The Geography of Recent Genetic Ancestry across Europe

20 Pages·2013·1.55 MB·English

The Geography of Recent Genetic Ancestry across
Europe
Peter Ralph*¤, Graham Coop*
DepartmentofEvolutionandEcology&CenterforPopulationBiology,UniversityofCalifornia,Davis,California,UnitedStatesofAmerica
Abstract
The recent genealogical history of human populations is a complex mosaic formed by individual migration, large-scale
population movements, and other demographic events. Population genomics datasets can provide a window into this
recent history, as rare traces of recent shared genetic ancestry are detectable due to long segments of shared genomic
material. We make use of genomic data for 2,257 Europeans (in the Population Reference Sample [POPRES] dataset) to
conductoneofthefirstsurveysofrecentgenealogicalancestryoverthepast3,000yearsatacontinentalscale.Wedetected
1.9millionsharedlonggenomicsegments,andusedthelengthsofthesetoinferthedistributionofsharedancestorsacross
timeandgeography.WefindthatapairofmodernEuropeanslivinginneighboringpopulationssharearound2–12genetic
commonancestorsfromthelast1,500years,andupwardsof100geneticancestorsfromtheprevious1,000years.These
numbersdropoffexponentiallywithgeographicdistance,butsincethesegeneticancestorsareatinyfractionofcommon
genealogical ancestors, individuals from opposite ends of Europe are still expected to share millions of common
genealogicalancestorsoverthelast1,000years.Thereisalsosubstantialregionalvariationinthenumberofsharedgenetic
ancestors.Forexample,thereareespeciallyhighnumbersofcommonancestorssharedbetweenmanyeasternpopulations
thatdateroughlytothemigrationperiod(whichincludestheSlavicandHunnicexpansionsintothatregion).Someofthe
lowest levels of common ancestry are seen in the Italian and Iberian peninsulas, which may indicate different effects of
historical population expansions in these areas and/or more stably structured populations. Population genomic datasets
have considerable power to uncover recent demographic history, and will allow a much fuller picture of the close
genealogicalkinship of individualsacross theworld.
Citation:RalphP,CoopG(2013)TheGeographyofRecentGeneticAncestryacrossEurope.PLoSBiol11(5):e1001555.doi:10.1371/journal.pbio.1001555
AcademicEditor:ChrisTyler-Smith,TheWellcomeTrustSangerInstitute,UnitedKingdom
ReceivedJuly16,2012;AcceptedMarch27,2013;PublishedMay7,2013
Copyright: (cid:2)2013 Ralph, Coop. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits
unrestricteduse,distribution,andreproductioninanymedium,providedtheoriginalauthorandsourcearecredited.
Funding:GC:SloanFoundationFellowship,www.sloan.org.PR:RuthL.KirschsteinFellowship,NIH#F32GM096686,grants.nih.gov.Thefundershadnorolein
studydesign,datacollectionandanalysis,decisiontopublish,orpreparationofthemanuscript.
CompetingInterests:Theauthorshavedeclaredthatnocompetinginterestsexist.
Abbreviations:IBD,identitybydescent;SNP,singlenucleotidepolymorphism;ya,yearsago.
*E-mail:[email protected](PR);[email protected](GC)
¤Currentaddress:DepartmentofMolecularandComputationalBiology,UniversityofSouthernCalifornia,LosAngeles,California,UnitedStatesofAmerica
Introduction relatedness,andsoobtaininsightintothepopulationhistoryofthe
past tens of generations. Here we investigate such patterns of
Even seemingly unrelated humans are distant cousins to each recent relatednessin alarge Europeandataset.
other,asallmembersofaspeciesarerelatedtoeachotherthrough Thepastseveralthousandyearsarerepletewitheventsthatmay
avastlyramifiedfamilytree(theirpedigree).Wecanseetracesof have had significant impact on modern European relatedness,
theserelationshipsingeneticdatawhenindividualsinheritshared suchastheNeolithicexpansionoffarming,theRomanempire,or
genetic material from a common ancestor. Traditionally, popu- the more recent expansions of the Slavs and the Vikings. Our
lation genetics has studied the distant bulk of these genetic current understanding of these events is deduced from archaeo-
relationships, which in humans typically date from hundreds of logical, linguistic, cultural, historical, and genetic evidence, with
thousands of years ago (e.g., [1,2]). Such studies have provided widely varying degrees of certainty. However, the demographic
deep insights into the origins of modern humans (e.g., [3]), and andgenealogicalimpactoftheseeventsisstilluncertain(e.g.,[9]).
into recentadmixture between divergedpopulations (e.g., [4,5]). Genetic data describing the breadth of genealogical relationships
Althoughmostsuchgeneticrelationshipsamongindividualsare can therefore add another dimension to our understanding of
very old, some individuals are related on far shorter time scales. these historical events.
Indeed, given that each individual has 2n ancestors from n Work from uniparentally inherited markers (mtDNA and Y
generationsago,theoreticalconsiderationssuggestthatallhumans chromosomes) has improved our understanding of human
are related genealogically to each other over surprisingly short demographichistory(e.g.,[10]). However,interpretation of these
time scales [6,7]. We are usually unaware of these close markersisdifficultsincetheyonlyrecordasinglelineageofeach
genealogical ties, as few of us have knowledge of family histories individual(thematernalandpaternallineages,respectively),rather
more than a few generations back, and these ancestors often do thantheentiredistributionofancestors.Genome-widegenotyping
not contribute any genetic material to us [8]. However, in large and sequencing datasets have the potential to provide a much
samples we can hope to identify genetic evidence of more recent richer picture of human history, as we can learn simultaneously
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than these other works, and describe continuous geographic
Author Summary
structure by obtaining average numbers of common ancestors
Few of us know our family histories more than a few shared by many populations across time in a relatively nonpara-
generations back. It is therefore easy to overlook the fact metric fashion.
