1/16/2016 GeneticEvidenceontheOriginsofIndianCastePopulations

GenomeRes.2001Jun11(6):994
1004.
PMCID:PMC311057
doi:10.1101/gr.173301

GeneticEvidenceontheOriginsofIndianCastePopulations
MichaelBamshad, 1,10,12ToomasKivisild, 2W.ScottWatkins, 3MaryE.Dixon, 3ChrisE.Ricker, 3BaskaraB.Rao, 4J.Mastan
Naidu, 4B.V.RaviPrasad, 4,5P.GovindaReddy, 6AraniRasanayagam, 7SurinderS.Papiha, 8RichardVillems, 2AlanJ.Redd, 7
MichaelF.Hammer, 7SonV.Nguyen, 9MarionL.Carroll, 9MarkA.Batzer, 9,11andLynnB.Jorde3
1 2
DepartmentofPediatrics,UniversityofUtah,SaltLakeCity,Utah84112,USA InstituteofMolecularandCellBiology,TartuUniversityandEstonian
3 4
Biocentre,Tartu51010,Estonia DepartmentofHumanGenetics,UniversityofUtah,SaltLakeCity,Utah84112,USA DepartmentofAnthropology,
5 6
AndhraUniversity,Visakhapatnam,AndhraPradesh,India AnthropologicalSurveyofIndia,Calcutta,India DepartmentofAnthropology,Universityof
7
Madras,Madras,TamilNadu,India LaboratoryofMolecularSystematicsandEvolution,UniversityofArizona,Tucson,Arizona85721,USA
8 9
DepartmentofHumanGenetics,UniversityofNewcastleuponTyne,UK DepartmentofPathology,BiometryandGenetics,Biochemistryand
MolecularBiology,StanleyS.ScottCancerCenter,LouisianaStateUniversityHealthScienceCenter,NewOrleans,Louisiana70112,USA
10
Presentaddress:EcclesInstituteofHumanGenetics,15North2030East,Room2100,UniversityofUtah,SaltLakeCity,UT841125330,USA.
11
Presentaddress:DepartmentofBiologicalSciences,BiologicalComputationandVisualizationCenter,LouisianaStateUniversity,508LifeSciences
Building,BatonRouge,LA70803,USA.
12
Correspondingauthor.

Received2000Nov29Accepted2001Mar22.

Copyright2001,ColdSpringHarborLaboratoryPress

ThisarticlehasbeencitedbyotherarticlesinPMC.

Abstract Goto:

Theoriginsandaffinitiesofthe1billionpeoplelivingonthesubcontinentofIndiahavelongbeencontested.
Thisisowing,inpart,tothemanydifferentwavesofimmigrantsthathaveinfluencedthegeneticstructureofIndia.
Inthemostrecentofthesewaves,IndoEuropeanspeakingpeoplefromWestEurasiaenteredIndiafromthe
Northwestanddiffusedthroughoutthesubcontinent.Theypurportedlyadmixedwithordisplacedindigenous
Dravidicspeakingpopulations.SubsequentlytheymayhaveestablishedtheHinducastesystemandplaced
themselvesprimarilyincastesofhigherrank.ToexploretheimpactofWestEurasiansoncontemporaryIndian
castepopulations,wecomparedmtDNA(400bpofhypervariableregion1and14restrictionsitepolymorphisms)
andYchromosome(20biallelicpolymorphismsand5shorttandemrepeats)variationin265malesfromeight
castesofdifferentrankto750Africans,Asians,Europeans,andotherIndians.FormaternallyinheritedmtDNA,
eachcasteismostsimilartoAsians.However,20%30%ofIndianmtDNAhaplotypesbelongtoWestEurasian
haplogroups,andthefrequencyofthesehaplotypesisproportionaltocasterank,thehighestfrequencyofWest
Eurasianhaplotypesbeingfoundintheuppercastes.Incontrast,forpaternallyinheritedYchromosomevariation
eachcasteismoresimilartoEuropeansthantoAsians.Moreover,theaffinitytoEuropeansisproportionatetocaste
rank,theuppercastesbeingmostsimilartoEuropeans,particularlyEastEuropeans.Thesefindingsareconsistent
withgreaterWestEurasianmaleadmixturewithcastesofhigherrank.Nevertheless,themitochondrialgenomeand
theYchromosomeeachrepresentsonlyasinglehaploidlocusandismoresusceptibletolargestochasticvariation,
bottlenecks,andselectivesweeps.Thus,toincreasethepowerofouranalysis,weassayed40independent,
biparentallyinheritedautosomalloci(1LINE1and39Aluelements)inallofthecasteandcontinentalpopulations
(600individuals).AnalysisofthesedatademonstratedthattheuppercasteshaveahigheraffinitytoEuropeans
thantoAsians,andtheuppercastesaresignificantlymoresimilartoEuropeansthanarethelowercastes.
Collectively,allfivedatasetsshowatrendtowarduppercastesbeingmoresimilartoEuropeans,whereaslower

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castesaremoresimilartoAsians.WeconcludethatIndiancastesaremostlikelytobeofprotoAsianoriginwith
WestEurasianadmixtureresultinginrankrelatedandsexspecificdifferencesinthegeneticaffinitiesofcastesto
AsiansandEuropeans.

