ArticlePDF Available

Reconstructing the genetic history of Italians: new insights from a male (Y-chromosome) perspective

Authors:
  • Human Technopole

Abstract and Figures

Background: Due to its central and strategic position in Europe and in the Mediterranean Basin, the Italian Peninsula played a pivotal role in the first peopling of the European continent and has been a crossroad of peoples and cultures since then. Aim: This study aims to gain more information on the genetic structure of modern Italian populations and to shed light on the migration/expansion events that led to their formation. Subjects and methods: High resolution Y-chromosome variation analysis in 817 unrelated males from 10 informative areas of Italy was performed. Haplogroup frequencies and microsatellite haplotypes were used, together with available data from the literature, to evaluate Mediterranean and European inputs and date their arrivals. Results: Fifty-three distinct Y-chromosome lineages were identified. Their distribution is in general agreement with geography, southern populations being more differentiated than northern ones. Conclusions: A complex genetic structure reflecting the multifaceted peopling pattern of the Peninsula emerged: southern populations show high similarity with those from the Middle East and Southern Balkans, while those from Northern Italy are close to populations of North-Western Europe and the Northern Balkans. Interestingly, the population of Volterra, an ancient town of Etruscan origin in Tuscany, displays a unique Y-chromosomal genetic structure.
Content may be subject to copyright.
Full Terms & Conditions of access and use can be found at
http://www.tandfonline.com/action/journalInformation?journalCode=iahb20
Annals of Human Biology
ISSN: 0301-4460 (Print) 1464-5033 (Online) Journal homepage: http://www.tandfonline.com/loi/iahb20
Reconstructing the genetic history of Italians: new
insights from a male (Y-chromosome) perspective
Viola Grugni, Alessandro Raveane, Francesca Mattioli, Vincenza Battaglia,
Cinzia Sala, Daniela Toniolo, Luca Ferretti, Rita Gardella, Alessandro Achilli,
Anna Olivieri, Antonio Torroni, Giuseppe Passarino & Ornella Semino
To cite this article: Viola Grugni, Alessandro Raveane, Francesca Mattioli, Vincenza Battaglia,
Cinzia Sala, Daniela Toniolo, Luca Ferretti, Rita Gardella, Alessandro Achilli, Anna Olivieri, Antonio
Torroni, Giuseppe Passarino & Ornella Semino (2018) Reconstructing the genetic history of
Italians: new insights from a male (Y-chromosome) perspective, Annals of Human Biology, 45:1,
44-56, DOI: 10.1080/03014460.2017.1409801
To link to this article: https://doi.org/10.1080/03014460.2017.1409801
View supplementary material Published online: 30 Jan 2018.
Submit your article to this journal View related articles
View Crossmark data Citing articles: 1 View citing articles
RESEARCH PAPER
Reconstructing the genetic history of Italians: new insights from a male
(Y-chromosome) perspective
Viola Grugni
a
, Alessandro Raveane
a
, Francesca Mattioli
a
, Vincenza Battaglia
a
, Cinzia Sala
b
, Daniela Toniolo
b
,
Luca Ferretti
a
, Rita Gardella
c
, Alessandro Achilli
a
, Anna Olivieri
a
, Antonio Torroni
a
, Giuseppe Passarino
d
and
Ornella Semino
a
a
Dipartimento di Biologia e Biotecnologie L. Spallanzani, Universit
a di Pavia, Pavia, Italy;
b
Divisione di Genetica e Biologia Cellulare, Istituto
Scientifico San Raffaele, Milano, Italy;
c
Dipartimento di Medicina Molecolare e Traslazionale, Universit
a di Brescia, Brescia, Italy;
d
Dipartimento di Biologia, Ecologia e Scienze della Terra, Universit
a della Calabria, Arcavacata di Rende, Cosenza, Italy
ABSTRACT
Background: Due to its central and strategic position in Europe and in the Mediterranean Basin, the
Italian Peninsula played a pivotal role in the first peopling of the European continent and has been a
crossroad of peoples and cultures since then.
Aim: This study aims to gain more information on the genetic structure of modern Italian populations
and to shed light on the migration/expansion events that led to their formation.
Subjects and methods: High resolution Y-chromosome variation analysis in 817 unrelated males from
10 informative areas of Italy was performed. Haplogroup frequencies and microsatellite haplotypes
were used, together with available data from the literature, to evaluate Mediterranean and European
inputs and date their arrivals.
Results: Fifty-three distinct Y-chromosome lineages were identified. Their distribution is in general
agreement with geography, southern populations being more differentiated than northern ones.
Conclusions: A complex genetic structure reflecting the multifaceted peopling pattern of the
Peninsula emerged: southern populations show high similarity with those from the Middle East and
Southern Balkans, while those from Northern Italy are close to populations of North-Western Europe
and the Northern Balkans. Interestingly, the population of Volterra, an ancient town of Etruscan origin
in Tuscany, displays a unique Y-chromosomal genetic structure.
ARTICLE HISTORY
Received 31 July 2017
Revised 17 November 2017
Accepted 20 November 2017
KEYWORDS
Y-chromosome variation;
haplogroups; genetic
history of Italy; Italian
population
Introduction
Due to its central and strategic position in Europe and in the
Mediterranean Sea, the Italian Peninsula played a pivotal role
in the first peopling of the continent and was, for millennia,
a crossroads of peoples, cultures, trades and languages (for
details, see Supplementary File S1).
Anatomically modern humans have inhabited the Italian
territory since the Upper Palaeolithic, as attested by archaeo-
logical and anthropological remains in caves like the Grotta
del Cavallo (Horse Cave) in Apulia, among which the oldest
(dated 4543 thousand years ago - kya) European skeletal
remains were found (Benazzi et al., 2011). During the Last
Glacial Maximum (LGM), 2519 kya, when large parts of
Europe were covered with thick ice sheets, Italy and the
Balkans were partly forested and probably acted as refuge
for Europeans escaping from the North. Traces of Neolithic
migratory events are spread all over Italy, with substantial
differences (especially between North and South) in the cer-
amics industry and archaeological remains. Signs of post-
Neolithic settlements are present in different areas of the
Italian territory, for example, the Nuraghe stones in Sardinia,
dated to the early Bronze Age, and the Villanovan culture,
mainly spread in the Tuscan-Emilian Apennine area during
the Iron Age.
A better knowledge of the genetic structure of the mod-
ern Italian population in the wider context of the European
continent and surrounding areas is, therefore, an essential
element to further reconstruct its genetic history and the
impact of ancient and more recent migration events.
Genetic variation of Italy
The first attempts to interpret the pattern of genetic variation
of the Italian Peninsula were made with classical polymor-
phisms, including the ABO blood group. Piazza et al. (1988)
studied the frequencies of 34 independentalleles at seven
loci (ABO,MNS,KELL,RH,HP, HLA-A and HLA-B) and their
Principal Component (PC) analyses and synthetic maps of the
first three PCs are generally considered the foundations for
the Italian genetic historyreconstruction. These initial results
revealed a very distinct pattern for Sardinia, which is located
far away from all other Italian regions and represents an out-
lier in the European genetic landscape. When Sardinia was
excluded from the PC analysis, the first principal component
CONTACT Ornella Semino ornella.semino@unipv.it Dipartimento di Biologia e Biotecnologie L. Spallanzani, Universit
a di Pavia, Pavia, Italy
Subject classification codes: BG.24 Evolution and Population Genetics.
Supplemental data for this article can be accessed here.
ß2017 Informa UK Limited, trading as Taylor & Francis Group
ANNALS OF HUMAN BIOLOGY, 2018
VOL. 45, NO. 1, 4456
https://doi.org/10.1080/03014460.2017.1409801
synthetic map, accounting for 27% of the total variation,
highlighted a North to South gradient, with similarities
between Northern Italy and Central Europe, in contrast to
the affinities between Central and Southern Italy with Greece
and other Mediterranean populations.
Later on, numerous studies introduced uniparental
markers to investigate the genetic structure of modern Italian
populations from either the maternal or paternal side
(Barbujani et al., 1995; Capelli et al., 2007; Destro Bisol et al.,
2008; Di Giacomo et al., 2003) and, in some cases, compara-
tively (Boattini et al., 2013; Brisighelli et al., 2012a,2012b).
Overall, these studies suggested that the genetic structure of
modern Italy reflects, at least in part, the ethnic stratification
of pre-Roman times.
From the male perspective, most of the Italian Y-chromo-
some gene pool can be related to five main haplogroups:
R1b-M269, J2-M172, I-M170, G-M201 and E1b-M78. R1b is
more frequent in Northern Italy, while E1b, G and J2 harbour
higher frequencies in the South, suggesting a greater affinity
to West Europe for G and to South-East and South-Central
Europe for J2. Indeed, in the European context, the Italian Y-
chromosome variation (Capelli et al., 2007) fits the South/
East-North/West cline described in previous studies, which
was ascribed to the genetic admixture between incoming
Near Eastern farmers and pre-existing Mesolithic hunter-gath-
erers (Rosser et al., 2000; Semino et al., 1996,2000,2004). On
the other hand, the identification of an Anatolian (Asia
Minor) input in most of the Italian samples underlined that
pre-Neolithic populations were not completely replaced
(Capelli et al., 2007).
Unlike the majority of authors, Boattini et al. (2013) inter-
preted the Italian distribution of Y-chromosome genetic
diversity as non-clinal, but structured into three main areas
according to latitude: North-West Italy (NWI), South-East Italy
(SEI) and Sardinia. The outlier position of Sardinia was attrib-
uted to the extremely high frequency of I2-M26, a sub-
branch of haplogroup I also observed in the Iberian
Peninsula and Great Britain, but virtually absent in continen-
tal Italy, a finding clearly indicating a major founder event in
the Mediterranean island. The common genetic background
of Southern Italy and the Adriatic coast and the discontinuity
with Northern Italy and Tuscany were explained as due to a
beltarea, where haplogroup frequencies changed more
rapidly than in other territories, possibly dating back to the
Neolithic when two independent and parallel diffusion proc-
esses occurred along the Adriatic and Tyrrhenian coastlines.
Our study provides novel Y-chromosome data, at a high-
resolution level, and extends comparative analyses to obtain
new insights concerning the genetic history of Italy and the
ancestral sources of the Italian gene pool.
Materials and methods
The sample
A total of 817 Italian individuals were newly-analysed in the
present study: 290 from Northern Italy (85 from the Borbera
Valley, an isolated valley of the Ligurian Apennine, at the
border between Piedmont and Liguria; 48 from the territories
of Voghera and Tortona, two towns at the border between
Pavia and Alessandria provinces; 157 from the Bergamo prov-
ince78 from isolated valleys and 79 from the plain area of
the province), 113 from Central Italy (Volterra, a town in the
core area of ancient Etruria), 350 from Southern Italy (82
from Grec
ıa Salentina, 102 Apulians, 93 Calabrians from the
Ionian Coast, 73 Calabrians from the Tyrrhenian Coast) and
64 from Sicily. The sampling areas are shown in Figure 1;
geographic and historical information on the areas is pro-
vided in Supplementary File S1.
Sampled individuals were unrelated males with the pater-
nal grandfather born in the collection area and/or carrying a
monophyletic surname with a geographical distribution within
the sampling area as previously described (Zei et al., 2003).
Ethics statement
This research has been approved by the Ethics Committee
for Clinical Experimentation of the University of Pavia, Board
minutes of 5 October 2010. Geographical and ethnological
information such as ethnicity, language and genealogy were
ascertained by interview of blood donors after obtaining
their written informed consent.
DNA extraction
All DNAs were obtained from blood samples according to
standard phenol/chloroform extraction procedures, followed
by ethanol precipitation.
SNP genotyping
A total of 58 Y-chromosome biallelic markers were analysed
in a hierarchical way (Supplementary Table S1). They were
genotyped by AFLP, RFLP, DHPLC and direct sequencing after
PCR amplification of pertinent fragments.