thatwearealldistantcousins,relatedtooneanotherviaa
vast network of relationships. Here we use genome-wide Definitions: Genetic Ancestry and Identity by Descent
data from European individuals to investigate these
We can only hope to learn from genetic data about those
relationships over the past 3,000 years, by looking for
common ancestors from whom two individuals have both
longstretchesofgenomethataresharedbetweenpairsof
inherited the same genomic region. If a pair of individuals have
individuals through their inheritance from common
genetic ancestors. We quantify this ubiquitous recent both inherited some genomic region from a common ancestor,
commonancestry,showingforinstancethatevenpairsof that ancestor is called a ‘‘genetic common ancestor,’’ and the
individuals from opposite ends of Europe share hundreds genomicregionisshared‘‘identicalbydescent’’(IBD)bythetwo.
of genetic common ancestors over this time period. Here we define an ‘‘IBD block’’ to be a contiguous segment of
Despitethisdegreeofcommonality,therearealsostriking genome inherited (on at least one chromosome) from a shared
regionaldifferences.SoutheasternEuropeans,forexample, common ancestor without intervening recombination (see
share large numbers of common ancestors that date Figure 1A). A more usual definition of IBD restricts to those
roughly to the era of the Slavic and Hunnic expansions segments inherited from some prespecified set of ‘‘founder’’
around 1,500 years ago, while most common ancestors individuals(e.g.,[8,27,28]),butweallowancestorstobearbitrarily
thatItalianssharewithotherpopulationslivedlongerthan
far back in time. Under our definition, everyone is IBD
2,500 years ago. The study of long stretches of shared
everywhere, but mostly on very short, old segments [29]. We
genetic material promises to uncover rich information
measure lengths of IBD segments in units of Morgans (M) or
about manyaspects ofrecent population history.
centiMorgans(cM),where1Morganisdefinedtobethedistance
over which an average of one recombination (i.e., a crossover)
occursper meiosis.SegmentsofIBDare brokenupovertimeby
about the diversity of ancestors that contributed to each
recombination, which implies that older shared ancestry tends to
individual’s genome.
result inshorter shared IBDblocks.
A number of genome-wide studies have begun to reveal
Sufficiently long segments of IBD can be identified as long,
quantitative insights into recent human history [11]. Within
contiguousregionsoverwhichthetwoindividualsareidentical(or
Europe, the first two principal axes of variation of the matrix of
nearlyidentical)atasetofsinglenucleotidepolymorphisms(SNPs)
genotypesarecloselyrelatedtoarotationoflatitudeandlongitude
thatsegregateinthepopulation.Formal,model-basedmethodsto
[12–14], as would be expected if patterns of ancestry are mostly
infer IBD are only computationally feasible for very recent
shaped by local migration [15]. Other work has revealed a slight
ancestry (e.g., [30]), but recently, fast heuristic algorithms have
decreaseindiversityrunningfromsouth-to-northinEurope,with
thehighesthaplotypeandallelicdiversityintheIberianpeninsula
(e.g., [14,16,17]), and the lowest haplotype diversity in England
and Ireland [18]. Recently, progress has also been made using
genotypes of ancient individuals to understand the prehistory of
Europe [19–21]. However, we currently have little sense of the
time scale of the historical events underlying modern geographic
patternsofrelatedness,northedegreesofgenealogicalrelatedness
they imply.
Inthisarticle,weanalyzethoserarelongchunksofgenomethat
are shared between pairs of individuals due to inheritance from
recent common ancestors, to obtain a detailed view of the
geographicstructureofrecentrelatedness.Todeterminethetime
scaleoftheserelationships,wedevelopmethodologythatusesthe
lengthsofsharedgenomicsegmentstoinferthedistributionofthe
ages of these recent common ancestors. We find that even
geographically distant Europeans share ubiquitous common
ancestry within the past 1,000 years, and show that common
ancestry from the past 3,000 years is a result of both local
migration and large-scale historical events. We find considerable
structure below the country level in sharing of recent ancestry,
lending furthersupport totheidea that looking at runsof shared Figure 1. The spread of genetic ancestry. (A) A hypothetical
portionofthepedigreerelatingtwosampledindividuals,whichshows
ancestry canidentify verysubtle populationstructure (e.g.,[22]).
six of their genealogical common ancestors, with the portions of
Our method for inferring ages of common ancestors is
ancestral chromosomes from which the sampled individuals have
conceptually similar to the work of [23], who use total amount inheritedshadedgrey.TheIBDblockstheyhaveinheritedfromthetwo
oflongrunsofsharedgenometofitsimpleparametricmodelsof geneticcommonancestorsarecoloredred,andthebluearrowdenotes
recenthistory,aswellasto[3]and[24],whouseinformationfrom thepaththroughthepedigreealongwhichoneoftheseIBDblockswas
short runs of shared genome to infer demographic history over inherited. (B) Cartoon of the spatial locations of ancestors of two
individuals—circle size is proportional to likelihood of genetic
muchlongertimescales.Otherconceptuallysimilarworkincludes
contribution, and shared ancestors are marked in grey. Note that
[25]and[26],whousedthelengthdistributionofadmixturetracts
common ancestors are likely located between the two, and their
to fit parametric models of historical admixture. We rely less on distributionbecomesmorediffusefurtherbackintime.
discrete,idealizedpopulationsorparametricdemographicmodels doi:10.1371/journal.pbio.1001555.g001
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beendevelopedthatcanbeappliedtothousandsofsamplestyped
Table1.Populations, abbreviations, sample sizes(n),mean
on genotyping chips (e.g.,[31,32]).
numberofIBDblockssharedbyapairofindividualsfromthat
Therelationshipbetweennumbersoflong,sharedsegmentsof population (‘‘self’’),and meanIBD rateaveragedacross all
genome, numbers of genetic common ancestors, and numbers of otherpopulations(‘‘other’’), sorted byregional groupings
genealogicalcommonancestorscanbedifficulttoenvision.Since described inthe text.
everyone has exactly two biological parents, every individual has
exactly 2n paths of length n meioses leading back through their
pedigree, each such path ending in a grandn–1parent. However,
Group Abbreviation n Self Other
duetoMendeliansegregationandlimitedrecombination,genetic
Egroup
material will only be passed down along a small subset of these
paths [8]. As n grows, these paths proliferate rapidly and so the Albania AL 9 14.5 v
genealogical paths of two individuals soon overlap significantly. Austria AT 14 1.3 0.9
(ThesepointsareillustratedinFigure1.)Byobservingthenumber Bosnia BO 9 4.1 1.6
ofsharedgenomicblocks,welearnaboutthedegreetowhichtheir
Bulgaria BG 1 — 1.3
genealogies overlap, or the number of common ancestors from
Croatia HR 9 2.8 1.6
whichbothindividuals haveinherited geneticmaterial.
