Reports

history of anatomically modern

Ancient Ethiopian genome reveals humans, by providing the
baseline against which other
extensive Eurasian admixture throughout events are defined. In the
absence of ancient DNA,
the African continent geneticists rely on contemporary
African populations, but a
number of historic events, in
M. Gallego Llorente,1*† E. R. Jones,2*† A. Eriksson,1,3 V. Siska,1 particular a genetic backflow
K. W. Arthur, J. W. Arthur, M. C. Curtis, J. T. Stock,
4 4 5,6 7 from West Eurasia into Eastern
Africa (3, 4), act as confounding
M. Coltorti, P. Pieruccini, S. Stretton, F. Brock,
8 8 9 10,11
T. Higham, 10
factors.
Y. Park,12 M. Hofreiter,13,14 D. G. Bradley,2 J. Bhak,15 R. Pinhasi,16* Here, we present an ancient
A. Manica1* human genome from Africa, and
1
Department of Zoology, University of Cambridge, Downing Street, Cambridge CB2 3EJ, UK. 2Smurfit Institute of Genetics, use it to disentangle the effects
Trinity College Dublin, Dublin, Ireland. 3Integrative Systems Biology Laboratory, King Abdullah University of Science and of recent population movement

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Technology (KAUST), Thuwal, 23955-6900, Kingdom of Saudi Arabia. 4Department of Society, Culture, and Language, into Africa. By sampling the pe-
University of South Florida St. Petersburg, 140 7th Avenue South, St. Petersburg, FL 33701, USA. 5Department of trous bone (5), we sequenced the
Anthropology, Ventura College, 4667 Telegraph Road, Ventura, CA 93003, USA. 6Humanities and Social Sciences
Program, UCLA Extension, University of California Los Angeles, 10995 Le Conte Avenue, Los Angeles, CA 90095, USA. genome of a male from Mota
7
Department of Archaeology and Anthropology, University of Cambridge, Pembroke Street, Cambridge CB2 3QG, UK. Cave (herein referred to as ‘Mo-
8
Department of Physical Sciences, Earth and Environment, University of Siena, Via di Laterina, 8-53100 Siena, Italy. ta’) in the southern Ethiopian
9
Department of Anthropology, University of Illinois at Urbana-Champaign, Public Service Archaeology and Architecture highlands, with a mean coverage
Program, 109 Davenport Hall, 607 South Mathews Avenue, Urbana, IL 61801, USA. 10Oxford Radiocarbon Accelerator Unit,
Research Laboratory for Archaeology and the History of Art, University of Oxford, Dyson Perrins Building, South Parks of 12.5x (6). Contamination was
Road, Oxford OX1 3QY, UK. 11Cranfield Forensic Institute, Cranfield University, Defence Academy of the United Kingdom, estimated to be between 0.29
Shrivenham, Oxon SN6 8LA, UK. 12Theragen BiO Institute, 2nd Floor B-dong, AICT bldg, Iui-dong, Youngtong-gu, Suwon, and 1.26% (6). Mota’s remains
443-270, Republic of Korea. 13Institute for Biochemistry and Biology, Faculty for Mathematics and Natural Sciences, were dated to ~4,500 years ago
University of Potsdam, Karl-Liebknechtstraße 24–25, 14476 Potsdam Golm, Germany. 14Department of Biology, University
15
of York, Wentworth Way, Heslington, York YO10 5DD, UK. The Genomics Institute, UNIST, Ulsan, 689-798, Republic of (direct calibrated radiocarbon
Korea. 16School of Archaeology, University College Dublin, Belfield, Dublin 4, Ireland. date (6)), and thus predate both
*Corresponding author. E-mail: mg632@cam.ac.uk (M.G.L.); joneser@tcd.ie (E.R.J.); ron.pinhasi@ucd.ie (R.P.); the Bantu expansion (7), and,
am315@cam.ac.uk (A.M.) more importantly, the 3ky-old
†These authors contributed equally to this work. West Eurasian backflow which
has left strong genetic signatures
Characterizing genetic diversity in Africa is a crucial step for most analyses
in the whole of Eastern and, to a
reconstructing the evolutionary history of anatomically modern humans.
lesser extent, Southern Africa (3,
However, historic migrations from Eurasia into Africa have affected many
4).
contemporary populations, confounding inferences. Here, we present a
We compared Mota to con-
12.5x coverage ancient genome of an Ethiopian male (‘Mota’) who lived
temporary human populations
approximately 4,500 years ago. We use this genome to demonstrate that
(6). Both Principal Component
the Eurasian backflow into Africa came from a population closely related to
Analysis (Fig. 1A) and outgroup
Early Neolithic farmers, who had colonized Europe 4,000 years earlier. The
f3 analysis using Ju|’hoansi
extent of this backflow was much greater than previously reported,
(Khoisan) from Southern Africa
reaching all the way to Central, West and Southern Africa, affecting even
as the outgroup (Fig. 1B,C) place
populations such as Yoruba and Mbuti, previously thought to be relatively
this ancient individual close to
unadmixed, who harbor 6-7% Eurasian ancestry.
contemporary Ethiopian popula-
tions, and more specifically to
The ability to sequence ancient genomes has revolutionized the Ari, a group of Omotic speakers from southern Ethiopia,
our understanding of human evolution. However, genetic to the West of the highland region where Mota lived. Our
analyses of ancient material have focused on individuals ancient genome confirms the view that the divergence of
from temperate and arctic regions, where ancient DNA is this language family results from the relative isolation of its
preserved over longer time frames (1). Africa has so far speakers (8), and indicates population continuity over the
failed to yield skeletal remains with much aDNA, with the last ~4,500 years in this region of Eastern Africa.
exception of a few poorly preserved specimens from which The age of Mota means that he should predate the West
only mitochondrial DNA could be extracted (2). This is Eurasian backflow, which has been dated to ~3,000 years
particularly unfortunate, as African genetic diversity is ago (3, 4). We formally tested this by using an f4 ratio esti-
crucial to most analyses reconstructing the evolutionary mating the West Eurasian component (6), following the ap-

