Barbujani y Sokal 1991 - Genetic Structur of Italy

Genetic Population Structure of Italy. I.
Geographic Patterns of Gene Frequencies

Author(s): GUIDO BARBUJANI and ROBERT R. SOKAL
Source: Human Biology, Vol. 63, No. 3 (June 1991), pp. 253-272
Published by: Wayne State University Press
Stable URL: http://www.jstor.org/stable/41464176
Accessed: 08-11-2015 00:09 UTC
REFERENCES
Linked references are available on JSTOR for this article:
http://www.jstor.org/stable/41464176?seq=1&cid=pdf-reference#references_tab_contents
You may need to log in to JSTOR to access the linked references.
Your use of the JSTOR archive indicates your acceptance of the Terms & Conditions of Use, available at http://www.jstor.org/page/
info/about/policies/terms.jsp
JSTOR is a not-for-profit service that helps scholars, researchers, and students discover, use, and build upon a wide range of content
in a trusted digital archive. We use information technology and tools to increase productivity and facilitate new forms of scholarship.
For more information about JSTOR, please contact support@jstor.org.
Wayne State University Press is collaborating with JSTOR to digitize, preserve and extend access to Human Biology.
http://www.jstor.org
This content downloaded from 130.237.165.40 on Sun, 08 Nov 2015 00:09:36 UTC
All use subject to JSTOR Terms and Conditions
Genetic Population Structure of Italy. I. Geographic
Patterns of Gene frequencies
ANDROBERT
GUIDOBARBUJANI1 R.SOKAL2
Abstract The diversity of spatialpatterasof 61 allelefrequencies

for20 geneticsystems(15 loci) in Italyis presented.Blood anti-
gens,enzymes, and proteins wereanalyzed.The totalnumberofdata
pointsoverall systems and localitieswas 1119. We used homogene-
itytests,one-dimensional and directional spatialcorrelograms, and
symapinterpolated surfaces.The datamatrices werereducedbyclus-
teringtechniquesto revealtheprincipalpatterns. Onlya fewallele
frequency surfaces are stronglycorrelated across loci. All systems
butone (ADA) exhibitsignificant heterogeneity in allelefrequencies
amongthe localities.Significant spatialpatternsare shownby 27
of the61 surfaces.Onlyone pattern(cde,system4.19) is clinal;an-
other( PGM1) exhibits a pureisolationbydistancepattern; theothers
showlong-range differentiation in additionto theshort-distance de-
clineofautocorrelation expectedunderisolationbydistance.There
is a markeddeclinein overallgeneticsimilarity withdistancefor
mostvariables.The 27 spatiallysignificant allelesin Italyare also
patterned
significantly in Europe,butin all but2 cases thecountry-
wideand continent-wide patterns The Italianpatterns
differ. aredue
selectionforallelesassociated
to forcesspecificto Italy.Differential
withmalariais stillevident.Whereasshort-range can
differentiation
be explainedbyisolationbydistance,long-range differentiationap-
pearsto be due to demographic changesin certainpopulationsthat
maybe maintained byphysicaland linguistic isolation.
The patternsof genetic variation in European populations are diverse

and complex. The frequenciesof virtuallyall markersare significantly
differentiatedamong populations (Sokal, Harding,and Oden 1989); only
in some cases, however, are their distributionssimple clines (mainly
HLA alleles) (Sokal and Menozzi 1982; Hedrick et al. 1986) or apparent
matchesforthe distributionof an environmentalfactorwithadaptive rel-
evance (such as malaria forthe ^-thalassemia locus) (Barrai et al. 1984).
In general,the geneticsimilarityof populations decreases withtheirdis-
forall markers
tance but not at the same rate or withthe same regularity
1Dipartimento Universita
diBiologia, 75,1-35121
viaTrieste
diPadova, Padova,
Italy.
ofEcology
2Department State
andEvolution, ofNewYork,
University NY11794-
Brook,
Stony
5245.
Human June
Biology, Vol.63,No.3,pp.253-272.
1991,
© Wayne
Copyright State
University 1991
Press,
254 / BARBUJANI
ANDSOKAL
(Sokal, Harding, and Oden 1989). Therefore,although the interaction

of random geneticdriftand individual dispersal (isolation by distance)
(Wright1943; Cavalli-Sforza 1984) may account fordifferences between
relativelyclose populations, possibly withinseveral hundredkilometers
(Barbujani 1988), long-rangedifferentiation of populations must have
involved more complex phenomena. Mass migration,asymmetricgene
flow,population admixture,and similar processes [reviewedby Slatkin
(1989)] are likelyto have played a role in determiningthe currentlevels
of geneticdiversity.
One way to evaluate the relative importance of the mentioned
demographicprocesses is to focus on populations and markersthat are
most likelyto permitevolutionaryinferences.Among the countriesand
regionsof Europe, Italy is by farthe most thoroughlydocumentedwith
respect to number of populations sampled and genetic systemstyped.
In this articlewe investigatethe geneticstructureof the populations of
Italy on the basis of 20 systemsrepresenting blood group markers,serum
proteins,and electrophoreticpolymorphisms.Two markersare included
that have evolved under selective pressuresin malarial areas, namely,
^-thalassemia (Th; autosomal) and glucose-6-phosphatedehydrogenase
(G6PD; sex-linked).
Seven of the systems(Sardinian populations excluded) were ana-
lyzedby Piazza et al. (1988), who employedprincipalcomponentanalysis
to associate the geographicpatternsof gene frequenciesto the distribu-
tion of prehistoricItalian populations.They recognizedthreemajor com-
ponents of variation and linked theirpatternsto the locations of three
ancient ethnic groups, Greeks, Etruscans,and Ligurians. Piazza et al.
(1988) based theirstudyon evaluation of some syntheticvariables that
summarize the variation of several markers.By contrast,in this study
we analyze separatelythe gene frequenciesat 20 systems,looking for
differencesamong the geographicpatternsshown by different gene fre-
quencies. We employ spatial autocorrelationanalysis (Sokal and Oden
1978a,b) and related statisticaltechniques followingthe protocols sug-
gested by Sokal and Oden (1978a,b), Sokal and Wartenberg(1981), and
Sokal (1986) to inferthe evolutionaryprocesses most likelyto have led
to the observed patterns.
In a companion article we address the question of whetherthe
genetic variation of Italian populations is related to their linguistic
differentiation, that is, to differencesin the spoken dialects (Barbujani
and Sokal 1991). These investigationsfollowtechniquesdeveloped foran
analogous studyof all of Europe [fora summary,see Sokal et al. (1990)].
Finally,we also investigatewhatlightsuch a relationshipcan throwon the
inferencesreachedin thepresentstudyconcerningthegeneticpopulation
structureof Italy.
GeneticPopulation Structureof Italy / 255
Materials and Methods