SharedIndoEuropeanlanguages(i.e.,HindiandmostEuropeanlanguages)suggestedtolinguistsofthenineteenth
andtwentiethcenturiesthatcontemporaryHinduIndiansaredescendantsofprimarilyWestEurasianswho
migratedfromEurope,theNearEast,Anatolia,andtheCaucasus30008000yearsago(Poliakov1974Renfrew
1989a,b).ThesenomadicmigrantsmayhaveconsolidatedtheirpowerbyadmixingwithnativeDravidicspeaking
(e.g.,Telugu)protoAsianpopulationswhocontrolledregionalaccesstoland,labor,andresources(CavalliSforza
etal.1994),andsubsequentlyestablishedtheHinducastehierarchytolegitimizeandmaintainthispower(Poliakov
1974CavalliSforzaetal.1994).ItisplausiblethattheseWestEurasianimmigrantsalsoappointedthemselvesto
predominantlycastesofhigherrank.However,archaeologicalevidenceofthediffusionofmaterialculturefrom
WesternEurasiaintoIndiahasbeenlimited(Shaffer1982).Therefore,informationonthegeneticrelationshipsof
IndianstoEuropeansandAsianscouldcontributesubstantiallytounderstandingtheoriginsofIndianpopulations.

PreviousgeneticstudiesofIndiancasteshavefailedtoachieveaconsensusonIndianoriginsandaffinities.Various
resultshavesupportedcloseraffinityofIndiancasteseitherwithEuropeansorwithAsians,andseveralfactors
underliethisinconsistency.First,erraticorlimitedsamplingofpopulationshaslimitedinferencesaboutthe
relationshipsbetweencasteandcontinentalpopulations(i.e.,Africans,Asians,Europeans).Theserelationshipsare
furtherconfoundedbythewidegeographicdispersalofcastepopulations.Geneticaffinitiesamongcaste
populationsare,inpart,inverselycorrelatedwiththegeographicdistancebetweenthem(MalhotraandVasulu
1993),anditislikelythataffinitiesbetweencasteandcontinentalpopulationsarealsogeographicallydependent
(e.g.,differentbetweenNorthandSouthIndiancastepopulations).Second,ithasbeensuggestedthatcastesof
differentrankmayhaveoriginatedfromoradmixedwithdifferentcontinentalgroups(MajumderandMukherjee
1993).Third,thesizeofcastepopulationsvarieswidely,andtheeffectsofgeneticdriftonsomesmall,
geographicallyisolatedcastesmayhavebeensubstantial.Fourth,mostofthepolymorphismsassayedoverthelast
30yearsareindirectmeasurementsofgeneticvariation(e.g.,ABOtyping),havebeensampledfromonlyafew
loci,andmaynotbeselectivelyneutral.Finally,onlyrarelyhavesystematiccomparisonsbeenmadewith
continentalpopulationsusingalarge,uniformsetofDNApolymorphisms(Majumder1999).

Toinvestigatetheoriginofcontemporarycastes,wecomparedthegeneticaffinitiesofcastepopulationsof
differingrank(i.e.,upper,middle,andlower)toworldwidepopulations.WeanalyzedmtDNA(hypervariable
region1[HVR1]sequenceand14restrictionsitepolymorphisms[RSPs]),Ychromosome(5shorttandemrepeats
[STRs]and20biallelicpolymorphisms),andautosomal(1LINE1and39Aluinserts)variationin265males
fromeightdifferentTeluguspeakingcastepopulationsfromthestateofAndhraPradeshinSouthIndia(Bamshad
etal.1998).Comparisonsweremadeto400individualsfromtribalandHindispeakingcasteandpopulations
distributedacrosstheIndiansubcontinent(Mountainetal.1995Kivisildetal.1999)andto350Africans,Asians,
andEuropeans(Jordeetal.1995,2000Seielstadetal.1999).

RESULTS Goto:

AnalysisofmtDNASuggestsaProtoAsianOriginofIndians

MtDNAHVR1geneticdistancesbetweencastepopulationsandAfricans,Asians,andEuropeansaresignificantly
differentfromzero(p<0.001)andrevealthat,regardlessofrank,eachcastegroupismostcloselyrelatedtoAsians
andismostdissimilarfromAfricans(Table1).Thegeneticdistancesfrommajorcontinentalpopulations(e.g.,
Europeans)differamongthethreecastegroups,andthecomparisonrevealsanintriguingpattern.Asonemoves
fromlowertouppercastes,thedistancefromAsiansbecomesprogressivelylarger.Thedistancebetween
EuropeansandlowercastesislargerthanthedistancebetweenEuropeansanduppercastes,butthedistance

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betweenEuropeansandmiddlecastesissmallerthantheuppercasteEuropeandistance.Thesetrendsarethesame
whethertheKshatriyaandVysyaareincludedintheuppercastes,themiddlecastes,orexcludedfromtheanalysis.
Thismaybeowing,inpart,tothesmallsamplesize(n=10)ofeachofthesecastes.Amongtheuppercastesthe
geneticdistancebetweenBrahminsandEuropeans(0.10)issmallerthanthatbetweeneithertheKshatriyaand
Europeans(0.12)ortheVysyaandEuropeans(0.16).AssumingthatcontemporaryEuropeansreflectWest
Eurasianaffinities,thesedataindicatethattheamountofWestEurasianadmixturewithIndianpopulationsmay
havebeenproportionatetocasterank.

Table1
MtDNA(HVR1Sequence)GeneticDistancesbetweenCasteGroupsfrom
AndhraPradeshandContinentalPopulations

Conventionalestimatesofthestandarderrorsofgeneticdistancesassumethatpolymorphicsitesareindependentof
eachother,thatis,unlinked.BecausemtDNApolymorphismsareincompletelinkagedisequilibrium(asare
polymorphismsonthenonrecombiningportionsoftheYchromosome),thisassumptionisviolated.Alternatively,
themtDNAgenomecanbetreatedasasinglelocuswithmultiplehaplotypes.However,evenifthisassumptionis
made,mtDNAdistancesdonotdiffersignificantlyfromoneanotherevenatthelevelofthethreemajorcontinental
populations(NeiandLivshits1989),thestandarderrorsbeinggreaterthanthegeneticdistances.Consideringthat
thedistancesbetweencastesandcontinentalpopulationsarelessthanthosebetweendifferentcontinental
populations,theestimatedmtDNAgeneticdistancesbetweenuppercastesandEuropeansversuslowercastesand
Europeanswouldnotbesignificantlydifferentfromeachother.Therefore,toresolvefurthertherelationshipsof
EuropeansandAsianstocontemporaryIndianpopulations,wedefinedtheidentitiesofspecificmtDNArestriction
sitehaplotypes.