The nomenclature used for haplogroup labelling is in
agreement with YCC conventions (The Y Chromosome
Consortium, 2002) and subsequent updates (Karafet et al.,
2008; King et al., 2011; Myres et al., 2011; Underhill et al.,
2010; van Oven et al., 2013).
STR genotyping
For each population, a sub-set of Y-chromosomes belonging
to the most representative haplogroups was analysed for the
microsatellite loci DYS19, DYS389I/II, DYS390, DYS391,
DYS392 and DYS393 (Kayser et al., 1997) in multiplex reac-
tions according to STRBase information (www.cstl.nist.gov/
biotech/strbase/y20prim.htm). The resulting STR haplotypes,
together with those available in the literature
(Supplementary Table S2), were used to investigate variation
and origins of haplogroups.
Statistical analyses
Y-chromosome haplotype and haplogroup variability of the
newly-analysed populations have been considered in the
ANNALS OF HUMAN BIOLOGY 45
wider Italian and European/Mediterranean context, together
with extended reference data available from the literature
(see Supplementary Table S3).
Haplogroup diversity was computed using the standard
method of Nei (1987). Comparison between groups was per-
formed using the Chi Square Test of independence (XLStat).
Genetic structure was examined through the Analysis of
Molecular Variance (AMOVA) (Excoffier et al., 1992) using the
Arlequin software Ver 3.5 and adopting different geographic
grouping criteria. Principal Components Analysis (PCA) on
haplogroup frequencies (Supplementary Tables S4 and S5)
was performed with XlStat, an Excel add-in, disregarding fre-
quencies below 5%. Median-Joining (MJ) networks (Bandelt
et al., 1999) were constructed using the Network 4.6.0.0 pro-
gram (Fluxus Engineering, http://www.fluxus.engineering.
com), after data processing with the reduced-median method
(Bandelt et al., 1995) and weighting of STR loci proportionally
to the inverse of the repeat variance. Geographical represen-
tations of the haplogroup frequency and mean STR variance
distributions were obtained with Surfer 6.0 (Golden Software)
following the Kriging procedure, as previously described
(Battaglia et al., 2009). Maps of microsatellite variances were
obtained after pooling data for locations with less than five
entries and assigning the resulting values to the centroid of
the pooled locations. Haplogroup ages were evaluated on
STR variation using the method proposed by Zhivotovsky
et al. (2004) and modified according to Sengupta et al.
(2006). A microsatellite evolutionary effective mutation rate
of 6.9 10
4
per generation (25 years) was used (Zhivotovsky
et al., 2004) since it is suitable in situations where the
elapsed time frame is >1000 years or 40 generations
(Zhivotovsky et al., 2006), like the pre-historic time depths
explored in this study. However, it is worth mentioning that
ambiguities related to past episodes of population history
(e.g. size fluctuations, bottlenecks, etc.) create inherent uncer-
tainties in the calibration of the Y-STR molecular clock, thus
age estimates of microsatellite variation should be consid-
ered with caution.
Results and discussion
Y-chromosome haplogroups in Italian populations
A total of 53 distinct lineages were identified; their frequency
distributions in the examined Italian populations are reported
in Supplementary Table S6 and illustrated according to their
phylogenetic relationships in Figure 2.
Haplogroup R is the most frequent (50.1%) with its two
main branches, R1a (4.7%) and R1b (45.3%), the latter mainly
accounted for by R1b-U152 (49.5% of the total R1b); R2 was
Figure 1. Geographical locations of the 10 analysed Italian population samples.
46 V. GRUGNI ET AL.
not observed. Next is haplogroup J (19.2%), mostly observed
as J2 (17.6%), and third is haplogroup E, as E1b (14.6%),
mostly represented by its Balkansub-clade E1b-V13. The
other main haplogroups show frequencies lower than 10%:
haplogroup G (8.4%) and haplogroup I (4.8%).
The frequency distributions of the three main haplogroups
(R, J and E) and those of their sub-clades in Italian popula-
tions are illustrated in Figure 3. The black sectors in the pri-
mary pies are proportional to the frequency of the main
haplogroup in the different populations, whereas the col-
oured sectors in the secondary pies are proportional to the
frequencies of the different sub-clades within the relative
main haplogroup. These haplogroups, which account for
more than 80% of our Italian samples, are also highly repre-
sented in Europe (Chiaroni et al., 2009). Frequency and vari-
ance distribution maps (Supplementary Figures S1 and S2)
were obtained for their most informative sub-haplogroups.
Networks of the associated STR-haplotypes were also con-
structed (Supplementary Figures S1S3) and relative coales-
cent ages were estimated for each population/area
(Supplementary Tables S7 and S8).
Northern Italy (Bergamo Valleys and plain, Tortona-
Voghera and Borbera Valley) is characterised by an extremely
high incidence of the R1b haplogroup (69.0%) when com-
pared to all the other main haplogroups whose frequencies
do not reach 10%. This haplogroup, which characterises a
wide portion of the gene pool of the examined populations,
shows a decreasing frequency pattern from North to South
Italy, where it shows its lowest incidence (27.5%). This pat-
tern is virtually totally ascribable to R1b-U152, the most rep-
resented R1b sub-lineage, whereas no frequency gradients
were detected for the other sub-lineages. R1b-S116(xU152,
M529) is equally represented in all the Italian populations
(Figure 3, dusty rose sector in secondary pies). This shows
the highest frequencies in two isolated areas of Northern
Italy: Borbera Valley (12.9%) and Bergamo Valleys (17.9%).
The frequency peak is particularly noticeable in Bergamo
Valleys in comparison to the neighbouring plain area (17.9%
vs 3.8%, respectively, p<.01). Global frequency and variance
distributions of haplogroups R1b-U152 (not shown) and R1b-
S116(Supplementary Figure S1) are coherent with a North
and West European origin, respectively. Network analyses
Figure 2. Haplogroup frequencies, as percentages, in the 10 analysed Italian population samples. BGV: Bergamo Valleys; BGP: Bergamo Plain; TO-VO: Tortona-
Voghera; VB: Borbera Valley; VOL: Volterra; AP: Apulia; GS: Grec
ıa Salentina; CAL-I: Ionian Calabria; CAL-T: Tyrrhenian Calabria; SIC: Sicily.
ANNALS OF HUMAN BIOLOGY 47
reveal high internal complexities, especially for R1b-U152
(Supplementary Figure S3), due to unequal contributions of
different sub-lineages, as previously noted by Valverde et al.
(2016) in Spain for R1b-S116(xU152, M529) and by Boattini
et al. (2013) and the FamilyTree dataset (http://www.davidk-
faux.org/R1b1c10_Resources.pdf) for R1b-U152. However,
both networks are characterised by a main demographic
expansion centred in North-West and Central-North Europe,
which strongly affected Northern Italy. Thus, taking into
account that the highest reported incidence of R1b-
S116(xU152, M529) is in Iberia (Adams et al., 2008; Myres
et al., 2011), its high frequency in the relatively isolated pop-
ulations of the Bergamo and Borbera Valleys could represent
the outcome of ancient gene flow from that area, possibly
magnified by genetic drift. On the other hand, R1b-M412,
so far described only in Turkey, Iran, Cyprus and Crete (Myres
et al., 2011; Voskarides et al., 2016), is observed in all the
four Southern Italian samples, all from the ancient Magna
Graecia area, but only sporadically in population groups from
Northern Italy. The R1b-M412Y chromosomes could, there-
fore, represent the legacy of an Eastern Mediterranean input
associated with the early Hellenic colonisation, and/or the
more recent Byzantine domination. This scenario is supported
by the high frequency of R1b-M412in the Griko-speaking
community of Grec
ıa Salentina (13.4%), where haplogroup
R1b-M412probably reflects ancient colonisation events
from Greek-speaking islands rather than continental Greece.
The R1a haplogroup is observed along the entire
Peninsula. With the exception of the Tortona-Voghera sam-
ple, it displays lower frequencies in the North and in the
Centre in comparison with the southern populations, espe-
cially those of the Ionian Coast (8.6% in Ionian Calabria, 5.9%
in Apulia and 15.8% in Grec
ıa Salentina). R1a-M17 represents
an important component of the modern gene pool of
Greece, where it reaches its highest frequencies (16.3% and
22.0%, in mainland Greece and in Thracia, respectively)
(Battaglia et al., 2009; Heraclides et al., 2017). Taking into
account that it is found virtually only as R1a-M17(xM458) in
both the Southern Italian samples and in mainland Greece, it
is likely that R1a-M17is a signature of the Southern Balkan
(mainland Greece) influence into Southern Italy. Thus, differ-
ently to haplogroup R1b-M412, R1a-M17seems a hallmark
of a significant male seaborne input from Balkan populations
towards the eastern coast of Southern Italy.
Unlike R1b, haplogroup J frequency increases from North
(8.3%) towards Central (13.3%) and Southern Italy, where it
reaches the highest value (28.5%). The distribution of hap-
logroup J1 is restricted to South Italy; this haplogroup, which
arose in the southern part of the Middle East (Malaspina
et al., 2000; Nebel et al., 2002; Semino et al., 2004), character-
ises Near Eastern and North African Arabic-speaking popula-
tions (Al-Zahery et al., 2011; Chiaroni et al., 2009; Heraclides
et al., 2017; Tofanelli et al., 2009). Its presence in the south-
ern part of the Italian Peninsula indicates gene flow from
these populations. In contrast, haplogroup J2, which most
likely arose in the northern part of the Middle East (King
et al., 2008; Malaspina et al., 2000; Nebel et al., 2002; Semino
et al., 2004) and spread in association to Neolithic and post-
Neolithic migrations, is present all over the Italian territory,
although with relevant differences in the distributions,
probably due to more recent migratory events. J2a is most
represented in southern populations, where its J2a-M530 and
J2a-Page55sub-lineages (with a remarkable frequency of
the latter in Apulia) were the most prevalent. Its lowest fre-
quencies were registered in the isolated populations of
Borbera Valley (3.5%, only represented by J2a-M530) and
Bergamo Valleys, where this clade was not observed at all.
J2a-M67, which is widely distributed in Europe, the Middle
East and North Africa (Supplementary Figure S2), with a not-
able peak in Portugal, is mainly present in South Italy, espe-
cially in Ionian Calabria. Its variance map shows instead a
different pattern, with high values in some Middle Eastern
Figure 3. Frequencies of the main Y-chromosome haplogroups E1b, J2 and R1b and their sub-clades in the 10 analysed Italian population samples. Black sectors in
the primary pies are proportional to the frequency of the main haplogroup in each population. Coloured sectors in the secondary pies are proportional to the fre-
quencies of sub-haplogroups within the relative main haplogroup.
48 V. GRUGNI ET AL.
regions, such as Iran, Turkey and Palestine, but also in the
two main islands of the eastern Mediterranean Sea as well as
along the other Mediterranean coastal regions. These data
indicate that this haplogroup might have spread by sea,
probably starting from the Middle East. The network analysis
reveals a complex internal heterogeneity as well as an expan-
sion that affected not only Middle Eastern populations but
also the Balkans and Southern Italy. The most frequent
haplotype in the network comprises subjects mainly from
Middle Eastern populations, including Crete and Cyprus, but
also from Southern Italy. Notably, Northern Italians are not
present in the central haplotype, suggesting a possible later
arrival to this area. The great majority of the Portuguese Y
chromosomes belong to only one haplotype, thus revealing
a very recent expansion of this lineage in western Iberia. The
oldest ages based on microsatellite variation are in Cyprus
(16.6 ± 4.7 kya), Crete (16.3 ± 5.5 kya) and Apulia (16.6 ± 7.0
kya), followed by those in the Middle Eastern populations.