Database. Allele frequenciesat 20 systems,74 alleles overall, were
collected from various compilations of human population data, such
as Mourant et al. (1976), Piazza et al. (1982), and Tills et al. (1983).
Most of these data have already been included in the European gene
frequencydatabase employed in previous studies (Sokal 1988; Sokal,
Oden, and Thomson 1988; Sokal et al. 1989, 1990; Sokal, Harding,and
Oden 1989; Harding and Sokal 1988; Barbujani and Sokal 1990). They
were updated througha computer search of the recent literature,and
allele frequenciesfor/^-thalassemiaand G6PD were added (Livingstone
1967). We chose to consider loci for which at least 19 localities had
been typed, at least 4 of them in Sardinia. Other systems, such as
glyoxalase and 6-phosphogluconatedehydrogenase(6PGD), for which
scantierinformationor less homogeneouslydistributedinformationwas
available, were not taken into account. The total number of samples
consideredwas 1119 (Table 1). One allele was excluded fromtheanalysis
at each ofthe 12 strictly
bi-allelicloci. Also, we eliminatedthose alleles at
multi-allelicloci thatare highlycorrelatedwithothersat the same locus.
Ultimately,52 alleles remainedforanalysis. We referto the distributions
of these allele frequenciesalso as gene frequencysurfaces.
Mapping of Gene frequencyDistributions. To obtain a visual repre-

sentationofgeneticvariationin space, we interpolatedthegene frequency
surfacesto obtain a quasi-continuousset of gene frequencyvalues from
discretedata points.The programemployed(symap;Dougenik and Shee-
han 1979) computed hypotheticalgene frequenciesat the nodes of a
74-row by 110-column grid coveringall of continentalItaly, plus Sar-
dinia and Sicily,by means of an inversesquared distance algorithm.The
interpolatedmaps, samples of which are presentedlater,helped in the
interpretation of the analyticalresultsof successive phases of the study.
Spatial AutocorrelationAnalysis. The hypothesisthat the observed

data representvarious samples drawn froma single population, that is,
homogeneityof allele frequencies,was tested at each locus by means of
a G testof independence (Sokal and Rohlf 1981, pp. 735-747).
The values of one variable (e.g., a gene frequency)are said to be
spatially autocorrelatedwhen there is positive or negative association
of theirvalues as measured in pairs of localities separated by a certain
distance. Two commonlyused measures of this association are Moran's
I, a product-momentcoefficient, and Geary's c, a distancelikecoefficient
(Sokal and Oden 1978a,b; Cliffand Ord 1981; Upton and Fingleton
1985). Both were employed in this study;because theirresultstend to
agree, only the values of Moran's I are given. For large samples the
256 / BARBUJANI
ANDSOKAL
'S ^
."*2
«nso© ON^ m
^ ON^ o'
^ °o r»
oo ON-«/">
oo<n
« n-v©
<nm vo
r--vo
m
SCr^ o'"
«aï
5 "5*
^S v3 ^
M fO-H(N-I ^ ^ VO -H-H-H-H<N-H- •
§,s Q
> ?> 55
1
1 ! ?&* V §
5 #^ 5*8 7* ^ £
U«- 5 V â
^ % . li 0<3Ü<3 £*<§*. «>7
s. ?"?"?*« 1 ^
1 t,t,^^S;Q(j'9o,3i*!tt>ê'(âô!,3^
Uh
<2
U3
.22
* I
V e ^
•O 9 8>
o
£ S "1
TD §-
LÜ ¥-
ÜJ Is
£»*5
£ ». § "§ *
a S _r « Q Q 12
3 V '». ^ ^
►2 ^ '7'*' ts i2
fc B î . V V „II
ö i .1 s '§ 'g ||I
cd c* '■£ _ s J3
S.
£" g
22
55 -S a ?■8 3
(U * * o S1??
£cd fi
5 '5 3 3 S >ï •&§•§,
ooz; s ss s sa «s ssg
•S << s s a- S <§ S ä ä x (S -ï S £
CA
S
Sf/3
en>*
&
sg ss Jg „ _
- ^ ^ '
s - •« - - rn - o
-
H Ä5 -h
§^Co>< : -h
«~i(N(N -. «m «mom -^ «in
t-.n: : 't Tt r oo
S-
Su-C
-tsI
'S « ^? ^ ooOs -on co ON
I §£ 2 =
> ft,
s
^ VJ
^^R V«SN -H <N - ' CM
§ a Q -H «O
ê £ s
A >»
.9 -a
RS
!N 8> 2
-E
t z
^ §5 S3
^ ^ cG °fa
<N
* 05^ a £»S
^ N<N £ ^ O I" P
Î «.s.si" CO
I fcSsTs I II
f ^ 1 Ii
°#
*7^ Ä fiq «or^«o o
_I_ •§ >>o
^^^n-aqajaqisit«, ^ t g
ON 4) -«-»
w Cd<3
•-3 >"»^
2w £cö
■*-»^
§ §i
1 îä m^ s
£ « « I
* a i3 | "
§8 i §*i
^ s « ^ 8 s
>>A
^P 8'l
2 § cd «
; S
O CS*
5 .S ^ *S h «taö S
50 u «> « ^3^-8
3 •§ I i s 3 =i -s
1§1 5 73 « 8 -s i ^
Iii ^ js
<<x X céL i*j<§i2ï1
^g
i£t.sf
2 2s S!
§ <2 ^ u ^
^ ^,< <D«o
*0 <U</i
<Dcd
g s b S s «SS t
III 7 S 8
O^ S © ^ f> grO
«è;Co< v0(f)0
«r>v©-h °- . p H cd ***
<N
258 / BARBUJANI
ANDSOKAL
values of I range from approximately1 (for positive autocorrelation)