ThepresenceofthemtDNArestrictionsitesDdeI10,394andAluI10,397definesahaplogroup(agroupof
haplotypesthatsharesomesequencevariants),M,thatwasoriginallyidentifiedinpopulationsthatmigratedfrom
mainlandAsiatoSoutheastAsiaandAustralia(Ballingeretal.1992Chenetal.1995Passarinoetal.1996)andis
foundatmuchlowerfrequencyinEuropeanandAfricanpopulations.Mostofthecommonhaplotypesfoundin
TeluguandHindispeakingcastepopulationsbelongtohaplogroupM(Table2)anddonotdifferentiateinto
languagespecificclustersinaphylogeneticreconstruction(Fig.1).Furthermore,theseIndianhaplogroupM
haplotypesaredistinctfromthosefoundinotherAsianpopulations(Fig.2)andindicatetheexistenceofIndian
specificsubsetsofhaplogroupM(e.g.,M3).AsexpectedifthelowercastesaremoresimilartoAsiansthanto
Europeans,andtheuppercastesaremoresimilartoEuropeansthantoAsians,thefrequenciesofMandM3
haplotypesareinverselyproportionaltocasterank(Table2).

Table2
MtDNAHaplogroupFrequenciesinDravidicandHindiSpeakingIndians

Figure1
PhylogenyofhaplogroupMinIndia.Phylogeneticrelationshipsbetween
HVR1haplotypeswereestimatedbyconstructingreducedmedian
networks.Thesizeofeachnodeisporportionaltothehaplotypefrequency.
Reticulationsindicateparallelmutational...

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Figure2
MajorsubsetsofhaplogroupM.PhylogeneticrelationshipsofHVR1haplotypesassignedto
haplogroupMwereestimatedfor:(a)343Indians(QuintanaMurcietal.1999athisstudy)
(b)16Turksand78CentralAsians(Comasetal.1998thisstudy)(...

OfthenonAsianmtDNAhaplotypesfoundinIndianpopulations,mostareofWestEurasianorigin(Table2
Torronietal.1994Richardsetal.1998).However,mostoftheseIndianWestEurasianhaplotypesbelongtoan
IndianspecificsubsetofhaplogroupU,thatis,U2i(Kivisildetal.1999),theoldestandsecondmostcommon
mtDNAhaplogroupfoundinEurope(Torronietal.1994).InagreementwiththeHVR1results,thefrequencyof
WestEurasianmtDNAhaplotypesissignificantlyhigherinuppercastesthaninlowercastes(p<0.05),the
frequencyofU2ihaplotypesincreasingasonemovesfromlowertohighercastes.Inaddition,thefrequencyof
mtDNAhaplogroupswithamorerecentcoalescenceestimate(i.e.,H,I,J,K,T)wasfivefoldhigherinupper
castes(6.8%)thaninlowercastes(1.4%).Thesehaplotypesarederivativesofhaplogroupsfoundthroughout
Europe(Richardsetal.1998),theMiddleEast(DiRienzoandWilson1991),andtoalesserextentCentralAsia
(Comasetal.1998).Collectively,themtDNAhaplotypeevidenceindicatethatcontemporaryIndianmtDNA
evolvedlargelyfromprotoAsianancestorswithWesternEurasianadmixtureaccountingfor20%30%ofmtDNA
haplotypes.

YChromosomeVariationConfirmsIndoEuropeanAdmixture

GeneticdistancesestimatedfromYchromosomeSTRpolymorphismsdiffersignificantlyfromzero(p<0.001)
andrevealadistinctlydifferentpatternofpopulationrelationships(Table3).IncontrasttothemtDNAdistances,
theYchromosomeSTRdatadonotdemonstrateacloseraffinitytoAsiansforeachcastegroup.Uppercastesare
moresimilartoEuropeansthantoAsians,middlecastesareequidistantfromthetwogroups,andlowercastesare
mostsimilartoAsians.ThegeneticdistancebetweencastepopulationsandAfricansisprogressivelylargermoving
fromlowertomiddletouppercastegroups(Table3).

Table3
YChromosome(STRs)GeneticDistancesbetweenCasteGroupsfrom
AndhraPradeshandContinentalPopulations

GeneticdistancesestimatedfromYchromosomebiallelicpolymorphismsdiffersignificantlyfromzero(p<0.05),
andthepatternsdifferfromthemtDNAresultsevenmorestrikinglythantheYchromosomeSTRs.ForY
chromosomebiallelicpolymorphismdata,eachcastegroupismoresimilartoEuropeans(Table4),andasone
movesfromlowertomiddletohighercastesthegeneticdistancetoEuropeansdiminishesprogressively.This
patternisfurtheraccentuatedbyseparatingtheEuropeanpopulationintoNorthern,Southern,andEastern
EuropeanseachcastegroupismostcloselyrelatedtoEasternEuropeans.Moreover,thegeneticdistancebetween
uppercastesandEasternEuropeansisapproximatelyhalfthedistancebetweenEasternEuropeansandmiddleor
lowercastes.TheseresultssuggestthatIndianYchromosomes,particularlyuppercasteYchromosomes,aremore
similartoEuropeanthantoAsianYchromosomes.ThisunderscoresthecloseaffinitiesbetweenHinduIndianand
IndoEuropeanYchromosomesbasedonapreviouslyreportedanalysisofthreeYchromosomepolymorphisms
(QuintanaMurcietal.1999b).

