ArticlePDF Available

Genetic Discontinuity Between Local Hunter-Gatherers and Central Europe's First Farmers


Abstract and Figures

After the domestication of animals and crops in the Near East some 11,000 years ago, farming had reached much of central Europe by 7500 years before the present. The extent to which these early European farmers were immigrants or descendants of resident hunter-gatherers who had adopted farming has been widely debated. We compared new mitochondrial DNA (mtDNA) sequences from late European hunter-gatherer skeletons with those from early farmers and from modern Europeans. We find large genetic differences between all three groups that cannot be explained by population continuity alone. Most (82%) of the ancient hunter-gatherers share mtDNA types that are relatively rare in central Europeans today. Together, these analyses provide persuasive evidence that the first farmers were not the descendants of local hunter-gatherers but immigrated into central Europe at the onset of the Neolithic.
Content may be subject to copyright.
DOI: 10.1126/science.1176869
, 137 (2009); 326Science
et al.B. Bramanti,
Hunter-Gatherers and Central Europe’s First
Genetic Discontinuity Between Local (this information is current as of October 6, 2009 ):
The following resources related to this article are available online at
version of this article at:
including high-resolution figures, can be found in the onlineUpdated information and services,
can be found at: Supporting Online Material
found at:
can berelated to this articleA list of selected additional articles on the Science Web sites
, 2 of which can be accessed for free: cites 9 articlesThis article
: subject collectionsThis article appears in the following
in whole or in part can be found at: this article
permission to reproduce of this article or about obtaining reprintsInformation about obtaining
registered trademark of AAAS.
is aScience2009 by the American Association for the Advancement of Science; all rights reserved. The title
CopyrightAmerican Association for the Advancement of Science, 1200 New York Avenue NW, Washington, DC 20005.
(print ISSN 0036-8075; online ISSN 1095-9203) is published weekly, except the last week in December, by theScience
on October 6, 2009 www.sciencemag.orgDownloaded from
Genetic Discontinuity Between Local
Hunter-Gatherers and Central Europes
First Farmers
B. Bramanti,
* M. G. Thomas,
W. Haak,
M. Unterlaender,
P. Jores,
K. Tambets,
I. Antanaitis-Jacobs,
M. N. Haidle,
R. Jankauskas,
C.-J. Kind,
F. Lueth,
T. Terberger,
J. Hiller,
§ S. Matsumura,
P. Forster,
J. Burger
After the domestication of animals and crops in th e Near East some 11,000 years ago, farming
had reached much of central Europe by 7500 years before the present. The extent to which these early
European farmers were immigrants or descendants of resident hunter-gatherers who had adopted
farming has been widely debated. We compared new mitochondrial DNA (mtDNA) sequences from late
European hunter-gatherer skeletons with those from early farmers and from modern Europeans. We
find large genetic differences between all three groups that cannot be explained by population
that are relatively rare in central Europeans today. Together, these analyses provide persuasive evidence
that the first farmers were not the descendants of local hunter-gatherers but immigrated into central
Europe at the onset of the Neolithic.
urope has witnessed several changes in
archaeological cultures since anatomically
modern humans displaced the Neandertal
population 30,000 to 40,000 years ago (1, 2).
Palaeolithic hunter-gatherers survived the Last
Glacial Maximum (LGM) about 25,000 years
ago in southern and eastern refugia (3)andre-
settled central Europe after the retreat of the ice
sheets. Wi th the end of the Ice Age at ~9600 B.C.E.,
their Mesolithic descendants or successors had
recolonized large parts of the deglaciated north-
ern latitudes (4, 5). From around 6400 B.C.E.,
the hunter-gatherer way of life gave way to
farming cultures in a transition known as the Ne-
olithic Revolution (6). The extent to which this
important cultural transition was mediated by the
arrival of new peoples, and the degree of Meso-
lithic and early Neolithic ancestry in Europeans
today, have been debated for more than a century
(710). To address these questions directly, we
obtained mitochondrial DNA (mtDNA) types from
22 central and northern European post-LGM
hunter-gather er skeletal remains (Fig. 1) and com-
pared 20 of these (those for which full sequence
information was available) to homologous mtDNA
sequences from 25 early farmers (11, 12) and 484
modern Europeans from the same geographic re-
gion (13). Our ancient sample spans a period from
circa (ca.) 13,400 to 2300 B.C.E. and includes
bones from Hohler Fels in the Ach valley (Late
Upper Paleolithic) and Hohlenstein-Stadel in the
Lone valley (Mesolithic). Extensive precautions
were taken to ensure sequence authenticity (14),
including extracting independent samples from
different skeletal locations of the same indi-
viduals and examining remains only from high
latitudes or cave sites with good biomolecular
Institute for Anthropology, University of Mainz, Mainz,
Research Department of Genetics, Evolution and
Environment, and the Arts and Humanities Research Council
Centre for the Evolution of Cultural Diversity, University College
Department of
Evolutionary Biology, Institute of Molecular and Cell Biology,
University of Tartu and Estonian Biocentre, Tartu, Estonia.
Department of Anatomy, Histology and Anthropology,
University of Vilnius, Lithuania.
Research Center The Role
of Culture in Early Expansions of Humans of the Heidelberg
Academy of Sciences and Humanities, Senckenberg Research
Institute, Frankfurt am Main, Germany.
Stuttgart, Landesamt r Denkmalpflege, Germany.
Germanische Kommission (RG K), Frankfu rt am Ma in, Germany.
Lehrstuhl r Ur- und Frühgeschichte, University of Greifswald,
Biophysics Group, Cardiff School of Optometry and
Vision Sciences, Card iff Univer sity, Cardiff, UK.
Institute for Applied Systems Analysis, Laxenburg, Austria.
Leibniz-Institute of Freshwater Ecology and Inland Fisheries,
Berlin, Germany.
Cambridge Society for the Application of
Research, Cambridge, UK.
*To whom correspondence should be addressed. E-mail:
Present address: Australian Centre for Ancient DNA, Univer-
sity of Adelaide, Adelaide, Australia.
Present address: Institute for Zoology, University of Mainz,
Mainz, Germany.
§Present address: Diamond Light Source, Harwell Science
and Innovation Campus, Chilton, UK.
Present address: Faculty of Applied Biological Sciences,
Gifu University, Gifu, Japan.