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proach adopted by Pickrell et al. (3). As expected, we failed
to find any West Eurasian component in Mota (Table S5),
thus providing support for previous dating of that event (3,
4).
Given that Mota predates the backflow, we searched for
its most likely source by modelling the Ari, the contempo-
rary population closest to our ancient genome, as a mixture
of Mota and another West Eurasian population (6). We in-
vestigated both contemporary sources (3) as well as other
Eurasian ancient genomes (5, 9). In this analysis, contempo-
rary Sardinians and the early Neolithic LBK (Stuttgart) ge-
nome stand out (Fig. 2A). Previous analyses have shown
Sardinians to be the closest modern representatives of early
Neolithic farmers (10, 11), implying that the backflow came
from the same genetic source that fuelled the Neolithic ex-
pansion into Europe from the Near East/Anatolia, before
recent historic events changed the genetic makeup of popu-
lations living in that region. An analysis with haplotype
sharing also identified a connection between contemporary
Ethiopians and Anatolia (4, 12). Interestingly, archaeological
evidence dates the arrival of Near Eastern domesticates
(such as wheat, barley and lentils) to the same time period
(circa 3,000 years ago) (13, 14), suggesting that the direct
descendants of the farmers that earlier brought agriculture
into Europe may have also played a role in the development
of new forms of food production in the Horn of Africa.
Using Mota as an unadmixed African reference and the
early farmer LBK as the source of the West Eurasian com-
ponent, it is possible to reassess the magnitude and geo-
graphic extent of historical migrations, avoiding the
complications of using admixed contemporary populations
(6). We estimated a substantially higher Eurasian backflow
admixture than previously detected (3), with an additional
4-7% of the genome of most African populations tracing
back to a Eurasian source, and, more importantly, we de-
tected a much broader geographical impact of the backflow,
going all the way to West and Southern Africa (Fig. 2B).
Even though the West Eurasian component in these regions
is smaller than in Eastern Africa, it is still sizeable, with Yo-
ruba and Mbuti, who are often used as African references
(15, 16), showing 7% and 6%, respectively, of their genomes
to be of Eurasian origin (Table S5).
Since Mota predates recent demographic events, his ge-
nome can act as an ideal African reference to understand
episodes during the out-of-Africa expansion. We used him as
the African reference to quantify Neanderthal introgression
in a number of contemporary genomes (6). Both Yoruba and
Mbuti, which are routinely used as African references for
this type of analysis (15, 16), show a marginally closer affini-
ty with Neanderthal than Mota based on D statistics, and an
f4 ratio analysis detected a small Neanderthal component in
these genomes at around 0.2-0.7%; greater than previously
suggested (16), and consistent with our estimates of the
magnitude of their Western Eurasian ancestry (6). While the
magnitude of Neanderthal ancestry in these contemporary
/ sciencemag.org/content/early/recent / 8 October 2015 / Page 2 / 10.1126/science.aad2879
African populations is not enough to change conclusions
qualitatively (estimates of Neanderthal ancestry in French
and Han only increased marginally when tested with Mota
as a reference), it should be accounted for when looking for
specific introgressed haplotypes (17) or searching for un-
known ancient hominins who might have hybridized with
African populations (18).
We also investigated the Mota genome for a number of
phenotypes of interest (6). As expected, Mota lacked any of
the derived alleles found in Eurasian populations for eye
and skin color, suggesting that he had brown eyes and dark