to -1 (negative autocorrelation),the expected value being - 1/(« - 1),
where n is the sample size. Geographic distances between localities
were computed as great circle distances, which also proved to be, by
and large, proportionalto the road distances between Italian localities
(Crumpacker et al. 1976). Autocorrelationcoefficientswere computed
within7 arbitrarydistanceclasses,whose upper limitswere 150,250, 350,
450, 550, 650, and 1200 km. The plot of the autocorrelationcoefficients
versus distance is referredto as a correlogram,the overall significanceof
which is assessed througha Bonferronitest(Oden 1984).
For nine systemsthe informationavailable was sufficient to disag-
gregatethe patternsof gene frequencyvariation in space by means of
directionalspatial correlograms(Oden and Sokal 1986). In this case the
autocorrelationcoefficients(Moran's I and Geary's c) were computed
in classes based not only on the distance betweenpairs of localities but
also on the mutual compass bearingof each pair of points. Five distance
classes werechosen,representedas annuli in the correlogramplots. Their
upper limits were 50, 200, 450, 800, and 1250 km. Althoughthe direc-
tional correlogramsare radially symmetric,they are presentedhere as
complete circularsets of coefficients forease of interpretation.
Correlation between Gene frequency Distributions. The clustering

techniquesdescribedin the next sectionassume statisticalindependence
of the gene frequenciesat the loci studied. However, independence is
difficultto testbecause the data points are distributeddifferently forthe
different systems;comparisons between systems cannot be based on only
the localities where allele frequenciesare available forboth markersbe-
cause the number of such localities is limited. The solution we chose
[firstput forwardby Sokal, Harding,and Oden (1989b)] was to employ
the interpolatedgene frequencysurfacesand subdivide them into 48
quadrats, whose sides are 1° latitude and longitude. The interpolated
allele frequencyvalues were averaged withinthese quadrats, and corre-
lation coefficientsbetweenpairs of surfaces,over all quadrats, were cal-
culated. To minimize the errorsresultingfrommissingdata, we did not
include in the correlationcoefficientthe quadrats occurringoutside an
envelope containingtheobserveddata points.The interpolationprogram
employedforthis purpose (surfer) is slightlydifferent fromthe one that
generatedthe gene frequencymaps but is based on the same principle
of inverse squared distance weighting.It yielded interpolatedvalues on
a lattice of 47 rows by 53 columns. Because of the autocorrelationof
spatial data, however,the interpolatedgene frequenciesare not indepen-
dent and the conventionaltestsof significanceof correlationcoefficients
are not applicable. Thereforewe referto correlationcoefficients greater
than 0.7 or lowerthan -0.7, as "high" coefficients and the corresponding
gene frequencysurfacesas "highlycorrelated"surfaces,withoutimplying

anythingwithrespectto theirsignificance.
Clusteringof Correlograms. Similaritiesof the Bonferroni-significant

nondirectionalcorrelogramswere estimatedby computingaverage Man-
hattan distances betweenthem based on the numberof distance classes
(Sneath and Sokal 1973). Because of the relative scarcityof alleles that
could be analyzed by directionalspatial autocorrelation,directionalcor-
relogramswere not clustered. We also applied a nonhierarchicalclus-
tering method, fc-meansclustering(Späth 1980), to the Bonferroni-
significantcorrelograms.The method findsthe minimum pooled sum
of squares within groups for a partitionof N items into k groups by
means of a hill-climbingalgorithm.The groupingobtained was the min-
imum solution after 100 trials with random initial startingpositions.
This procedurewas repeated forthe values of k = 4, 5, . . ., 10, and the
numberk of clusterschosen was determinedby examiningthe slope of
the curve of sum of squares plotted against k. By using this technique,
we found that k = l clustersappears to be optimal. Ultimately,average
correlogramswere computed foreach of the k clusters.
Results
Only a fewallele frequencysurfacesappear to be highlycorrelated
across loci. Taking into account only comparisons based on at least 20
1° quadrats, the product-momentcorrelationcoefficientexceeds 0.7 in
absolute value only for 7° versus CDe (system 4.19) and cde (system
4.19) and M versus D. In addition, the two Rh systemsthat could be
compared (4.1 and 4.19) yielded high correlations,as expected. Even
when lower correlationcoefficients (i.e., absolute value of r greaterthan
0.6) or comparisons based on fewer quadrats (more than 15) were
considered,only 5 pairs of surfaceswere highlycorrelated(within-locus
correlationswere disregarded). We conclude that the different genetic
systemsprovide independentinformationabout the geneticstructureof
the studypopulations.
All allele frequencysurfaces,except that forthe adenosine deami-
nase (ADA) system,exhibitnominallysignificantheterogeneity by the G
test.Table 2 summarizesthe spatial correlogramsfor61 alleles. Twenty-
seven of the 52 correlogramsare overall significantat P < 0.05. Among
the significantcorrelograms,only one, cde (system 4.19), was perfectly
clinal; that is, it showed monotonicallydecreasingautocorrelationfrom
significantpositive values at short distances to significantnegativeval-
ues at large distances. The patternshown by PGM 1-1 correspondsto
the one expected under pure isolation by distance [Barbujani 1987; see
also Sokal and Wartenberg(1983)], that is, positive autocorrelationfor
ANDSOKAL
260 / BARBUJANI
u u 'O U U U u vu
S ^ <NO O O <NO ^ O O ^ O O »-«O O «/">
O O <NO <N<N
^ ÖÖÖÖÖÖÖÖÖÖÖÖÖÖÖÖÖÖÖÖÖÖÖÖÖÖÖÖ
I I I I I II I III I I I I I I I
4) O U "O-I-4--f--I--♦-■+- 4) "OU dj
Ä
o r^t^«r>©r-OTi-oor^r--«n<N~HSOT|-<Nt"«*m~HOON©Ttcn-*~Hr"".r->*^-
- « -HO - ; VO- <o o <Nro^ p ^ p coo io O O -Ho O CO
8 ÖÖÖÖÖÖÖÖÖÖÖÖÖÖÖÖÖÖÖÖÖÖÖÖÖÖÖÖ
I I I I I I I I I I I I I I I I I I II | Il
a> o 73 qj u *00*0 u
o »oî^^TtvofsgNTfo^-roorNirsr^raiooorsi^Hîoo-HfNfOso
-HO-HO'HMp^P'H'HfO^^p^ppnp^NOfop^^rs
ÎP ÖÖÖÖÖÖÖÖÖÖÖÖÖÖÖÖÖÖÖÖÖÖÖÖÖÖÖÖ
I I I I I I I I I I I III II I I I I III
CA
<L>
c<L> 4
§ <-v ;u£3;i<<N9£&tr,o-H^£3£'-;<'r>MDoo'5-o,'TroN<NT}-i/->^r--oor--'3-^-
o ppp^p^TtpvOOppÔOO-HO-HO-HOOOO-HOO
p2
s-> Ç ÖÖÖÖÖÖÖÖÖÖÖÖÖÖÖÖÖÖÖÖÖÖÖÖÖÖÖÖ
,8
bu ss: I I I I I I I I I I I I. Ill
<L> a
a<u •S3
Ü
§ o op-Hi-;-;qn-H(N-H^-Hqq^qfso-Hp'HOO-HOO(NO
fQ ÖÖÖÖÖÖÖÖÖÖÖÖÖÖÖÖÖÖÖÖÖÖÖÖÖÖÖÖ
II I I I I I I II II
I
<4-1
0
t/3
^0 pp(Np-
E:£b'-,£2&Of2£iooQvo©oooso'oo~Hvofôs-Hi^^-rocot^Novo
1
"ts J'-Hpp^tprvjrsjp- ;-Hpp- jmootô-Hpp^m
ÖÖÖÖÖÖÖÖÖÖÖÖÖÖÖÖÖÖÖÖÖÖÖÖÖÖÖÖ
I I I I I I I I I II I
<N
«/%
tn <u<u
<2 a> o T3 <u a> o u u
^"S o_ ôoo-HôcnTt^Hôooooôpcnppoooo-Hrsjom
^S'OôO^ÔsvOOÔ-HW^ÎûS^^^NON^^ÔN^ÔOfOnvO
JJÎ IQ ÖÖÖÖÖÖÖÖÖÖÖÖÖÖÖÖÖÖÖÖÖÖÖÖÖÖÖÖ
I I II I I I I
o
s
CA
x>
'S
1 ^
ë 4& iiicSicÄiic c 8 c c S a c $ c eSSSSfi c$
o
O l§
73
S
ÇX
Cfl
ci
So* I
H t.i.'s, ^ § 5 o 8 8 3 ^ 'S ^ 8 3 'S ? ^ "I ^ ^ ^
&r^^"*ta'-H^^«o*-<<NTfroocomso©<NTtoooboov©î-i
m»-HfOO<NOO'-HOOO'-HO«^<Np<NOO<N<Np-Hfr)
ÖÖÖÖÖÖÖÖÖÖÖÖÖÖÖÖÖÖÖÖÖÖÖÖ
III III I I II I III
4JÜ 4>o o'Oo'O u "O"O u 1