Fig. 1. mtDNA types
from prehistoric samples
of hunter-gatherers and
farmers. The green shad-
ing represents the first
farming areas [dark
green: early LBK, 5650
to 5400 calibrated years
B.C.E. (calBC); light
green: LBK, 5400 to
4900 calBC] in central
Europe, based on archae-
ological finds, whereas
squares represent suc-
cessfully analyzed Late
Palaeolithic, Mesolithic,
and Ceramist hunter-
gatherers dating from
13,400 to 2300 B.C.E.
The term Neolithic is
sometimes applied to the
Eastern European Ceram-
ist culture because of their use of pottery, but this does not imply a farming
economy (21). Previo usly analyzed (11, 12) LBK farming sites are marked with
circles for comparison. The area of each square or circle is proportional to the
number of individuals successfully investigated. In red are labeled archaeolog-
ical sites with one or more U4/U5 individuals; in yellow, sites with other mtDNA
types, highlighting the specificity of U types in the prehistoric hunter-gatherers.
The sites are as follows: 1, Ostorf; 2, Bad Dürrenberg; 3, Falkensteiner Höhle; 4,
Hohler Fels; 5, Hohlenstein-Stadel; 6, Donkalnis; 7, Spiginas; 8, Dudka; 9,
Unterwiederstedt; 15, Derenburg/Meerenstieg; 16, Eilsleben; 17, Halberstadt;
18, Seehausen; 19, Flomborn; 20, Vaihingen an der Enz; 21, Schwetzingen;
22, Asparn/Schletz; 23, Ecsegfalva. SCIENCE VOL 326 2 OCTOBER 2009 137
on October 6, 2009 www.sciencemag.orgDownloaded from
An analysis of the molecular variance (15)
showed that our early farmers and hunter-gatherers
were from two well-differentiated populations;
the among-populations proportion of genetic
variation (F
) = 0.163, P <10
. To put this
value into perspective, we compared a range of
modern human populations, randomly sampling
20 individuals from each. The maximum F
in all comparisons among eight modern European
samples was 0.0327, and among 13 modern
European, Middle Eastern, Indian, Chinese,
Papua New Guinean, and Australian samples it
was 0.133 (14). We also found that our modern
European sample was significantly different from
the early farmer (F
= 0.0580, P =10
hunter-gatherer (F
= 0.0858, P <10
ples. To test whether these genetic differences
can be explained under the null hypothesis of
population continuity alone, we performed coales-
cent simulations across a wide range of ancestral
population size combinations. We conservatively
assumed a modern female effective population
size of N
= 12,000,000 (one-10th of the current
female population size of central and northern
Europe) and two periods of exponential growth:
the first after the Upper Paleolithic colonization
of Europe 45,000 years ago of female effective
population size N
, sampled from an ancestral
African population of constant female effectiv e size
= 5000; and the second after the Neolithic
transition in central Europe 7500 years ago of
effective population size N
. We sampled se-
quences from each simulation according to the
numbers (hunter-gatherer n = 20, early farmer
n = 25, modern n = 484) and dates (Table 1)
of the sequences presented here and found the
proportion of simulated F
values that were
greater than those observed (P
)(14). By ex-
ploring all combinations of 100 values for N
(ranging from 10 to 5000) and 100 values for
(ranging from 1000 to 100,000), we found
that the maximum P
value between hunter-
gatherers and early farmers was 0.022 (for N
4960 and N
= 1000), and the maximum P
value between hunter-gatherers and modern cen-
tral Europeans was 0.028 (for N
= 1000). Most P
values were considera-
bly lower (Fig. 2). These results allow us to reject
direct continuity between hunter-gatherers and
early farmers, and between hunter-gatherers and
modern Europeans.
When we considered continuity between early
farmers and modern Europeans, we did identify an-
cestral population size combinations where P
0.05 (black shaded area in Fig. 2C). Thus, there
are demographic conditions under which the ob-
served genetic differences between early European
farmers and modern Europeans can be explained
by assuming population continuity. Those condi-
tions include assuming N
< 3000, an effective
female population size that may be considered
implausibly low and is certainly lower than the
current archaeological census estimates of 124,000
(16). However, we note that (i) ancestral popula-
tion sizes are notoriously difficult to estimate from
archaeological data, and (ii) the relationship be-
tween effective and census population size is de-
pendent on unknown factors, including mating
systems and population substructure.
Most modern European mtDNA lineages can
be assigned to one of the following clades or
haplogroups: H, V, U (including K), J, or T, all
deriving from clade R; or I, W, or X, the de-
scendants of clade N. Although some subclades,
such as U5, are fairly specific to Europe, most are
shared with adjacent areas of Asia and North
Africa and are of uncertain antiquity in Europe.
We are therefore cautious about treating specific
clades as markers of particular past population
groups or demographic episodes (17). Nonethe-
less, it is intriguing to note that 82% of our 22
hunter-gatherer individuals carried clade U (14
U5, 2 U4, and 2 unspecified U types; T able 1). A
high incidence of U types (particularly those be-
longing to the U5 subclade) in Stone Age Euro-
peans has been inferred from modern mtDNA
(7), but the frequencies found here are surpris-
ingly high. Europeans today have moderate fre-
quencies of U5 types, ranging from about 1 to
5% along the Mediterranean coastline to 5 to 7%
in most core European areas, and rising to 10 to
20% in northeastern European Uralic speakers,
with a maximum of over 40% in the Scandinavian
Saami. U4 types show frequencies between 1 and
5% in most parts of Europe, with Western Europe
at the lower end of this range and northeastern
Europe and central Asia showing percentages in
excess of 7% (13).
The diversity among the hunter-gatherer U
types presented here, together with their contin-
ued presence over 11 millennia, and the fact that
U5 is rare outside Europe, raises the possibility
that U types were common by the time of the
post-LGM repopulation of central Europe, which
started around 23,000 years ago (3). In a previous
study, we showed that the early farmers of central
Europe carried mainly N1a, but also H, HV, J, K,
1000 23000 45000 67000 89000
10 1110 2210 3310 4410
at onset of LBK 7,500 BP
at colonization of Europe 45,000 BP
1000 23000 45000 67000 89000
10 1110 2210 3310 4410
at onset of LBK 7,500 BP
at colonization of Europe 45,000 BP
1000 23000 45000 67000 89000
10 1110 2210 3310 4410
at onset of LBK 7,500 BP
at colonization of Europe 45,000 BP
Probability of obtaining
value greater
than that observed
Fig. 2. Probabilities of obtaining observed genetic differences, as measured by F
gatherers and LBK early farmers, (B) hunter-gatherers and modern Europeans, and (C) LBK early farmers
and modern Europeans, across a range of assumed ancestral populatio n size combinations. Two phases of
exponential growth were considered, the first after the initial colonization of Europe 45,000 years ago, of
assumed effective female population size N
(y axis), and ending when farming began in central Europe
7500 years ago, when the assumed effective female population size was N
(x axis); and the second
leading up to the present, when the assumed effective female population size is 12 million. The initial
colonizers of Europe were sampled from a constant ancestral African population of 5000 effective
females. The F
values are those observed from the data presented in this study. Black shaded areas
indicate probabilities >0.05.
on October 6, 2009 www.sciencemag.orgDownloaded from
T, V, and U3 types (11, 12). We found no U5 or
U4 types in that early farmer sample. Conversely ,
no N1a or H types were observed in our hunter-
gatherer sample, confirming the genetic distinc-
tiveness of these two ancient population samples.