Notably, North Sardinia, Tuscany and Sicily also have high
coalescent times (Supplementary Table S7). These data sug-
gest an overall diffusion of J2a-M67both by sea and by
land. The finding of such high variance and coalescence
times in the two main islands of the Aegean Sea, character-
ised by an early spread of agriculture, is in agreement with
the scenario that the first steps of the Neolithic spread were
indeed towards Cyprus and Crete (King et al., 2008). On the
other hand, diffusion by land from the Middle East towards
the Southern Balkans is less likely. The high variance and
coalescent time values observed in Southern Italian regions,
overall comparable to those of the Middle East, can be the
outcome of seaborne migrations from different geographic
sources at different times. For example it is known that, in
post-Neolithic times 5 kya, North West Anatolia developed
a complex society engaged in a widespread Aegean trade
referred to as Maritime Trojan culture, involving both the
Western Anatolian mainland and several large islands in the
Eastern Aegean Sea (Korfmann, 1997). Interestingly, J2a-M67
also harbours a high microsatellite variation age in Volterra,
which is located in the core area of ancient Etruria. Multiple
hypotheses have been proposed concerning the origin of
Etruscans, but our observations tend to support the view
that Asia Minor was the ancestral source of the Etruscan
gene pool, as already proposed by Achilli et al. (2007) on the
basis of mtDNA data.
J2a-M92 is widely distributed in the Middle East, the
Balkans, and along the Mediterranean coast. In Italy, it shows
a high frequency in the South, especially in the Southern
part of Apulia. The variance map shows peaks in Turkey and
Sicily, followed by the Southern Balkans. The highest ages
based on microsatellite variation are observed in Sicily
(11.8 ±3.4 kya) and Turkey (11.7 ± 4.9 kya). Since the fre-
quency and variance maps suggest a possible origin of J2a-
M92 in and around Turkey, the observation of an age in
Sicily that is close to that observed in Turkey may indicate an
ancient migration from Turkey to Sicily. Comparable high
coalescent times based on microsatellite variation are
observed in Greece (7.2 ± 2.0 kya), Apulia (7.3 ± 3.1 kya) and
Tuscany (8.7 ± 2.7 kya). These data most likely testify sea-
borne contacts of these Italian regions with Eastern
Mediterranean Neolithic civilisations, although the stratifica-
tion of different migratory events could also have contrib-
uted to the internal heterogeneity, especially in Tuscany.
J2b is most frequent in the Tortona-Voghera sample,
which is located in the open Po Valley, and in Apulia, which
faces the Adriatic Sea, while it is present at low frequencies
in the Tyrrhenian sample of Calabria and not observed in
Sicily. Interestingly, its incidence in the Volterra sample is
comparable to that observed along the Salentina Coast and,
as in the northern samples, it is mainly represented by the
BalkanJ2b-M241.
On the whole, the heterogeneous distribution of J2 sub-
haplogroups in modern Italians highlights different diffusion
routes. Sub-haplogroups J2a-M530 and J2a-Page55, as J2a-
M67, probably mark gene flow events from the Middle East
(they display the highest frequency and variances in Iran
(Grugni et al., 2012)) across the Caucasus, Turkey (data not
shown), Cyprus (Voskarides et al., 2016) and Crete (King
et al., 2011) towards Southern Europe, that affected mainly
the southern regions of Italy. Differently, J2b-M241 which dis-
plays a strong expansion in the Southern Balkans (Battaglia
et al., 2009; Cruciani et al., 2007; Karachanak et al., 2013) and
has been associated with Neolithic and post-Neolithic migra-
tions from Greece and the Balkans (Battaglia et al., 2009;
King et al., 2008), marks a seaborne route whose contribution
is still detectable along the Adriatic coast (Boattini et al.,
2013) as well as in populations along the Po Valley. It is
worth underlining the presence of sub-haplogroup J2a-M92
at 7.3% in Grec
ıa Salentina. This value, comparable with that
observed in the sample from Lecce (Boattini et al., 2013), is
suggestive of a direct, or Balkan-mediated, seaborne contri-
bution from Asia Minor (Grugni et al., 2012).
Haplogroup E, mostly represented by E1b-M78, increases
in frequency from North (8.3%) to South, where it reaches an
incidence of 21.3%. Its main sub-clade, E1b-V13, displays a
decreasing frequency cline from the Southern Balkans to
Western Europe (Supplementary Figure S2) and is also pre-
sent, at lower frequencies, in Anatolia and all along the
Italian Peninsula. Similar to J2b-M241, the E1b-V13 sub-clade,
which spread from the Balkans (Battaglia et al., 2009;
Cruciani et al., 2007; Karachanak et al., 2013), is mainly
observed in the South of Italy, with frequencies higher than
10% in Apulia; however, unlike the Balkan J2 branch, it is
also found in Sicily. The distribution of its variance
(Supplementary Figure S2) parallels the frequency clinal pat-
tern, although high variance values are also observed in
Central-Eastern Europe and a major peak is present in
Anatolia. In Italy, the variance is highest in the South. The
highest microsatellite age estimates (Supplementary Table
S7) are in Turkey (10.0 ± 3.4 kya), where this clade likely origi-
nated (Battaglia et al., 2009; Cruciani et al., 2007; Karachanak
et al., 2013). Indeed, the variance is also highest in the same
areas. The archaeological congruence between the Greek and
Southern Anatolia Mesolithic may explain the similar E1b-V13
expansion times (Perl
es, 2001). In Italy, E-V13 shows coales-
cent age and variance values similar to the Northern Balkan
ones. These data are in agreement with a first migration of
E1b-V13 from Anatolia towards the Southern Balkans, where
it underwent a demographic expansion, followed by a later
ANNALS OF HUMAN BIOLOGY 49
spread towards Southern Italy (Battaglia et al., 2009). The
relatively recent expansion times in the Balkans are consist-
ent with the Balkan Bronze Age, a period that saw strong
demographic changes as demonstrated by archaeological
records (Childe, 2013; Kristiansen, 2000), and could therefore,
represent a possible time frame for the population move-
ment into the South of Italy.
E1b-V13 is also observed in Volterra and the Northern
Italian groups, mainly in the most accessible areas (Boattini
et al., 2013). This observation supports a Balkan influence in
Northern Italian populations as well, most likely through an
Adriatic route and along the Po Valley and, to a lesser extent
in lateral, more isolated, mountainous valleys. Among the
other E sub-clades, the Middle Eastern E1b-M34 lineage is
restricted to Apulia, Calabria and Sicily, whereas the North
African E1b-M81, E1b-V22 and E1b-M35are observed in
Calabria and Sicily. In particular, E1b-M81, which is very fre-
quent in North Africa, reaches an incidence of 6.3% in Sicily.
This marker has also been observed at significant frequencies
in Southern Iberia and its presence in Southern Europe has
been attributed, due to its low microsatellite variation, to
relatively recent migration(s) from North Africa (Adams et al.,
2008; Di Gaetano et al., 2009; Flores et al., 2003,2004;
Semino et al., 2004). On the other hand, the finding of E1b-
M35Y chromosomes (3.5%) in the Borbera Valley is not
completely unexpected. Indeed, the so called Vie del Sale -
Salt Pathsin the high Valley could have been the entry
route of North-East African Y chromosomes either during the
passage of the Attila Army in the 5th century and/or the
numerous Saracen invasions around the year 1000 A.D.
Haplogroup G is not characterised by a clinal distribution
pattern. Frequencies higher than 10% were registered in the
Borbera Valley (15.3%), Volterra (13.3%), Tyrrhenian Calabria
(12.3%) and Apulia (11.8%). Interestingly, most of the samples
belong to the sub-haplogroup G2a-L497, which, as R1b-U152,
displays a pattern of expansion from Central-North Europe
(Supplementary Figure S1). Its influence in Italy is mainly
appreciable in the Borbera Valley, where it accounts for more
than 80% of haplogroup G, and in Volterra. On the other
hand, almost all the G clades seem to be present in Southern
Italy. The G2a-L91 branch, common among Anatolian farmers
of 8 kya (Lazaridis et al., 2016; Mathieson et al., 2017) and
characterising the
Otzis Y chromosome with its sub-clade
G2a-L166, was observed in Tyrol (Berger et al., 2013), Tuscany
(Francalacci et al., 2013) and in a great portion of the
Southern Corsican (25%) and North Sardinian (9%) Y-chromo-
some gene pools (Keller et al., 2012). In this study, it was
recorded in one subject from the Borbera Valley and one
from Apulia, indicating that, although rare, the G2a-L91 hap-
logroup is present in the entire Peninsula.
The frequency of haplogroup I is similar in North and
South Italy (4.8% and 4.1%, respectively) and higher in the
Centre (7.1%), with most of the samples belonging to the
I1-M253 and I2-M223 lineages. The detection of I2-M26 Y
chromosomes in Volterra is noteworthy. This sub-haplogroup
is known for its high frequency (>30%) in Sardinia
(Francalacci et al., 2013; Rootsi et al., 2004; Zei et al., 2003),
so its presence in the Volterra sample suggests a connection
between Tuscany and Sardinia. This link could be related to
the first peopling of the island or represent the signature of
the extensive trade exchanges that Etruscans had with
Sardinia, or alternatively could be due to the rather recent
migration of numerous shepherds from the island to
Tuscany. However, taking into account that (i) all the Volterra
I2-M26 Y chromosomes belong to the deepest and less rep-
resented branches (-star- and alfa) of I2-M26 (data not
shown), not involved in the expansion of this clade in
Sardinia (Francalacci et al., 2013), (ii) the carriers of these
chromosomes belong to families that reside in Volterra from
at least four generations and (iii) all are characterised by local
monophyletic surnames, we can exclude that their presence
in Tuscany is due to recent gene flow.
Finally, haplogroup T, which arose and began to differenti-
ate in the Near East about 25 kya (Mendez et al., 2011) and
is observed at low frequencies in Europe and in parts of the
Middle East, North and East Africa (Heraclides et al., 2017),
could be a potentially informative marker to discriminate
movements in the Mediterranean area. In Italy, it displays fre-
quency spots in central and southern regions (Boattini et al.,
2013) and appears sporadically in the North-West; however,
the present level of resolution does not provide any useful
information to better understand its diffusion.
Gene Diversity values based on haplogroup frequencies
for each of the analysed Italian populations are reported in
Table 1.
Lower indexes characterise northern populations com-
pared to southern ones, indicating a minor Y-chromosome
haplogroup variation in the North. The lowest values were
observed in the Bergamo populations followed by those in
Tortona-Voghera and Borbera Valley, whereas the highest
ones were in Calabria (with no differences among the two
sub-sets) and Sicily, followed by Apulia and Grec
ıa Salentina.
This high Y-chromosome diversity characterising Southern
Italian populations is in agreement with the complex and
extensive patterns of pre- and proto-historical admixture
recently reported for the populations of this area on the
basis of genome-wide data (Sarno et al., 2017).
The Italian Y-chromosome gene pool in the European
and Mediterranean contexts
In order to visualise the relationships between the analysed
groups with other Italian populations and place them in a
wider European and Mediterranean context, PCAs on hap-
logroup frequencies were carried out exploiting available
data from the literature normalised to the highest possible
level of phylogenetic resolution.
A first PCA was performed by using the largest dataset
taken from the literature (Supplementary Table S4), but at a
low level of haplogroup resolution, in order to compare the
Table 1. Gene diversity in Italian populations.
BGV BGP TO-VO VB VOL AP GS CAL-I CAL-T SIC
0.774 0.701 0.861 0.865 0.916 0.948 0.933 0.960 0.960 0.959
BGV: Bergamo Valleys; BGP: Bergamo Plain; TO-VO: Tortona-Voghera; VB:
Borbera Valley; VOL: Volterra; AP: Apulia; GS: Grec
ıa Salentina; CAL-I: Ionian
Calabria; CAL-T: Tyrrhenian Calabria; SIC: Sicily.
50 V. GRUGNI ET AL.
majority of the analysed samples. The plot of the first two
PCs, which together explain more than 29% of the variance,
is shown in Figure 4, together with an inset plot illustrating
haplogroup contributions.