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Table4
YChromosome(BiAllelicPolymorphisms)GeneticDistancesbetweenCasteGroupsfrom
AndhraPradeshandContinentalPopulationsa

Overall,theseresultsindicatethattheaffinitiesofIndianstocontinentalpopulationsvariesaccordingtocasterank
anddependsonwhethermtDNAorYchromosomedataareanalyzed.However,conclusionsdrawnfromthese
dataarelimitedbecausemtDNAandtheYchromosomeiseacheffectivelyasinglehaploidlocusandismore
sensitivetogeneticdrift,bottlenecks,andselectivesweepscomparedtoautosomalloci.Theselimitationsofour
analysiscanbeovercome,inpart,byanalyzingalargersetofindependentautosomalloci.Consequently,we
assayed1LINE1and39unlinkedAlupolymorphisms.

AffinitiestoEuropeansandAsiansStratifiedbyCasteRank

GeneticdistancesestimatedfromautosomalAluelementscorrespondtocasterank,thegeneticdistancebetween
theupperandlowercastesbeingmorethan2.5timeslargerthanthedistancebetweenupperandmiddleormiddle
andlowercastes(uppertomiddle,0.0069uppertolower,0.018middletolower,0.0071).Thesetrendsarethe
samewhethertheKshatriyaandVysyaareincludedintheuppercastes,themiddlecastes,orexcludedfromthe
analysis(datanotshown).Furthermore,aneighborjoiningnetworkofgeneticdistancesbetweenseparatecastes
(Fig.3)clearlydifferentiatescastesofdifferentrankintoseparateclusters.Thisissimilartotherelationship
betweengeneticdistancesandcasterankestimatedfrommtDNA(Bamshadetal.1998).Itisimportanttonote,
however,thattheautosomalgeneticdistancesareestimatedfrom40independentloci.Thisaffordedusthe
opportunitytotestthestatisticalsignificanceofthecorrespondencebetweengeneticdistanceandcastestatus.The
Mantelcorrelationbetweeninterindividualgeneticdistancesanddistancesbasedonsocialrankwaslowbuthighly
significantforindividualsrankedintoupper,middle,andlowergroups(r=0.08p<0.001)andintoeightseparate
castes(r=0.07p<0.001).Giventheresolvingpowerofthisautosomaldataset,wenexttestedwhetherwecould
reconciletheresultsoftheanalysisofmtDNAandYchromosomemarkersincastesandcontinentalpopulations.

Figure3
Neighborjoiningnetworkofgeneticdistancesamongcastecommunities
estimatedfrom40Alupolymorphisms.Distancesbetweenuppercastes(U
Brahmin,Vysya,Kshatriya),middlecastes(MYadava,Kapu),andlower
castes(LMala,Madiga,Relli)aresignificantly...

Genotypicdifferentiationwassignificantlydifferentfromzero(p<0.0001)betweeneachpairofcastepopulations
andbetweeneachcasteandcontinentalpopulation.SimilartotheresultsofboththemtDNAandYchromosome
analyses,thedistancebetweenuppercastesandEuropeanpopulationsissmallerthanthedistancebetweenlower
castesandEuropeans(Table5).However,incontrasttothemtDNAresultsbutsimilartotheYchromosome
results,theaffinitybetweenuppercastesandEuropeansishigherthanthatofuppercastesandAsians(Table5).If
theKshatriyaandVysyaareexcludedfromtheanalysisorincludedinthemiddlecastes,thegeneticdistance
betweentheuppercaste(Brahmins)andEuropeansremainssmallerthanthedistancebetweenthelowercastesand
EuropeansandthedistancebetweenuppercastesandAsians(Table5).Analysisofeachcasteseparatelyreveals
thatthegeneticdistancebetweentheBrahminsandEuropeans(0.013)islessthanthedistancebetweenEuropeans
andKshatryia(0.030)orVysya(0.020).Nevertheless,eachseparateuppercasteismoresimilartoEuropeansthan
toAsians.

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Table5
AutosomalGeneticDistancesabetweenCasteGroupsfromAndhraPradeshandContinental
Populations

BecausehistoricalevidencesuggestsgreateraffinitybetweenuppercastesandEuropeansthanbetweenlower
castesandEuropeans(Balakrishnan1978,1982CavalliSforzaetal.1994),itisappropriatetouseaonetailedtest
ofthedifferencebetweenthecorrespondinggeneticdistances.The90%confidencelimitsofNei'sstandard
distancesestimatedbetweenuppercastesandEuropeans(0.0060.016)versuslowercastesandEuropeans(0.017
0.037)donotoverlap,indicatingstatisticalsignificanceatthe0.05level.Significanceat0.05isnotachievedifthe
KshatriyaandVysyaareexcluded.Theseresultsofferstatisticalsupportfordifferencesinthegeneticaffinityof
Europeanstocastepopulationsofdifferingrank,withgreaterEuropeanaffinitytouppercastesthantolower
castes.

DISCUSSION Goto:

PreviousgeneticstudieshavefoundevidencetosupporteitheraEuropeanoranAsianoriginofIndiancaste
populations,withoccasionalindicationsofadmixturewithAfricanorprotoAustraloidpopulations(Chenetal.
1995Mountainetal.1995Bamshadetal.1996,1997Majumderetal.1999QuintanaMurcietal.1999a).Our
resultsdemonstratethatforbiparentallyinheritedautosomalmarkers,geneticdistancesbetweenupper,middle,and
lowercastesaresignificantlycorrelatedwithrankuppercastesaremoresimilartoEuropeansthantoAsiansand
uppercastesaresignificantlymoresimilartoEuropeansthanarelowercastes.Thisresultappearstobeowingto
theamalgamationoftwodifferentpatternsofsexspecificgeneticvariation.