At least one parent of each genetic common ancestor of two CzechRepublic CZ 9 2.1 1.3
individuals is also a genetic common ancestor, so the number of Greece EL 5 1.8 0.9
genetic common ancestors at each point back in time is strictly Hungary HU 19 1.9 1.2
increasing. A more relevant quantity is the rate of appearance of
Kosovo KO 15 9.9 1.7
most recent common genetic ancestors. This quantity can be much
Montenegro ME 1 – 1.8
moreintuitive,andiscloselyrelatedtothecoalescentrate[33],as
Macedonia MA 4 2.5 0.4
we demonstrate later. For this reason, when we say ‘‘genetic
commonancestor’’or‘‘rateofgeneticcommonancestry,’’weare Poland PL 22 3.8 1.5
referring to only the most recent genetic common ancestors from Romania RO 14 2.1 1.2
which the individuals in question inherited their shared segments Russia RU 6 4.3 1.4
of genome.
Slovenia SI 2 5.0 1.3
Serbia RS 11 2.7 1.5
Results
Slovakia SK 1 — 0.7
WeappliedthefastIBDmethod,implementedinBEAGLEv3.3 Ukraine UA 1 — 1.5
[31],totheEuropeansubsetofthePopulationReferenceSample
Yugoslavia YU 10 3.4 1.5
(POPRES) dataset (dbgap accession phs000145.v1.p1, [34]),
TCgroup
which includes language and country-of-origin data for several
Cyprus CY 3 2.7 0.4
thousandEuropeansgenotypedat500,000SNPs.Oursimulations
showed that we have good power to detect long IBD blocks Turkey TR 4 2.2 0.5
(probability of detection 50% for blocks longer than 2 cM, rising Ngroup
to98%forblockslongerthan4 cM),andalowfalsepositiverate Denmark DK 1 — 0.9
(discussed further in the Materials and Methods section). We
Finland FI 1 — 1.2
excludedfromouranalysesindividualswhoreportedgrandparents
Latvia LV 1 — 1.6
originating from non-European countries or more than one
distinctcountry(andrefertotheremainderas‘‘Europeans’’).After Norway NO 2 2.0 0.8
removing obvious outlier individuals and close relatives, we were Sweden SE 10 3.4 1.0
leftwith2,257individualswhowegroupedusingreportedcountry Wgroup
oforiginandlanguageinto40populations,listedwithsamplesizes
Belgium BE 37 1.1 0.6
and average IBD levels in Table 1. For geographic analyses, we
England EN 22 1.3 0.7
located each population at the largest population city in the
France FR 86 0.7 0.5
appropriateregion.Pairsofindividualsinthisdatasetwerefound
toshareatotalof1.9millionsegmentsofIBD,anaverageof0.74 Germany DE 71 1.1 0.9
perpairofindividuals,or831perindividual.Themeanlengthof Ireland IE 60 2.6 0.6
these blocks was 2.5cM, the median was 2.1 cM, and the 25th Netherlands NL 17 1.9 0.7
and 75th quantiles are 1.5cM and 2.9cM, respectively. The
Scotland SC 5 2.2 0.7
majority of pairs sharing some IBD shared only a single block of
SwissFrench CHf 839 1.3 0.6
IBD (94%). The total length of IBD blocks an individual shares
SwissGerman CHd 103 1.6 0.6
withallothersrangedbetween30%and250%(average128%)of
the length of the genome (greater than 100% is possible as Switzerland CH 17 1.1 0.5
individualsmayshareIBDblockswithmorethanoneotheratthe UnitedKingdom UK 358 1.2 0.7
same genomiclocation). Igroup
TheobservedgenomicdensityoflongIBDblocks(percM)can
Italy IT 213 0.6 0.5
be affected by recent selection [35] and by cis-acting recombina-
Portugal PT 115 1.9 0.5
tionmodifiers.WefindthatthelocaldensityofIBDblocksofall
lengths is relatively constant across the genome, but in certain Spain ES 130 1.5 0.4
regions the length distribution is systematically perturbed (see
doi:10.1371/journal.pbio.1001555.t001
Figure S1), including around certain centromeres and the large
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Figure2.Substructurein(A)Italianand(B)U.K.samples.Theleftmostplotsof(A)showhistogramsofthenumbersofIBDblocksthateach
ItaliansampleshareswithanyFrench-speakingSwiss(top)andanyonefromtheUnitedKingdom(bottom),overlaidwiththeexpecteddistribution
(Poisson)iftherewasnodependencebetweenblocks.NextisshownascatterplotofnumbersofblockssharedwithFrench-speakingSwissandU.K.
samples,forallsamplesfromFrance,Italy,Greece,Turkey,andCyprus.WeseethatthenumbersofrecentancestorseachItalianshareswiththe
French-speakingSwissandwiththeUnitedKingdomarebothbimodal,andthatthesetwoarepositivelycorrelated,rangingcontinuouslybetween
valuestypicalforTurkey/CyprusandforFrance.Figure(B)issimilar,showingthatthesubstructurewithintheUnitedKingdomispartofacontinuous
trendrangingfromGermanytoIreland.TheoutliersvisibleinthescatterplotofFigure2Bareeasilyexplainedasindividualswithimmigrantrecent
ancestors—thethreeoutlyingU.K.individualsinthelowerleftsharemanymoreblockswithItaliansthanallotherU.K.samples,andtheindividual
labeled‘‘SK’’isaclearoutlierforthenumberofblockssharedwiththeSlovakiansample.