The first PC (F1) which explains 16.22% of the total vari-
ance, clearly separates all the Middle East, Asia Minor and
Caucasus samples characterised by high frequencies of hap-
logroups E, G and J, from the European ones, showing a
high frequency of haplogroup R instead. The second PC (F2)
explains 13.70% of the total variance and distinguishes the
Middle East and Asia Minor populations from the Caucasus
groups based on different frequencies of haplogroups J and
G and Eastern from Western European groups based on
uneven R1a and R1b frequencies. Italian populations are dis-
tributed among these four groupings, but with a broad lati-
tudinal separation generated by the first PC, since some
populations from the South reside close to those of North
Italy and vice versa. This distribution, even if based on low-
resolution data, underlines the variegated pattern of genetic
variation in Italy and is rather informative in terms of past
migration inputs. For instance, the closeness of Southern
Italians to the Middle East is due to a high frequency of hap-
logroup J, which is typical of the Middle East and has been
associated with migrations from this area, including the
spread of agriculture by Middle Eastern farmers during the
Neolithic period. Therefore, the low genetic distance between
South Italian and Middle Eastern populationsand, con-
versely, the higher distance between Middle Eastern and
North Italian populationscan be explained by a greater
influence of Middle Eastern Neolithic farmers and post-
Neolithic migrants from Eastern Mediterranean populations
into the South rather than in the North of Italy. On the other
hand, Northern Italians show a general closeness to the
Basques, sharing a high incidence of the R1b clade.
Furthermore, the proximity of some North-Eastern Italian
groups to the Balkan cluster, mainly due to haplogroups R1a-
M17, E1b-M78 and I-M170, suggests a Balkan contribution.
This is the case, for example, of the Udine (UD) and Vicenza
(VI) samples. The separation of Treviso (TV) from the geo-
graphically close Vicenza, due to the second PC, reflects
instead the high incidence of the western R1b-M269 lineage
in the former. A major Balkan influence on Vicenza rather
than on Treviso could explain this observation, but it is worth
noting that both groups are rather small (VI ¼40 and
TV ¼33) and that the second PC encompasses only a part of
the genetic variance.
Although low-resolution haplogroups capture only some
of the total variability, regional differences are also identified
Figure 4. Principal Components (PC) plot based on the frequencies of low-resolution Y-chromosome haplogroups (Supplementary Table S4). Numbers in parenthe-
ses indicate the proportion of the total genetic information retained by a given PC. The inset plot illustrates the contribution of each haplogroup. The three non-
Italian groupings (Middle East-Asia Minor-Caucasus, West Europe, East Europe) are circled. AG: Agrigento; AMA: Appenine Marche; AP: Apulia; AQ: LAquila; Bas:
Baschi; BGP: Bergamo Plain; BGV: Bergamo Valleys; BN: Benevento; BO: Bologna; BS: Brescia; Bulg: Bulgaria; CAL-I: Ionic Calabria; CAL-T: Tyrrhenian Calabria; Cau:
Caucasus; CCK: Cosenza/Catanzaro/Crotone; CE: Piceni; CE SARD: Central-East Sardinia; CMA: Central Marche; CN: Cuneo; CO: Como; CP: Campobasso; Cre: Crete; Cro:
Croatia; CS SARD: Central-South Sardinia; CT: Catania; CTU: Central Tuscany; ELB: Elba Island; ES: East Sicily; GR-SN: Grosseto/Siena; Gre: Greece; GS: Grec
ıa Salentina;
Iran: Iran; LE: Lecce; LIG: Liguria; Mac: Macedonia; MC: Macerata; MT: Matera; N SARD: North Sardinia; NEI: North-East Italy; NEL: North-East Latium; NWA: North-West
Apulia; PG: Foligno; PT: Pistoia; PUGR: Grecanici; RG-SR: Ragusa/Siracusa; RN: Rimini; SAN: Sanniti; SAP: South Apulia; Serb: Serbia; SIC: Sicily; SIC SW: South-West
Sicily; SLA: South Latium; SP-MS: La Spezia/Massa; SV-GE: Savona/Genova; SW: Belvedere; TLB: Tuscany Latium Border; TO-VO: Tortona-Voghera; Turk: Turkey; TV:
Treviso; UD: Udine; VB: Borbera Valley; VI: Vicenza; VLB: Badia Valley; VM: Valmarecchia; VOL: Volterra; WCL: West Calabria; WCP: West Campania; WS: West Sicily.
ANNALS OF HUMAN BIOLOGY 51
in other areas of the Peninsula. For instance, South Apulian
groups (GS, AP and LE) turned out to be far away from
North-Western Apulia (NWA) and located between the Near
Eastern and Balkan population clusters, a finding that is
strongly suggestive of a Greek influence, especially for the
Grec
ıa Salentina (GS). Conversely, the proximity of the non-
GrecanicApulians (AP) to Crete, one of the first areas
reached by Neolithic Near Eastern farmers, supports the scen-
ario that the same genetic stock also reached Apulia by sea.
The relationships between the different Italian groups in
the general context of the European and Mediterranean pop-
ulations became much clearer when the PCAs were per-
formed at a higher level of haplogroup resolution. The plot
of the two PCs obtained from this analysis and a plot display-
ing the contribution of each haplogroup to the first and
second PC are shown in Figure 5.
On the whole, the first two PC plots explained 37.33% of
the total variance. The obtained distribution shows an overall
general agreement with geography: while the first compo-
nent accounts for a northwestsoutheast separation, the
second component discriminates mainly according to lati-
tude. Thus, as in the previous analysis, the Basque groups are
at the opposite extreme of the first PC relative to the Middle
East, Turkey and the Caucasus cluster. Balkan populations are
sub-divided into two groups, one including Greece and
Bulgaria and the other encompassing all the populations
from the Northern Balkans and Macedonia. It is worth noting
that the Italian populations do not group together in this
analysis, but are scattered in the space comprising the
above-mentioned clusters. The first component separates
Bergamo Valleys (BGV) and Central-East Sardinia (CE SARD)
from all other Italian populations for their high frequency of
haplogroup R1b, especially R1b-S116, whereas Tortona-
Voghera (TO-VO) and the Borbera Valley (VB) are closer to
the Balkans due to the high incidence of I2-M423, I2-M438
and E1b-M78, markers that are largely present in Eastern
Europe. Sardinian groups have been pulled down in the plot
by the high prevalence of I2-M26 marker, also observed at
low frequency in some Basque and Italian groups. Notably,
while Bergamo plain (BGP) appears more related to the
Eastern European populations, Bergamo Valley (BGV) is closer
to Basques. For a long time, Basque populations have been
considered the living fossilsof the earliest modern
European inhabitants, both from genetic and linguistic points
of view (Cavalli-Sforza et al., 1994; Richards et al., 1996), but
more recent studies based on ancient genome-wide sequenc-
ing data suggest that they are the results of long-lasting iso-
lation of a population group originated by the admixture of
Figure 5. Principal Components (PC) plot based on the frequencies of high-resolution Y-chromosome haplogroups (Supplementary Table S5). Numbers in parenthe-
ses indicate the proportion of the total genetic information retained by a given PC. The inset plot illustrates the contribution of each haplogroup. The three non-
Italian groupings (Middle East-Asia Minor-Caucasus, West Europe, Balkans) are circled. Ala: Araba; AP: Apulia; Bba: Bizkaia; Bea: Bearn; BGP: Bergamo Plain; BGV:
Bergamo Valleys; Big: Bigorre; Boc: West Bizcaia; Bulg: Bulgaria; BUR: Burgos; CAL-I: Ionian Calabria; CAL-T: Tyrrhenian Calabria; Can: Cantabria; Cau: Caucasus; CE
SARD: Central-East Sardinia; Cha: Chalosse; Cre: Crete; Cro: Croatia; CS SARD: Central-South Sardinia; Gre: Greece; GS: Grec
ıa Salentina; Gso: South-West Gipuzkoa;
Gui: Gipuzkoa; Herz: Herzegovina; Mac: Macedonia; Nar: North Aragon; Nco: Central-West Nafarroa; Nla: Lapurdi Nafarroa; Nno: North-West Nafarroa; N SARD: North
Sardinia; Rio: La Rioja; Ron: Roncal: Salazar Valley; Serb: Serbia; SIC: Sicily; Sou: Zuberoa; TO-VO: Tortona-Voghera; Turk: Turkey; VB: Borbera Valley; VOL: Volterra;
Zmx: Lapurdi Baztan.
52 V. GRUGNI ET AL.
local hunter-gatherers and early farmers (G
unther et al.,
2015). This might be interpreted as indicating that the valley
populations of the Bergamo province were more isolated
than those inhabiting the plain and, thus, they might have
better retained traces of the Y-chromosome gene pool of
Western European hunter-gatherers. Thus, the first compo-
nent indicates contiguity of the Y-chromosome haplogroup
composition between Basques, North Italy (in particular with
Bergamo Valleys) and Sardinia, especially the Central-East
area of the island, which is known as the archaic zone. The
Volterra sample (VOL) occupies an intermediate position,
between North and South. As already suggested by the low
resolution PCA (Figure 4), different gene flows affected
Southern Italian populations: Ionian Calabria (CAL-I) and
Grec
ıa Salentina (GS) are very close to Greece and Bulgaria,
whereas the other samples from Apulia (AP) are closer to
Crete. The differences among the Apulian populations are
explained by a dissimilar incidence of R1b-M412and R1a-
M17, which are considerably higher in Grec
ıa Salentina than
in its neighbouring areas, and of G2a-P15, which is higher in
Apulia. A great difference is also observed among Calabrian
populations: the sample from the Ionian coast (CAL-I), due to
the higher incidences of E1b-M78 and R1a-M17, is closer to
the Southern Balkans than the one from the Tyrrhenian coast
(CAL-T). In the absence of data from African groups, individu-
als from Sicily (SIC) appear in the proximity of Central-South
Sardinia (CS-SARD), the only other Italian population showing
a considerable incidence of haplogroup E1b-M81. When a
PCA was performed at lower resolution (data not shown) in
order to include samples from North Africa, where hap-
logroup E1b-M81 reaches high frequencies, Sicily further sep-
arated from other Italian populations. On the whole, the
high-resolution PC analysis confirms a strong Middle Eastern
influence in Southern Italian populations, which show
high frequencies of haplogroups J2a and G2a (J2a-M410 and
G2a-P15).
To further investigate the significance of the Italian gen-
etic structure displayed by PCAs, we also carried out analyses
of molecular variance (AMOVA) on the population samples
from this study, as well as those from Boattini et al. (2013).
The results are summarised in Table 2.
Boattini et al. (2013) reported that North-West and South-
East Italy are not separated according to latitude, but by a
longitudinal line, and explained this difference by at least
two independent diffusion processes involving the western
and the eastern coasts of the Italian Peninsula during the
Neolithic revolution. To evaluate this scenario, we performed
first an AMOVA with both datasets and grouped the samples
according to the previously employed criteria (Boattini et al.,
2013). Specifically, three groups were considered: North-West,
South-East and Sardinia. In subsequent tests, alternative
groupings were investigated, but none produced better
results. For example, when Volterra, a potential derivative of
the ancient Etruscan people, was excluded, the variation
among groups decreased (from 10.62% to 9.32%), thus con-
firming the pattern of variation uncovered by Boattini et al.
(2013). However, this analysis was at a very low level of hap-
logroup resolution, which is inadequate for micro-geographic
analyses, thus further AMOVA tests were carried out on our
data at the maximum level of haplogroup resolution and the
population samples were assembled according to the high-
resolution PCA grouping (Figure 5). The results are reported
in Table 3.