ThemajorityofIndianmtDNArestrictionsitehaplotypesbelongtoIndianspecificsubsets(e.g.,M3)ofa
predominantlyAsianhaplogroupM,althoughasubstantialminorityofmtDNArestrictionsitehaplotypesbelongto
WestEurasianhaplogroups.AhigherproportionofprotoAsianmtDNArestrictionsitehaplotypesisfoundin
lowercastescomparedtomiddleoruppercastes,whereasthefrequencyofWestEurasianhaplotypesispositively
correlatedwithcasterank,thatis,ishighestintheuppercastes.ForYchromosomeSTRvariationtheuppercastes
exhibitgreatestsimilaritywithEuropeans,whereasthelowercastegroupsaremostsimilartoAsians.ForY
biallelicpolymorphismvariation,eachcastegroupismoresimilartoEuropeansthantoAsians,andtheaffinityto
Europeansisproportionaltocasterank,thatis,ishighestintheuppercastes.

Importantly,fivedifferenttypesofdata(mtDNAHVR1sequence,mtDNARSPs,YchromosomeSTRs,Y
chromosomebiallelicpolymorphisms,andautosomalAlupolymorphisms)supportthesamegeneralpattern:
relativelysmallergeneticdistancesfromEuropeanpopulationsasonemovesfromlowertomiddletouppercaste
populations.GeneticdistancesfromAsianpopulationsbecomelargerasonemovesfromlowertomiddletoupper
castepopulations.ItisespeciallynoteworthythattheanalysisofYbiallelicpolymorphisms,whichinvolvedan
independentsetofcomparativeAsian,European,andAfricanpopulations,againindicatedthesamepattern.
Additionalsupportisofferedbythefactthattheautosomalpolymorphismsyieldedastatisticallysignificant
differencebetweentheuppercasteEuropeanandlowercasteEuropeangeneticdistances.Withadditionalloci,
otherdifferences(e.g.,thedistancesbetweendifferentcastegroupsandAsians)mayalsoreachstatistical
significance.

Themostlikelyexplanationforthesefindings,andtheonemostconsistentwitharchaeologicaldata,isthat
contemporaryHinduIndiansareofprotoAsianoriginwithWestEurasianadmixture.However,admixturewith
WestEurasianmaleswasgreaterthanadmixturewithWestEurasianfemales,resultinginahigheraffinityto
EuropeanYchromosomes.ThissupportsanearliersuggestionofPassarinoetal.(1996),whichwasbasedona
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comparisonofmtDNAandbloodgroupresults.Furthermore,thedegreeofWestEurasianadmixturewas
proportionaltocasterank.ThisexplanationisconsistentwitheitherthehypothesisthatproportionatelymoreWest
Eurasiansbecamemembersoftheuppercastesattheinceptionofthecastehierarchyorthatsocialstratification
precededtheWestEurasianincursionandthatWestEurasianstendedtoinsertthemselvesintohigherranking
positions.OneconsequenceisthatsharedIndoEuropeanlanguagesmaynotreflectacommonoriginofEuropeans
andmostIndians,butratherunderscoresthetransferoflanguagemediatedbycontactbetweenWestEurasiansand
nativeprotoIndians.

WestEurasianadmixtureinIndianpopulationsmayhavebeentheresultofmorethanonewaveofimmigration
intoIndia.Kivisildetal.(1999)determinedthecoalescence(50,000yearsbeforepresent)oftheIndianspecific
subsetoftheWestEurasianhaplotypes(i.e.,U2i)andsuggestedthatWestEurasianadmixturemayhavebeen
mucholderthanthepurportedDravidianandIndoEuropeanincursions.OuranalysisofIndianmtDNArestriction
sitehaplotypesthatdonotbelongtotheU2isubsetofWestEurasianhaplotypes(i.e.,H,I,J,K,T)isconsistent
withmorerecentWestEurasianadmixture.Itisalsopossiblethathaplotypeswithanoldercoalescencewere
introducedbyDravidians,whereashaplotypeswithamorerecentcoalescencebelongedtoIndoEuropeans.This
hypothesiscanbetestedbyamoredetailedcomparisontoWestEurasianmtDNAhaplotypesfromIran,Anatolia,
andtheCaucasus.Alternatively,thecoalescencedatesofthesehaplotypesmaypredatetheentryofWestEurasians
populationsintoIndia.Regardlessoftheirorigin,WestEurasianadmixtureresultedinrankrelateddifferencesin
thegeneticaffinitiesofcastestoEuropeansandAsians.Furthermore,thefrequencyofWestEurasianhaplotypesin
thefoundingmiddleanduppercastesmaybeunderestimatedbecauseoftheupwardsocialmobilityofwomen
fromlowercastes(Bamshadetal.1998).ThesewomenwerepresumablymorelikelytointroduceprotoAsian
mtDNAhaplotypesintothemiddleanduppercastes.