doi:10.1371/journal.pbio.1001555.g002
inversion on chromosome 8 [36], also seen by [35]. Somewhat Two of the more striking examples of substructure are
surprisingly,theMHCdoesnotshowanunusualpatternofIBD, illustratedinFigure2.Here,weseethatvariationwithincountries
despitehavingshownupinothergenomicscansforIBD[35,37]. can be reflective of continuous variation in ancestry that spans a
However, therearea fewotherregions wheredifferences inIBD broader geographic region, crossing geographic, political, and
rate are not predicted by differences in SNP density. Notably, linguistic boundaries. Figure 2A shows the distinctly bimodal
there are two regions, on chromosomes 15 and 16, which are distributionofnumbersofIBDblocksthateachItalianshareswith
nearly as extreme in their deviations in IBD as the inversion on both French-speaking Swiss and the United Kingdom, and that
chromosome 8, and may also correspond to large inversions these numbers are strongly correlated. Furthermore, the amount
segregatinginthesample.Theseonlymakeupasmallportionof that Italians sharewith these twopopulations varies continuously
thegenome,anddonotsignificantlyaffectourotheranalyses(and from values typical for Turkey and Cyprus, to values typical for
so arenot removed); weleave furtheranalysisfor future work. France and Switzerland. Interestingly, the Greek samples (EL)
placenearthemiddleoftheItaliangradient.Itisnaturaltoguess
Substructure and Recent Migrants thatthereisanorth-southgradientofrecencyofcommonancestry
We should expect significant within-population variability, as along the length of Italy, and that southern Italy has been
modern countries are relatively recent constructions of diverse historicallymorecloselyconnectedtotheeasternMediterranean.
assemblagesoflanguagesandheritages.Toassesstheuniformityof In contrast, within samples from the United Kingdom and
ancestrywithinpopulations,weusedapermutationtesttomeasure, nearbyregions,weseeanegativecorrelationbetweennumbersof
for each pair of populations x and y, the uniformity with which blocks shared with Irish and numbers of blocks shared with
relationshipswithxaredistributedacrossindividualsfromy.Most Germans. From our data, we do not know if this substructure is
comparisonsshowstatisticallysignificantheterogeneity(FigureS2), also geographically arranged within the United Kingdom (our
which is probably due to population substructure (as well as sampleofwhichmayincludeindividualsfromNorthernIreland).
correlationsintroducedbythepedigree).Anotableexceptionisthat However,anobviousexplanationofthispatternisthatindividuals
nearly all populations showed no significant heterogeneity of within the United Kingdom differ in the number of recent
numbers of common ancestors with Italian samples, suggesting ancestors shared with Irish, and that individuals with less Irish
thatmostcommonancestorssharedwithItalylivedlongeragothan ancestryhavealargerportionoftheirrecentancestrysharedwith
thetimethatstructurewithinmodern-daycountriesformed. Germans. This suggests that there is variation across the United
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GeographyofRecentGeneticAncestry
Kingdom—perhaps a geographic gradient—in terms of the largedifferenceintheratesofIBDsharingbetweenregionscannot
amount ofCeltic versus Germanicancestry. be explained by plausible differences in false positive rates or
Thefirsttwoprincipalcomponentsofthematrixofgenotypes, power between populations, since this pattern holds even at the
after suitable manipulations, can reproduce the geographic longest length scales,where blockidentification isnearly perfect.
positions of European populations (e.g., [12–14]). Therefore, it is To better understand IBD within these groupings, we show in
natural to compare the structure we see within populations in Figure3G–IhowaveragenumbersofIBDblocksshared,inthree
termsofIBDsharingtothepositionsontheprincipalcomponents different length categories, depend on the geographic distance
map. (A PCA map of these populations, produced by EIGEN- separatingthetwopopulations.Evenwithouttakingintoaccount
STRAT [38], is shown in Figure S4.) It is not known what the regional variation, mean numbers of shared IBD blocks decay
geographic resolution of the principal components map is, but if exponentially with distance, and further structure is revealed by
relative positions within populations is meaningful, then compar- breaking out populations by the regional groupings described
ison of IBD to PCA can stand in for comparison to geography. above. The exponential decays shown for each pair of groupings
Indeed,asseeninFiguresS5andS6,thesubstructureofFigure2 emphasize how the decay of IBD with distance becomes more
correlateswellwiththepositiononcertainprincipalcomponents, rapid for longer blocks. This is expected under models where
furthersuggestingthatthestructureisgeographicallymeaningful. migration ismostlylocal, since asonelooks furtherbackin time,
Conversely, since the substructure we see is highly statistically the distribution of each individual’s ancestors is less concentrated
significant, this demonstrates that the scatter of positions within aroundtheindividual’slocation(recallFigure1B).Therefore,the
populations on the European PCA map is at least in part signal, expected number of ancestors shared by a pair of individuals
rather than noise. decreases as the geographic distance between the pair increases;
andthisdecrease isfasterfor morerecentancestry.
Europe-Wide Patterns of Relatedness This wider spread of older blocks can also explain why the
IndividualsusuallysharethehighestnumberofIBDblockswith decay of IBD with distance varies significantly by region even if
others from the same population, with some exceptions. For dispersal rates have been relatively constant. For instance, the
example, individuals in the United Kingdom share more IBD gradual decay of sharing with the Iberian and Italian peninsulas
blocks on average, and hence more close genetic ancestors, with couldoccurbecausetheseblocksareinheritedfrommuchlonger
individuals from Ireland than with other individuals from the ago than blocks of similar lengths shared by individuals in other
United Kingdom (1.26 versus 1.09 blocks at least 1 cM per pair, populations.