The first analysis was performed by considering the fol-
lowing three population groups: North Italy, made up by all
North Italian samples; South-East Italy, which included Apulia,
Grec
ıa Salentina and Ionian Calabria; and South-West Italy,
which comprises Sicily and Tyrrhenian Calabria. The analysis
produced a value of variation among groups of 10.69%, simi-
lar to that (10.62%) obtained by using low-resolution hap-
logroups and the population sub-division proposed by
Boattini et al. (2013). A higher percentage of variation among
groups (11.68%) was obtained when the Borbera Valley and
Volterra samples were set apart; this could indicate that
these two populations differ from the others, likely represent-
ing genetically isolated groups. However, when only the
Table 2. AMOVA analysis with low-resolution haplogroups.
Sub-division criterion Source of variation Variance components Percentage of variation
North-West Italy vs South-East Italy vs Sardinia (3 groups) Among groups 0.39217 10.62
Among populations within groups 0.05303 1.44
Within populations 3.24769 87.94
North Italy vs South Italy vs Central Italy vs Sardinia (4 groups) Among groups 0.33912 9.32
Among populations within groups 0.05154 1.42
Within populations 3.24769 89.26
p<.01.
Table 3. AMOVA analysis with high-resolution haplogroups.
Sub-division criterion Source of variation Variance components Percentage of variation
North Italy vs South-East Italy vs South-West Italy (3 groups) Among groups 0.5630510.69
Among populations within groups 0.10577 2.01
Within populations 4.60023 87.31
North Italy vs South Italy vs Borbera Valley vs Volterra (4 groups) Among groups 0.61477 11.68
Among populations within groups 0.046690.89
Within populations 4.60023 87.43
North Italy vs South Italy vs Volterra (3 groups) Among groups 0.6534912.31
Among populations within groups 0.056691.07
Within populations 4.60023 86.63
p<.05;  p<.01.
ANNALS OF HUMAN BIOLOGY 53
Volterra sample was kept separate and the Borbera Valley
was pooled with the northern samples, the among-group
variation increased, reaching the highest value among
groups (12.31%), while the variance among populations
within groups remained almost the same. This suggests a
notable difference among the three groups and, in particular,
underlines a significantly different Y-chromosome haplogroup
composition between modern Volterra and the rest of Italy.
Since the population from Volterra could be, at least in part,
of Etruscan ancestry, it would be interesting to verify if other
populations from Tuscany (analysed at high-resolution level)
show the same peculiarity. If so, our observation would be in
line with the scenario of a foreign source for the ancient
Etruscan people, instead of an autochthonous origin.
Conclusions
In this paper, Y chromosomes of 817 subjects from inform-
ative areas of the Italian Peninsula were analysed at a high
level of haplogroup resolution. The results, compared with
those available from the literature, provided a more detailed
overview of the Y-chromosome variation in Italy relative to
previous studies. A genetic structure characterised by high
complexity emerged, probably reflecting the multifaceted
pattern of peopling of the Italian Peninsula. Specifically, the
southern groups are characterised by a higher haplogroup
variation in comparison with those from the North. This is
well illustrated by the AMOVA analysis with high-resolution
haplogroups, which provided the best results when three
groupings were considered: Northern Italy, Southern Italy
and Volterra sample. Thus, the population groups are better
separated according to their latitude rather than their longi-
tude, as proposed by Boattini et al. (2013), and also con-
firmed by our analysis at a comparable low-resolution level.
However, isolated populations such as those from the
Borbera Valley and Grec
ıa Salentina still preserve unique hap-
logroup distributions, due to either genetic drift and/or the
legacy of distinctive ancestral sources.
When compared to other populations, Italian samples do
not cluster all together, but are distributed among European
and Mediterranean people. Southern samples show a higher
similarity with Middle Eastern and Southern Balkan popula-
tions than northern ones; conversely, northern samples are
genetically closer to North-West Europe and Northern Balkan
groups. The intermediate position of Volterra, between South
and North Italy, is a mark of its unique Y-chromosomal gen-
etic structure. However, the long-lasting debate concerning
the origin of Etruscans remains open. As a matter of fact,
while the presence of J2a-M67suggests contacts by sea
with Anatolian people, in agreement with the Herodotus
hypothesis of an external Anatolian source of Etruscans, the
finding of the Central European lineage G2a-L497 at consid-
erable frequency would rather support a Northern European
origin of Etruscans. On the other hand, the high incidence of
European R1b lineages cannot rule out the scenario of an
autochthonous process of formation of the Etruscan civilisa-
tion from the preceding Villanovan society, as first suggested
by Dionysius of Halicarnassus; a detailed analysis of
haplogroup R1b-U152 could prove very informative in this
regard.
Acknowledgements
The authors are grateful to all the donors for providing biological speci-
mens and acknowledge two anonymous reviewers for valuable sugges-
tions and comments on the manuscript. This study is part of the
University of Pavia strategic theme Towards a governance model for
international migration: an interdisciplinary and diachronic perspective
(MIGRAT-IN-G) (to A.O., A.A., O.S. and A.T.).
Disclosure statement
The authors report no conflicts of interest. The authors alone are respon-
sible for the content and writing of the paper.
Funding
This work was funded by Ministero dell'Istruzione, dell'Università e della
Ricerca [RBFR126B8I (to A.O. and A.A.)].
References
Achilli A, Olivieri A, Pala M, Metspalu E, Fornarino S, Battaglia V,
Accetturo M, et al. 2007. Mitochondrial DNA variation of modern
Tuscans supports the Near Eastern origin of Etruscans. Am J Hum
Genet 80:759768.
Adams SM, Bosch E, Balaresque PL, Ballereau SJ, Lee AC, Arroyo E,
L
opez-Parra AM, et al. 2008. The genetic legacy of religious diversity
and intolerance: paternal lineages of Christians, Jews, and Muslims in
the Iberian Peninsula. Am J Hum Genet 83:725736.
Al-Zahery N, Pala M, Battaglia V, Grugni V, Hamod MA, Hooshiar Kashani
B, Olivieri A, et al. 2011. In search of the genetic footprints of
Sumerians: a survey of Y-chromosome and mtDNA variation in the
Marsh Arabs of Iraq. BMC Evol Biol 11:288.
Bandelt HJ, Forster P, R
ohl A. 1999. Median-joining networks for inferring
intraspecific phylogenies. Mol Biol Evol 16:3748.
Bandelt HJ, Forster P, Sykes BC, Richards MB. 1995. Mitochondrial por-
traits of human populations using median networks. Genetics
141:743753.
Barbujani G, Bertorelle G, Capitani G, Scozzari R. 1995. Geographical
structuring in the mtDNA of Italians. Proc Natl Acad Sci USA
92:91719175.
Battaglia V, Fornarino S, Al-Zahery N, Olivieri A, Pala M, Myres NM, King
RJ, et al. 2009. Y-chromosomal evidence of the cultural diffusion of
agriculture in southeast Europe. Eur J Hum Genet 17:820830.
Benazzi S, Douka K, Fornai C, Bauer CC, Kullmer O, Svoboda J, Pap I,
et al. 2011. Early dispersal of modern humans in Europe and implica-
tions for Neanderthal behaviour. Nature 479:525528.
Berger B, Niederst
atter H, Erhart D, Gassner C, Schennach H, Parson W.
2013. High resolution mapping of Y haplogroup G in Tyrol (Austria).
Forensic Sci Int Genet 7:529536.
Boattini A, Martinez-Cruz B, Sarno S, Harmant C, Useli A, Sanz P, Yang-
Yao D, et al. 2013. Uniparental markers in Italy reveal a sex-biased
genetic structure and different historical strata. PLoS One 8:e65441.
Brisighelli F, Blanco-Verea A, Boschi I, Garagnani P, Pascali VL, Carracedo
A, Capelli C, Salas A. 2012a. Patterns of Y-STR variation in Italy.
Forensic Sci Int Genet 6:834839.
Brisighelli F,
Alvarez-Iglesias V, Fondevila M, Blanco-Verea A, Carracedo A,
Pascali VL, Capelli C, Salas A. 2012b. Uniparental markers of contem-
porary Italian population reveals details on its pre-Roman heritage.
PLoS One 7:e50794.
Capelli C, Brisighelli F, Scarnicci F, Arredi B, CagliaA, Vetrugno G,
Tofanelli S, et al. 2007. Y chromosome genetic variation in the Italian
peninsula is clinal and supports an admixture model for the
Mesolithic-Neolithic encounter . Mol Phylogenet Evol 44:228239.
54 V. GRUGNI ET AL.
Cavalli-Sforza LL, Menozzi P, Piazza A. 1994. The history and geography
of human genes. Princeton, NJ: Princeton University Press.
Chiaroni J, Underhill PA, Cavalli-Sforza LL. 2009. Y chromosome diversity,
human expansion, drift, and cultural evolution. Proc Natl Acad Sci
USA 106:2017420179.
Childe VG. 2013. The dawn of European civilization. Abingdon:
Routledge.
Cruciani F, La Fratta R, Trombetta B, Santolamazza P, Sellitto D, Colomb
EB, Dugoujon JM, et al. 2007. Tracing past human male movements
in northern/eastern Africa and western Eurasia: new clues from
Y-chromosomal haplogroups E-M78 and J-M12. Mol Biol Evol
24:13001311.
Destro Bisol G, Anagnostou P, Batini C, Battaggia C, Bertoncini S, Boattini
A, Caciagli L, et al. 2008. Italian isolates today: geographic and linguis-
tic factors shaping human biodiversity. J Anthropol Sci 86:179188.
Di Gaetano C, Cerutti N, Crobu F, Robino C, Inturri S, Gino S, Guarrera S,
et al. 2009. Differential Greek and northern African migrations to Sicily
are supported by genetic evidence from the Y chromosome. Eur J
Hum Genet 17:9199.
Di Giacomo F, Luca F, Anagnou N, Ciavarella G, Corbo RM, Cresta M,
Cucci F, et al. 2003. Clinal patterns of human Y chromosomal diversity
in continental Italy and Greece are dominated by drift and founder
effects. Mol Phylogenet Evol 28:387395.
Excoffier L, Smouse PE, Quattro JM. 1992. Analysis of molecular variance
inferred from metric distances among DNA haplotypes: application to
human mitochondrial DNA restriction data. Genetics 131:479491.
Flores C, Maca-Meyer N, Gonz
alez AM, Oefner PJ, Shen P, P
erez JA, Rojas
A, et al. 2004. Reduced genetic structure of the Iberian peninsula
revealed by Y-chromosome analysis: implications for population dem-
ography. Eur J Hum Genet 12:855863.
Flores C, Maca-Meyer N, P
erez JA, Gonz
alez AM, Larruga JM, Cabrera VM.
2003. A predominant European ancestry of paternal lineages from
Canary islanders. Ann Hum Genet 67:138152.
Francalacci P, Morelli L, Angius A, Berutti R, Reinier F, Atzeni R, Pilu R,
et al. 2013. Low-pass DNA sequencing of 1200 Sardinians reconstructs
European Y-chromosome phylogeny. Science 341:565569.
Grugni V, Battaglia V, Hooshiar Kashani B, Parolo S, Al-Zahery N, Achilli A,
Olivieri A, et al. 2012. Ancient migratory events in the Middle East:
new clues from the Y-chromosome variation of modern Iranians. PLoS
One 7:e41252.
G
unther T, Valdiosera C, Malmstr
om H, Ure~
na I, Rodriguez-Varela R,
Sverrisd
ottir
O, Daskalaki EA, et al. 2015. Ancient genomes link early
farmers from Atapuerca in Spain to modern-day Basques. Proc Natl
Acad Sci USA 112:1191711922.
Heraclides A, Bashiardes E, Fern
andez-Dom
ınguez E, Bertoncini S,
Chimonas M, Christofi V, King J, et al. 2017. Y-chromosomal analysis
of Greek Cypriots reveals a primarily common pre-Ottoman paternal
ancestry with Turkish Cypriots. PLoS One 12:e0179474.