Ouranalysisof40autosomalmarkersindicatesclearlythattheuppercasteshaveahigheraffinitytoEuropeans
thantoAsians.ThehighaffinityofcasteYchromosomeswiththoseofEuropeanssuggeststhatthemajorityof
immigratingWestEurasiansmayhavebeenmales.AsmightbeexpectedifWestEurasianmalesappropriatedthe
highestpositionsinthecastesystem,theuppercastegroupexhibitsalowergeneticdistancetoEuropeansthanthe
middleorlowercastes.ThisisunderscoredbytheobservationthattheKshatriya(anuppercaste),whosemembers
servedaswarriors,areclosertoEuropeansthananyothercaste(datanotshown).Furthermore,the32bpdeletion
polymorphisminCCchemokinereceptor5,whosefrequencypeaksinpopulationsofEasternEurope,isfound
onlyintwoBrahminmales(M.BamshadandS.K.Ahuja,unpubl.).ThestratificationofYchromosomedistances
withEuropeanscouldalsobecausedbymalespecificgeneflowamongcastepopulationsofdifferentrank.
However,weandothershavedemonstratedthatthereislittlesharingofYchromosomehaplotypesamongcastes
ofdifferentrank(Bamshadetal.1998Bhattacharyyaetal.1999).

TheaffinityofcastepopulationstoEuropeansismoreapparentforYchromosomebiallelicpolymorphismsthan
YchromosomeSTRs.ThiscouldbeattributedtotheuseofdifferentEuropeanpopulationsincomparisonsusing
STRsandbiallelicpolymorphisms.Alternatively,itmayreflect,inpart,theeffectsofhighmutationratesfortheY
chromosomeSTRs,whichwouldtendtoobscurerelationshipsbetweencasteandcontinentalpopulations.Alack
ofconsistentclusteringatthecontinentallevelhasbeenobservedinseveralstudiesofYchromosomeSTRs(Deka
etal.1996Torronietal.1996deKnijffetal.1997).TheautosomalAluandbiallelicYchromosome
polymorphisms,incontrast,haveaslowerrateofdriftthanYchromosomeSTRsbecauseofahighereffective
populationsize,andtheirmutationrateisverylow.Thus,theYchromosomebiallelicpolymorphismsand
autosomalAlumarkersmayserveasmorestablemarkersofworldwidepopulationaffinities.

Ouranalysismayhelptoexplainwhyestimatesoftheaffinitiesofcastegroupstoworldwidepopulationshave
variedsowidelyamongdifferentstudies.AnalysesofrecentcastehistorybasedononlymtDNAorY
chromosomepolymorphismsclearlywouldsuggestthatcastesaremorecloselyrelatedtoAsiansortoEuropeans,
respectively.Furthermore,weattemptedtominimizetheconfoundingeffectofgeographicdifferencesbetween
populationsbysamplingfromahighlyrestrictedregionofSouthIndia.Becauseoftheubiquityofthecastesystem
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inIndia'shistory,itisreasonabletopredictsimilarpatternsincastepopulationslivinginotherareas.Indeed,any
geneticresultbecomesmorecompellingwhenitisreplicatedinotherpopulations.Therefore,comparablestudiesin
castepopulationsfromotherregionsofIndiamustbecompletedtotestthegeneralityoftheseresults.

ThedispersalandsubsequentgrowthofIndianpopulationssincetheNeolithicAgeisoneofthemostimportant
eventstoshapethehistoryofSouthAsia.However,theoriginanddispersalrouteoftheaboriginalinhabitantsof
theIndiansubcontinentisunclear.OurfindingssuggestaprotoAsianoriginoftheIndianspecifichaplogroupM
haplotypes.HaplogroupMhaplotypesarealsofoundatappreciablefrequenciesinsomeEastAfricanpopulations
18%ofEthiopians(QuintanaMurcietal.1999a)and16%ofKenyans(M.BamshadandL.B.Jonde,
unpubl.).AcomparisonofhaplogroupMhaplotypesfromEastAfricaandIndiahassuggestedthatthissouthern
routemayhavebeenoneoftheoriginaldispersalpathwaysofanatomicallymodernhumansoutofAfrica
(QuintanaMurcietal.1999a).Together,thesedatasupportourprevioussuggestion(Kivisildetal.1999)thatIndia
mayhavebeeninhabitedbyatleasttwosuccessivelatePleistocenemigrations,consistentwiththehypothesisof
LahrandFoley(1994).ItalsoaddstothegrowingevidencethatthesubcontinentofIndiahasbeenamajor
corridorforthemigrationofpeoplebetweenAfrica,WesternAsia,andSoutheastAsia(CavalliSforzaetal.1994).

ItshouldbeemphasizedthattheDNAvariationstudiedhereisthoughttobeselectivelyneutralandthusrepresents
onlytheeffectsofpopulationhistory.Theseresultspermitnoinferencesaboutphenotypicdifferencesbetween
populations.Inaddition,allelesandhaplotypesaresharedbydifferentcastepopulations,reflectingasharedhistory.
Indeed,thesefindingsunderscorethelongstandingappreciationthatthedistributionofgeneticpolymorphismsin
Indiaishighlycomplex.FurtherinvestigationofthespreadofanatomicallymodernhumansthroughoutSouthAsia
willneedtoconsiderthatsuchcomplexpatternsmaybethenormratherthantheexception.

METHODS Goto:

SampleCollection

AllstudiesofSouthIndianpopulationswereperformedwiththeapprovaloftheInstitutionalReviewBoardofthe
UniversityofUtah,AndhraUniversity,andthegovernmentofIndia.Adultmaleslivinginthedistrictof
Visakhapatnam,AndhraPradesh,werequestionedabouttheircasteaffiliationsandsurnamesandthebirthplacesof
theirparents.Thosewhowereunrelatedtoanyothersubjectbyatleastthreegenerationswereconsideredeligible
toparticipate.