M
<N0000«NTt<N00mi^vO0N,rrv000rNO<NC50ÔmrN0NTf OÛ
ÖÖÖÖÖÖÖÖÖÖÖÖÖÖÖÖÖÖÖÖÖÖÖÖ P
I I I I I I I I I I I I I I I I I I I I g
o
a
"O o v >
u u u "Oo o ü (j a *Kn
(NO-ifSrn(N^Tj-*0'û'H(N^r^q(N(Nfn^-HfO(N-HTt &
ÖÖÖÖÖÖÖÖÖÖÖÖÖÖÖÖÖÖÖÖÖÖÖÖ O
I I I I I I I I I I I I I I I I I I I II g
^r^^HOOfOooôomoN^-'*toor^vO(NON«o^'0«oONTl- S'
-S1
<N©^-0^©vOr*">^,<frO'-*c^~Hm©~Hpp'-H<cn^<N<N
ÖÖÖÖÖÖÖÖÖÖÖÖÖÖÖÖÖÖÖÖÖÖÖÖ _
I I I I I I I I I I I I I I I I I I I I -g
>
o
u.
u "O
ONVovot^ÔNu^ror^^-^-oofo-HvooovoaNôovom- « *> »Q
z*
55
ÔMOÔfN(NO'HÔ(NÔOq(NOqfS^Mi-H
ÖÖÖÖÖÖÖÖÖÖÖÖÖÖÖÖÖÖÖÖÖÖÖÖ 3 ti
III I I I I I I s I
2
U =3
<A
&C3 a4>
Trr0^-<Nrn*oopnor-^,^r-0sôr0r0r><0NV0as'^,0N o
PQ 5o
ÖÖÖÖÖÖÖÖÖÖÖÖÖÖÖÖÖÖÖÖÖÖÖÖ S> CÖ
1 1 É. s
O
M co
<u
a>"O "O"ö « vuu'O « «> o "O 4> u cj . §
rij s g*
^Hcnrôsoo*nvomforî^,^,coôoiôvo«oONVoaNONO
'^csim^rn .ti ««5 .o 5
ÖÖÖÖÖÖÖÖÖÖÖÖÖÖÖÖÖÖÖÖÖÖÖÖ Ë 3 £
I il I - :-3 go
a a &
s«O-3S ä'S
o »
a> a Ö£
ê=J<3 Se
t 2
c 'S ^ r*
g <5 8 £
SSS S S fi$ S 3§ a cSScSc S $ S S2 S S g g ^1*5
S -2 . -t-S
a 8 .® s ts
.2 -a £ s c -S
^
1 §t .'Il
il 8
-, •5mV_ög§
xr^ £ S 8
^ 1a o C>VIï |
I ^ "TS oôo t~ H O ft, V5*Q
^Û^^^^^^^^^^DQÛqOQÛQÛQOQÛQÛQDQÛQOQÛQt-i céX>Ü T) <L> <«-î +-
262 / BARBUJANI
ANDSOKAL
1. Directional
Figure fortworepresentative
spatialcorrelograms alleles,D and Th+.
Thefivecircular
annulirepresent
fivedistance
classes, whoseupperlimits are
50,200,450,800,and1250km.Eachsector is an autocorrelation coefficient,
computed bytaking intoaccount
boththedistance between populationsand
thecompassdirectionalongwhichtheyareconnected. Shading correspondsto
approximate oftheoverall
quintiles distribution
ofautocorrelation coefficients;
darkestshadings standforpositiveautocorrelation.Significantcoefficients
(p < 0.05) are represented
byfullwidthsectors; nonsignificantonesare
bynarrower
represented sectors.
Dashedrectangles indicatecoefficients
based
on lessthan20 pairsoflocalities.
Notethatthedirectional autocorrelation
indexesareradially butcomplete
symmetric circles aregivenforthesakeof
clarity.
the short-distanceclasses, decreasing to near 0 at large distances. All