This is particularly surprising as there is clear
evidence for some continuity in the material cul-
ture between the central European Mesolithic
and the earliest settlements of the Neolithic
Linearbandkeramik culture (LBK) (18). Thus, it
seems that despite the exchange of stone artifacts,
genetic exchange between both groups, at least
on the female side, was initially limited. The only
exception is the site Ostorf (northern Germany),
where two individuals carried haplogroup T2,
which is also found in our LBK sample. We are
cautious about interpreting this as a signature of
local admixture (17), particularly because the
hunter-gatherer and early farmer T2 types belong
to different sublineages, but it is notable that
Ostorf is culturally a Mesolithic enclave sur-
rounded by Neolithic funnel-beaker farmers and
is the only hunter-gatherer site where any non-U
mtDNA types were observed (Table 1). Further
sampling from such local contexts should shed
light on the details of Mesolithic-Neolithic inter-
actions after the arrival of farming. We note that
any genetic exchange between hunter-gatherers
and early farmers at this site would reduce the
overall genetic differentiation between the two
groups, so inclusion of this site has, if anything, a
conservative effect on our conclusions regarding
Taken together, our results indicate that the
transition to farming in central Europe was ac-
companied by a substantial influx of people from
outside the region who, at least initially, did not
mix significantly with the resident female hunter-
gatherers. We accept that alternative, more com-
plex demographic scenarios, such as strong local
population structure and high group extinction
and fission rates, might also explain our data.
However , the ubiquity of U types in our hunter-
gatherer samples is inconsistent with extensive
population structuring and indicates that the de-
mographic processes that shaped the observed
patterns of genetic variation extend beyond the
local scale.
The extent to which modern Europeans are
descended from incoming farmers, their hunter-
gatherer forerunners, or later incoming groups re-
mains unresolved. The predominant mtDNA types
found in the ancient samples considered in this
study are found in modern Europeans, but at con-
siderably lower frequencies, suggesting that the
diversity observed today cannot be explained by
admixture between hunter-gatherers and early
Table 1. Stone Age individuals and their mtDNA results. A, DNA of the
archaeologists available for comparison; D, diagenetical analysis; M, multiple
extractions and number of these; C, clones of the hypervariable segment 1 and
number of these; N, positive amplification of nuclear DNA; Rf, restriction
fragment length polymorphism analysis; SNP, single-nucleotide polymorph-
isms from the coding region of mtDNA obtained by means of multiplex
amplification; BP, before the present; ca., circa. The mtDNA was sequenced
from nucleotide position (np) 15997 to np 16409. mtDNA positions are num-
bered according to the revised Cambridge reference sequence (22), minus
16,000. Fourteen individuals did not yield results (table S1), whereas for two
individuals the mtDNA sequences were not determined (n.d.) and thus not
considered in the AMOVA analysis and simulations.
Country Site, skeleton Basis of dating* Dating calBC* Analyses mtDNA sequence Clade
Lithuania Spiginas 4 GIN-5571: 7470 T 60 BP ca. 6350 calBC A, M3, C109, Q, Rf 356c U4
Donkalnis 1 Cultural context Mesolithic A, D, M4, C79, N, Rf, SNP 192t 270t U5b2
Kretuonas 3 OxA-5926: 5580 T 65 BP ca. 4450 calBC A, M4, C72, N, Rf, SNP 192t 270t U5b2
Kretuonas 1 OxA-5935: 5350 T 130 BP ca. 4200 calBC A, M5, C56, N, Rf, SNP 192t 270t U5b2
Poland Dudka 2
C date on charcoal ca. 3650 calBC A, M3, C80, N, Rf 189c 270t U5b1
Dudka 3 Cultural context 4000-3000 calBC A, M3, C127, Q, Rf 189c 265 g 270t U5b1
Drestwo 2 Ua-13085: 3805 T 70 BP ca. 2250 calBC D, M4, C102, N, Rf 192t 256t 270t U5a
Russia Chekalino IVa
C date on shell
Chekalino IVb
ca. 7800 calBC A, D, M2, C83, Rf 192t 256t 270t 294t U5a
Lebyazhinka IV
C date on shell and
cultural context
80007000 calBC A, D, M2, C60, Rf 192t 241a/c
256t 270t 399 g
Germany Bad Dürrenberg 2 OxA-3136: 7930 T90 BP ca. 6850 calBC A, D, M2, C 119, Rf 356c U4
Stadel, 5830a
7835 T 80 BP
ca. 6700 calBC M1, SNP 114a 192t
256t 294t 311c
Stadel, 5830b
7835 T 80 BP
ca. 6700 calBC M1, SNP 192t 270t U5b2
Hohler Fels,
49 Ib1 66
C dates on bone
(H 5312-4907: 12,770 T
110 BP; H 5119-4601:
13,085 T 95 BP) and
cultural context
ca. 13,400 calBC
Germany Hohler Fels,
10 Ic 405
C dates on bone
(H 5312-4907: 12,770 T
110 BP; H 5119-4601:
13,085 T 95 BP) and
cultural context
ca. 13,400 calBC
M2, SNP n.d. U
Höhle, FH
8185 T 80 BP
ca. 7200 calBC M2, SNP n.d. U5b2
Ostorf SK28a
C dates and context ca. 3200 calBC A, M2, C18 224c 311c K
Ostorf SK8d
C dates and context ca. 3200 calBC A, M2, C16 270t U5
Ostorf SK35
C dates and context ca. 3100 calBC A, M2 270t U5
Ostorf SK12a
C dates and context ca. 3000 calBC A, M2 093y 126c 153a 294t T2e
Ostorf SK45a
C dates and context ca. 3000 calBC A, M2, C16 069t 126c J
Ostorf SK18
C dates and context ca. 3000 calBC A, M4 093c 126c 153a 294t T2e
Ostorf SK19
C dates and context ca. 2950 calBC A, M3 168t 192t 256t 270t 302 g U5a
*Radiocarbon dates with laboratory numbers refer to direct dates of the skeleton and were calibrated with the program CalPal (23) on the basis of Intcal04. Corrections of reservoir effects were
applied where identified. SCIENCE VOL 326 2 OCTOBER 2009 139
on October 6, 2009 www.sciencemag.orgDownloaded from
farmers alone. If this is the case, then subsequent
dilution through migration and admixture, after
the arrival of the first farmers, would need to be
invoked, implying multiple episodes of popula-
tion turnover , which are not necessarily observ-
able in the archaeological record. This, in turn,
would mean that the classic model of European
ancestry components (contrasting hunter-gatherers
with early Neolithic farming pioneers) requires
The geographic origin of the demographic
processes that brought the early farmer mtDNA
types to central Europe now becomes a major
question. On the one hand, all of the early farmer
remains analyzed here are associated with the
LBK culture of central Europe. Based on ceramic
typology , the LBK culture is thought to have orig-
inated in present-day western Hungary and south-
western Slovakia, with a possible predecessor in the
southeast European Starçevo-Kris culture (19, 20).