Weclassifiedcastepopulationsbaseduponthetraditionalrankingofthesecastesbyvarna(definedbelow),
occupation,andsocioeconomicstatus.AccordingtovariousSanskrittexts,Hindupopulationswerepartitioned
originallyintofourcategoriesorvarna:Brahmin,Kshatriya,Vysya,andSudra(Tambia1973Elder1996).Those
ineachvarnaperformedoccupationsassignedtotheircategory.BrahminswerepriestsKshatriyawerewarriors
VysyaweretradersandSudraweretoservethethreeothervarna(Tambia1973Elder1996).Eachvarnawas
assignedastatusBrahmin,Kshatriya,andVysyawereconsideredofhigherstatusthantheSudrabecausethe
Brahmin,Kshatriya,andVysyaareconsideredthetwiceborncastesandaredifferentiatedfromallothercastesin
thecastehierarchy.Thisistherationalebehindclassifyingthemastheuppergroupofcastes(Tambia1973).

TheKapuandtheYadavaarecalledonceborncastesthathavetraditionallybeenclassifiedintheSudra,the
lowestoftheoriginalfourvarna.However,thestatusoftheSudrawasactuallyhigherthanthatofafifthvarna,
thePanchama.Thisfifthvarnawasaddedatalaterdatetoincludethesocalleduntouchables,whowereexcluded
fromtheotherfourvarna(Elder1996).TheuntouchablevarnaincludestheMalaandMadiga.Thepositionofthe
Relliinthecastehierarchyissomewhatambiguous,buttheyhaveusuallybeenclassifiedinthelowercastegroup.
Therefore,priortothecollectionofanydata,malesfromeightdifferentTeluguspeakingcastes(n=265)were
rankedintoupper(NiyogiandVydikiBrahmin,Kshatriya,Vysya[n=80]),middle(TelegaandTurpuKapu,
Yadava[n=111]),andlower(Relli,Madiga,Mala[n=74])groups(Bamshadetal.1998).Thisrankinghasbeen
usedbypreviousinvestigators(KrishnanandReddy1994).
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Afterobtaininginformedconsent,8mLofwholebloodor5pluckedscalphairswerecollectedfromeach
participant.ExtractionswereperformedatAndhraUniversityusingestablishedmethods(Belletal.1981).

MtDNAPolymorphisms

ThemtDNAdataconsistedof68,116,and73HVR1sequencesand79,159,and72restrictionsitehaplotypes
fromlargelythesameindividualsinupper,middle,andlowercastes,respectively.Thesedatawerecomparedto
datafrom143Africans(15SothoTswana,7Tsonga,14Nguni,24San,5BiakaPygmies,33MbutiPygmies,9
Alur,18Hema,and18Nande),78Asians(12Cambodians,17Chinese,19Japanese,6Malay,9Vietnamese,2
Koreans,and13Asiansofmixedancestry),and99Europeans(20unrelatedmalesoftheFrenchCEPHkindreds,
69unrelatedUtahmalesofNorthernEuropeandescent,and10Poles)(Jordeetal.1995,1997).Mitochondrial
sequencedatafromthese597individualsareavailableat:http://www.genome.org/supplemental/.

Inadditiontooursamples,thephylogeneticanalysesalsoincludeddatafrom98publishedHVR1sequencesfrom
twocastes(48Havlikand43Mukri),andatribalpopulation(7Kadar)livinginsouthwesternIndia(Mountainet
al.1995)andrestrictionsitehaplotypesfromonecaste(62Lobana)fromNorthernIndia,threetribalpopulations
fromNorthern(12Tharuand18Bhoksa)andSouthern(86Lambadi)India,and122individualsfromvariouscaste
populationsinUttarPradesh(Kivisildetal.1999).PhylogeneticrelationshipsofHVR1sequencesassignedto
haplogroupMwereestimatedforIndians(thisstudy),Turks(thisstudy),CentralAsianpopulations(Comasetal.
1998),Mongolians(Kolmanetal.1996),Chinese(Horaietal.1996),andJapanese(Horaietal.1996Seoetal.
1998).

ThemtDNAHVR1sequencewasdeterminedbyfluorescentSangersequencingusingaDyeterminatorcycle
sequencingkit(AppliedBiosystems)accordingtothemanufacturer'sspecifications(Bamshadetal.1998).
SequencingreactionswereresolvedonanABI377automatedDNAsequencer,andsequencedatawereanalyzed
usingABIDNAanalysissoftwareandSEQUENCHERsoftware(Genecodes).ToidentifymtDNAhaplotypesand
haplogroups(agroupofhaplotypesthatsharesomesequencevariants),majorcontinentspecificgenotypes
(Torronietal.1994,1996Wallace1995)forthefollowingpolymorphicmtDNArestrictionsitesweredetermined:
HpaI3592,DdeI10394,AluI10397,AluI13262,BamHI13366,AluI5176,HaeIII4830,AluI7025,HinfI12308,AccI14465,
AvaII8249,AluI10032,BstOI13704,andHaeII9052.

YChromosomeandAutosomalPolymorphisms

YchromosomespecificSTRs(DYS19,DYS288,DYS388,DYS389A,DYS390)wereamplifiedusingpublished
conditions(Hammeretal.1998).PCRproductswereseparatedonanABI377automatedsequencerandscored
usingABIGenotypersoftware.YchromosomeSTRdatawerecollectedfrom622malesincluding280South
Indians,200Africans(Seielstadetal.1999thisstudy),40Asians,and102Europeans.Autosomaldatawere
collectedfrom608individualsincluding265SouthIndians,155Africans,70Asians,and118Europeans.