othersignificantcorrelogramsshowed long-rangedifferentiation of allele
frequenciesbut variable spatial structure,which in no case could be un-
ambiguouslydefinedas clinal.
The allele frequencypatternsdescribedby directionalautocorrela-
tion statisticsshow significantif not unambiguous spatial structurefor
all the alleles considered. Examples are given in Figure 1. Autocorrela-
tion is positive and generallysignificantup to 50 km and decreases with
distance, oftenalong a north-southor a northwest-southeast axis. Long-
distance differentiation is apparent for most alleles, in agreementwith
that described by nondirectionalcorrelograms.
The seven fc-meansclustersyieldedtheaveragecorrelogramsshown
in Figure 2. Schematically,the seven spatial patternscan be classifiedas
follows[see Sokal (1979) fora detailed explanation of the terminology].
1. Differentiationin patches. Only the glucose-6-phosphatedehy-

drogenase (Gd) correlogrambelongs to this group. The autocor-
relation coefficientsreflectthe patchy distributionof formerly
2.
Figure Average forsevenclusters
correlograms ofalleles.Cluster in
1 (differentiation
patches)includesGd.Cluster2 (long-distance 7A,/B,/A1,/B,
differentiation):
D,Fy-a, Hp-l,PGM'-', AK-l.Cluster 3 (depression1): M, Al, A3,B7,
BW17.Cluster 4 (depression2): NS,cDE (system 4.19),P-c,A10,All, B14.
Cluster5 (doubledepression):BW22,BW35.Cluster 6 (clines):cde(system
7 (intrusion):
4.19),B8, Th+. Cluster PL
malarial areas where the polymorphismforthis markeris pro-

tectedby a mechanismof heterozygoteadvantage.
2. Long-distancedifferentiation. Autocorrelationis positive in the
firstthreedistance classes, thusdefiningregionsof homogeneous
gene frequencies,the total diameter of which is approximately
350 km. Autocorrelationis negativeat largedistances; however,
the absolute values of Moran's I are all small, that is, less than
0.20.
3. Depression 1. In these surfacesgeneticsimilaritydecreases with
distance in the first6 distance classes, which is consistentwith
clinal variation withina range of roughly650 km; the farthest
populations do not seem geneticallydifferentiated.
4. Depression 2. These surfaces are the same as depression 1
surfacesbut theregionsof clinal variationspan 550 km and there
is some residual negativeautocorrelationat the largestdistances.
264 / BARBUJANI
ANDSOKAL
5. Double depression. There are two negativepeaks of autocorre-

lation, roughlyat 400 and 650 km.
6. Clines. The autocorrelationcoefficientsdecrease steadily with
distance, althoughnot exactlyso between the last two distance
classes. This group also includes thalassemia, the other marker
whose polymorphismhas been maintainedby a selectivemech-
anism favoringthe heterozygotesin formerlymalarial environ-
ments.
In all six groups listed so far,autocorrelationis positive at short dis-

tances, as expected under isolation by distance; the exception is group
7.
7. Intrusion.This groupincludes only one marker.PI, whose allele

frequenciesshow maximum similarityat 450 km and negative
autocorrelationat both shorterand largerdistances.
Examples of the four major patterns of allele frequencies described

by correlograms(regionaldifferentiation,depression,double depression,
and cline) are given as contourmaps in Figures 3 through6.
Discussion
The majorityof markersshow positive and decreasingautocorre-
lation in the firstdistance classes. This is the expected consequence of
population divergenceresultingfromgenetic drift,partlycounteredby
individual dispersal or isolation by distance (Barbujani 1987). However,
only 53PGM (phosphoglucomutase)shows the absence of long-distance
autocorrelationof gene frequenciesthat is expected when only isolation
by distance determinesgeneticdifferentiation. All other markerswhose
geographicpatternsof gene frequenciesare significantwere probablyaf-
fectedby other types of evolutionarypressure.The positive spikes for
correlogramclusters 1, 5, and 7 at 350, 450, and 550 km, respectively,
relate to patchysurfacescomprisingthese clusters,with similar patches
occurringat the distances indicated. The increase in autocorrelationat
the largestdistance classes in clusters3 and 5 occurs when the farthest
sampled locations are similarin gene frequency.For an example see Fig-
ure 4, where the frequencyof Al is highin Piedmont and in Puglia and
Calabria.
Comparison of the resultsof this studywith the analysis of Euro-
pean gene frequencies(Sokal, Harding, and Oden 1989) shows that all
the 27 markersthat are significantly differentiated in Italy show signifi-
cant structurein Europe as well but thatforonly 2 alleles, namely,D and
3.
Figure SYMAPcontour mapof thefrequency of/B,an exampleoflong-distance
basedon 195 localities.
differentiation, The interpolatedgenefrequencies
aregroupedintoquintiles andrepresented bydifferentshadings(highgene
shownas darkareas).The locationoftheoriginal
frequencies datapoints
areshownbynumbers (1 to 5) referring
to thequintileto whichtheir
gene
frequency
belongs."S" standsforseveral datapointsat verycloselocations.
Approximate limits
quintile are0.02,0.06,0.07,0.08,0.09,and0.16.
Fy-a, are the spatial patternsthe same in the two studies (long-distance
However, the long-distancedifferentiation
differentiation). refersto dif-
ferentscales in the two studies: >2250 km for Europe and >650 km
forItaly.The correlogramsof allele frequenciesfor24 othermarkersare
different(Th was not included in the European study). ThereforeItaly
does not appear to be just a section of a largerarea affectedby uniform
evolutionarypressures.On the contrary,the extantlevels and modes of
gene frequencyvariationappear to resultmostlyfromspecificprocesses
that acted on the Italian population duringits history.
Among these processes differential selection resultingin protected
polymorphismsis still easily detectable. Both G6PD and Th are poly-
morphic only in formerlymalarial areas; their spatial patternsare dif-
ferentbecause the frequencyof the /^-thalassemiaallele decreases in
a fairlyuniformfashion with the distance fromthe formerlymalarial
266 / BARBUJANI
ANDSOKAL
4.
Figure SYMAPcontour mapof thefrequency ofAl, an exampleofa depression
basedon 19localities.
pattern, ExplanationofsymbolsgiveninFigure 3.The
twolatitudinal ofallelefrequencies
gradients andthedifferentiation
ofSardinia
areevident.
Approximate quintilelimits
are0.00,0.11,0.12,0.13,0.14,and
0.16.
areas, resultingin short-range clines in most (Barrai et al. 1984) if not all
(Barrai et al. 1987) regions;conversely,gene frequencychange is sharper
forGd- at the boundaries of the two areas wherethe polymorphismwas
maintained(Po delta and Sardinia).
Only two otherallele frequencies(cde in system4.19 and B8) show
wide gradients.Paucityof data does not allow us to testthe directionof
these gradientsby means of directionalcorrelograms.However, inspec-
tion of gene frequencysurfacesindicates that theyfall on a north-south
axis. The limited number of gene frequencygradientsobserved is sur-
prisingfortwo reasons: (1) We had suspected that the long and narrow
peninsula of Italy would tend to channel population movements and
hence clines, and (2) clinal patternshad been shown by other mark-
ers in Italy,such as glyoxalaseI (GLOl) (Beretta,Mazzetti, and Barbu-
jani 1986) and phosphoglycolatephosphatase(PGP) (Santolamazza et al.
1986); in addition,the plot of the firstprincipalcomponentcalculated by
Piazza et al. (1988) on 34 allele frequenciesshowed a clear north-south
trend.However, this latterresultwas obtained when Sardinian popula-
5.
Figure SYMAPcontour mapof thefrequency of BW35, an exampleof a double
depression basedon 19 localities.
pattern, Explanationofsymbols givenin
3.Approximate
Figure quintile are0.04,0.11,0.14,0.16,0.17,and0.20.
limits
tions were excluded fromthe analysis; if theirdegree of differentiation

