latvians ; man , Mansi ; ME , Mari ; MNG , Mongolians ; MO , Mordvinians ; NEN _ A , eastern Nenets ; NEN _ E , western Nenets ; nga , Nganasans ; niv , Nivkhs ; nog , Nogays ; NOR , Norwegians ; POL , Poles ; PRT , Portuguese ; PSE , Palestinans ; ROU , Romanians ; RUS , Russians ; SA , Yakuts ; saa , Saami ; SAU , Saudi Arabians ; SE , Ossets ; sel , Selkups ; sho , Shors ; SVK , Slovakians ; SVN , Slovenians ; SWE , Swedes ; SYR , Syrians ; TA , Tatars ; tel , Telenghits ; tof , Tofalars ; tub , Tubalars ; TUR , Turks ; tuv , Tuvinians ; UD , Udmurts ; UKR , Ukrainians ; ulc , Ulchi ; vep , Vepses ; yuk , Yukaghirs . https : / / doi . org / 10 . 1371 / journal . pgen . 1003296 . g 002 Comparison of Mesolithic Yuzhnyy Oleni Ostrov / Popovo ( aUzPo ) with extant populations of EurasiaThe hg distribution in the Mesolithic aUzPo population : U 4 ( 37 %), C ( 27 %), U 2 e ( 18 %), U 5 a ( 9 %), and H ( 9 %), indicated an ‘ admixed ’ composition of ‘ European ’ ( U 4 , U 2 e , U 5 a and H , 73 %) and ‘ Central / East Siberian ’ ( C , 27 %) hgs , based on the PCA plot ( Figure 2 ) . Interestingly , the population of aUzPo did not group with modern NEE populations , including Saami , but fell instead between the present - day ‘ European ’ and ‘ Central / East Siberian ’ clusters on the PCA graph , and more precisely between populations of the VUB ( in light green ) and West Siberia ( in dark green ) . The high frequency of hg U 4 is a feature shared between Mesolithic aUzPo , present - day VUB ( Komi , Chuvashes , Mari ) , and West Siberian populations ( Kets , Selkups , Mansi , Khants , Nenets ) , with the latter group also being characterized , like aUzPo , by the presence of hg C . The genetic affinity between Mesolithic aUzPo and present - day West Siberian populations could be visualized on the genetic distance map of North Eurasia ( Figure 3 A ) , on which locally lighter colorings indicated low values of genetic distances , and therefore an affinity between aUzPo and extant West Siberians . Download : PPTPowerPoint slidePNGlarger imageTIFForiginal imageFigure 3 . Map of genetic distances between modern - day populations of Eurasia and from aUzPo and aBOO . Genetic distances were computed between 144 modern - day populations geographically delineated across Eurasia ( red dots ) and the eleven individuals from aUzPo ( A ) and the 23 individuals from aBOO ( B ) . The colour gradient represents the degree of similarity between the modern and ancient populations , interpolated between sampling points : from ‘ green ’ for high similarity or small genetic distance to ‘ brown ’ for low similarity . ‘ K ’ designates the number of populations used for distance computation and mapping ; ‘ N ’ represents the number of points in the grid used for extrapolation ; ‘ min ’, corresponds to the minimal values respectively of the computed distances between ancient and modern populations . https : / / doi . org / 10 . 1371 / journal . pgen . 1003296 . g 003 In order to test the potential population affinities formulated on the basis of the hg - frequency PCA and the distance map , we examined the present - day geographical distribution of the haplotypes found in aUzPo via haplotype sharing analyses ( Figure 4 ) . These analyses are less impacted by biases due to small population sizes or unidentified maternal relationships in ancient populations , and thus are less prone to artefacts . Although the highest percentages of shared haplotypes for aUzPo were observed in pools of West Siberian Khants / Mansi / Nenets / Selkups ( 2 . 8 %), South Siberian Altaians / Khakhassians / Shors / Tofalars ( 2 . 2 %) and Urals populations ( Chuvash / Bashkirs , 2 . 0 %), matches were widely distributed across Eurasia . This was consistent with the observation that most haplotypes sequenced in aUzPo were basal and hence , not informative in terms of geographical population affinity . Haplogroup - based analyses suggested that the genetic affinity between aUzPo and present - day West Siberians was partly due to the presence of hg C , implying that the non - basal haplotype C 1 found in aUzPo ( 16189 C - 16223 T - 16298 C - 16325 C - 16327 T , detected in three individuals ) could be a clear genetic link with extant Siberian populations . However , the C 1 haplotype found in aUz did not belong to hg C 1 a , the only C 1 clade restricted to Asia ( characterized by a transition at np 16356 [ 48 ] ) . Indeed , no exact match was found for the C 1 haplotype in the comparative database of Eurasian populations ( comprising 168 , 000 haplotypes ) , although 47 derivatives ( showing one to three np differences ) were found in extant populations broadly distributed throughout Eurasia ( Table S 1 ) . Therefore , the C 1 haplotype sequenced in aUzPo is currently uninformative about population affinity . In addition , all three aUzPo individuals showed identical C 1 haplotypes , which meant that a close maternal kinship between these individuals could not be rejected . Biases due to the overestimation of the hg C 1 frequency and small sample size of aUzPo may have led to an overestimation of the genetic affinity with modern - day West Siberians in the hg - based analyses . To account for this , we assumed a scenario of extreme maternal kinship , in which identical haplotypes found in several individuals at the same site ( redundant haplotypes ) were only counted once ( Figure S 2 A ) . Under this scenario , the genetic affinity between aUzPo and present - day Western Siberians was less distinctly pronounced ( Figure S 2 B ) . Download : PPTPowerPoint slidePNGlarger imageTIFForiginal imageFigure 4 . Percentages of haplotypes from aUzPo and aBOO matched in modern - day Eurasian population pools . Percentages of matches for the haplotypes from aBOO are represented by white bars . Percentages of matches for the haplotypes from aUzPo are independently represented by superimposed black bars . https : / / doi . org / 10 . 1371 / journal . pgen . 1003296 . g 004 To further evaluate the apparent significant genetic discontinuity between aUzPo and modern extant populations of NEE and Saami , we analyzed Bayesian Serial SimCoal ( BayeSSC ) coalescent simulations [ 49 ] using Approximate Bayesian Computation ( ABC , [ 50 ] ) and tested whether discontinuity could be better explained by genetic drift or by migration . Models of genetic continuity between aUzPo and the present - day population of NEE or Saami ( H 0 a ) were compared to models in which genetic discontinuity between aUzPo and the extant population of NEE was introduced by migration ( H 1 a , Figure 5 ) . Ancestors of individuals from CE were selected as a source population for the migration on the basis of the PCA plot ( Figure 2 ) showing that present - day populations of NEE shared the most genetic similarities with those of CE . The model of genetic discontinuity between aUzPo and present - day Saami was not tested since no source population for a potential migration could be identified from the PCA plot . The model of genetic continuity between aUzPo and present - day Saami was found to fit the observed data better than the model of genetic continuity between aUzPo and present - day NEE . This can be attributed to the low haplotypic diversities ( 0 . 74 and 0 . 81 , respectively , in contrast to 0 . 