Mann-Whitneyp,10210),andGermanssharesimilarlymorewith Conversely, there is a high level of sharing for ‘‘E–E’’
PolishthanwithotherGermans(1.24versus1.05,p=5.761026), relationships over a broad range of distances. This is especially
apatternwhichcouldbeduetorecentasymmetricmigrationfrom trueforourshortest(oldest)blocks:individualsinourEgrouping
a smaller population into a larger population. In Figure 3 we
share on average more short blocks with individuals in distant E
depict the geography of rates of IBD sharing between popula-
populationsthandopairsofindividualsinthesameWpopulation.
tions—that is, the average number of IBD blocks shared by a
We argue below that this is because modern individuals in these
randomly chosen pair of individuals. Above, maps show the IBD
locationshavealargerproportionoftheirancestorsinarelatively
raterelativetocertainchosenpopulations,andbelow,allpairwise
smallpopulation that subsequently expanded.
sharing rates are plotted against the geographic distance separat-
Havingseenthecontinent-widepatternsofIBDinFigure3,itis
ing the populations. It is evident that geographic proximity is a
naturaltowonderifsimilarinformationiscontainedinsingle-site
majordeterminantofIBDsharing(andhencerecentrelatedness),
summaries of relatedness, such as mean Identity by State (IBS)
withtherateofpairwiseIBDdecreasingrelativelysmoothlyasthe
values across European populations. The mean IBS between
geographic separation of the pair of populations increases. Note
populations x and y is defined as the probability that two
that even populations represented by only a single sample are
randomly chosen alleles from x and y are identical (‘‘By State’’),
included, as these showed a surprisingly consistent signal despite
averagingoverSNPsandindividuals.IntheanalogousplotofIBS
thesmallsample size.
againstgeographicdistance(FigureS9),someofthepatternsseen
Superimposedonthisgeographicdecaythereisstrikingregional
inFigure3arepresent,andsomearenot.Forinstance,thereisa
variation in rates of IBD. To further explore this variation, we
continuous decay with geographic distance (linear, not exponen-
divided the populations into the four groups listed in Table 1,
tial), andcomparisons tothesouthern ‘‘I’’groupandtoCyprus/
using geographic location and correlations in the pattern of IBD
Turkey are even more well-separated below the others. On the
sharing with other populations (shown in Figure S7). These five
otherhand,the‘‘E–E’’comparisonsdonotshowhigherIBSthan
groupings are defined as: Europe ‘‘E,’’ lying to the east of
thebulk of theremainingcomparisons.
GermanyandAustria;Europe‘‘N,’’lyingtothenorthofGermany
and Poland; Europe ‘‘W,’’ to the west of Germany and Austria
Ages and Numbers of Common Ancestors
(inclusive); the Iberian and Italian peninsulas ‘‘I’’; and Turkey/
Cyprus ‘‘TC.’’ Although the general pattern of regional IBD Each block of genome shared IBD by a pair of individuals
variationisstrong,noneofthesegroupshavesharpboundaries— represents genetic material inherited from one of their genetic
for instance, Germany, Austria, and Slovakia are intermediate commonancestors.SincethedistributionoflengthsofIBDblocks
between E and W. Furthermore, we suspect that the Italian and differsdependingontheageoftheancestors—forexample,older
Iberianpeninsulaslikelydonot grouptogetherbecause ofhigher blocks tend to be shorter—it is possible to use the distribution of
shared ancestry with each other, but rather because of similarly lengths of IBD blocks to infer numbers of most recent pairwise
low rates of IBD with other European populations. The overall genetic common ancestors back through time averaged across
meanIBDratesbetweentheseregionsareshowninTable2,and pairs of individuals. For this inference, we restricted to blocks
comparisonsbetweendifferentgroupingsarecoloreddifferentlyin longer than 2 cM, where we had good power to detect true IBD
Figure 3G–I, showing that rates of IBD sharing between E blocks.Weobtaindatesinunitsofgenerationsinthepast,andfor
populationsandbetweenNpopulationsaverageafactorofabout ease of discussion convert these to years ago (ya) by taking the
three higher than other comparisons at similar distances. Such a mean human generation timetobe30years [39].
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GeographyofRecentGeneticAncestry
Figure3.Geographicdecayofrecentrelatedness.Inallfigures,colorsgivecategoriesbasedontheregionalgroupingsofTable1.(A–F)The
areaofthecirclelocatedonaparticularpopulationisproportionaltothemeannumberofIBDblocksoflengthatleast1cMsharedbetweenrandom
individualschosenfromthatpopulationandthepopulationnamedinthelabel(alsomarkedwithastar).BothregionalvariationofoverallIBDrates
and gradual geographic decay are apparent. (G–I) Mean number of IBD blocks of lengths 1–3cM (oldest), 3–5cM, and .5cM (youngest),
respectively,sharedbyapairofindividualsacrossallpairsofpopulations;theareaofthepointisproportionaltosamplesize(numberofdistinct
pairs),cappedatareasonablevalue;andlinesshowanexponentialdecayfittoeachcategory(usingaPoissonGLMweightedbysamplesize).
ComparisonswithnosharedIBDareusedinthefitbutnotshowninthefigure(duetothelogscale).‘‘E–E,’’‘‘N–N,’’and‘‘W–W’’denoteanytwo
populationsbothintheE,N,orWgrouping,respectively;‘‘TC-any’’denotesanypopulationpairedwithTurkeyorCyprus;‘‘I-(I,E,N,W)’’denotesItaly,
Spain,orPortugalpairedwithanypopulationexceptTurkeyorCyprus;and‘‘betweenE,N,W’’denotestheremainingpairs(whenbothpopulations
areinE,N,orW,butthetwoareindifferentgroups).TheexponentialfitfortheN–Npointsisnotshownduetotheverysmallsamplesize.SeeFigure
S8foranSVGversionoftheseplotswhereitispossibletoidentifyindividualpoints.
doi:10.1371/journal.pbio.1001555.g003
Nature of the results on age inference. There are two overcome by careful estimation and modeling of error, described
major difficulties to overcome, however. First, detection is noisy: in the Materials and Methods section. The second problem is
we do not detect all IBD segments (especially shorter ones), and moreseriousandunavoidable:theinferenceproblemisextremely
someofourIBDsegmentsarefalsepositives.Thisproblemcanbe ‘‘ill conditioned’’ (in the sense of [40]), meaning in this case that
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GeographyofRecentGeneticAncestry
histories. The reader should also bear in mind that we do not
Table2. RatesofIBD withinand betweeneach geographic
depict thedependence of uncertaintybetween intervals.
groupinggiveninTable 1.