had been considered, the gene frequencydistributionin the peninsula
would have been virtuallyuniform.In this studymost significant correl-
ograms showed maximum geneticdissimilarityaround 550 km (cluster
4) and 650 km (cluster 3), which are the distance classes in which the
majorityof mainland versus Sardinia comparisons fall.When Sardinian
data are omitted,9 of the 11 correlogramsin clusters3 and 4 become
clinal or lose significance.
For the remainingtwo markersin clusters 3 and 4, NS and P-c,
the depressionpatternresultedfromgeneticdifferentiation of the central
populations. These correlogramsare consistentwiththe presenceof two
opposite gene frequencygradientsconvergingin thecentralsectionof the
may account forwhat Piazza et al. (1988)
peninsula. This differentiation
referredto as the "Etruriancomponent,"that is, a regionof high values
of the second principal component that corresponds approximatelyto
the area inhabitedby the Etruscans.
As observed in Europe as a whole, the heterogeneityof gene
frequenciesamong populations rules out the hypothesisof panmixia.
ANDSOKAL
268 / BARBUJANI
6.
Figure SYMAPcontour mapofthefrequency ofcde(system 4.19),an example
of
basedon 38 localities.
clinalpattern, Explanationofsymbols giveninFigure
3. Approximate limits
quintile are0.11,0.21,0.26,0.33,0.36,and0.49.
In Italy local population units are not only abstractions useful for
computation of gene frequenciesbut also isolates; theyexchange genes
withone anotherat different ratesaccordingto various factors.One such
factoris surelythe geographicdistance,as demonstratedby the general
decline of genetic similarityin the firstdistance classes for virtually
all correlograms.It is difficultto test whetheror not such a decline
is exponential,as predictedby models of genetic population structure
(Kimura and Weiss 1964) and observedin smaller-scalestudiesof Italian
populations (Barrai et al. 1983; Berettaet al. 1986), because the amount
of data necessary to discriminatethis from other modes of decrease
is enormous (Wijsman and Cavalli-Sforza 1984). However, isolation by
distance seems a conservativeand reasonableexplanationforshort-range
differentiation.
By contrast,long-rangedifferentiation requiresmore complexexpla-
nations. The lack of correlationbetweenpairs of surfacesand the variety
ofgeographicpatternsargueagainsta major role of one or fewpopulation
movements,which would be expected to affectequally all differentiated
allele frequencies(Sokal and Oden 1978b; Slatkin 1985). Alternatively,
both independentselectionmechanismsat the various loci and a combi-

nation of various demographicprocesses are compatible withthe results
of thisstudy.Althoughnot impossible in principle,differentiation ofgene
frequenciesin responseto environmentalpressures(i.e., differential selec-
tion) seems highlyimprobable,even more so ifone considersthe limited
population size of various isolates, which is expected to resultin wide,
random gene frequencyfluctuationsthatmay conceal the effectsof selec-
tion. In addition, the limitedrangeof climatic conditionsin Italy seems
hardlyconsistentwiththe highlyheterogeneousenvironmentalpressures
requiredfora model of differential selection.Thereforeit is reasonable to
regard the high level of variationamong Italian populations as a resultof
demographic changes that affectedvarious A similar
areas differentially.
conclusion was reachedby Piazza et al. (1988), who associated the extant
patternsof gene frequencieswiththe migrationalnetworkthatconnected
the ancientpopulations. As stressedby Chakrabortyand Nei (1977) [see
also Slatkin (1989)], demographicepisodes, such as population bottle-
necks resultingfromepidemics (some of which are well documented),
are expected to lead to gene frequencydivergenceand can account for
the consistentlylarge degreeof geneticdifferentiation in naturalpopula-
tions.Simulationstudies(Sokal, Jacquez,and Wooten 1989) suggestthat,
when various migrationsoccur across the same area, the last population
movementwill leave the most apparentmark on the distributionof gene
frequencies.Thereforeit is still unclear whetherthe gradientscurrently
detected result from phenomena that occurred in prehistorictimes or
more recently.
By and large, the Italian population appears to be composed of
distinctgroups that differentiated probablybecause of theirlimited size
and the limited exchange of genes among them; these groups have
not been made geneticallyuniformby recent population movements.
Sardinian populations are sharply differentiated(the rate of genetic
changeper unit distance is greatestforSardinians versus Italians among
all European and Asian populations; Barbujani et al. 1990), whereas
geneticdifferences are much less sharpbetweenothergroupsand notably
betweenSicilians and southernItalians. This suggeststhat isolation has
played a major role in bringingabout geneticdifferentiation and that a
large fraction of genetic variation can be accounted for by the presence
of barriersthat limited gene flow.The location of such barriersin Italy
and the possible role of language differencesin preventingpopulation
admixtureare discussed by Barbujani and Sokal (1991).
770 in Ecologyand Evolution,