98 for NEE ; Table 2 ) of both aUzPo and Saami populations . The migration model provided a better fit for the genetic data than the model of genetic continuity ( H 0 a ) , as indicated by a low Akaike Information Criterion ( AIC , [ 51 ] ) and a high Akaike weight ω [ 52 ] –[ 53 ] . The lowest AIC ( Figure 5 ) and highest Akaike ' s ω ( Table 3 ) were obtained for migration models , the best fit being obtained for the model involving 10 % of migrants over the last 7 , 500 years ( H 1 b ; ω  =  1 . 00 E + 0 as opposed to ω  =  2 . 57 E - 7 for the continuity model H 0 a ) . Our analyses of coalescent simulations therefore supported a genetic discontinuity between aUzPo and the present - day population of NEE , which was better explained by a migration from CE than by genetic drift . Download : PPTPowerPoint slidePNGlarger imageTIFForiginal imageFigure 5 . Graphical representation and Akaike Information Criterions of the demographic models compared by coalescent simulation analyses . The timeline indicates the age of populations in generations ( G ) . For models H 0 a to H 0 e , genetic continuity is tested between combinations of ancient populations and present - day populations of North East Europe ( NEE ) or Saami ( saa ) , as indicated in the column ‘ P 0 ’. For models H 1 a and H 1 b , genetic discontinuity between aUzPo or aBOO , and NEE is tested assuming a migration from Central Europe ( CE ) . The percentage of migrants from the source population into the sink population ( 10 %, 50 % and 75 %) is indicated in the column ‘%’. The cells containing Akaike Information Criterion ( AIC ) values were colored according to the gradient of AIC represented below the figure : from white for the highest value of AIC ( worst model fit , 199 . 1 for H 0 b ) to red for the lowest value of AIC ( best model fit , 81 . 9 for H 0 a ) . https : / / doi . org / 10 . 1371 / journal . pgen . 1003296 . g 005 Download : PPTPowerPoint slidePNGlarger imageTIFForiginal imageTable 2 . Population parameters and statistics used in Bayesian Serial SimCoal coalescent simulation analyses . https : / / doi . org / 10 . 1371 / journal . pgen . 1003296 . t 002 Download : PPTPowerPoint slidePNGlarger imageTIFForiginal imageTable 3 . Relative model likelihood of the demographic models simulated in Bayesian Serial SimCoal , as indicated by Akaike weights ω . https : / / doi . org / 10 . 1371 / journal . pgen . 1003296 . t 003 Comparison of 3 , 500 uncal . yBP Bol ' shoy Oleni Ostrov ( aBOO ) with extant populations of EurasiaAt the 3 , 500 uncal . yBP site of aBOO , we observed 39 % ‘ European ’ hgs : U 5 a ( 26 %), U 4 ( 9 %), T ( 4 %), and 61 % ‘ Central / East Siberian ’ hgs : C ( 35 %), Z ( 13 %), D ( 13 %). Concordant with this admixed hg make - up , PCA indicated a position close to present - day Siberians ( Figure 2 ) . This position did not change when potential maternal relationships among individuals were accounted for by excluding redundant haplotypes ( Figure S 2 B ) . The genetic relationship between aBOO and Siberians was also evident on the genetic distance map , where the area representing the lowest genetic distance covered a broader area of Siberia than for aUzPo ( Figure 3 B ) . The extant populations that showed most genetic similarity to aBOO were found in Central and East Siberia . In contrast , the area of maximum similarity for aUzPo lay in West Siberia ( Figure 3 A ) ; this observation however could be influenced by low sample size in aUzPo . Haplotype sharing analyses for aBOO confirmed the genetic affinity with modern - day West and Central / East Siberians inferred from the PCA ( Figure 4 ) , but also identified a close relationship with the VUB population pool . The distribution of haplotype matches observed in pools of the VUB , West Siberia and Central / East Siberia was partly due to the presence of basal C * ( 16223 T - 16298 C - 16327 T ) and D * ( 16223 T - 16362 C ) haplotypes in these pools , whereas these types were absent in Middle Eastern and European pools . Central Siberian Tuvinians displayed the highest percentage of shared haplotypes with aBOO ( 12 . 2 %) although all shared haplotypes belong to hgs C * and D *. A more explicit genetic link between aBOO and extant East Siberians was seen in the presence of the derived C 5 haplotype ( 16148 T - 16223 T - 16288 C - 16298 C - 16311 C - 16327 T ) in aBOO and in one single Buryat individual of Central Siberia [ 54 ] . The Z 1 a haplotype ( 16129 A - 16185 T - 16223 T - 16224 C - 16260 T - 16298 C ) detected in aBOO had a broad but interesting distribution in Eurasia . It was found in all Central / East Siberian pools except in Tuvinians , but also in the Bashkirs of the Urals , in the VUB pool , as well as in Scandinavian and Baltic populations ( Norwegians , Swedes , Finns , Ingrians , Karelians , and the Saami ) . Although haplotype sharing analyses revealed genetic links between aBOO and extant populations of NEE , a strong genetic differentiation was obvious between aBOO , modern - day NEE and Saami . This genetic discontinuity was further supported by BayeSSC analyses ( Figure 5 ; Table 3 ) . Similarly to aUzPo , a better fit was obtained for the model involving a 10 % migration from CE over the last 3 , 500 years ( H 1 b ; ω  =  1 . 00 E + 0 ) than for the model of genetic continuity between aBOO and NEE ( H 0 b ; ω  =  3 . 86 E - 10 ) . Comparison among ancient Eurasian populationsPreviously described populations of hunter - gatherers of Central / East Europe ( aHG [ 12 ] , [ 14 ] ) and Scandinavia ( aPWC , [ 13 ] ) were characterized by high frequencies and diversity of hg U 4 , U 5 a and U 5 b , which caused the two ancient datasets to group outside the cluster of extant European populations on the PCA plot ( Figure 2 ) . This matches previous studies that have shown that genetic continuity between hunter - gatherers and present - day Europeans can be rejected [ 12 ] –[ 13 ] . Like other European hunter - gatherers , aUzPo is characterized by high frequencies and diversity of hgs U 4 and U 5 , but was genetically differentiated from aHG and aPWC due to the occurrence of hg C . Despite the fact that high frequencies of hgs U 5 b and V cluster the aHG and aPWC hunter - gatherer groups on the PCA plot ( Figure 2 ) , and that these hgs are also common in modern - day Saami , the ‘ Saami motif ’ is absent from aPWC and genetic continuity between aPWC and modern - day Saami was rejected [ 13 ] . Although the aBOO individuals were also characterized by high frequencies of hg U , the group appeared less close to the Palaeolithic / Mesolithic hunter - gatherers aHG and aPWC on the PCA plot than aUzPo . Haplotype sharing analyses ( Figure 6 ) also showed that aBOO shared less haplotypes with aHG and aPWC than aUzPo ( 4 . 76 % and 0 . 00 %, respectively , versus 9 . 52 % and 36 . 84 %). This observation was confirmed by the analyses of our coalescent simulations , in which a model of genetic continuity between aHG , aPWC and aUzPo ( ω  =  9 . 91 E - 1 ; H 0 d ) was better supported than a model of genetic continuity between aHG , aPWC and aBOO ( ω  =  1 . 10 E - 4 ; H 0 e ) . As demonstrated above , aBOO exhibited greater genetic affinities with extant populations of Siberia than aUzPo . Accordingly , aBOO shared more haplotypes with ancient samples from Siberia aEG ( 10 . 87 % [ 55 ] ) and aKUR ( 7 . 69 % [ 56 ] ) than aUzPo ( 0 . 00 % and 7 . 