These cultural source locations may provide the
most plausible origins or routes for the geographic
spread of the early farmers, considering that the
LBK was the first major farming culture in central
and northern Europe and is archaeologically
attested to have disseminated over five centuries
an d cove r e d nearly a million square kilometers.
Alternatively, the farmers mtDNA types may
have an origin closer to the Neolithic core zone in
southwestern Asia. Further ancient DNA analysis
of earl y farm e r samples from southeastern Europe
and Anatolia will be required to resolve this
References and Notes
1. P. Mellars, Nature 432, 461 (2004).
2. K. Harvati, in Handbook of Paleoanthropology,W.Henke,
I. Tattersall, Eds. (Springer, Berlin, 2007), vol. 3,
pp. 17171748.
3. T. Terberger, M. Street, Antiquity 76, 691 (2002).
4. B. V. Eriksen, in Recent Studies in the Final Palaeolithic
of the European Plain, B. V. Eriksen, B. Bratlund, Eds.
(Jutland Archaeological Society, Højbjerg, Denmark,
2002), pp. 2542.
5. G. Eberhards, I. Zagorska, in Recent Studies in the Final
Palaeolithic of the European Plain, B. V. Eriksen,
B. Bratlund, Eds. (Jutland Archaeological Society, Højbjerg,
Denmark, 2002), pp. 8590.
6. V. G. Childe, The Dawn of European Civilization (Kegan
Paul, London, 1925).
7. M. Richards et al., Am. J. Hum. Genet. 67, 1251 (2000).
8. A. Achilli et al., Am. J. Hum. Genet. 75, 910 (2004).
9. M. Currat, L. Excoffier, Proc. Biol. Sci. 272, 679 (2005).
10. G. de Mortillet, La Formation de la Nation Française.
(F. Alcan, Paris, 1897)
11. W. Haak et al., Science 310, 1016 (2005).
12. W. Haak, thesis, Mainz University, Mainz, Germany (2006).
13. A. Roehl, B. Brinkmann, L. Forster, P. Forster, Int. J.
Legal Med. 115, 29 (2001).
14. Information on materials and methods is available as
supporting material on Science Online.
15. S. Schneider, D. Roessli, L. Excoffier, Arlequin: A software
for population genetics data analysis. Ver 2.000 (Genetics
and Biometry Lab, Department of Anthropology, University
of Geneva, Geneva, Switzerland, 2000).
16. A. Zimmermann, J. Richter, J, Th. Frank, P. Wendt, Ber.
Rom.-Ger.Komm. 85, 37 (2004).
17. R. Nielsen, M. A. Beaumont, Mol. Ecol. 18, 1034 (2009).
18. D. Gronenborn, Silexartefakte der A
Kultur (Universitätsforschungen zur prähistorischen
Archäologie 37, Habelt, Bonn, Germany, 1997).
19. J. Pavuk, in Die Bandkeramik im 21. Jahrhundert:
Symposium in der Abtei Brauweiler bei Ko
ln 2002,
J. ning, C. Frirdich, A. Zimmermann Eds. (VML Vlg
Marie Leidorf, Rahden/Westfahlen, Germany, 2005),
pp 1739.
20. I. Mateici ucová, Arch. Inf. 26, 299 (2003).
21. M. Zvelebil, in Harvesting the Sea, Farming the Forest.
The Emergence of Neolithic Societies in the Baltic Region,
M. Zvelebil, L. Domanska, R. Dennell, Eds. (Sheffield
Academic Press, Sheffield, UK, 1998), pp. 927.
22. R. M. Andrews et al., Nat. Genet. 23, 147 (1999).
23. U. Danzeglocke, O. ris, B. Weninger, CalPal Online
(2007) (
24. The authors are grateful to W. Guminski (Institute of
Archeology and Ethnology, Polish Academy of Sciences,
Warsaw, Poland), J. Siemaszko (Suwalki Province
Museum, Suwalki, Poland), A. Khokhlov (Institute of Cell
Biophysics, Russian Academy of Sciences, Pushchino,
Moscow oblast, Russia), H. Meller and M. Porr (Landesamt
r Archäologie Sachsen-Anhalt, Halle/Saale, Germany),
and L. P. Louwe Kooijmans and L. Smits (Faculty of
Archeology, Leiden University, Leiden, Netherlands) for
providing them with the archaeological samples. The
authors are indebted to R. Villems, A. Zimmermann,
and J. ning for comments and to D. Kasperaviciute
for Lithuanian sequences. We also thank M. Forster
for editorial comments. Research grants were
provided by the Bundesministerium r Bildung
und Forschung, the Deutsche Forschungsgemeinschaft,
and the Estonian Science Foundation (grant no.
6040 to K.T).
Supporting Online Material
Materials and Methods
Fig. S1
Tables S1 to S6
27 May 2009; accepted 21 August 2009
Published online 3 September 2009;
Include this information when citing this paper.