Acknowledgments Thisarticleis Contribution
of New York,StonyBrook.We wouldliketo thankBarbara
StateUniversity
Thomsonforherconscientiousand competentexecutionof thecomputations.
ANDSOKAL
270 / BARBUJANI
Donna DiGiovanniand ChesterWilsonassistedwithtablepreparation

and word
Guido Barbujani'sexpenseswerein partmetthrough
processing. supportofthe
ofEducationResearchFund.The research
ItalianMinistry was supported
bythe
NationalInstitutes
ofHealthundergrantGM28262-09to RobertR. Sokal.
Received16 March1990; revision 15 October1990.

received
Literature Cited
Barbujani, G. 1987.Autocorrelation of genefrequencies underisolation by distance.
Genetics 117:777-782.
Barbujani, G. 1988.Diversity ofsomegenefrequencies inEuropean andAsianpopulations.
IV. Geneticpopulation structureassessedbythevariogram. Ann.Hum.Genet.
52:213-225.
Barbujani, G.,andR.R.Sokal.1990.Thezonesofsharp geneticchange inEurope arealso
language boundaries. Proc.Natl.Acad.Sei. USA87:1816-1819.
Barbujani, G.,andR.R.Sokal.1991.Genetic population structureofItaly.II. Physical
and
cultural barrierstogeneflow. Am.J.Hum.Genet. 48:398-41 1.
Barbujani, G., G.M.Jacquez, andL. Ligi.1990.Diversity ofsomegenefrequencies in
European andAsianpopulations. V. Steepmultilocus clines.Am.J.Hum.Genet.
47:867-875.
narrai,i., u. tsaroujam, m. tseretta,
ana u. vuiio. Heterozygosity ana geograpmc
distances ina limited area.J.Hum.Evol.12:403-408.
Barrai,I., G. Schiliro,M. Beretta,R Mazzetti, A. Russo,andG. Russo-Mancuso. 1987.
Population structureofSicily:
Beta-thalassemia andHbS.Hum.Genet. 75:1-3.
Barrai,I., A. Rosito,G. Cappellozza, G. Cristofori,C. Vullo,C. Scapoli,andG. Barbu-
jani. 1984.Beta-thalassemia in thePo delta:Selection, geography, andpopulation
structure. Am.J.Hum.Genet. 36:1121-1134.
Beretta,M.,P. Mazzetti, andG. Barbujani.1986.A clineforglyoxalase I allelefrequencies
inItaly. Ann.Hum.Biol 13:341-345.
Beretta,M.,P. Mazzetti, G. Frosina,
G. Schiliro,
A. Russo,G. Russo,andI. Barrai.1986.
Population structureofeastern Hum.Hered.
Sicily. 36:379-387.
Cavalli-Sforza,L.L. 1984.Isolationbydistance. In HumanPopulation Genetics:The
Pittsburgh Symposium ,A.Chakravarti,ed.NewYork:vanNostrand-Reinhold, 229-
248.
Chakraborty, R.,andM.Nei.1977.Bottleneck effects
onaverage heterozygosity andgenetic
distance withthestepwise mutation model.Evolution 31:347-356.
A.D.,andJ.K.Ord.1981.SpatialProcesses.
Cliff, London: Pion.
Crumpacker, D.W.,G. Zei,A. Moroni, andL.L.Cavalli-Sforza. 1976.Airdistance versus
roaddistance as a geographical
measure forstudiesonhuman populations structure.
Geogr. Anal.8:215-223.
Dougenik, J.A.,andD.E. Sheehan. 1979.SYMAPUser'sReference Manual:Version 5.20.
Bedford, Mass.:CameraStat.
Harding, R.M.,andR.R.Sokal.1988.Classification oftheEuropean language families
by
genetic distance.Proc.Natl.Acad.Sei. USA85:9370-9372.
Hedrick,P.W.,G. Thomson, and W. Klitz.1986.Evolutionary genetics: HLA as an