Karachanak S, Grugni V, Fornarino S, Nesheva D, Al-Zahery N, Battaglia V,
Carossa V, et al. 2013. Y-chromosome diversity in modern Bulgarians:
new clues about their ancestry. PLoS One 8:e56779.
Karafet TM, Mendez FL, Meilerman MB, Underhill PA, Zegura SL, Hammer
MF. 2008. New binary polymorphisms reshape and increase resolution
of the human Y chromosomal haplogroup tree. Genome Res
18:830838.
Kayser M, de Knijff P, Dieltjes P, Krawczak M, Nagy M, Zerjal T, Pandya A,
et al. 1997. Applications of microsatellite-based Y chromosome haplo-
typing. Electrophoresis 18:16021607.
Keller A, Graefen A, Ball M, Matzas M, Boisguerin V, Maixner F, Leidinger
P, et al. 2012. New insights into the Tyrolean Icemans origin and
phenotype as inferred by whole-genome sequencing. Nat Commun
3:698.
King RJ, Di Cristofaro J, Kouvatsi A, Triantaphyllidis C, Scheidel W, Myres
NM, Lin AA, et al. 2011. The coming of the Greeks to Provence and
Corsica: Y-chromosome models of archaic Greek colonization of the
western Mediterranean. BMC Evol Biol 11:69.
King RJ, Ozcan SS, Carter T, Kalfo
glu E, Atasoy S, Triantaphyllidis C,
Kouvatsi A, et al. 2008. Differential Y-chromosome Anatolian influen-
ces on the Greek and Cretan Neolithic. Ann Hum Genet 72:205214.
Korfmann M. 1997. Troia: Ausgrabungen 1996. Zabern.
Kristiansen K. 2000. Europe before history. Cambridge: Cambridge
University Press.
Lazaridis I, Nadel D, Rollefson G, Merrett DC, Rohland N, Mallick S,
Fernandes D, et al. 2016. Genomic insights into the origin of farming
in the ancient Near East. Nature 536:419424.
Malaspina P, Cruciani F, Santolamazza P, Torroni A, Pangrazio A, Akar N,
Bakalli V, et al. 2000. Patterns of male-specific inter-population diver-
gence in Europe, West Asia and North Africa. Ann Hum Genet
64:395412.
Mathieson I, Roodenberg SA, Posth C, Sz
ecs
enyi-Nagy A, Rohland N,
Mallick S, Olalde I, et al. 2017. The genomic history of southeastern
Europe. bioRxiv.135616.
Mendez FL, Karafet TM, Krahn T, Ostrer H, Soodyall H, Hammer MF. 2011.
Increased resolution of Y-chromosome haplogroup T defines relation-
ships among populations of the Near East, Europe, and Africa. Hum
Biol 83:3953.
Myres NM, Rootsi S, Lin AA, J
arve M, King RJ, Kutuev I, Cabrera VM, et al.
2011. A major Y-chromosome haplogroup R1b Holocene era founder
effect in Central and Western Europe. Eur J Hum Genet 19:95101.
Nebel A, Landau-Tasseron E, Filon D, Oppenheim A, Faerman M. 2002.
Genetic evidence for the expansion of Arabian tribes into the
Southern Levant and North Africa. Am J Hum Genet 70:15941596.
Nei M. 1987. Molecular evolutionary genetics. New York: Columbia
University Press.
Perl
es C. 2001. The early Neolithic in Greece: the first farming commun-
ities in Europe. Cambridge: Cambridge University Press.
Piazza A, Cappello N, Olivetti E, Rendine S. 1988. A genetic history of
Italy. Ann Hum Genet 52:203213.
Richards M, C^
orte-Real H, Forster P, Macaulay V, Wilkinson-Herbots H,
Demaine A, Papiha S, et al. 1996. Paleolithic and Neolithic lineages in
the European mitochondrial gene pool. Am J Hum Genet 59:185203.
Rootsi S, Magri C, Kivisild T, Benuzzi G, Help H, Bermisheva M, Kutuev I,
et al. 2004. Phylogeography of Y-chromosome haplogroup I reveals
distinct domains of prehistoric gene flow in Europe. Am J Hum Genet
75:128137.
Rosser ZH, Zerjal T, Hurles ME, Adojaan M, Alavantic D, Amorim A, Amos
W, et al. 2000. Y-chromosomal diversity in Europe is clinal and influ-
enced primarily by geography, rather than by language. Am J Hum
Genet 67:15261543.
Sarno S, Boattini A, Pagani L, Sazzini M, De Fanti S, Quagliariello A,
Gnecchi Ruscone GA, et al. 2017. Ancient and recent admixture layers
in Sicily and Southern Italy trace multiple migration routes along the
Mediterranean. Sci Rep 7:1984
Semino O, Magri C, Benuzzi G, Lin AA, Al-Zahery N, Battaglia V, Maccioni
L, et al. 2004. Origin, diffusion, and differentiation of Y-chromosome
haplogroups E and J: inferences on the neolithization of Europe and
later migratory events in the Mediterranean area. Am J Hum Genet
74:10231034.
Semino O, Passarino G, Brega A, Fellous M, Santachiara-Benerecetti AS.
1996. A view of the Neolithic demic diffusion in Europe through two
Y chromosome-specific markers. Am J Hum Genet 59:964968.
Semino O, Passarino G, Oefner PJ, Lin AA, Arbuzova S, Beckman LE, De
Benedictis G, et al. 2000. The genetic legacy of Paleolithic Homo sapi-
ens sapiens in extant Europeans: a Y-chromosome perspective.
Science 290:11551159.
Sengupta S, Zhivotovsky LA, King R, Mehdi SQ, Edmonds CA, Chow CE,
Lin AA, et al. 2006. Polarity and temporality of high-resolution Y-
chromosome distributions in India identify both indigenous and
exogenous expansions and reveal minor genetic influence of Central
Asian pastoralists. Am J Hum Genet 78:202221.
The Y Chromosome Consortium. 2002. A nomenclature system for the tree
of human Y-chromosomal binary haplogroups. Genome Res 12:339348.
Tofanelli S, Ferri G, Bulayeva K, Caciagli L, Onofri V, Taglioli L, Bulayev O,
et al. 2009. J1-M267 Y lineage marks climate-driven pre-historical
human displacements. Eur J Hum Genet 17:15201524.
Underhill PA, Myres NM, Rootsi S, Metspalu M, Zhivotovsky LA, King RJ,
Lin AA, et al. 2010. Separating the post-glacial coancestry of European
and Asian Y chromosomes within haplogroup R1a. Eur J Hum Genet
18:479484.
ANNALS OF HUMAN BIOLOGY 55
Valverde L, Illescas MJ, Villaescusa P, Gotor AM, Garc
ıa A, Cardoso
S, Algorta J, et al. 2016. New clues to the evolutionary history
of the main European paternal lineage M269: dissection of the
Y-SNP S116 in Atlantic Europe and Iberia. Eur J Hum Genet
24:437441.
van Oven M, Toscani K, van den Tempel N, Ralf A, Kayser M. 2013.
Multiplex genotyping assays for fine-resolution subtyping of the
major human Y-chromosome haplogroups E, G, I, J and R in anthropo-
logical, genealogical, and forensic investigations. Electrophoresis
34:30293038.
Voskarides K, Mazi
eres S, Hadjipanagi D, Di Cristofaro J, Ignatiou A,
Stefanou C, King RJ, et al. 2016. Y-chromosome phylogeographic
analysis of the Greek-Cypriot population reveals elements
consistent with Neolithic and Bronze Age settlements. Investig
Genet 7:1.
Zei G, Lisa A, Fiorani O, Magri C, Quintana-Murci L, Semino O,
Santachiara-Benerecetti AS. 2003. From surnames to the history of Y
chromosomes: the Sardinian population as a paradigm. Eur J Hum
Genet 11:802807.
Zhivotovsky LA, Underhill PA, Cinnioglu C, Kayser M, Morar B, Kivisild T,
Scozzari R, et al. 2004. The effective mutation rate at Y chromosome
short tandem repeats, with application to human population-diver-
gence time. Am J Hum Genet 74:5061.
Zhivotovsky LA, Underhill PA, Feldman MW. 2006. Difference between
evolutionarily effective and germ line mutation rate due to stochastic-
ally varying haplogroup size. Mol Biol Evol 23:22682270.
56 V. GRUGNI ET AL.
... In Italy, population genetics analyses have brought to light a heterogeneous genetic background mostly imputable to repeated colonization and migratory waves and to an uneven geographical landscape, which has also facilitated the appearance of genetic isolates [13][14][15][16][17][18]. With respect to the BRCA1/2 genes, a few PVs recurring in defined geographical areas and/or isolated populations have been described, e.g., in Calabria [19], Sardinia [20], Tuscany [21,22], Veneto [23], and Friuli-Venezia Giulia [24], reviewed in [3]. ...
... Of course, other such variants could exist outside breast cancer genes. Consistently, a study on the frequency of the Y-chromosome haplogroups showed that individuals from the Bergamo valleys did not cluster with the other Italian populations [16]. ...
Article
Full-text available
Germline pathogenic variants (PVs) in the BRCA1 or BRCA2 genes cause high breast cancer risk. Recurrent or founder PVs have been described worldwide including some in the Bergamo province in Northern Italy. The aim of this study was to compare the BRCA1/2 PV spectra of the Bergamo and of the general Italian populations. We retrospectively identified at five Italian centers 1019 BRCA1/2 PVs carrier individuals affected with breast cancer and representative of the heterogeneous national population. Each individual was assigned to the Bergamo or non-Bergamo cohort based on self-reported birthplace. Our data indicate that the Bergamo BRCA1/2 PV spectrum shows less heterogeneity with fewer different variants and an average higher frequency compared to that of the rest of Italy. Consistently, four PVs explained about 60% of all carriers. The majority of the Bergamo PVs originated locally with only two PVs clearly imported. The Bergamo BRCA1/2 PV spectrum appears to be private. Hence, the Bergamo population would be ideal to study the disease risk associated with local PVs in breast cancer and other disease-causing genes. Finally, our data suggest that the Bergamo population is a genetic isolate and further analyses are warranted to prove this notion.
... Edhe në Itali, frekuenca lëviz nga zero deri në 8,3% sipas rajonit. 49 Në planin filogjenetik, jashtë dy fiseve në shqyrtim, lidhja më e afërt e gjetur deri sot, llogaritur nga YFull si rreth 800-vjeçare, është me një person po nga Tropoja, e fisit Gashi e nga fshati Luzhë. Fqinjësia e sotshme gjeografike mes Krasniqes, Nikajve dhe Gashit ka vijuar me pak ndryshime të paktën prej fillimit të shek. ...
Article
Full-text available
Abstrakt: Nevoja e ndërmarrjes së studimeve ndërdisiplinore në hulumtimin historik bëhet gjithnjë e më e theksuar me shtimin e të dhënave shkencore të disponueshme të cilat shpien në sinteza gjithnjë e më të sakta të dukurive historike. Në këtë punim, si rast studimi kemi zgjedhur fiset Krasniqe dhe Nikaj si dy ndër fiset më të mëdha shqiptare, prej të cilave kemi mbledhur 23 mostra për sekuencim gjenetik. Të dhënat gjenetike mbështesin një sërë të dhënash të tjera të karakterit historik, etnografik, antropologjik dhe njëkohësisht shërbejnë si pasurim i mëtejshëm i historisë së këtyre fiseve dhe si plotësim i mozaikut të të dhënave mbi popullatat apo fiset që përbëjnë etninë shqiptare. Rezultatet tregojnë se vëllazëritë kryesore të të dy fiseve kanë prejardhje të përbashkët në vijë atërore, dhe se vëllazëritë e Krasniqes lidhen më afër mes tyre se me ato të Nikajve. Gjithashtu, anëtarë të të dy fiseve trashëgojnë një haplogrup karakteristik për shqiptarët e Veriut, i cili lidhet edhe me disa rezultate të lashta nga rajoni. Të dhënat gjenetike duke u trajtuar dhe përdorur në cilësinë e burimit historik, shërbejnë për historicizimin e të dhënave të mjegulluara nga koha dhe të parikthyeshme përmes metodave tradicionale historiografike. Hyrje Nevoja e ndërmarrjes së studimeve ndërdisiplinore në hulumtimin e së kaluarës bëhet gjithnjë e më e theksuar me shtimin e të dhënave shkencore të disponueshme. Qasja ndërdisiplinore, pra, nënkupton nivele të shumëfishta analize të cilat shpien në sinteza e përfundime gjithnjë e
... The ongoing expansion of this study to a West Eurasian scale may reveal patterns of haplogroup dispersal and diversity behind the MCH that were not visible in the investigated single Southern European country and differences in contributing haplogroups. The extended population sample might clarify if the enormous variation reported in this study is a general phenomenon or the consequence of the complex genetic composition of the Italian population, resulting from the large extent, geographic position, and important historic role of the peninsula and the two largest Mediterranean islands, with multiple historic population inputs and migrations across the country, mirrored by both haploid [37,38,42,83,84] and autosomal genomes [85][86][87][88][89][90][91]. ...