69 %, respectively ; Figure 6 ) . Download : PPTPowerPoint slidePNGlarger imageTIFForiginal imageFigure 6 . Percentages of haplotypes from aUzPo and aBOO matched in selected ancient Eurasian populations . The cells were colored according to the gradient of percentages of shared haplotypes represented below the figure : from white for the lowest value of percentages of shared haplotypes ( 0 . 00 %) to dark blue for the highest value of percentages of shared haplotypes ( 36 . 84 % between aUzPo and aPWC ) . https : / / doi . org / 10 . 1371 / journal . pgen . 1003296 . g 006 DiscussionTo date , all studies on ancient Mesolithic / Palaeolithic hunter - gatherers from Europe have reported large proportions of hg U : 64 % in aUzPo , 73 % in aHG , 74 % in aPWC ; and hg U was also found in three out of five Mesolithic individuals of Spain [ 20 ] , [ 57 ] . on the basis of the distribution of hg U 5 b , it was proposed that the Mesolithic population has remained genetically homogeneous over a wide geographical area and for a long period of time [ 57 ] . The new data from aUzPo suggests that hg U 5 a may be a representative of Central and North East Europe ' s Mesolithic mtDNA diversity , whereas elevated frequencies of hg U 4 appear more characteristic of populations of the peri - Baltic area ( aUzPo and aPWC ) . Haplogroup U also represents a significant genetic component of aBOO ( 35 %), as well as Bronze Age Central Asians ( 14 % in aKAZ ; 2 , 700 – 3 , 400 yBP ) , and pre - Iron Age Siberians ( 54 % in aKUR ; Andronovo and Karasuk cultures ; 2 , 800 – 3 , 800 yBP ) . Today , hg U is found in 7 % of Europeans and displays a wide distribution in Europe , West Siberia , south west Asia , the Near East and North Africa [ 5 ] . Both the widespread distribution and high variability of hg U in extant and prehistoric populations are consistent with the description of hg U as one of the oldest hgs in Europe . on the basis of modern genetic data , hg U was proposed to have originated in the Near East and spread throughout Eurasia during the initial peopling by anatomically modern humans in the early Upper Palaeolithic ( around 45 , 000 yBP , [ 5 ] ) . It is then plausible that hg U constituted the major part of the Palaeolithic / Mesolithic mtDNA substratum from Southern , Central and North East Europe to Central Siberia . It can also be suggested that the Palaeolithic / Mesolithic mtDNA substratum has been preserved longer in NEE than in Central and southern parts of Europe , where new lineages arrived with incoming farmers during the Neolithisation from the Near East [ 16 ] . This is supported by ancient genomic data obtained from hunter - gatherers of Scandinavia [ 58 ] and Spain [ 57 ] , that shows a genetic affinity between Mesolithic individuals and present - day northern Europeans and supports genetic discontinuity between Mesolithic and Neolithic populations of Europe . The detection of haplogroup H in the Mesolithic site of aUz ( one haplotype ) is noteworthy . To date , haplogroup H has either been rare or absent in groups of hunter - gatherers previously described . It has not been found in hunter - gatherer mtDNA datasets of eastern Europe [ 12 ] and Scandinavia [ 13 ] , but has been found in two hunter - gatherers of the Upper Palaeolithic sites of La Pasiega and La Chora in northern Spain [ 20 ] . The closest match to the ancient H haplotype in aUzPo belongs to sub - haplogroup H 2 a 2 [ 59 ] , which is more common in eastern Europe [ 60 ] with highest frequencies in the Caucasus . Current ancient data is too scarce to investigate the past phylogeography of haplogroup H in full detail . However , together with U 4 , U 5 haplotypes this H haplotype suggests continuity of some maternal lineages in ( North ) East Europe since the Mesolithic . While the Mesolithic aUzPo site showed genetic affinities with extant populations of West Siberia in hg - based analyses , the precise genetic origins of aUzPo individuals was more difficult to identify from haplotypic data due to the high number of basal haplotypes . At the archaeological level also , the Siberian connection with aUzPo is less clear . The material culture present in the burials of aUz links these populations with the neighboring regions in the West but also in the East and South - East [ 26 ] , [ 61 ] . As for Siberia , it has undergone a complicated early and mid - Holocene migration history due to repeated environmental changes [ 62 ] . With the data at hand , it is therefore difficult to make any definite statement about sixth millennium connections between Karelia and Siberia . Interestingly , samples from aBOO , which are 4 , 000 years younger and located further North - West than aUzPo , were characterized by a large proportion and elevated diversity of mtDNA lineages showing a clear ‘ Central / East Siberian ’ origin ( hgs C , D , and Z ) . Haplogroups C and D are the most common hgs in northern , central and eastern Asia . They are thought to have originated in eastern Asia and expanded through multiple migrations after the Late Glacial Maximum ( ∼ 20 , 000 yBP [ 63 ] ) . Notably , haplotypic matches were observed between aBOO and modern - day central Siberian Buryats of the peri - Baikal region , which was proposed to be the origin of ancient migrations that disseminated hgs C and D [ 63 ] . Today , the sharp western boundary for the distribution of hgs C , D and Z lies in the VUB , where they display intermediate frequencies : C ( 0 . 3 – 11 . 8 %), Z ( 0 . 2 – 0 . 9 %), and D ( 0 . 6 – 12 %) [ 64 ] . Sub - hgs Z 1 and D 5 are also present in modern - day Saami , with highest cumulated frequencies ( 15 . 9 %) in the Saami of Finland , the easternmost part of the Saami geographical distribution [ 32 ] . A precise date for the arrival of these ‘ Central / East Siberian ’ lineages in NEE is difficult to estimate , although the presence of ‘ Central / East Siberian ’ lineages in the 3 , 500 year - old aBOO site indicates that an eastern genetic influence pre - dates historical westward expansions from Central / East Siberia of , e . g . , the Huns and the Mongols ( ∼ 400 – 1 , 500 AD ) . We present here direct genetic evidence for a prehistoric gene - flow from Siberia . on the basis of modern - day genetic data , hg Z 1 was proposed to have been introduced into populations of the VUB and Saami by migrations from Siberia via the southern Urals to the Pechora and Vychegda basins ( northwest Urals ) , associated with the appearance of the Kama culture ∼ 8 , 000 yBP [ 22 ] , [ 32 ] . The presence of hg Z 1 in aBOO establishes a direct genetic link between aBOO and modern - day populations of the VUB and Saami , and possibly indicates the trajectory of the migration that brought ‘ Central / East Siberian ’ lineages into NEE . The fact that aBOO did not contain any other Saami - specific haplotypes , suggests an independent origin and contribution of Z 1 to the Saami gene pool . The genetic links between the sample populations of aUzPo / aBOO and the extant populations of Siberia follow a general pattern discussed for the early and mid - Holocene ( 6 , 000 – 10 , 000 yBP ) . Facilitated by the East - West extension of vegetation zones between the Russian Far East and Eastern Europe [ 65 ] , long - distance contacts and connections across Eurasia have been proposed for a number of cases . For example , the North East and East European hunter - gatherer