skin. Mota lacked any of the currently known alleles that
give lactose tolerance, which may have implications con-
cerning when pastoralism appeared in southwestern Ethio-
pia. In addition, Mota did possess all three selected alleles
that have been recently shown to play a role in the adapta-
tion to altitude in contemporary highland Ethiopian popula-
tions (19). The presence of these mutations supports our
conclusion that Mota is the descendant of highland dwell-
ers, who have lived in this environment long enough to ac-
cumulate adaptations to the altitude (20, 21).
Until now, it has been necessary to use contemporary Af-
rican populations as the baseline against which events dur-
ing the worldwide expansion of Anatomically Modern
Humans are defined (16, 22–24). By obtaining an ancient
whole genome from this continent, we have shown that hav-
ing an unadmixed reference that predates the large number
of recent historical migrations can greatly improve our in-
ference. This result stresses the importance of obtaining
unadmixed baseline data to reconstruct demographic
events, and the limitations of analyses that are solely based
on contemporary populations. Even older African genomes
will thus be needed to investigate key demographic events
that predate Mota, such as earlier instances of back-flows
into Africa (25).
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ACKNOWLEDGMENTS
A.M. was supported by ERC Consolidator Grant 647787 ‘LocalAdaptation’; R.P. by
ERC Starting Grant: ERC- 2010-StG 26344; M.H. by ERC Consolidator Grant
310763 ‘GeneFlow’; J.B. by the 2014 Research Fund (1.140113.01, 1.140064.01)
of UNIST (Ulsan National Institute of Science and Technology) and Geromics
internal research funding; J.T.S. by ERC Consolidator Grant 617627 'ADaPt';
K.W.A. by NSF award 1027607; D.G.B. by ERC Investigator Grant 295729-CodeX;
V.S. by a scholarship from the Gates Cambridge Trust; and M.G. by a BBSRC
DTP studentship. Permission for the archaeology was given by the Ethiopian
Authority for Research and Conservation of Cultural Heritage and offices of the
Ministry of Culture and Tourism for the Southern Nations, Nationalities, and
Peoples Region. Raw reads from Mota are available for download through NCBI,
BioProject ID PRJNA295861, and the corresponding BAM and VCF files are
available at africangenome.org.
SUPPLEMENTARY MATERIALS
www.sciencemag.org/cgi/content/full/science.aad2879/DC1
Supplementary Text
Figs. S1 to S8
Tables S1 to S14
References (26–74)

25 August 2015; accepted 28 September 2015

Published online 8 October 2015
10.1126/science.aad2879

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Fig. 1. Mota shows a very high degree of similarity with the highland Ethiopian Ari populations. (A) PCA
showing Mota projected onto components loaded on contemporary African and Eurasian populations. The
inset magnifies the PCA space occupied by Ethiopian and Eastern African populations. (B) Outgroup f3
quantifying the shared drift between Mota and contemporary African populations, using Ju|’hoansi (Khoisan)
as an outgroup; bars represent standard error. (C) Map showing the distribution of outgroup f3 values across
the African continent. In (A) and (B), populations speaking Nilo-Saharan languages are marked with blue
shades, Omotic speakers with red, Cushitic with orange, Semitic with yellow, and Bantu with green. Mota is
denoted by a black symbol.

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Fig. 2. Quantifying the geographic extent and origin of the West Eurasian component in Africa.
(A) Admixture f3 identifying likely sources of the West Eurasian component (lowest f3 values). Contemporary
populations in blue, ancient genomes in red; bars represent standard error. (B) Map showing the proportion of
West Eurasian component, λMota,LBK, across the African continent.

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