Ribosomal Protein S6 Kinase 1 Signaling
Regulates Mammalian Life Span
Colin Selman,
* Jennifer M. A. Tullet,
Daniela Wieser,
Elaine Irvine,
Steven J. Lingard,
Agharul I. Choudhury,
Marc Claret,
Hind Al-Qassab,
Danielle Carmignac,
Faruk Ramadani,
Angela Woods,
Iain C. A. Robinson,
Eugene Schuster,
Rachel L. Batterham,
Sara C. Kozma,
George Thomas,
David Carling,
Klaus Okkenhaug,
Janet M. Thornton,
Linda Partridge,
David Gems,
Dominic J. Withers
Caloric restriction (CR) protects against aging and disease, but the mechanisms by which this
affects mammalian life span are unclear. We show in mice that deletion of ribosomal S6 protein
kinase 1 (S6K1), a component of the nutrient-responsive mTOR (mammalian target of rapamycin)
signaling pathway, led to increased life span and resistance to age-related pathologies, such as
bone, immune, and motor dysfunction and loss of insulin sensitivity. Deletion of S6K1 induced
gene expression patterns similar to those seen in CR or with pharmacological activation of
adenosine monophosphate (AMP)activated protein kinase (AMPK), a conserved regulator of the
metabolic response to CR. Our results demonstrate that S6K1 influences healthy mammalian life
span and suggest that therapeutic manipulation of S6K1 and AMPK might mimic CR and could
provide broad protection against diseases of aging.
enetic studies in Saccharomyces cerevi-
siae, Caenorh abditis elegans,andDr o-
sophila melanogaster implicate several
mechanisms in the regulation of life span. These
include the insulin and insulin-like growth factor
1 (IGF-1) signaling (IIS) pathway and the mam-
malian target of rapamycin (mTOR) pathway ,
which both activate the downstream effector
ribosomal protein S6 kinase 1 (S6K1) (1, 2).
Although the role of these pathways in mammalian
aging is less clear, there is mounting evidence that
IIS regulates life span in mice (1). Global deletion
of one allele of the IGF-1 receptor (Igf1r), adipose-
specific deletion of the insulin receptor (Insr),
global deletion of insulin receptor substrate protein
1(Irs1), or neuron-specific deletion of Irs2,all
increasemouselifespan(1). Life-spanextending
mutations in the somatotropic axis also appear to
work through attenuated IIS (3). Igf1r has also been
implicated as a modulator of human longevity (4).
However , the action of downstream effectors of IIS
or mTOR signaling in mammalian longevity is not
fully understood.
S6K1 transduces anabolic signals that indi-
cate nutritional status to regulate cell size and
Institute of Healthy Ageing, Centre for Diabetes and
Endocrinology, Department of Medicine, University College
London, London WC1E 6JJ, UK.
Institute of Healthy Ageing,
Department of Genetics, Evolution and Environment, University
College London, London WC1E 6BT, UK.
European Bioinfor-
matics Institute, Wellcome Trust Genome Campus, Hinxton,
Cambridge CB10 1SD, UK.
Division of Molecular Neuroendo-
crinology, Medical Research Council National Institute for
Medical Research, London NW7 1AA, UK.
Laboratory of
Lymphocyte Signalling and Development, The Babraham
Institute, Cambridge CB22 3AT, UK.
Cellular Stress Group,
Medical Research Council Clinical Sciences Centre, Imperial
College, London W12 0NN, UK.
Department of Cancer and
Cell Biology, Genome Research Institute, University of
Cincinnati, Cincinnati, OH 45237, USA.
Metabolic Signaling
Group, Medical Research Council Clinical Sciences Centre,
Imperial College, London W12 0NN, UK.
*Present address: Institute of Biological and Environmental
Sciences, University of Aberdeen, Aberdeen AB24 2TZ, UK.
To whom correspondence should be addressed. E-mail: or
2 OCTOBER 2009 VOL 326 SCIENCE www.sciencemag.org140
on October 6, 2009 www.sciencemag.orgDownloaded from

Supplementary resources (20)

... Cavalli-Sforza cautioned that this conclusion was not justified [46]. He was shown to be right four years later, when DNA of European hunter-gatherers became available and it turned out that they were extremely different genetically from present Europeans, ruling out the possibility that the latter descend mainly from hunter-gatherers [47]. The implication for N1a was that its frequency decreased during the elapsed millennia until today. ...
... The implication for N1a was that its frequency decreased during the elapsed millennia until today. It was also noted that most hunter-gathers displayed U5 or U4 haplogroups (i.e., groups of alleles sharing one or more ancestral mutations), which were absent in early farmers, so the latter must have definitely come from other regions (demic diffusion) [47]. In this way, the importance of demic diffusion in the spread of the Neolithic across most of Europe finally became overwhelmingly accepted in the archaeological and genetics communities. ...
... In the model by Ackland et al. the cultural boundary forms even in homogeneous space [87], so its location is not due only to non-homogeneities such as the presence or absence of loess. According to Figure 2E by Ackland et al. [114] farming in all of Germany, Denmark, Italy, France and Spain would have been introduced by hunter-gatherers converted into farming and their descendants, which is opposite to the genetic replacement that has been observed using ancient genetic data in all of these regions [47,[117][118][119][120] (although it is possible that in some specific locations, a substantial portion of hunter-gatherers transformed into farmers). ...
Full-text available
The seminal book The Neolithic transition and the genetics of populations in Europe by Ammerman and Cavalli-Sforza (1984) contains the analysis of archaeological data that led to the result that the spread rate of the Neolithic in Europe was on average about 1 km/yr. It also contains the direct application of a mathematical model that provides an explanation for this value (1 km/yr), the so-called 'wave-of-advance model'. The book also reviews work on the possibility that genetic clines were formed due to the spread of the Neolithic in Europe. This paper is a review of work on both topics since their first joint paper, which was published 50 years ago (Ammerman and Cavalli-Sforza 1971). We also discuss the importance of these and related contributions by Cavalli-Sforza, the present state of the art, and possible lines of future progress. Based on "Ammerman AJ, Cavalli-Sforza LL. The Neolithic transition and the genetics of populations in Europe. New Jersey: Princeton University Press. 1984”.
... Χρησιμοποιώντας δεδομένα αρχαίου DNA ήδη γνωρίζουμε ότι υπήρξε εν μέρει γενετική ασυνέχεια μεταξύ των τοπικών κυνηγών-τροφοσυλλεκτών και των πρώτων γεωργών της κεντρικής Ευρώπης (Bramanti et al., 2009), καθώς και γενετική συγγένεια ανάμεσα στους γεωργούς της κεντρικής Ευρώπης -συγκεκριμένα των ομάδων με πολιτισμικά στοιχεία γραμμικής ταινιωτής κεραμικής (Linearbandkeramik-LBK)-και τους σύγχρονους πληθυσμούς της δυτικής Ευρασίας (Haak et al., 2010). Επιπλέον, διαπιστώθηκε γενετική ασυνέχεια μεταξύ των κυνηγών-τροφοσυλλεκτών και των πρώτων γεωργών της Σκανδιναβίας και μεγαλύτερη γενετική ομοιότητα των γεωργών με σύγχρονους ευρωπαϊκούς πληθυσμούς της Μεσογείου. ...