Article
Full-text available
The high number of matching haplotypes of the most common mitochondrial (mt)DNA lineages are considered to be the greatest limitation for forensic applications. This study investigates the potential to solve this constraint by massively parallel sequencing a large number of mitogenomes that share the most common West Eurasian mtDNA control region (CR) haplotype motif (263G 315.1C 16519C). We augmented a pilot study on 29 to a total of 216 Italian mitogenomes that represents the largest set of the most common CR haplotype compiled from a single country. The extended population sample confirmed and extended the huge coding region diversity behind the most common CR motif. Complete mitogenome sequencing allowed for the detection of 163 distinct haplotypes, raising the power of discrimination from 0 (CR) to 99.6% (mitogenome). The mtDNAs were clustered into 61 named clades of haplogroup H and did not reveal phylogeographic trends within Italy. Rapid individualization approaches for investigative purposes are limited to the most frequent H clades of the dataset, viz. H1, H3, and H7.
... Although establishing the chronological context for this affinity using present-day genomes might be challenging, our results are in accordance with archaeological and historical sources that attributed the origin of Greek colonies in South-Eastern Sicily and Apulia from populations inhabiting the southern and Eastern parts of the Peloponnese [31,32]. Uniparental Y-chromosome findings are also in agreement with these observations revealing Eastern Peloponnesian ancestries in East Sicily [33] and shared haplogroups among modern-day Greeks and populations living in Southern Italian areas colonised by Greeks such as the Salento (Apulia) and the Ionian coast of Calabria [60]. The lower affinity with other Balkan populations could be attributed to a lower influence by inland populations, such as Slavic-related people [61] and/or genetic drift in Tsakones and Maniots as suggested by historical sources [39]. ...
Article
Full-text available
Southern Italy was characterised by a complex prehistory that started with different Palaeolithic cultures, later followed by the Neolithization and the demic dispersal from the Pontic-Caspian Steppe during the Bronze Age. Archaeological and historical evidences point to a link between Southern Italians and the Balkans still present in modern times. To shed light on these dynamics, we analysed around 700 South Mediterranean genomes combined with informative ancient DNAs. Our findings revealed high affinities of South-Eastern Italians with modern Eastern Peloponnesians, and a closer affinity of ancient Greek genomes with those from specific regions of South Italy than modern Greek genomes. The higher similarity could be associated with a Bronze Age component ultimately originating from the Caucasus with high Iranian and Anatolian Neolithic ancestries. Furthermore, extremely differentiated allele frequencies among Northern and Southern Italy revealed putatively adapted SNPs in genes involved in alcohol metabolism, nevi features and immunological traits.
... Although establishing the chronological context for this affinity using present-day genomes might be challenging, our results are in accordance with archaeological and historical sources that attributed the origin of Greek colonies in South-Eastern Sicily and Apulia from populations inhabiting the southern and Eastern parts of the Peloponnese (31,32). Uniparental Y-chromosome findings are also in agreement with these observations revealing Eastern Peloponnesian ancestries in East Sicily (34) and shared haplogroups among modern-day Greeks and populations living in Southern Italian areas colonised by Greeks such as the Salento (Apulia) and the Ionian coast of Calabria (56). The lower affinity with other Balkan populations could be attributed to a lower influence by inland populations, such as Slavic-related people (57) and/or genetic drift in Tsakones and Maniots as suggested by . ...
Preprint
Full-text available
Southern Italy was characterised by a complex prehistory that started with different Palaeolithic cultures, later followed by the Neolithic transition and the demic dispersal from the Pontic-Caspian Steppe during the Bronze Age. Archaeological and historical evidence points to demic and cultural influences between Southern Italians and the Balkans, starting with the initial Palaeolithic occupation until historical and modern times. To shed light on the dynamics of these contacts, we analysed a genome-wide SNP dataset of more than 700 individuals from the South Mediterranean area (102 from Southern Italy), combined with ancient DNA from neighbouring areas. Our findings revealed high affinities of South-Eastern Italians with modern Eastern Peloponnesians, and a closer affinity of ancient Greek genomes with those from specific regions of South Italy than modern Greek genomes. The higher similarity could be associated with the presence of a Bronze Age component ultimately originating from the Caucasus and characterised by high frequencies of Iranian and Anatolian Neolithic ancestries. Furthermore, to reveal possible signals of natural selection, we looked for extremely differentiated allele frequencies among Northern and Southern Italy, uncovering putatively adapted SNPs in genes involved in alcohol metabolism, nevi features and immunological traits, such as ALDH2, NID1 and CBLB.
... As concern population relationships analyses, overall our results support a paternal genetic continuity of the analyzed population from the 16th century until today. In general, the predicted Y-chromosome haplogroups reflect lineages commonly observed in Italy (Grugni et al., 2018) and revealed a homogeneous genetic composition through centuries between the ancient and modern samples of Roccapelago, as supported even by both Y-chromosome haplogroup frequencies and RSTs genetic distances. The connection between ancient and modern individuals of Roccapelago is well documented also in the network analysis (Figure 2), where both mummies' and present-day haplotypes clustered together based on haplogroups assignment. ...
Article
Full-text available
Roccapelago (MO) is a small village located in the Northern Central Apennines, with a population of 31 inhabitants (2014). In 2010, more than 400 individuals dated between the end of the 16th and the 18th century, many of which partially mummified, were discovered in the crypt of the church. This small village, because of its geographical location and surrounding environment, seems to possess the characteristics of a genetic isolate, useful for population genetics and genealogical analyses. Thus, a diachronic study of DNA aimed at investigating the structure and dynamics of the population of Roccapelago over the about 4 centuries, was conducted by analyzing ancient and modern inhabitants of the village. The 14 modern samples were selected by considering both the founder surnames of the village, identified thanks to the study of parish registers, and the grandparent’s criterion. From 25 ancient mummies, morphologically assigned to male individuals, the petrous bone, that harbors high DNA amounts, was selected for the DNA extraction. The quantification and qualitative assessment of total human male DNA were evaluated by a real-time PCR assay using the Quantifiler Trio DNA Quantification Kit and multiplex PCR of 27 Y-chromosome short tandem repeat (Y-STR) markers included in the Yfiler Plus PCR Amplification Kit, with seven rapidly mutating Y-STR loci for improving discrimination of male lineages, was performed to genotype the samples. Y-STRs were analyzed according to the criteria of ancient DNA (aDNA) analysis to ensure that authentic DNA typing results were obtained from these ancient samples. The molecular analysis showed the usefulness of the Y chromosome to identify historically relevant remains and discover patterns of relatedness in communities moving from anthropology to genetic genealogy and forensics.
... To explore how the two studied Arab populations (Kairouan and Wesletia) were integrated in the diversity context of other populations not only from Tunisia but also from North Africa, Sub-Sahara, Europe and the Middle East, we recruited the available population data (Supporting Information Table S4) [53][54][55][56][57][58] . Up to now in North Africa, T lineages were sporadically found in most populations, peaking, however, in the eastern ones such as Egyptian (6.7%) and Libyan (2.28%) 30,34 . ...
Article
Full-text available
To obtain refreshed insights into the paternal lineages of Tunisian populations, Y-chromosome diversity was assessed in two populations belonging to an Arab genealogical lineage, Kairouan and Wesletia, as well as in four Tunisian Andalusian populations, Testour, Slouguia, Qalaat-El-Andalous and El Alia. The Arabs from Kairouan revealed 73.47% of E-M81 and close affinities with Berber groups, indicating they are likely arabized Berbers, clearly differentiated from the Arabs from Wesletia, who harbored the highest frequency (71.8%) of the Middle Eastern component ever observed in North Africa. In the Tunisian Andalusians, the North African component largely prevailed, followed by the Middle Eastern contribution. Global comparative analysis highlighted the heterogeneity of Tunisian populations, among which, as a whole, dominated a set of lineages ascribed to be of autochthonous Berber origin (71.67%), beside a component of essentially Middle Eastern extraction (18.35%), and signatures of Sub-Saharan (5.2%), European (3.45%) and Asiatic (1.33%) contributions. The remarkable frequency of T-M70 in Wesletia (17.4%) prompted to refine its phylogeographic analysis, allowing to confirm its Middle Eastern origin, though signs of local evolution in Northern Africa were also detected. Evidence was clear on the ancient introduction of T lineages into the region, probably since Neolithic times associated to spread of agriculture.
... DYS448 lies in the proximal part of the azoospermia factor c (AZFc) region, important in spermatogenesis, and is made up of ampliconic repeats that act as substrates for nonallelic homologous recombination (NAHR), resulting in deletion/ duplication events at this locus [69]. This duplication has been previously observed in African, African American and European individuals [70,71], furthermore, the haplotype of the Italian subject described in ref. 70 was predicted to be E1a by the mutation equivalent to E1a-M33 E1a-M132, which is a lineage mainly observed in Africa and is also present in low frequencies in Italy [59,70,[72][73][74][75]. The Afro-Ecuadorian individuals observed in our study that display the DYS448 duplication all belong to haplogroup E1a-M33 too, which seems to suggest a unique origin of the E1a Y chromosomes. ...
... DYS448 lies in the proximal part of the azoospermia factor c (AZFc) region, important in spermatogenesis, and is made up of ampliconic repeats that act as substrates for nonallelic homologous recombination (NAHR), resulting in deletion/ duplication events at this locus [69]. This duplication has been previously observed in African, African American and European individuals [70,71], furthermore, the haplotype of the Italian subject described in ref. 70 was predicted to be E1a by the mutation equivalent to E1a-M33 E1a-M132, which is a lineage mainly observed in Africa and is also present in low frequencies in Italy [59,70,[72][73][74][75]. The Afro-Ecuadorian individuals observed in our study that display the DYS448 duplication all belong to haplogroup E1a-M33 too, which seems to suggest a unique origin of the E1a Y chromosomes. ...
Article
Ecuador is a multiethnic and pluricultural country with a complex history defined by migration and admixture processes. The present study aims to increase our knowledge on the Ecuadorian Native Amerindian groups and the unique South American Y-chromosome haplogroup C3-MPB373 through the analysis of up to 23 Y-chromosome STRs (Y-STRs) and several Y-SNPs in a sample of 527 Ecuadorians from 7 distinct populations and geographic areas, including Kichwa and non-Kichwa Native Amerindians, Mestizos and Afro-Ecuadorians. Our results reveal the presence of C3-MPB373 both in the Amazonian lowland Kichwa with frequencies up to 28% and, for the first time, in notable proportions in Kichwa populations from the Ecuadorian highlands. The substantially higher frequencies of C3-MPB373 in the Amazonian lowlands found in Kichwa and Waorani individuals suggest a founder effect in that area. Notably, estimates for the time to the most recent common ancestor (TMRCA) in the range of 7.2 – 9.0 kya point to an ancient origin of the haplogroup and suggest an early Holocene expansion of C3-MPB373 into South America. Finally, the pairwise genetic distances (R ST) separate the Kichwa Salasaka from all the other Native Amerindian and Ecuadorian groups, indicating a so far hidden diversity among the Kichwa-speaking populations and suggesting a more southern origin of this population. In sum, our study provides a more in-depth knowledge of the male genetic structure of the multiethnic Ecuadorian population, as well as a valuable reference dataset for forensic use.