TheYchromosomespecificbiallelicpolymorphismstestedincluded:DYS188792,DYS194469,DYS211105,
DYS221136,DYS257108,DYS287,M3,M4,M9,M12,M15,SRY4064,SRY10831.1,SRY10831.2,p12f2,PN1,
PN2,PN3,RPS4Y711,andTat(HammerandHorai1995Hammeretal.1997,1998,2000Underhilletal.1997
Zerjaletal.1997Karafetetal.1999).AllindividualstestednegativefortheYAluinsert(DYS287).Acomplete
descriptionoftheYchromosomeSTRlocicanbefoundinKayseretal.(1997).AtableofthebiallelicY
chromosomehaplotypefrequenciesintheupper,middle,andlowercastesisavailableat
http://www.genome.org/supplemental/.

FortheYchromosomebiallelicdataset,comparisonsweremadetoadifferentsetofworldwidepopulations
including:EastAsiansfromJapan,Korea,China,andVietnam(n=460)WesternEuropeansfromBritainand
Germany(n=77)SouthernEuropeansfromItalyandGreece(n=148)andEasternEuropeansfromRussiaand
Romania(n=102)(M.F.Hammer,unpubl.).ThecompletedatasetofIndiansconsistedof55Brahmin,111

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YadavaandKapu,and74Relli,Mala,andMadiga.

Autosomalpolymorphismswereamplifiedusingconditionsspecificallyoptimizedforeachsystem.Further
informationontheseconditionsisavailableattheWebsite:http://www.genetics.utah.edu/
swatkins/pub/Alu_data.htmorhttp://www.genome.org/supplemental.Withminorexceptionscausedbytyping
failuresorothercauses,thesameindividualsfromeachpopulationwereusedtocreateeachdataset(i.e.,mtDNA,
Ychromosome,andautosomal).Thecompletedatasetofgenotypesfromall40autosomallociisavailableat:
http://www.genome.org/supplemental/.

StatisticalAnalyses

GeneticdistancesforYchromosomeSTRswereestimatedusingthemethodofShriveretal.(1995),which
assumesastepwisemutationmodel.Geneticdistancesformitochondrialandautosomalmarkerswerecalculatedas
pairwiseFSTdistances,usingtheARLEQUINpackage(Schneideretal.1997).Forautosomalpolymorphisms,Nei's
standarddistancesandtheirstandarderrorswereestimatedusingDISPAN(http://www.bio.psu.edu/IMEG)and90%
confidenceintervalswereestimatedbymultiplyingthestandarderrorby1.65.ThesignificanceoftheFST
distancesbetweenpopulationswasestimatedbygeneratinganulldistributionofpairwiseFSTdistancesby
permutinghaplotypesbetweenpopulations.Thepvalueofthetestistheproportionofpermutationsleadingtoan
FSTvaluelargerthanorequaltotheobservedone.GenotypicdifferentiationwasestimatedusingGENEPOP
(RaymondandRousset1995)vers.3.2(http://www.cefe.cnrsmop.fr/).Thenullhypothesistestedisthatthereisa
randomdistributionofKdifferenthaplotypesamongrpopulations(thecontingencytable).Allpotentialstatesof
thecontingencytableareexploredwithaMarkovchain,andtheprobabilityofobservingatablelessthanor
equallylikelytotheobservedsampleconfigurationisestimated.

Estimatesofsignificanceforthecorrelationbetweeninterindividualcasterankdifferencesandinterindividual
autosomalgeneticdistancesweremadebyformingtwonnmatrices,wherenisthenumberofindividuals.For
thefirstmatrix,interindividualgeneticdistanceswerebasedontheproportionofAluinsertions/deletionssharedby
eachpairofindividuals.Toformthesecondmatrix,eachindividualwasassignedascoreaccordingtohisrankin
thecastehierarchyforcastegroups(i.e.,uppercaste=1,middlecaste=2,lowercaste=3)andalsoforseparate
castes(i.e.,Brahmin=1,Kshatriya=2,Vysya=3,Kapu=4,Yadava=5,Relli=6,Mala=7,andMadiga=8).An
interindividualmatrixofscoredistanceswasformedbycomparingtheabsolutevalueofthedifferencebetweenthe
scoresofeachpairofindividuals.Thematrixofgeneticdistanceswascomparedto10,000permutedmatricesof
scoredistancesusingaMantelmatrixcomparisontest(Mantel1967).

Toillustratephylogeneticrelationshipsweconstructedreducedmedian(Bandeltetal.1995)andneighborjoining
networks(Felsenstein1989).CoalescencetimeswerecalculatedasinForsteretal.(1996),usingtheestimator,
whichistheaveragetransitionaldistancefromthefounderhaplotype.

Acknowledgments Goto:

Wethankallparticipants,thefacultyandstaffofAndhraUniversityfortheirdiscussionandtechnicalassistance,as
wellasHenryHarpendingforcommentsandcriticisms.Weacknowledgethecontributionsofananonymous
reviewerwhosuggestedthattheKshatriyaandVysyabeanalyzedseparatelyfromtheotheruppercastes.Genetic
distancesbetweenSTRswereestimatedbytheprogramDISTNEW,kindlyprovidedbyL.Jin.Thisworkwas
supportedbyNSFSBR9514733,SBR9700729,SBR9818215,NIHgrantsGM59290andPHSMO100064,
theEstonianScienceFund(1669and2887),andtheNewcastleUniversitysmallgrantscommittee.

Thepublicationcostsofthisarticleweredefrayedinpartbypaymentofpagecharges.Thisarticlemusttherefore
beherebymarkedadvertisementinaccordancewith18USCsection1734solelytoindicatethisfact.

Footnotes Goto:

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC311057/ 10/14
1/16/2016 GeneticEvidenceontheOriginsofIndianCastePopulations
EMAILmike@genetics.utah.eduFAX(801)5859148.

Articlepublishedonlinebeforeprint:GenomeRes.,10.1101/gr.173301.

Articleandpublicationareatwww.genome.org/cgi/doi/10.1101/gr.173301.

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