Full-text available
Το σύγγραμμα έχει ως στόχο να καλύψει ένα πραγματικό κενό στην ελληνική ακαδημαϊκή βιβλιογραφία σχετικά με την έρευνα και τη σημασία της μελέτης των σκελετικών καταλοίπων στην ανθρώπινη εξέλιξη, ποικιλομορφία και πολιτισμό. Βασισμένο σε μια ενημερωμένη βιβλιογραφία και σε πρωτότυπο φωτογραφικό υλικό, απευθύνεται σε φοιτητές φυσικής και δικαστικής ανθρωπολογίας και βιοαρχαιολογίας. Το βιβλίο αποτελείται από 12 κεφάλαια και χωρίζεται σε 4 θεματικές ενότητες. Η πρώτη ενότητα αφορά τη βασική μακροσκοπική μελέτη των σκελετικών καταλοίπων (κεφάλαια 1-3). Γίνεται αναφορά στους βασικούς όρους ανατομικής και ιστολογίας του ανθρώπινου σκελετού και δίνεται έμφαση στην αναγνώριση κατεστραμμένων και κατακερματισμένων οστών. Παρουσιάζονται κλασικές, αλλά και νεότερες μέθοδοι προσδιορισμού φύλου, ηλικίας και αναστήματος, το θεωρητικό υπόβαθρο κάτω από το οποίο αναπτύχθηκαν, καθώς και μια κριτική αξιολόγηση αυτών. Η δεύτερη ενότητα περιλαμβάνει θέματα παλαιοπαθολογίας και παλαιοδιατροφής. Γίνεται μια αναλυτική περιγραφή των συχνότερων παθολογιών που παρατηρούνται στα ανθρώπινα οστά και δόντια, ενώ αναφέρονται όλες οι μικροσκοπικές, μακροσκοπικές, ακτινολογικές και βιοχημικές μεθόδοι που χρησιμοποιούνται στη διάγνωση και στην περιγραφή των ασθενειών, καθώς και στην ανασύσταση της παλαιοδιατροφής (κεφάλαια 4-6). Η τρίτη ενότητα αναφέρεται στις μεταναστεύσεις και στη βιολογική ιστορία των προϊστορικών πληθυσμιακών ομάδων και παρουσιάζονται οι οστεομετρικές και οι ανατομικές μέθοδοι που χρησιμοποιούνται για τη διερεύνηση αυτών των ερωτημάτων. Γίνεται, επίσης, εκτεταμένη αναφορά στο αρχαίο DNA και στην παλαιογενετική, στις προοπτικές και στους περιορισμούς της νέας μεθόδου, καθώς και στις σύγχρονες τεχνικές που χρησιμοποιούνται (κεφάλαια 7-8). Στην τέταρτη ενότητα, παρουσιάζονται ειδικά θέματα ταφονομίας, όπως αποτυπώνονται στην αρχαιολογία και τη δικαστική ανθρωπολογία και αφιερώνεται ένα κεφάλαιο στην ανάλυση και μελέτη μουμιοποιημένων καταλοίπων. Η ίδια ενότητα περιλαμβάνει τεχνικές πεδίου, δημιουργία βάσεων δεδομένων και βασικές αρχές στατιστικής για την ανάλυση οστεολογικών δεδομένων. Στο τελευταίο κεφάλαιο, γίνεται αναφορά στο θεσμικό πλαίσιο και σε θέματα βιοηθικής που ανακύπτουν από τη μελέτη των ανθρώπινων καταλοίπων (κεφάλαια 9-12). Το σύγγραμμα στοχεύει στον συνδυασμό πρακτικών γνώσεων για την αναγνώριση και τη μελέτη ανθρώπινων σκελετικών καταλοίπων, αλλά και στην παρουσίαση θέσεων, απόψεων και ερευνητκών παραδειγμάτων, μέσα από την παράθεση της σημαντικότερης διεθνούς βιβλιογραφίας.
... The observed subclusters U5a1 indicate the possibility that they were involved in the settlement of the region of northeastern Bosnia, probably at the end of LGM. Although other characterizing haplogroups of the hunther -gather (U4, U1 and U8) (Bramanti et al., 2009) are less frequent, however, they may indicate influence of expansions from different periods of the Late Glacial and LGM post recolonization, in the area of northeastern Bosnia, especially the Konjuh region. The Middle Upper Paleolithic haplogroups, U4 and U1 (Richards et al., 1998; were detected only in the Konjuh population with a low frequency (2.94%). ...
Full-text available
This study is the first report on the mtDNA profile of human settlements of the Konjuh and Majevica mountains of northeastern Bosnia. The aims of this study were: a) determination of mitochondrial genetic structure of populations of the Konjuh and Majevica mountains of northeastern Bosnia; b) detection of trace of ancient of mtDNA variations; and c) assessment of genetic relations with other Bosnian and Herzegovina populations and neighboring populations from the Balkan region. The genetic structure of populations of Konjuh and Majevica is shaped by western Eurasian maternal signals, which may trace their ancestry to the Paleolithic, pre-Neolithic and Neolithic. Especially interesting is the feature of the Neolithic expansion in this area. This applies especially to the presence of the pre-Neolithic lineages HV*and N1a in northeastern Bosnia, which can indicate an early settlement of this region of Bosnia by pre-Neolithic populations from the Middle East. This region abounds with resources of salt sites, which might suggest in favor of the thesis that the early-Neolithic colonists needed a safe source of salts so as to settle in the Balkan area. The populations of mountains of northeastern Bosnia indicate elements of the local population history, but they do not show strict genetic closure in relation to the neighboring populations of the Balkans. This may be a consequence of the population size, degree of geographic isolation and events of migration.