Article
Full-text available
The Y chromosome has been widely explored for the study of human migrations. Due to its paternal inheritance, the Y chromosome polymorphisms are helpful tools for understanding the geographical distribution of populations all over the world and for inferring their origin, which is really useful in forensics. The remarkable historical context of Europe, with numerous migrations and invasions, has turned this continent into a melting pot. For this reason, it is interesting to study the Y chromosome variability and how it has contributed to improving our knowledge of the distribution and development of European male genetic pool as it is today. The analysis of Y lineages in Europe shows the predominance of four haplogroups, R1b-M269, I1-M253, I2-M438 and R1a-M420. However, other haplogroups have been identified which, although less frequent, provide significant evidence about the paternal origin of the populations. In addition, the study of the Y chromosome in Europe is a valuable tool for revealing the genetic trace of the different European colonizations, mainly in several American countries, where the European ancestry is mostly detected by the presence of the R1b-M269 haplogroup. Therefore, the objective of this review is to compile the studies of the Y chromosome haplogroups in current European populations, in order to provide an outline of these haplogroups which facilitate their use in forensic studies.
Article
Full-text available
European farmers' first strides from the south The early spread of farmers across Europe has previously been thought to be part of a single migration event. David Reich and colleagues analyse genome-wide data from 225 individuals who lived in southeastern Europe and the surrounding regions between 12000 and 500 BC. They analyse this in combination with previous genomic datasets to characterize genetic structure and update existing models of the spread of farming into and across Europe. They find that southeastern Europe served as a contact zone between east and west, with interactions between diverged groups of hunter-gatherers starting before the arrival of farming. The authors also find evidence for male-biased admixture between hunter-gatherers and farmers in central Europe during the Middle Neolithic. Elsewhere in this issue, David Reich and colleagues report genomic insights into the Beaker culture—characterized by the use of a distinctive pottery style during the end of the Neolithic—based on genome-wide data from 400 Neolithic, Copper Age and Bronze Age Europeans, from 136 different archaeological sites, and including 226 Beaker-associated individuals.
Article
Full-text available
Genetics can provide invaluable information on the ancestry of the current inhabitants of Cyprus. A Y-chromosome analysis was performed to (i) determine paternal ancestry among the Greek Cypriot (GCy) community in the context of the Central and Eastern Mediterranean and the Near East; and (ii) identify genetic similarities and differences between Greek Cypriots (GCy) and Turkish Cypriots (TCy). Our haplotype-based analysis has revealed that GCy and TCy patrilineages derive primarily from a single gene pool and show very close genetic affinity (low genetic differentiation) to Calabrian Italian and Lebanese patrilineages. In terms of more recent (past millennium) ancestry, as indicated by Y-haplotype sharing, GCy and TCy share much more haplotypes between them than with any surrounding population (7–8% of total haplotypes shared), while TCy also share around 3% of haplotypes with mainland Turks, and to a lesser extent with North Africans. In terms of Y-haplogroup frequencies, again GCy and TCy show very similar distributions, with the predominant haplogroups in both being J2a-M410, E-M78, and G2-P287. Overall, GCy also have a similar Y-haplogroup distribution to non-Turkic Anatolian and Southwest Caucasian populations, as well as Cretan Greeks. TCy show a slight shift towards Turkish populations, due to the presence of Eastern Eurasian (some of which of possible Ottoman origin) Y-haplogroups. Overall, the Y-chromosome analysis performed, using both Y-STR haplotype and binary Y-haplogroup data puts Cypriot in the middle of a genetic continuum stretching from the Levant to Southeast Europe and reveals that despite some differences in haplotype sharing and haplogroup structure, Greek Cypriots and Turkish Cypriots share primarily a common pre-Ottoman paternal ancestry.
Article
Full-text available
The Mediterranean shores stretching between Sicily, Southern Italy and the Southern Balkans witnessed a long series of migration processes and cultural exchanges. Accordingly, present-day population diversity is composed by multiple genetic layers, which make the deciphering of different ancestral and historical contributes particularly challenging. We address this issue by genotyping 511 samples from 23 populations of Sicily, Southern Italy, Greece and Albania with the Illumina GenoChip Array, also including new samples from Albanian- and Greek-speaking ethno-linguistic minorities of Southern Italy. Our results reveal a shared Mediterranean genetic continuity, extending from Sicily to Cyprus, where Southern Italian populations appear genetically closer to Greek-speaking islands than to continental Greece. Besides a predominant Neolithic background, we identify traces of Post-Neolithic Levantine- and Caucasus-related ancestries, compatible with maritime Bronze-Age migrations. We argue that these results may have important implications in the cultural history of Europe, such as in the diffusion of some Indo-European languages. Instead, recent historical expansions from North-Eastern Europe account for the observed differentiation of present-day continental Southern Balkan groups. Patterns of IBD-sharing directly reconnect Albanian-speaking Arbereshe with a recent Balkan-source origin, while Greek-speaking communities of Southern Italy cluster with their Italian-speaking neighbours suggesting a long-term history of presence in Southern Italy.
Article
Full-text available
The Mediterranean shores stretching between Sicily, Southern Italy and the Southern Balkans witnessed a long series of migration processes and cultural exchanges. Accordingly, present-day population diversity is composed by multiple genetic layers, which make the deciphering of different ancestral and historical contributes particularly challenging. We address this issue by genotyping 511 samples from 23 populations of Sicily, Southern Italy, Greece and Albania with the Illumina GenoChip Array, also including new samples from Albanian- and Greek-speaking ethno-linguistic minorities of Southern Italy. Our results reveal a shared Mediterranean genetic continuity, extending from Sicily to Cyprus, where Southern Italian populations appear genetically closer to Greek-speaking islands than to continental Greece. Besides a predominant Neolithic background, we identify traces of Post-Neolithic Levantine- and Caucasus-related ancestries, compatible with maritime Bronze-Age migrations. We argue that these results may have important implications in the cultural history of Europe, such as in the diffusion of some Indo-European languages. Instead, recent historical expansions from North-Eastern Europe account for the observed differentiation of present-day continental Southern Balkan groups. Patterns of IBD-sharing directly reconnect Albanian-speaking Arbereshe with a recent Balkan-source origin, while Greek-speaking communities of Southern Italy cluster with their Italian-speaking neighbours suggesting a long-term history of presence in Southern Italy.
Article
Full-text available
We report genome-wide ancient DNA from 44 ancient Near Easterners ranging in time between ~12,000 and 1,400 BCE, from Natufian hunter–gatherers to Bronze Age farmers. We show that the earliest populations of the Near East derived around half their ancestry from a ‘Basal Eurasian’ lineage that had little if any Neanderthal admixture and that separated from other non-African lineages before their separation from each other. The first farmers of the southern Levant (Israel and Jordan) and Zagros Mountains (Iran) were strongly genetically differentiated, and each descended from local hunter–gatherers. By the time of the Bronze Age, these two populations and Anatolian-related farmers had mixed with each other and with the hunter–gatherers of Europe to drastically reduce genetic differentiation. The impact of the Near Eastern farmers extended beyond the Near East: farmers related to those of Anatolia spread westward into Europe; farmers related to those of the Levant spread southward into East Afri
Article
Full-text available
Background: The archeological record indicates that the permanent settlement of Cyprus began with pioneering agriculturalists circa 11,000 years before present, (ca. 11,000 y BP). Subsequent colonization events followed, some recognized regionally. Here, we assess the Y-chromosome structure of Cyprus in context to regional populations and correlate it to phases of prehistoric colonization. Results: Analysis of haplotypes from 574 samples showed that island-wide substructure was barely significant in a spatial analysis of molecular variance (SAMOVA). However, analyses of molecular variance (AMOVA) of haplogroups using 92 binary markers genotyped in 629 Cypriots revealed that the proportion of variance among the districts was irregularly distributed. Principal component analysis (PCA) revealed potential genetic associations of Greek-Cypriots with neighbor populations. Contrasting haplogroups in the PCA were used as surrogates of parental populations. Admixture analyses suggested that the majority of G2a-P15 and R1b-M269 components were contributed by Anatolia and Levant sources, respectively, while Greece Balkans supplied the majority of E-V13 and J2a-M67. Haplotype-based expansion times were at historical levels suggestive of recent demography. Conclusions: Analyses of Cypriot haplogroup data are consistent with two stages of prehistoric settlement. E-V13 and E-M34 are widespread, and PCA suggests sourcing them to the Balkans and Levant/Anatolia, respectively. The persistent pre-Greek component is represented by elements of G2-U5(xL30) haplogroups: U5*, PF3147, and L293. J2b-M205 may contribute also to the pre-Greek strata. The majority of R1b-Z2105 lineages occur in both the westernmost and easternmost districts. Distinctively, sub-haplogroup R1b- M589 occurs only in the east. The absence of R1b- M589 lineages in Crete and the Balkans and the presence in Asia Minor are compatible with Late Bronze Age influences from Anatolia rather than from Mycenaean Greeks.
Article
Full-text available
Significance The transition from a foraging subsistence strategy to a sedentary farming society is arguably the greatest innovation in human history. Some modern-day groups—specifically the Basques—have been argued to be a remnant population that connect back to the Paleolithic. We present, to our knowledge, the first genome-wide sequence data from eight individuals associated with archaeological remains from farming cultures in the El Portalón cave (Atapuerca, Spain). These individuals emerged from the same group of people as other Early European farmers, and they mixed with local hunter–gatherers on their way to Iberia. The El Portalón individuals showed the greatest genetic affinity to Basques, which suggests that Basques and their language may be linked with the spread of agriculture across Europe.
Book
Farmers made a sudden and dramatic appearance in Greece around 7000 BC, bringing with them new ceramics and crafts, and establishing settled villages. They were Europe's first farmers, and their settlements provide the link between the first agricultural communities in the Near East and the subsequent spread of the new technologies to the Balkans and on to Western Europe. In this 2001 book, Catherine Perlès argues that the stimulus for the spread of agriculture to Europe was a colonisation movement involving small groups of maritime peoples. Drawing evidence from a wide range of archaeological sources, including often neglected 'small finds', and introducing daring new perspectives on funerary rituals and the distribution of figurines, she constructs a complex and subtle picture of early Neolithic societies, overturning the traditional view that these societies were simple and self-sufficient.
Article
The dissection of S116 in more than 1500 individuals from Atlantic Europe and the Iberian Peninsula has provided important clues about the controversial evolutionary history of M269. First, the results do not point to an origin of M269 in the Franco-Cantabrian refuge, owing to the lack of sublineage diversity within M269, which supports the new theories proposing its origin in Eastern Europe. Second, S116 shows frequency peaks and spatial distribution that differ from those previously proposed, indicating an origin farther west, and it also shows a high frequency in the Atlantic coastline. Third, an outstanding frequency of the DF27 sublineage has been found in Iberia, with a restricted distribution pattern inside this peninsula and a frequency maximum in the area of the Franco-Cantabrian refuge. This entire panorama indicates an old arrival of M269 into Western Europe, because it has generated at least two episodes of expansion in the Franco-Cantabrian area. This study demonstrates the importance of continuing the dissection of the M269 lineage in different European populations because the discovery and study of new sublineages can adjust or even completely revise the theories about European peopling, as has been the case for the place of origin of M269.European Journal of Human Genetics advance online publication, 17 June 2015; doi:10.1038/ejhg.2015.114.