Resultsofageinference. InFigure4weshowhowtheage
andnumberofsharedpairwisegeneticcommonancestorschanges
as we move away from the Balkans (left column) and the United
IBDRate E I N TC W
Kingdom (right column), along with two examples of how the
E 2.57 0.44 0.99 0.62 0.53 observed block length distribution is composed of ancestry from
I 0.44 0.80 0.43 0.41 0.45 differentdepths.[Theaveragenumberofsharedpairwisegenetic
N 0.99 0.43 2.62 0.33 0.86 common ancestors from generation n is the probability that the
most recent common ancestor of a pair at a single site lived in
TC 0.62 0.41 0.33 1.43 0.25
generation n (i.e., the coalescent rate) multiplied by the expected
W 0.53 0.45 0.86 0.25 0.93
number of segments that recombination has broken a pair of
doi:10.1371/journal.pbio.1001555.t002 individuals’genomesintothatmanygenerationsback,asshownin
the Materials and Methods section.] More plots of this form are
there are many possible histories of shared ancestry that fit the shown in Figure S16, and coalescent rates between pairs of
data nearly equally well. For this reason, there is a fairly large, populations are shown inthe(equivalent) FigureS15.
unavoidablelimittothetemporalresolution,butwestillobtaina Mostdetectable recentcommonancestors livedbetween 1,500
good dealofuseful information. and2,500yearsago,andonlyasmallproportionofblockslonger
We deal with this uncertainty by describing the set of histories than 2cM are inherited from longer ago than 4,000 years.
(i.e., historical numbers of common genetic ancestors) that are Obviously,thereareavastnumberofgeneticcommonancestors
consistentwiththedata,summarizedintwoways.First,itisuseful older than this, but the blocks inherited from such common
to look at individual consistent histories, which gives a sense of ancestorsaresufficiently unlikelytobelonger than2 cMthatwe
recurrent patterns and possible historical signals. Figure 4 shows do not detect many. For the most part, blocks longer than 4 cM
for several populations both the best-fitting history (in black) and come from 500–1,500 years ago, and blocks longer than 10cM
thesmoothesthistorythatstillfitsthedata(inred).Wecanmake fromthelast 500years.
general statements if they hold across all (or most) consistent Inmostcases,onlypairswithinthesamepopulationarelikelyto
histories. Second, we can summarize the entire set of consistent share genetic common ancestors within the last 500 years.
histories by finding confidence intervals (bounds) for the total Exceptions are generally neighboring populations (e.g., United
numberofcommonancestorsaggregatedincertaintimeperiods. KingdomandIreland).Duringtheperiod500–1,500ya,individuals
TheseareshowninFigure5,givingestimates(coloredbands)and typicallysharetenstohundredsofgeneticcommonancestorswith
bounds (vertical lines) for the total numbers of genetic common others in the same or nearby populations, although some distant
ancestors in each of three time periods, roughly 0–500 ya, 500– populationshaveverylowrates.Longeragothan1,500ya,pairsof
1,500 ya,and 1,500–2,500ya(‘‘ya’’denotes ‘‘yearsago’’). Figure individuals from any part of Europe share hundreds of genetic
S12 (and S13) is a version of Figure 5 with more populations (in ancestorsincommon,andsomesharesignificantlymore.
coalescentunits,respectively),andplotsanalogoustoFigure4for Regional variation: Interesting cases. We now examine
all these histories are shown in Figure S16. For a precise some ofthemore striking patterns wesee in moredetail.
description of the problem and our methods, see the Materials There is relatively little common ancestry shared between the
and Methods section. We validated the method through simula- Italian peninsula and other locations, and what there is seems to
tion (details in Text S1), and found that it performed well to the derivemostlyfromlongeragothan2,500ya.Anexceptionisthat
temporal resolution discussed here. We note that in simulations Italy and the neighboring Balkan populations share small but
where the population size changes smoothly, the maximum significant numbers of common ancestors in the last 1,500 years,
likelihood solution is often overly peaky, whereas the smoothed as seen in Figures S16 and S17. The rate of genetic common
solution can smear out the signal of rapid change in population ancestry between pairs of Italian individuals seems to have been
size.Inlightofthatweencouragethereadertoviewtruthaslying fairly constant for the past 2,500 years, which combined with
somewhere between these twosolutions, andtonot overinterpret significant structure within Italy suggests a constant exchange of
specificpeaksinthemaximumlikelihood,whichmayoccurdueto migrants between coherentsubpopulations.
numerical properties of the inference. That said, there are a Patterns for the Iberian peninsula are similar, with both Spain
number of sharp peaks in common ancestry shared across many and Portugal showing very few common ancestors with other
population comparisons older than 2,000 ya, which may populations over the last 2,500 years. However, the rate of IBD
potentially indicate demographic events in a shared ancestral sharing within the peninsula is much higher than within Italy—
population. A more thorough investigation of these older shared duringthelast1,500yearstheIberianpeninsulasharesfewerthan
signals would potentially need a more model-based approach, so twogeneticcommonancestorswithotherpopulations,compared
we restrict ourselves here to talking about the broad differences to roughly 30 per pair within the peninsula; Italians share on
between the distribution of common shared ancestors between average onlyabout eightwith eachother during thisperiod.
regions. The higher rates of IBD between populations in the ‘‘E’’
The time periods we use for these bounds are quite large, but groupingshowninFigure3seemtoderivemostlyfromancestors
this is unavoidable, because of a trade-off between temporal living1,500–2,500ya,butalsoshowincreasednumbersfrom500–
resolutionanduncertaintyinnumbersofcommonancestors.Also 1,500 ya, as shown in Figure 5 and Figure S17. For comparison,
note that the lower bounds on numbers of common ancestors the IBD rate is high enough that even geographically distant
during each time interval are often close to zero. This is because individuals in these eastern populations share about as many
onecan(roughlyspeaking)obtainahistorywithequallygoodfitby commonancestorsasdotwoIrishortwoFrench-speakingSwiss.