... Keywords: Neolithic, Linearbandkeramik (LBK), expansion, colonisation, agent-based-model L'expansion de l'économie agro-pastorale en Europe tempérée, entre 5550 et 4950 avant JC, a fait l'objet de nombreuses interprétations (Divišová 2012) qui ne seront qu'évoquées ici. Depuis l'interprétation migrationniste (Childe 1929 ; jusqu'à celle de son exact opposé, indigéniste (Hodder 1990 ;, en passant par tout le spectre de leurs combinaisons (Whittle 2008 ;Zvelebil 2009), ces hypothèses, fondées sur l'analyse toujours partielle des traces de la culture à Céramique Linéaire (LBK) et des groupes chasseurs-collecteurs contemporains, doivent maintenant aussi prendre en compte les résultats des recherches bio-archéologiques (Bentley et al. 2012 ;Price et al. 2002) et paléogénétiques (Bramanti et al. 2009 ;Haak et al. 2010 ;Szécsényi-Nagy et al. 2015). Ces dernières réensemencent l'hypothèse du déplacement des hommes de manière directe quoiqu'encore partielle. ...
Obwohl seit rund 80 Jahren mittelsteinzeitliches Fundgut aus der Niederlausitz veröffentlicht wird, blieb doch eine zusammenfassende Betrachtung aus. Die aktuelle Untersuchung gliedert erstmals nicht nur das veröffentlichte Fundmaterial, sondern liefert einen Überblick beginnend im frühen Präboreal ab ca. 9600 cal. ВС sowie einen Vergleich mit den Nachbarregionen. Eine kontinuierliche Nutzung des Landschaftsraums über mehr als fünf Jahrtausende wird aufgezeigt, wonach das Mesolithikum erst mit dem Beginn der Trichterbecher-Kultur um ca. 4000 cal. ВС endete. Die wenigen frühneolithischen Funde werden genannt und erweisen sich als nicht ausreichend für den Nachweis von Siedlungen und einer primären Wirtschaftweise auf der Basis von Ackerbau und Viehzucht. Für die Niederlausitz wird die bäuerliche Lebensweise erst ab dem späten Neolithikum beleg- und rekonstruierbar.
Compared to traditional population genetic datasets, composed of a single time point, ancient deoxyribonucleic acid (aDNA) enables the direct assessment of genetic diversity in different time transects and allows for the recovery of lost genetic lineages. This chapter discusses the techniques used to obtain aDNA from archaeological material, the analytical methods used in paleogenomics, and the applications of aDNA data in biological anthropology. Ancient DNA molecules can be obtained from organic remains such as teeth, bones, soft tissues like skin, and coprolites. DNA can also be obtained from objects used by humans or from the soil. The two most common aDNA sources are teeth and bones, in particular the petrous portion of the temporal bone. Early paleogenomics studies revealed that part of the genetic ancestry of human populations from the past was not seen in present‐day people.
Rather than presenting a detailed account on the origins and main migrations of humankind, this chapter provides a critical overview of the role of ancient DNA (aDNA) in deciphering such human population movements, paying special attention to how the results have been integrated within archaeology. It focuses on how the technical innovations in the aDNA field have propelled the knowledge on human population movement. The chapter discusses the main population movements that have shaped the genetic background of modern Europeans and how these new results have been assimilated in the field of archaeology. Recent technical advances in the field of aDNA have dramatically changed the way scientists in the field currently approach the study of human variability. Before embarking in the discussion of how aDNA can be used to trace human migration, it is important to address the concepts of population and migration , and how they are understood by human population geneticists and archaeologists.
Full-text available
We present a complete ancient human genome and oral microbiome sequenced from a piece of resinous "chewing gum" recovered from a Stone Age site on the island of Lolland, Denmark, and directly dated to 5,8585,661 cal. BP (GrM13305; 5,007±11). We sequenced the genome to an average depthofcoverage of 2.3× and find that the individual who chewed the resin was female and genetically more closely related to western huntergatherers from mainland Europe, than huntergatherers from central Scandinavia. We use imputed genotypes to predict physical characteristics and find that she had dark skin and hair, and blue eyes. Lastly, we also recovered microbial DNA that is characteristic of an oral microbiome and faunal reads that likely associate with diet. The results highlight the potential for this type of sample material as a new source of ancient human and microbial DNA.
Background: Mitochondrial DNA haplogroup J is the third most frequent haplogroup in modern-day Scandinavia, although it did not originate there. To infer the genetic history of haplogroup J in Scandinavia, we examined worldwide mitogenome sequences using a maximum-likelihood phylogenetic approach. Methods: Haplogroup J mitogenome sequences were gathered from GenBank (n = 2245) and aligned against the ancestral Reconstructed Sapiens Reference Sequence. We also analyzed haplogroup J Viking Age sequences from the European Nucleotide Archive (n = 54). Genetic distances were estimated from these data and projected onto a maximum likelihood rooted phylogenetic tree to analyze clustering and branching dates. Results: Haplogroup J originated approximately 42.6 kya (95% CI: 30.0-64.7), with several of its earliest branches being found within the Arabian Peninsula and Northern Africa. J1b was found most frequently in the Near East and Arabian Peninsula, while J1c occurred most frequently in Europe. Based on phylogenetic dating, subhaplogroup J1c has its early roots in the Mediterranean and Western Balkans. Otherwise, the majority of the branches found in Scandinavia are younger than those seen elsewhere, indicating that haplogroup J dispersed relatively recently into Northern Europe, most plausibly with Neolithic farmers. Conclusions: Haplogroup J appeared when Scandinavia was transitioning to agriculture over 6 kya, with J1c being the most common lineage there today. Changes in the distribution of haplogroup J mtDNAs were likely driven by the expansion of farming from West Asia into Southern Europe, followed by a later expansion into Scandinavia, with other J subhaplogroups appearing among Scandinavian groups as early as the Viking Age.
Technical Report
This is the first book to present a comprehensive, up to date overview of archaeological and environmental data from the eastern Mediterranean world around 6000 BC. It brings together the research of an international team of scholars who have excavated at key Neolithic and Chalcolithic sites in Syria, Anatolia, Greece, and the Balkans. Collectively, their essays conceptualize and enable a deeper understanding of times of transition and changes in the archaeological record. Overcoming the terminological and chronological differences between the Near East and Europe, the volume expands from studies of individual societies into regional views and diachronic analyses. It enables researchers to compare archaeological data and analysis from across the region, and offers a new understanding of the importance of this archaeological story to broader, high-impact questions pertinent to climate and culture change.