pottery is thought to have originated in the early ceramic traditions of the Russian Far East and Siberia [ 66 ] –[ 68 ] . An eastern Asian origin followed by a westward expansion was also discussed for domesticated broomcorn millet ( Panicum miliaceum L . ) [ 69 ] . While the exact scenario behind these two examples of long - distance connections is unclear , migrations are a common interpretative model for evidence from later periods [ 70 ] . In any case , long - distance connections across Eurasia are not unusual . A later migration from the East was associated with the spread of the Imiyakhtakhskaya culture from Yakutia ( East Siberia ) through northwestern Siberia to the Kola Peninsula during the Early Metal Age ( 3 , 000 – 4 , 000 yBP , [ 24 ] ) . Interestingly , one individual of the aBOO site ( grave 10 , not sampled for aDNA here ) was archaeologically associated with this culture , but its cultural relationships to other individuals of the same site remain unclear . The apparent genetic discontinuity between aUzPo and aBOO is consistent with craniometrical analysis that have proposed a genetic discontinuity between the two groups despite the finding of ‘ caucasoid ’ and unusual ‘ mongoloid ’ cranial features at both sites [ 28 ] . Samples of aBOO were also shown to display craniometrical affinities with ancient populations of West Siberia and the Altai , in line with the ancient genetic data presented here [ 42 ] . The ‘ admixed ’ nature of the aUzPo and aBOO populations is supported by the apparent random distribution of mtDNA lineages within the corresponding graveyards , i . e . , there is no structure in the sites reflecting the ‘ Western ’ or ‘ Eastern ’ origins of the buried individuals [ 26 ] . The present - day Saami populations display clear haplotypic differences from all the ancient populations sampled for DNA so far ( prehistoric hunter - gatherer populations of North / South / Central / East Europe , aUzPo and aBOO ) where none of the hg V and U 5 b 1 b 1 a lineages distinctive of the Saami could be detected . We show here that the mitochondrial ancestors of the Saami could not be identified in the ancient NEE populations of aUzPo or aBOO , despite the latter site being within the area occupied by Saami today . The widespread modern - day distribution of U 5 b 1 and V lineages makes it difficult to identify the origins of the Saami [ 32 ] . Sub - haplogroup U 5 b 1 b 1 to which the ‘ Saami motif ’ belongs was proposed to have originated and spread from southern / central Europe after the Late Glacial Maximum [ 32 ] –[ 33 ] . Despite its clear association with Saami ancestry , the ‘ Saami motif ’ also occurs at low frequency ( below 1 %) in a wide range of non - Saami populations in Europe , and haplotypes closely related to the ‘ Saami motif ’ have even been found in modern Berbers of North Africa [ 33 ] . Two origins have been proposed on the basis of archaeological and genetic evidence [ 24 ] , [ 32 ] . First , ancestors of the Saami were suggested to have reached Fennoscandia from Western Europe along the Atlantic cast of Norway as part of the expansion of Mesolithic post - Ahrensburgian cultures ( Fosna - Hensbacka and Komsa ) in the early Holocene ( ∼ 10 , 000 – 11 , 000 yBP ) . Alternatively , the Saami were proposed to find their origins in Mesolithic post - Swiderian cultures ( Kunda , Veretye , Suomusjärvi ) , which had moved from Poland into NEE also in the early Holocene [ 24 ] . The data from aUzPo , in which neither U 5 b 1 or V could be detected , does not support the latter hypothesis . If migrations brought U 5 b 1 and V to Fennoscandia from the East , they must have occurred after 7 , 500 yBP or have had a weak genetic impact on surrounding populations of NEE . Saami mtDNA diversity has been influenced by a combination of founder event ( s ) , ( multiple ) bottlenecks , and reproductive isolation , which are likely due to the challenging conditions of life in the subarctic taiga / tundra [ 32 ] . The complex demographic history of Saami renders their population history difficult to reconstruct on the basis of modern genetic data alone . Further temporal population samples will be required , especially along the proposed alternative western migration route into sub - arctic Europe . Individuals from 7 , 500 year - old aUzPo and 3 , 500 year - old aBOO show remarkable genetic dissimilarities with present - day North East Europeans : high frequencies of hg U , the presence of mtDNA lineages of ‘ Central / East Siberian ’ origin , and near absence ( one out of 34 samples ) of hg H which comprises up to ∼ 50 % in extant European populations [ 5 ] . The results of our coalescent simulation analyses show that the models that take account of genetic input ( s ) from CE are better supported and could explain the genetic discontinuity observed between either aUzPo or aBOO and the modern population of NEE ( Figure 5 ) . The mtDNA lineages with a clear Central / Western European signature and currently prevalent in NEE might have reached the western Baltic and southern Scandinavia during the continuing influx of farming populations from Central or lastly southeastern Europe [ 13 ] , [ 58 ] , as from 6 , 000 yBP onwards [ 71 ] –[ 74 ] . However , intruding Neolithic farmers never reached Karelia and Fennoscandia [ 75 ] , so the change in population would have to be a post - Neolithic process or to be due to migrations from other sources . The major prehistoric migration in this area was associated with the spread of early pottery from the East into the Baltic , Karelia and Fennoscandia starting around 7 , 000 yBP . This migration might have contributed to an early population change in Karelia and Fennoscandia as well , but the mtDNA characteristics of the populations involved is presently unknown [ 76 ] –[ 78 ] . As for Siberia , a general push - back of populations by an expansion of populations from the South - West is discussed [ 62 ] . Thus , the present - day distribution of populations similar to aUzPo and aBOO might just be a remnant of a once much larger extension across western and Central northern Eurasia , which is consistent with frequencies of hgs U 4 and U 5 , i . e . the Palaeolithic / Mesolithic genetic substratum , have remained higher in extant populations of NEE , the VUB and Western Siberia than in central Europeans , where these were largely replaced at the onset of the Neolithic [ 16 ] , [ 79 ] . Genetic discontinuity between aUzPo , aBOO and present - day populations of NEE was also observed at the haplotype level , as seen by the lack of matches between lineages from ancient individuals and from present - day NEE ( e . g . , ‘ Central / East Siberian ’ lineages in aBOO ) , or by their total absence in all Eurasian populations of the comparative dataset . A good example is the haplotype C 1 found in aUzPo , which is absent in modern - day Eurasians and in all other foraging populations of Europe . This indicates that hg C 1 was rare and probably preserved in aUzPo by a relative reproductive isolation , previously proposed for Mesolithic hunter - gatherers of NEE on the basis of odontometric [ 41 ] and craniometric [ 80 ] analyses . These results do not exclude a common origin for European foragers but highlight differentiating consequences of post - glacial founder effects followed by reproductive isolation among Palaeolithic / Mesolithic groups . Genetic discontinuity between prehistoric populations of Europe may have been caused by the random loss of genetic diversity through drift , which is likely to have been accelerated in small and isolated groups , such as aUzPo and aBOO . In the Kola Peninsula , the scarcity in the archaeological records observed in the Kola Peninsula for the Early Metal Age was interpreted as an indication of drastic size reductions of human groups , as a response to deteriorating climatic conditions ∼ 2 , 500 yBP [ 24 ] . This could have lead to the local extinction of mtDNA lineages of Siberian origin detected in aBOO in the Kola Peninsula . Overall , our results illustrate the power of aDNA to reconstruct the complex genetic history of NEE , which is made of past migrations from both Siberia and Europe . Ancient DNA also reveals the plasticity of demographic events in human populations at both the scale of NEE and Eurasia . Future accumulation of genetic data from ancient populations will make it possible to establish more genetic relationships between past human populations in space and time . Materials and MethodsSample description and archaeological contextA total of 146 human teeth — representing 74 individuals — were collected from three archaeological sites in northwestern Russia : Yuzhnyy Oleni Ostrov , Popovo , and Bolshoy Oleni Ostrov ( under custody of the Kunstkamera Museum , St Petersburg , Russia ; Figure S 1 , Table S 2 ) . The oldest samples were collected in the Mesolithic graveyards of Yuzhnyy Oleni Ostrov ( aUz ; ‘ Southern Reindeer Island ’ in Russian ) and Popovo ( aPo ) . Ninety - six teeth representing 48 individuals were obtained from the Yuzhnyy Oleni Ostrov archaeological site , which is located on Yuzhnyy Oleni Island , onega Lake , Karelia ( 61 ° 30 ′ N 35 ° 45 ′ E ) . The site was first discovered in the 1920 s during quarrying excavations , which led to the subsequent destruction of most parts of the graveyard . Scientific excavation of the site by Soviet archaeologists in the 1930 s and the 1950 s eventually unearthed a total of 177 individuals in 141 different mortuary features [ 81 ] . The population size of the burial ground before its partial destruction was estimated at around 500 individuals [ 82 ] . The Yuzhnyy Oleni Ostrov graveyard stands out from other Mesolithic sites in Europe by its abundance and diversity of mortuary features . First identified as a Neolithic graveyard , a later reanalysis and radiocarbon dating revealed an age of around 7 , 000 – 7 , 500 uncal . yBP [ 83 ] . For Popovo , 6 teeth belonging to 3 individuals were obtained from the archaeological site located on the bank of the Kinema River , in the Archangelsk region ( 64 ° 32 ′ N 40 ° 32 ′ E ) . The wide range of dates obtained for this site ( 9 , 000 – 9 , 500 uncal . yBP and 7 , 500 – 8 , 000 uncal . yBP [ 84 ] ) . We expect that the radiocarbon dates for both the sites of Popovo and Yuzhnyy Oleni Ostrov will be revised , as potential freshwater - derived reservoir effects impacting the dates are currently investigated ( T . Higham , personal communication ) . The sites of aUz and aPo are located along one of the proposed eastern routes for the introduction of Saami - specific mtDNA lineages [ 32 ] . Results from odontometric analyses suggested a direct genetic continuity between the Mesolithic population of Yuzhnyy Oleni Ostrov and present - day Saami [ 41 ] . Due to the small sample size , and the temporal and geographic proximity of aPo and aUz , the specimens from these sites were pooled for statistical analyses ( aUzPo ) . We also analyzed human remains from the Early Metal Age archaeological site of Bol ' shoy Oleni Ostrov ( aBOO ; ‘ Great Reindeer island ’ in Russian ) in the Kola Peninsula . This site is located within the area currently inhabited by Saami individuals . Fourty - five teeth representing 23 individuals were obtained from this archaeological site , located in the Murmansk region , Kola Peninsula ( 68 ° 58 ′ N 33 ° 05 ′ E ) . Several excavation campaigns have been undertaken between 1927 and 2006 . Radiocarbon dates for two graves were obtained from the Oxford Radiocarbon Accelerator Unit , United Kingdom , and revealed an age of around 3237 ± 32 yBP ( calibrated dates in years before 1950 , 3525 – 3440 BC ( 68 . 2 %) and 3610 – 3420 BC ( 95 . 4 %)) and 3195 ± 39 yBP ; calibrated dates , 3500 – 3430 BC ( 68 . 2 %) and 3530 – 3390 BC ( 95 . 4 %)) for grave 12 and grave 13 , respectively , corresponding to the Early Metal Age . The organic preservation of artifacts made of bone , antlers and wood in this site is exceptional for this time period and geographical location [ 42 ] . Ancient DNA workDNA isolation , amplification and quantitation were performed at the aDNA laboratory of the Australian Centre for Ancient DNA ( ACAD ) , University of Adelaide . Whenever possible , two distinct teeth were analyzed for each ancient individual . The outer surface of each tooth was decontaminated , first , through exposure to ultra - violet ( UV ) light for 20 min on each side , then , through gentle wiping using a paper towel soaked in sodium hypochlorite ( bleach ) . The protocol described in [ 85 ] was followed to isolate DNA from powdered teeth . Given the archaeological and anthropological value of the samples from aUz , aPo and aBOO , their morphological integrity had to be maintained : tooth powder was collected by cutting off the crown of each tooth and drilling inside the root using a dental drill at low speed . Collecting material from only the dental pulp and dentin may prevent the risk of contamination by exogenous DNA , as the inside of the teeth may be protected from the environment by the enamel . The mtDNA HVR - I was amplified and sequenced between np 16056 and 16410 as described in [ 85 ] . The GenoCore 22 reaction described in [ 85 ] was used to type 22 haplogroup - diagnostic SNPs in the mtDNA coding - region ( Table S 3 ) . Twenty - two fragments of mtDNA were amplified simultaneously in a multiplex reaction and SNPs were detected using Single - Base Extension ( SNaPshot kit , Applied Biosystems ) . The copy - number of two HVR - I fragments - L 16209 / H 16303 ( 133 bp ) and L 16209 / H 16348 ( 179 bp ) - was estimated in selected aDNA extracts ( individuals UZOO - 43 , UZOO - 79 , BOO 72 - 1 , and BOO 72 - 9 ) by quantitative real - time PCR following the protocol detailed in [ 16 ] ( Table S 4 ) . Six individuals were randomly selected ( UZOO - 77 , BOO 57 - 1 , BOO 72 - 1 , BOO 72 - 4 , BOO 72 - 7 , and BOO 72 - 15 ) , for which the second sample was sent to G . B . at the Johannes Gutenberg University of Mainz for independent replication of DNA extraction , HVR - I amplification and direct sequencing . PCR products were cloned and sequenced . Ancient DNA work at the Johannes Gutenberg University was carried out according to protocols described in [ 85 ] . Authentication of the mtDNA dataStrict precautions were taken in order to minimize the risk of contamination by modern DNA and detect artefactual mutations arising from contamination and aDNA degradation . Seven criteria support the authenticity of the mtDNA data presented here . Pre - PCR DNA work was carried out at the ACAD , a purpose - built laboratory dedicated to aDNA studies . The laboratory is under positive air - pressure and physically isolated from any