moving ancestors from that time interval into the neighboring ByfarthehighestratesofIBDwithinanypopulationsisfound
ones,resultinginpeaksoneithersideoftheselectedtimeinterval betweenAlbanianspeakers—around90ancestorsfrom0–500ya,
(seeFigureS14),eventhoughthesedonotgenerallyreflectrealistic andaround600ancestorsfrom500–1,500ya(sohighthatweleft
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GeographyofRecentGeneticAncestry
Figure4.Estimatedaveragenumberofmostrecentgeneticcommonancestorspergenerationbackthroughtime.Estimatedaverage
numberofmostrecentgeneticcommonancestorspergenerationbackthroughtimesharedby(A)pairsofindividualsfrom‘‘theBalkans’’(former
Yugoslavia, Bulgaria, Romania, Croatia, Bosnia, Montenegro, Macedonia, Serbia, and Slovenia, excluding Albanian speakers) and shared by one
individualfromtheBalkanswithoneindividualfrom(B)Albanian-speakingpopulations,(C)Italy,or(D)France.Theblackdistributionisthemaximum
likelihoodfit;showninredissmoothestsolutionthatstillfitsthedata,asdescribedintheMaterialsandMethods.(E)showstheobservedIBDlength
distributionforpairsofindividualsfromtheBalkans(redcurve),alongwiththedistributionpredictedbythesmooth(red)distributionin(A),asa
stackedareaplotpartitionedbytimeperiodinwhichthecommonancestorlived.Thepartitionswithsignificantcontributionarelabeledontheleft
verticalaxis(ingenerationsago),andthelegendin(J)givesthesamepartitions,inyearsago;theverticalscaleisgivenontherightverticalaxis.The
secondcolumnoffigures(F–J)issimilar,exceptthatcomparisonsarerelativetosamplesfromtheUnitedKingdom.
doi:10.1371/journal.pbio.1001555.g004
themoutofFigure5;seeFigureS12).Beyond1,500ya,therates Europe, These differences reflect the impact of major historical
of IBD drop to levels typical for other populations in the eastern and demographic events, superimposed against a background of
grouping. localmigrationandgenerallyhighgenealogicalrelatednessacross
Therearecleardifferencesinthenumberandtimingofgenetic Europe. We now turn to discuss possible causes and implications
common ancestors shared by individuals from different parts of of these results.
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GeographyofRecentGeneticAncestry
Figure 5. Estimated average total numbers of genetic common ancestors shared per pair of individuals in various pairs of
populations, in roughly the time periods 0–500 ya, 500–1,500 ya, 1,500–2,500 ya, and 2,500–4,300 ya. We have combined some
populationstoobtainlargersamplesizes:‘‘S-C’’denotesSerbo-CroatianspeakersinformerYugoslavia,‘‘PL’’denotesPoland,‘‘R-B’’denotesRomania
andBulgaria,‘‘DE’’denotesGermany,‘‘UK’’denotestheUnitedKingdom,‘‘IT’’denotesItaly,and‘‘Iber’’denotesSpainandPortugal.Forinstance,the
greenbarsintheleftmostpanelstellusthatSerbo-CroatianspeakersandGermansmostlikelyshare0–0.25mostrecentgeneticcommonancestor
fromthelast500years,3–12fromtheperiod500–1,500yearsago,120–150from1500–2,500ya,and170–250from2,500–4,400ya.Althoughthe
lowerboundsappeartoextendtozero,theyaresignificantlyabovezeroinnearlyallcasesexceptforthemostrecentperiod0–540ya.
doi:10.1371/journal.pbio.1001555.g005
Discussion From our numerical results, the average number of genetic
commonancestorsfromthelast1,000yearssharedbyindividuals
Genetic common ancestry within the last 2,500 years across living at least 2,000 km apart is about 1/32 (and at least 1/80);
Europe has been shaped by diverse demographic and historical between 1,000 and 2,000ya they share about one; and between
events. There are both continental trends, such as a decrease of 2,000and3,000yatheyshareabove10.Sincethechanceissmall
shared ancestry with distance; regional patterns, such as higher that anygenetic material has been transmitted along a particular
IBD in eastern and northern populations; and diverse outlying genealogical path from ancestor to descendent more than eight
signals. We have furthermore quantified numbers of genetic generationsdeep[8]—about.008at240ya,and2.561027at480
common ancestors that populations share with each other back ya—thisimplies,conservatively,thousandsofsharedgenealogical
through time, albeit with a (unavoidably) coarse temporal ancestors in only the last 1,000 years even between pairs of
resolution. These numbers are intriguing not only because of the individuals separated by large geographic distances. At first sight
differences between populations, which reflect historical events, thisresultseemscounterintuitive.However,as1,000yearsisabout
butthehighdegreeofimpliedgenealogicalcommonalitybetween 33 generations, and 233<1010 is far larger than the size of the
even geographically distantpopulations. European population, so long as populations have mixed
Ubiquityofcommonancestry. Wehaveshownthattypical sufficiently, by 1,000 years ago everyone (who left descendants)
pairsofindividualsdrawnfromacrossEuropehaveagoodchance wouldbeanancestorofeverypresent-dayEuropean.Ourresults
ofsharinglongstretchesofidentitybydescent,evenwhentheyare are therefore one of the first genomic demonstrations of the
separated by thousands of kilometers. We can furthermore counterintuitive but necessary fact that all Europeans are
conclude that pairs of individuals across Europe are reasonably genealogically related over very short time periods, and lends
likely to share common genetic ancestors within the last 1,000 substantial support to models predicting close and ubiquitous
years, and are certain to share many within the last 2,500 years. commonancestry ofall modern humans[7].