exemplary system. In Evolutionary Processes and Theory , S. KarlinandE. Nevo,
eds.Orlando, Fla.:Academic Press,583-606.
Kimura, M.,andG.H.Weiss. 1964.Thestepping stonemodelofpopulation structure,and
thedecrease ofgenetic correlation withdistance. Genetics 49:561-576.
Livingstone,F.B. 1967.Abnormal Hemoglobins in HumanPopulations. Chicago,111.:
Aldine.
Mourant, A.E.,A.C. Kopec,and K. Domaniewska-Sobczak. 1976.TheDistributions of
HumanBloodGroups. Oxford: Oxford University Press.
Oden,N.L. 1984.Assessing thesignificance ofa spatialcorrelogram. Anal.16:1-16.
Geogr.
Oden,N.L.,andR.R. Sokal.1986.Directional autocorrelation: An extension ofspatial
correlograms totwodimensions. Syst.Zool.35:608-617.
Piazza,A.,N. Cappello, E. Olivetti,
andS. Rendine. 1988.A genetic history ofItaly.Ann.
Hum.Genet. 52:203-213.
Piazza,A.,E. Olivetti,O. Carbonara, M. Bargagna, F. Pecori,P. Benciolini,P. Cortivo,F.
Breda, R. Domenici, andS. Jayakar. 1982.La Distribuzione diAlcuni Polimorfismi
GeneticiinItalia.Milan:II Ponte.
Santolamazza, C., A. Benincasa, and R. Scozzari.1986.Phosphoglycolate phosphatase
polymorphism: Genefrequencies inthree Italiansamples. Hum.Hered. 36:281-285.
M. 1985.Geneflowinnatural
Slatkin, populations. Annu.Rev.Ecol.Syst.16:393-430.
M. 1989.Population
Slatkin, structure andevolutionary progress.Genome 31:196-202.
Sneath,P.H.A.,andR.R.Sokal.1973.Numerical Taxonomy. SanFrancisco, Cal.:Freeman.
Sokal,R.K.1979.bcological parameters interredtromspatialcorrelograms. in contempo-
raryQuantitative Ecology andRelated Ecometrics, G.P.PatilandM.L.Rosenzweig,
eds.Fairland, Md.:International Cooperative Publishing House,167-196.
Sokal,R.R. 1986.Spatialdataanalysis and historical processes.In Data Analysis and
Informatics IV, E. Diday,Y. Escoufier, L. Lebart, J.Pages,Y. Schektman, andR.
Tomassone, eds.Amsterdam: North-Holland, 29-43.
Sokal,R.R.1988.Genetic, geographic,andlinguistic distances inEurope. Proc.Natl.Acad.
Sei. USA85:1722-1726.
Sokal,R.R.,andP. Menozzi.1982.Spatialautocorrelation ofHLAfrequencies inEurope
support demiediffusion ofearlyfarmers. Am.Natur.119:1-1 17.
Sokal,R.R.,andN.L. Oden.1978a.Spatialautocorrelation in biology. 1. Methodology.
Biol.J.Linn.Soc.10:199-228.
Sokal,R.R.,andN.L.Oden.1978b.Spatialautocorrelation inbiology.2. Somebiological
implications, andfourapplications ofevolutionary andecological interest.Biol.J.
Linn.Soc.10:229-249.
Sokal,R.R.,andF.J.Rohlf.1981.Biometry , 2ded.SanFrancisco, Cal.:Freeman.
Sokal,R.R.,and D.E. Wartenberg. 1981.Spaceand population structure.In Dynamic
SpatialModels , D. Griffithsand R. McKinnon, eds.Alphenaan denRijn,The
Netherlands: SijthoffandNoordhoff, 186-213.
Sokal,R.R.,andD.E.Wartenberg. 1983.A testofspatial autocorrelationusing anisolation-
by-distance model.Genetics 105:219-237.
Sokal,R.R.,R.M.Harding, andN.L.Oden.1989.Spatialpatterns ofhuman genefrequen-
ciesinEurope. Am.J.Phys.Anthropol. 80:267-294.
Sokal,R.R.,G.M. Jacquez, and M. Wooten.1989.Spatialautocorrelation analysisof
migration andselection. Genetics 121:845-855.
Sokal,R.R.,N.L. Oden,and B.A. Thomson.1988.Geneticchanges acrosslanguage
boundaries inEurope. Am.J.Phys.Anthropol. 76:337-361.
Sokal,R.R.,N.L.Oden,P.Legendre, M.-J. Fortin,andA.Vaudor. 1989.Genetic differences
amonglanguage familiesinEurope. Am.J.Phys.Anthropol. 79:489-502.
272 / BARBUJANI
ANDSOKAL
Sokal,R.R.,N.L.Oden,P.Legendre, J.Kim,M.-J. B.A.Thomson,

Fortin, A.Vaudor, R.M.
Harding, andG. Barbujani. 1990.GeneticsandlanguageinEuropean populations.
Am.Natur.135:157-175.
Späth,H. 1980.Cluster Analysis: forData Reduction
Algorithms and Classification
of
Chichester
Objects. EllisHorwood.
Tills,D., A.C.Kopec,andR.E.Tills.1983.TheDistribution oftheHumanBloodGroups
andOther Polymorphisms , suppl.1.London: OxfordUniversityPress.
Upton,G.J.,andG.B.Fingleton. 1985.SpatialData analysis
byExample , vol.1,Point
PatternsandQuantitative Data.NewYork:Wiley.
Wijsman, E.M.,andL.L.Cavalli-Sforza. 1984.Migrationandgeneticpopulationstructure
withparticular referencetohumans. Annu. Rev.Ecol.Syst.15:279-301.
Wright, S. 1943.Isolation
bydistance. Genetics
28:114-138.

Barbujani y Sokal 1991 - Genetic Structur of Italy

Uploaded by

Document Information

Original Title

Copyright

Available Formats

Share this document

Share or Embed Document

Sharing Options

Did you find this document useful?

Is this content inappropriate?

Copyright:

Available Formats

Barbujani y Sokal 1991 - Genetic Structur of Italy

Uploaded by

Copyright:

Available Formats

Genetic Population Structure of Italy. I.

Geographic Patterns of Gene Frequencies

You may need to log in to JSTOR to access the linked references.

Abstract The diversity of spatialpatterasof 61 allelefrequencies

The patternsof genetic variation in European populations are diverse

(Sokal, Harding, and Oden 1989). Therefore,although the interaction

Materials and Methods

Mapping of Gene frequencyDistributions. To obtain a visual repre-

Spatial AutocorrelationAnalysis. The hypothesisthat the observed

values of I range from approximately1 (for positive autocorrelation)

Correlation between Gene frequency Distributions. The clustering

gene frequencysurfacesas "highlycorrelated"surfaces,withoutimplying

Clusteringof Correlograms. Similaritiesof the Bonferroni-significant

4JÜ 4>o o'Oo'O u "O"O u 1

the short-distanceclasses, decreasing to near 0 at large distances. All

1. Differentiationin patches. Only the glucose-6-phosphatedehy-

malarial areas where the polymorphismforthis markeris pro-

5. Double depression. There are two negativepeaks of autocorre-

In all six groups listed so far,autocorrelationis positive at short dis-

7. Intrusion.This groupincludes only one marker.PI, whose allele

Examples of the four major patterns of allele frequencies described

tions were excluded fromthe analysis; if theirdegree of differentiation

both independentselectionmechanismsat the various loci and a combi-

770 in Ecologyand Evolution,

Donna DiGiovanniand ChesterWilsonassistedwithtablepreparation

Received16 March1990; revision 15 October1990.

Hedrick,P.W.,G. Thomson, and W. Klitz.1986.Evolutionary genetics: HLA as an

Sokal,R.R.,N.L.Oden,P.Legendre, J.Kim,M.-J. B.A.Thomson,

You might also like