molecular biology laboratory amplifying DNA . Routine decontamination of the laboratory surfaces and instruments involves exposure to UV radiation and thorough cleaning using bleach , decon 90 ( decon ) and ethanol . In order to protect the laboratory environment from modern human DNA , researchers are required to wear protective clothes consisting of a whole body suit , a face - mask , a face - shield , gumboots , and three pairs of surgical gloves that are changed between individual working steps . Blank controls ( one extraction blank for every five ancient samples and two PCR / GenoCoRe 22 blank controls for every six reactions ) allowed monitoring and controlling large - scale and systematic contamination within the laboratory or in the reagents . In addition , haplotypes similar to those of the users of the laboratory could not be observed from aDNA extracts . Mitochondrial DNA data from the archaeologists and anthropologists involved in the collection of the samples was not available . However , we estimate as rather low the probability that contamination by a few modern - day individuals would generate the diversity and specific patterns of mtDNA lineage distribution observed in the ancient populations under investigation . Multiple replications of HVR - I amplification and direct sequencing were performed in order to detect artefactual sequences due to contamination , DNA degradation or jumping PCR events . When possible , two teeth were collected for each individual and DNA was extracted independently from each sample ( i . e . , a minimum of two extractions per individual ) . For each extract , each PCR fragment and each GenoCore 22 SNP position was genotyped from at least two independent PCR products ( i . e . , a minimum of four independent PCRs per fragment and four GenoCoRe 22 reactions per individual ) . This strategy was chosen over cloning for most of the individuals examined here . In low - template conditions , clone sequences can represent the small population of highly degraded starting DNA templates that were exponentially amplified by the one single PCR . In our opinion , a hierarchical replication strategy based on multiple independent amplifications is a powerful alternative to cloning in order to detect artefactual mutations and provides confidence about the authenticity of our DNA sequences . The independent replications of DNA extraction / amplification / direct sequencing carried out at the Johannes Gutenberg University confirmed the diagnostic mutations initially identified at the ACAD in the six selected individuals : UZOO - 77 , BOO 57 - 1 , BOO 72 - 1 , BOO 72 - 4 , BOO 72 - 7 , and BOO 72 - 15 ( Figure S 3 ) . Sequencing of cloned PCR products for six individuals ( individuals UZOO - 77 , BOO 57 - 1 , BOO 72 - 1 , BOO 72 - 4 , BOO 72 - 7 , and BOO 72 - 15 ) allowed the corresponding haplotypes to be verified . The sequences showed nucleotide positions modified by post - mortem damage as inconsistent cytosine to thymine or guanine to adenosine base changes ( Figure S 3 ) . For one individual ( BOO 57 - 1 ) , independent replications and cloning did not allow allelic resolution at np 16390 R . At this position , double peaks ( A / G ) were observed in direct sequencing , and alleles A and G showed an equal distribution among clones ( Figure S 3 B ) . This position might be heteroplasmic in the BOO 57 - 1 individual , as np 16390 has been described as a mutational hotspot [ 86 ] , and therefore might as well be a hotspot for post - mortem DNA damage exhibiting a high rate of post - mortem cytosine deamination . The amount of template mtDNA molecules for two fragments of different sizes ( 133 bp and 179 bp ) was estimated and compared in order to test whether they were consistent with low concentrations of recent human mtDNA contaminants in six selected aDNA extracts ( UZOO 43 , UZOO 74 , BOO 72 - 1 , BOO 79 - 9 , and two ancient co - extracts from a related study ; data not shown ) . The size distribution of endogenous aDNA molecules was previously shown to be skewed towards smaller fragment sizes due to post - mortem damage , i . e . DNA fragmentation [ 87 ] –[ 90 ] . Here , the Shapiro - Wilk W test was first used to verify that the number of copies for each fragment followed a normal distribution ( p  =  0 . 2215 for the 133 bp short fragment and p  =  0 . 5381 for the 179 bp long fragment ) . A significantly larger number of copies for the shorter ( 133 bp ) compared to the larger ( 179 bp ) fragment was statistically confirmed by a one - tailed paired t - test ( p  =  0 . 04337 ) in R version 2 . 12 ( R Development Core Team , http : / / www . R - project . org ) . Quantitative PCR results suggest a low level of contaminating DNA molecules , the presence of which would have been detected by higher copy - number of longer ( less fragmented ) DNA molecules . The phylogenetic consistency of the haplotypes and matching hgs assignments of both HVR - I data and coding region SNPs , were indicative of the robustness of the mtDNA typing approach presented here . Populations used in comparative analysesMitochondrial DNA data from aUzPo and aBOO were compared to data obtained from other ancient and present - day populations . Data for extant populations were compiled in the MURKA mtDNA database and integrated software , which currently contains 168 , 000 HVR - I records from published studies and is curated by co - authors V . Z . , O . B . and E . B . of the Russian Academy of Medical Sciences , Moscow . A sub - sample of 91 ancient and modern Eurasian populations ( ∼ 28 , 652 individuals ) was used for comparative analysis . Names of modern - day populations were abbreviated using ISO codes in capital letters , and in small letters when ISO codes were not available . Unless specified otherwise , the same population labels were used for all the maps and analyses in this study , i . e . , PCA , haplotype sharing and analysis of coalescent simulations ( Table S 5 ) . Principal Component AnalysisPCA was performed using the hg frequency database for ancient and modern - day populations described in Table S 5 . We used a total of 19 variables to perform the PCA . Seventeen of these variables were frequencies of hgs C , D , H , HV , I , J , K , N 1 , T , U 2 , U 4 , U 5 a , U 5 b , V , W , X , and Z . In addition , the frequencies of six ‘ east Eurasian ’ hgs were pooled into one ‘ EAS ’ group including hgs A , B , E , F , G , and Y . Finally , frequencies of eight hgs found at lower frequencies in Eurasia were pooled into the ‘ misc ’ group including hgs L , M *, N *, U 1 , U 6 , U 7 , U 8 . By pooling and removing rare hgs ( with frequencies below 1 %) we could reduce statistical noise . In order to assess the impact of potential maternal kinship within the sites of aUzPo and aBOO , we performed an additional PCA , in which redundant haplotypes , i . e . haplotypes found in more than one individual at a given site , were counted only once ( Figure S 2 A and Figure S 2 B ) . PCA was carried out using a customized script based on the function prcomp in R version 2 . 