Full-text available
Founder analysis is a method for analysis of nonrecombining DNA sequence data, with the aim of identification and dating of migrations into new territory. The method picks out founder sequence types in potential source populations and dates lineage clusters deriving from them in the settlement zone of interest. Here, using mtDNA, we apply the approach to the colonization of Europe, to estimate the proportion of modern lineages whose ancestors arrived during each major phase of settlement. To estimate the Palaeolithic and Neolithic contributions to European mtDNA diversity more accurately than was previously achievable, we have now extended the Near Eastern, European, and northern-Caucasus databases to 1,234, 2, 804, and 208 samples, respectively. Both back-migration into the source population and recurrent mutation in the source and derived populations represent major obstacles to this approach. We have developed phylogenetic criteria to take account of both these factors, and we suggest a way to account for multiple dispersals of common sequence types. We conclude that (i) there has been substantial back-migration into the Near East, (ii) the majority of extant mtDNA lineages entered Europe in several waves during the Upper Palaeolithic, (iii) there was a founder effect or bottleneck associated with the Last Glacial Maximum, 20,000 years ago, from which derives the largest fraction of surviving lineages, and (iv) the immigrant Neolithic component is likely to comprise less than one-quarter of the mtDNA pool of modern Europeans.
Full-text available
We believe that the radiocarbon-dated archaeological record for western central Europe in the period 23, 000-14,000 BP demonstrates neither an extended hiatus in settlement nor continuous occupation. Humans showed great flexibility in their reactions to the extreme climatic fluctuations of the last glacial period and hunter-gatherer groups appear to have occupied (or at least traversed or exploited) regions deserted during the LGM as soon as improved conditions (e.g. Greenland Interstadial 2/Laugerie Interstadial) allowed (FIGURE 1). As a result, the period around and following the LGM was characterized not only by the generally accepted cultural isolation of eastern and western Europe, but also by phases of contact between them, across central Europe north of the Alps (Terberger 2001). These would inevitably lead to exchanges and influencing of material culture and technology. At an earlier period, now documented by this paper, the direction of this influence on lithic technology appears to be from east to west, leading to the development of 'rudimentary' flake-dominated industries, while during the much better documented Late Glacial 'recolonization' (cf. Housley et al. 1997) the direction of influence (Upper Magdalenian expansion) is clearly from the west to the east.
Full-text available
This article concerns the development of a model hierarchy that connects archaeological knowledge across differing levels of scale. These connections lead to generalized measures such as population density, which can be utilized for historical interpretation. When dealing with hunter-gatherer societies, because of their mobile way of living, one must reckon with larger areas of activity and therefore conduct evaluation on another scale as when dealing with sedentary societies. Among the latter, the magnitude of the usable land is dependent on the population density and so, too, the estimate of the ratio of wooded to open land and the quantity of exchanged goods. On a small scale, in well-investigated key areas (20 km2 to some 100 km2), houses as well as graves are counted and set in relation to the available area. On distribution maps of a medium order of magnitude, the site densities (isolines) can be compared. In this way, one can ascertain the spatial dimensions of areas in which intensive use can be assumed. The ratios determined from the key areas should be transferred to these areas in order to arrive at regionally differentiated estimates of population density. Preliminary results for the Bandkeramik are presented. In the key areas, one house per km2 is estimated. If one calculates six persons per household for the map section of the “Historischer Atlas der Rheinlande” with an approximate area of 32 000 km2, one arrives at a population density of 0,44 residents per / km2. The goal is to develop such estimates for additional time periods. This is only possible for the better-known pre- and early-historic periods: in other phases, these must be interpolated with the help of pollen analytic studies. For example, it is already possible to state that, in this section of the map the area of land used for the construction of settlements is larger by a factor of 6.6 in the Metal Ages than in the Bandkeramik. On a larger scale, an attempt is being made to calculate the estimated number of households existing contemporaneously during the Bandkeramik in Germany on the basis of the map “Das Neolithikum in Mitteleuropa” (Preuss [Ed.] 1998). In this way, certain consequences for cultural-historical development, but also, for example, for the extent of the flow of goods, can be made clear. At this time, for sections of the Metal Ages and the Roman Period, ideas concerning the scale transformation of key areas can already be cross-referenced to maps at a medium level, as seen in figures 11 and 12. However, the main interest of this article lies in the realm of methodology. For each of the superimposed scale-pairs in figure 1, a transformation module for scaling upwards is proposed. These transformation-steps may well be methodologically improved in future; given another source-situation, it is likely that different means to a solution will become apparent. However, the present study shows that it is fundamentally possible, with a convincing chain argument, to connect all scale levels to one another through suitable interfaces. This article should be viewed as an invitation to share in the development of methodology for the estimation of regionally and temporally differentiated population densities. It must be taken into account that the ideas presented here as well as other arguments in the discussion of such initial stages will have an influence on future archaeological fieldwork. It is already clear that excavations and surveys as well as pollen analytic studies must be carried out on a large scale in order to improve our knowledge of settlement history. The intensity of the investigation in regions with varying site density and with differing natural conditions would, however, be dependent on how one implemented the process of upward scaling.
Full-text available
The ancestry of modern Europeans is a subject of debate among geneticists, archaeologists, and anthropologists. A crucial question is the extent to which Europeans are descended from the first European farmers in the Neolithic Age 7500 years ago or from Paleolithic hunter-gatherers who were present in Europe since 40,000 years ago. Here we present an analysis of ancient DNA from early European farmers. We successfully extracted and sequenced intact stretches of maternally inherited mitochondrial DNA (mtDNA) from 24 out of 57 Neolithic skeletons from various locations in Germany, Austria, and Hungary. We found that 25% of the Neolithic farmers had one characteristic mtDNA type and that this type formerly was widespread among Neolithic farmers in Central Europe. Europeans today have a 150-times lower frequency (0.2%) of this mtDNA type, revealing that these first Neolithic farmers did not have a strong genetic influence on modern European female lineages. Our finding lends weight to a proposed Paleolithic ancestry for modern Europeans.
Neanderthals are the group of fossil humans that inhabited Western Eurasia from the mid Middle Pleistocene until approximately 30 thousand years ago (ka), when they disappear from the fossil record, only a few millennia after the first modern humans appear in Europe. They are characterized by a suite of morphological features, which in combination produce a unique morphotype. They are commonly associated with the Mousterian lithic industry, although toward the end of their tenure they are sometimes found with assemblages resembling those produced by early modern humans. Although there is still discussion over their taxonomic status and relationship with modern humans, it is now commonly recognized that they represent a distinct, Eurasian evolutionary lineage sharing a common ancestor with modern humans sometime in the early Middle Pleistocene. This lineage is thought to have been isolated from the rest of the Old World, probably due to the climatic conditions of the glacial cycles. Glacial climate conditions are often thought to have been at least in part responsible for the evolution of some of the distinctive Neanderthal morphology, although genetic drift was probably also very important. The causes for the Neanderthal extinction are not well understood. Worsening climate and competition with modern humans are implicated.