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ThefactthatmostpeoplealivetodayinEuropesharenearlythe Clearly the ancestry of Europeans is far more diverse than those
same set of (European, and possibly world-wide) ancestors from represented here, but such steps seemed necessary to make best
only1,000yearsagoseemstocontradictthesignalsoflong-term, initial use ofthisdataset.
albeit subtle, population genetic structure within Europe (e.g., Ages of particular common ancestors. We have shown
[13,14]). These two facts can be reconciled by the fact that even that the problem of inferring the average distribution of genetic
thoughthedistributionofancestors(ascartoonedinFigure1B)has common ancestors back through time has a large degree of
spread to cover the continent, there remain differences in degree fundamental uncertainty. The data effectively leave a large
ofrelatednessofmodernindividualstotheseancestralindividuals. number of degrees of freedom unspecified, so one must either
Forexample,someoneinSpainmayberelatedtoanancestorin describe the set of possible histories, as we do, and/or use prior
theIberianpeninsulathroughperhaps1,000differentroutesback information torestrict these degrees offreedom.
through the pedigree, but to an ancestor in the Baltic region by A related but far more intractable problem is to make a good
only 10 different routes, so that the probability that this Spanish guess of how long ago a certain shared genetic common ancestor
individual inherited genetic material from the Iberian ancestor is lived,aspersonalgenomeserviceswouldliketodo,forinstance:if
roughly 100 times higher. This allows the amount of genetic youandIsharea10cMblockofgenomeIBD,whendidourmost
materialsharedbypairsofextantindividualstovaryeveniftheset recent common ancestor likely live? Since the mean length of an
of ancestors isconstant. IBDblockinheritedfromfivegenerationsagois10cM,wemight
Relationtosingle-sitesummaries. Otherworkhasstudied expecttheaverageageoftheancestorofa10cMblocktobefrom
fine-scaledifferentiationbetweenpopulationswithinEuropebased around five generations. However, a direct calculation from our
on statistics such as F , IBS (e.g., [14,18]), or PCA [13], that results says that the typical age of a 10cM block shared by two
ST
summarize in various ways single-marker correlations, averaged individuals from the United Kingdom is between 32 and 52
acrossloci.LikeratesofIBD,thesemeasuresofdifferentiationcan generations (depending on the inferred distribution used). This
be thought of as weighted averages of past coalescent rates [41– discrepancy results from the fact that you are a priori much more
44], but take much of their information from much more distant likelytoshareacommongeneticancestorfurtherinthepast,and
times(tensofthousandsofgenerations).Asexpected,wehaveseen this acts to skew our answers away from the naive expectation—
bothstrongconsistencybetweenthesemeasuresandIBD(e.g.,the even though it is unlikely that a 10cM block is inherited from a
decay with geographic distance), as well as distinct patterns (e.g., particular shared ancestor from 40 generations ago, there are a
highersharingineasternEurope).Theseresultshighlightthefact greatnumberofsucholdersharedancestors.Thisalsomeansthat
thatlongsegmentsofIBDcontaininformationaboutmuchmore estimatedagesmustdependdrasticallyonthepopulations’shared
recenteventsthandosingle-site summaries,informationthatcan histories:forinstance,theageofsucha block sharedbysomeone
be leveragedtolearn about thetimingof these events. fromtheUnitedKingdomwithsomeonefromItalyisevenolder,
Limitationsofsampling. Aconcernaboutourresultsisthat usually from around 60 generations ago. This may not apply to
theEuropeanindividualsinthePOPRESdatasetwereallsampled ancestors from the past very few (perhaps less than eight)
in either Lausanne or London. This might bias our results, for generations, from whom we expect to inherit multiple long
instance, if an immigrant community originated mostly from a blocks—in this case, we can hope to infer a specific genealogical
particularsmallportionoftheirhomepopulation,therebysharing relationshipwithreasonablecertainty(e.g.,[49,50]),althougheven
aparticularlyhighnumberofrecentcommonancestorswitheach thencaremustbetakentoexcludethepossibilitythatthesemultiple
other.Weseeremarkablylittleevidencethatthisisthecase:there blockshavenotbeeninheritedfromdistinctcommonancestors.
is a high degree of consistency in numbers of IBD blocks shared Although the sharing of a long genomic segment can be an
across samples from each population, and between neighboring intriguing sign of some recent shared ancestry, the ubiquity of
populations.Forinstance,wecouldarguethatthehighdegreeof shared genealogical ancestry only tens of generations ago across
shared common ancestry among Albanian speakers was because Europe(andlikelytheworld,[7])makessuchsharingunsurprising,
most of these sampled originated from a small area rather than andassignmenttoparticulargenealogicalrelationshipsimpossible.
uniformly across Albania and Kosovo. However, this would not What is informative about these chance sharing events from
explain the high rate of IBD between Albanian speakers and distant ancestors is that they provide a fine-scale view of an
neighboring populations. Even populations from which we only individual’s distribution of ancestors (e.g., Figure 3), and that in
have one or two samples, which we at first assumed would be aggregate they can provide an unprecedented view into even
unusably noisy, provide generally reliable, consistent patterns, as small-scale human demographic history.
evidenced by,forexample, Figure S3. Where do your nth cousins live? Our results also offer a
Conversely, it might be a concern that individuals sampled in waytounderstandthegeographiclocationofindividualsofagiven
Lausanne or London are more likely to have recent ancestors degreeofrelatedness.ThevaluesofFigure5(andFigureS12)can
morewidelydispersedthanistypicalfortheirpopulationoforigin. be interpreted as the distribution of distant cousins for any
This is a possibility we cannot discard, and if true, would mean reference population—for instance, the set of bars for Poland
there is more structure within Europe than what we detect. (‘‘PL’’)inthetoprowshowsthatarandomlychosendistantcousin
However, by the incredibly rapid spread of ancestry, this is ofaPolishindividualwiththecommonancestorlivinginthepast
unlikelytohaveaneffectovermorethanafewgenerationsandso 500yearsmostlikelylivesinPolandbuthasareasonablechance
does not pose a serious concern about our results about the of living in the Balkan peninsula or Germany. Here ‘‘randomly
ubiquitous levels of common ancestry. Fine-scale geographic chosen’’ means chosen randomly proportional to the paths
sampling of Europe as a whole is needed to address these issues, through the pedigree—concretely, take a random walk back
and these efforts are underway in a number of populations (e.g., through the pedigree to an ancestor in the appropriate time
[45–48]). period, and then take a random walkback down. If onestarts in
Finally, we have necessarily taken a narrow view of European Poland, then the chance of arriving in, say, Romania is
ancestry as we have restricted our sample to individuals who are proportionaltotheaveragenumberof(genetic)commonancestors
notoutlierswithrespecttogeneticancestry,andwhenpossibleto sharedbyapairfromPoland andRomania,whichisexactlythe
those having all four grandparents drawn from the same county. number estimated inFigure 5.
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