12 ( R Development Core Team , http : / / www . R - project . org ) . Genetic distance mappingThe genetic distances between 144 pools of extant Eurasian populations and each of the aUzPo and aBOO populations were calculated using the software DJ ( written by Yuri Seryogin , and freely available at http : / / genofond . ru , also see [ 29 ] ) . The software GeneGeo written by S . K . was used to plot genetic distances onto geographic maps ( as described in [ 16 ] ) . Haplotype sharing analysisIn haplotype sharing analyses , we calculated the percentages of shared haplotypes between 29 extant populations and the ancient populations of aUzPo and aBOO . A database of mtDNA haplotypes was collated for modern - day populations , each containing 500 individuals . We pooled populations of less than 500 individuals on the basis of their geographical and / or linguistic similarities . For extant populations of more than 500 individuals , we randomly sub - sampled 500 individuals from the populations . For each haplotype of aUzPo and aBOO , we counted the number of haplotype matches found in each of the extant populations of the comparative database . This number was divided by the sample size in order to obtain the percentage of shared haplotypes . The same procedure was applied to calculate the percentage of shared haplotypes between the ancient populations studied here ( aUzPo and aBOO ) and previously described ancient populations . Percentages of shared haplotypes between ancient and present - day populations were represented in a bar plot . Percentages of shared haplotypes among ancient populations were represented in a table , the cells of which were colored according to a gradient reflecting the haplotypic similarities between the populations compared . Coalescent simulationsIn coalescent simulation analyses we considered the ancient populations of aUzPo , aBOO , Central / East / Scandinavian European hunter - gatherers ( aHG [ 12 ] , [ 14 ] , aPWC [ 13 ] ) , and the modern populations of NEE , CE , and Saami ( saa ) . Population statistics ( haplotype diversity and fixation indexes , FST ) for the ancient and extant populations were calculated in Arlequin version 3 . 11 ( Table 2 , [ 91 ] ) . In BayeSSC [ 49 ] , genealogies were simulated under the following model of sequence evolution : a generation time of 25 years , a mutation rate of 7 . 5 . 10 − 6 substitutions / per site / per generation [ 92 ] , a transition / transversion ratio of 0 . 9841 , and parameters for the gamma distribution of rates along the sequence of 0 . 205 ( theta ) and 10 ( kappa ) [ 16 ] . Under the models of genetic continuity H 0 , the effective population size ( Ne ) of a single population was allowed to grow exponentially . The values of the growth rate were drawn from a uniform prior distribution , such that the population has evolved from a Palaeolithic population of Ne 5 , 000 that lived 1 , 500 generations ago . The values for the modern - day ( NEE or saa ) Newere drawn from a uniform distribution : we explored present - day Ne between 100 , 000 and 30 , 000 , 000 for NEE and 1 , 000 to 500 , 000 for saa . Population statistics were estimated at various points in time , corresponding to the age of the ancient populations considered in models H 0 a to H 0 e ( aUzPo , aBOO , aHG and aPWC ) . Under the models of migration H 1 , we assumed a single NEE population undergoing an exponential growth in Ne and being the recipient ( sink population ) of a migration from CE ( source population ) . Population sizes of each of the present - day sink population ( NEE ) and source population ( CE ) were drawn from a uniform distribution of Ne varying from 100 , 000 to 15 , 000 , 000 individuals . Migration and divergence times were estimated from uniform distributions ( from 2 to 139 generations for migration and from 620 to 2 , 600 generations for divergence ) . Three different percentages of the source population size were tested for the value of percentages of migrants : 10 %, 50 % and 75 %. Population statistics were calculated for 100 , 000 genealogies simulated using BayeSSC ( available at http : / / www . stanford . edu / group / hadlylab / ssc / index . html ) . The distribution of six selected population statistics ( haplotype diversity and fixation indices FST ) were drawn from the simulations and compared to the corresponding observed population statistics in an ABC framework [ 50 ] , [ 93 ] . The 1 % of the simulations for which simulated population statistics exhibited the smallest Euclidian distance with observed population statistics was retained to construct posterior distributions of population parameters . From these distributions , values of population parameters that optimized the likelihood of a given model were estimated and used in replacement of priors in demographic models . We finally generated 10 , 000 genealogies in BayeSSC for these models . BayeSSC outputs were analyzed in R version 2 . 12 using scripts available on request at http : / / www . stanford . edu / group / hadlylab / ssc / index . html . Goodness of fit of the different models tested was compared using AICs [ 51 ] and Akaike ' s weights ω [ 52 ] –[ 53 ] ( Table 3 ) . Accession numbersThe Genbank accession numbers for the 34 mtDNA sequences reported in this paper are KC 414891 – KC 414924 . Supporting Information Figure _ S 1 . pdf figshare 1 / 8 downloadPictures of selected samples from Yuzhnyy Oleni Ostrov , Popovo and Bol ' shoy Oleni Ostrov . The macroscopic preservation of the selected samples is representative of the general preservation observed in the corresponding sites . Yuzhnyy Oleni Ostrov sample ACAD 4719 did not yield reliable mitochondrial hypervariable region I sequences . Figure S 1 . Pictures of selected samples from Yuzhnyy Oleni Ostrov , Popovo and Bol ' shoy Oleni Ostrov . The macroscopic preservation of the selected samples is representative of the general preservation observed in the corresponding sites . Yuzhnyy Oleni Ostrov sample ACAD 4719 did not yield reliable mitochondrial hypervariable region I sequences . https : / / doi . org / 10 . 1371 / journal . pgen . 1003296 . s 001 ( PDF ) Figure S 2 . Principal Component Analysis of mtDNA haplogroup frequencies , non - redundant ancient haplotypes only . A . Recalculated frequencies . B . PCA plots . The first two dimensions account for 42 . 4 % of the total variance . Grey arrows represent hg loading vectors , i . e . , the contribution of each hg . Red dots represent ancient populations described in this study ( non - redundant haplotypes only ) : aUzPo 2 , Yuzhnyy Oleni Ostrov / Popovo ( 7 , 500 uncal . yBP ) ; aBOO 2 , Bol ' shoy Oleni Ostrov ( 3 , 500 uncal . yBP ) . Other ancient populations were labelled as follows : aEG , confederated nomads of the Xiongnu ( 4 , 250 - 2 , 300 yBP ) ; aHG , Palaeolithic / Mesolithic hunter - gatherers of Central / East Europe ( 4 , 250 - 30 , 000 yBP ) ; aKAZ , Nomads from Kazakhstan ( 2 , 100 – 3 , 400 yBP ) ; aKUR , Siberian Kurgans ( 1 , 600 – 3 , 800 yBP ) ; aLBK , Neolithic individuals from Germany ( 7 , 000 – 7 , 500 yBP ) ; aLOK , Lokomotiv Kitoi Neolithic individuals ( 6 , 130 – 7 , 140 yBP ) ; aSP , Neolithic individuals from Spain ( 5 , 000 – 5 , 500 yBP ) ; aPWC , Scandinavian Pitted - Ware Culture foragers ( 4 , 500 – 5 , 300 yBP ) ; aUST , Ust ' Ida Neolithic population ( 4 , 000 – 5 , 800 yBP ) . Extant populations were abbreviated as follows : ALB , Albanians ; ale , Aleuts ; alt , Altaians ; ARM , Armenians ; aro , Arorums ; AUT , Austrians ; AZE , Azerbaijani ; BA , Bashkirs ; bas , Basques ; BEL , Belarusians ; BGR , Bulgarians ; BIH , Bosnians ; BU , Buryats ; CHE , Swiss ; CHU , Chukchi ; CU , Chuvashes ; CYP , Cypriots ; CZE , Czechs ; DEU , Germans ; esk , Eskimos ; ESP , Spanish ; EST , Estonians ; eve , Evenks ; evn , Evens ; FIN , Finns ; FRA , French ; GBR , British ; GEO , Georgians ; GRC , Greeks ; HRV , Croatians ; HUN , Hungarians ; ing , Ingrians ; IRL , Irish ; IRN , Iranians ; IRQ , Iraqi ; ISL , Icelanders ; IT - 88 , Sardinians ; ITA , Italians ; JOR , Jordanians ; kab , Kabardians ; ket , Kets ; kham , Khamnigans ; khan , Khants ; KK , Khakhassians ; KO , Komi ; kor , Koryaks ; KR , Karelians ; kur , Kurds ; LTU , Lithuanians ; LVA , Latvians ; man , Mansi ; ME , Mari ; MNG , Mongolians ; MO , Mordvinians ; NEN _ A , eastern Nenets ; NEN _ E , western Nenets ; nga , Nganasans ; niv , Nivkhs ; nog , Nogays ; NOR , Norwegians ; POL , Poles ; PRT , Portuguese ; PSE , Palestinans ; ROU , Romanians ; RUS , Russians ; SA , Yakuts ; saa , Saami ; SAU , Saudi Arabians ; SE , Ossets ; sel , Selkups ; sho , Shors ; SVK , Slovakians ; SVN , Slovenians ; SWE , Swedes ; SYR , Syrians ; TA , Tatars ; tel , Telenghits ; tof , Tofalars ; tub , Tubalars ; TUR , Turks ; tuv , Tuvinians ; UD , Udmurts ; UKR , Ukrainians ; ulc , Ulchi ; vep , Vepses ; yuk , Yukaghirs . https : / / doi . org / 10 . 1371 / journal . pgen . 1003296 . s 002 ( PDF ) Figure S 3 . Direct and clone sequences for six selected samples . A . UZOO 77 . B . BOO 57 - 1 . C . BOO 72 - 1 . D . BOO 72 - 4 . E . BOO 72 - 7 . F . BOO 72 - 15 . “ _ 1 ” after the individual identification number signifies that the sequences have been obtained after DNA extraction and sequencing from a first sample at the Australian Centre for Ancient DNA . “ _ 2 ” after the individual identification number signifies that the sequences have been obtained after DNA extraction , cloning and sequencing from a second sample at the Institute of Anthropology , Johannes Gutenberg University of Mainz . https : / / doi . org / 10 . 1371 / journal . pgen . 1003296 . s 003 ( PDF ) Table S 1 . Description and references for hg C 1 HVR - I sequences found in modern - day populations of Eurasia . https : / / doi . org / 10 . 1371 / journal . pgen . 1003296 . s 004 ( PDF ) Table S 2 . Grave and museum collection number for Yuzhnyy Oleni Ostrov , Popovo and Bol ' shoy Oleni Ostrov specimens . https : / / doi . org / 10 . 1371 / journal . pgen . 1003296 . s 005 ( PDF ) Table S 3 . Results of SNP typing in the mtDNA coding region using the GenoCore 22 SNaPshot assay . SNPs typed on the L - strand are reported in capital letters in the reference rCRS profile , whereas SNPs typed on the H - strand are reported in small letters . Missing data signifies allelic dropout or fluorescence signal below the background threshold ( 100 relative fluorescent units , rfu ) . ‘ g / a ’ indicates the presence of a mixed signal for the position interrogated . A mixed signal was repeatedly obtained at position 8994 ( haplogroup W ) with the detection of an additional G base . However , the rest of the profile never could support phylogenetically the presence of the G base at this particular position . For each individual , profiles were obtained from two independent extracts , except for individual BOO 72 - 9 for which a second samples was not available and for UZOO - 77 , BOO 57 - 1 , BOO 72 - 10 , BOO 72 - 4 , BOO 72 - 7 , BOO 72 - 15 , and BOO 72 - 1 , for which the second individual was extracted in an independent laboratory . rCRS , revised Cambridge Reference Sequence ; hg , haplogroup . https : / / doi . org / 10 . 1371 / journal . pgen . 1003296 . s 006 ( PDF ) Table S 4 . Results of quantitative PCR . https : / / doi . org / 10 . 1371 / journal . pgen . 1003296 . s 007 ( PDF ) Table S 5 . Details of ancient and modern - day populations used in comparative analyses . https : / / doi . org / 10 . 1371 / journal . pgen . 1003296 . s 008 ( PDF ) AcknowledgmentsWe thank Simon Longstaff for his advice regarding the ethics of this research . We thank Marta Kasper for help with project logistics ; Agnar Helgason , Martin Richards , Jeremy Austin , Jessica Metcalf , David Soria , and Andrew Clarke for helpful comments . Members of The Genographic Project Consortium : Syama Adhikarla ( Madurai Kamaraj University , Madurai , Tamil Nadu , India ) , Christina J . Adler ( University of Adelaide , South Australia , Australia ) , Jaume Bertranpetit ( Universitat Pompeu Fabra , Barcelona , Spain ) , Andrew C . Clarke ( University of Otago , Dunedin , New Zealand ) , David Comas ( Universitat Pompeu Fabra , Barcelona , Spain ) , Matthew C . Dulik ( University of Pennsylvania , Philadelphia , Pennsylvania , United States ) , Jill B . Gaieski ( University of Pennsylvania , Philadelphia , Pennsylvania , United States ) , ArunKumar GaneshPrasad ( Madurai Kamaraj University , Madurai , Tamil Nadu , India ) , Marc Haber ( Universitat Pompeu Fabra , Barcelona , Spain ; Lebanese American University , Chouran , Beirut , Lebanon ) , Li Jin ( Fudan University , Shanghai , China ) , Matthew E . Kaplan ( University of Arizona , Tucson , Arizona , United States ) , Shilin Li ( Fudan University , Shanghai , China ) , Begoña Martínez - Cruz ( Universitat Pompeu Fabra , Barcelona , Spain ) , Elizabeth A . Matisoo - Smith ( University of Otago , Dunedin , New Zealand ) , Nirav C . Merchant ( University of Arizona , Tucson , Arizona , United States ) , R . John Mitchell ( La Trobe University , Melbourne , Victoria , Australia ) , Amanda C . Owings ( University of Pennsylvania , Philadelphia , Pennsylvania , United States ) , Laxmi Parida ( IBM , Yorktown Heights , New York , United States ) , Ramasamy Pitchappan ( Madurai Kamaraj University , Madurai , Tamil Nadu , India ) , Daniel E . Platt ( IBM , Yorktown Heights , New York , United States ) , Lluis Quintana - Murci ( Institut Pasteur , Paris , France ) , Colin Renfrew ( University of Cambridge , Cambridge , United Kingdom ) , Daniela R . Lacerda ( Universidade Federal de Minas Gerais , Belo Horizonte , Minas Gerais , Brazil ) , Ajay K . Royyuru ( IBM , Yorktow Heights , New York , United States ) , Fabrício R . Santos ( Universidade Federal de Minas Gerais , Belo Horizonte , Minas Gerais , Brazil ) , Theodore G . Schurr ( University of Pennsylvania , Philadelphia , Pennsylvania , United States ) , Himla Soodyall ( National Health Laboratory Service , Johannesburg , South Africa ) , David F . Soria Hernanz ( National Geographic Society , Washington , District of Columbia , United States ) , Pandikumar Swamikrishnan ( IBM , Somers , New York , United States ) , Chris Tyler - Smith ( The Wellcome Trust Sanger Institute , Hinxton , United Kingdom ) , Arun Varatharajan Santhakumari ( Madurai Kamaraj University , Madurai , Tamil Nadu , India ) , Pedro Paulo Vieira ( Universidade Federal do Rio de Janeiro , Rio de Janeiro , Brazil ) , Miguel G . Vilar ( University of Pennsylvania , Philadelphia , Pennsylvania , United States ) , R . Spencer Wells ( National Geographic Society , Washington , District of Columbia , United States ) , Pierre A . Zalloua ( Lebanese American University , Chouran , Beirut , Lebanon ) , and Janet S . Ziegle ( Applied Biosystems , Foster City , California , United States ) . Author ContributionsConceived and designed the experiments : CDS WH OB AC . Performed the experiments : CDS WH GB . Analyzed the data : CDS WH OB VZ SK . 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