Tracing the Route of Modern Humans out of Africa by Using 225 Human Genome Sequences from Ethiopians and Egyptians
Open accessAbstract
The predominantly African origin of all modern human populations is well established, but the route taken out of Africa is still unclear. Two alternative routes, via Egypt and Sinai or across the Bab el Mandeb strait into Arabia, have traditionally been proposed as feasible gateways in light of geographic, paleoclimatic, archaeological, and genetic evidence. Distinguishing among these alternatives has been difficult. We generated 225 whole-genome sequences (225 at 8× depth, of which 8 were increased to 30×; Illumina HiSeq 2000) from six modern Northeast African populations (100 Egyptians and five Ethiopian populations each represented by 25 individuals). West Eurasian components were masked out, and the remaining African haplotypes were compared with a panel of sub-Saharan African and non-African genomes. We showed that masked Northeast African haplotypes overall were more similar to non-African haplotypes and more frequently present outside Africa than were any sets of haplotypes derived from a West African population. Furthermore, the masked Egyptian haplotypes showed these properties more markedly than the masked Ethiopian haplotypes, pointing to Egypt as the more likely gateway in the exodus to the rest of the world. Using five Ethiopian and three Egyptian high-coverage masked genomes and the multiple sequentially Markovian coalescent (MSMC) approach, we estimated the genetic split times of Egyptians and Ethiopians from non-African populations at 55,000 and 65,000 years ago, respectively, whereas that of West Africans was estimated to be 75,000 years ago. Both the haplotype and MSMC analyses thus suggest a predominant northern route out of Africa via Egypt.
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
The data indicate close admixture and affinity at a much earlier date than the ~750 years ago midpoint estimated by Pagani and colleagues.
“Our data seem to indicate close admixture and affinity at a much earlier date, which is unsurprising given the long and complex connections between Egypt and the Middle East.”
From Ancient Egyptian mummy genomes suggest an increase of Sub-Saharan African ancestry in post-Roman periods (2017) · cites this paper as [17]
Genetic continuity between ancient and modern Egyptians cannot be ruled out by the formal test despite the sub-Saharan African influx, while continuity with modern Ethiopians is not supported.
“Genetic continuity between ancient and modern Egyptians cannot be ruled out by our formal test despite this sub-Saharan African influx, while continuity with modern Ethiopians17, who carry >60% African L lineages, is not supported (Supplementary Data 5).”
From Ancient Egyptian mummy genomes suggest an increase of Sub-Saharan African ancestry in post-Roman periods (2017) · cites this paper as [17]
Modern Egyptians share the ancient haplogroup profile but show a marked increase of African mtDNA lineages L0-L4 up to 20%.
“Modern Egyptians share this profile but in addition show a marked increase of African mtDNA lineages L0–L4 up to 20% (consistent with nuclear estimates of 80% non-African ancestry reported in Pagani et al.17).”
From Ancient Egyptian mummy genomes suggest an increase of Sub-Saharan African ancestry in post-Roman periods (2017) · cites this paper as Pagani et al. [17]
Modern humans subsequently colonized the rest of the world after expanding out of Africa.
“followed by an expansion out of Africa around 50,000–60,000 ya and subsequent colonization of the rest of the world [4].”
From Ancient DNA and the rewriting of human history: be sparing with Occam’s razor (2016) · cites this paper as [4]
Modern humans expanded out of Africa around 50,000-60,000 years ago.
“followed by an expansion out of Africa around 50,000–60,000 ya and subsequent colonization of the rest of the world [4].”
From Ancient DNA and the rewriting of human history: be sparing with Occam’s razor (2016) · cites this paper as [4]
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Cites
PLINK: a tool set for whole-genome association and population-based linkage analyses.
Purcell, S., Neale, B., Todd-Brown, K., Thomas, L., Ferreira, M. A. R., Bender, D., Maller, J., Sklar, P., de Bakker, P. I. W., Daly, M. J., et al. (2007) · The American Journal of Human Genetics · doi:10.1086/519795 · Cited by 34,089 · see citing works
Principal components analysis corrects for stratification in genome-wide association studies
Price, A. L., Patterson, N. J., Plenge, R. M., Weinblatt, M. E., Shadick, N. A., & Reich, D. (2006) · Nature Genetics · doi:10.1038/ng1847 · Cited by 10,248 · see citing works
Fast model-based estimation of ancestry in unrelated individuals
Alexander, D. H., Novembre, J., & Lange, K. (2009) · Genome Research · doi:10.1101/gr.094052.109 · Cited by 9,898 · see citing works
EVOLUTION IN MENDELIAN POPULATIONS
Wright, S. (1931) · Genetics · doi:10.1093/genetics/16.2.97 · Cited by 9,078 · see citing works
An integrated map of genetic variation from 1,092 human genomes
The 1000 Genomes Project Consortium (2012) · Nature · doi:10.1038/nature11632 · Cited by 7,711 · see citing works
A draft sequence of the Neandertal genome
Green, R. E., Krause, J., Briggs, A. W., Maricic, T., Stenzel, U., Kircher, M., Patterson, N., Li, H., Zhai, W., Fritz, M. H.-Y., et al. (2010) · Science · doi:10.1126/science.1188021 · Cited by 4,318 · see citing works
The History and Geography of Human Genes
Cavalli-Sforza, L. L., Menozzi, P., & Piazza, A. (2018) · Princeton University Press eBooks · doi:10.2307/j.ctv301gjp · Cited by 3,175 · see citing works
Inference of human population history from individual whole-genome sequences
Li, H., & Durbin, R. (2011) · Nature · doi:10.1038/nature10231 · Cited by 2,590 · see citing works
Self-citationA linear complexity phasing method for thousands of genomes
Delaneau, O., Marchini, J., & Zagury, J.-F. (2012) · Nature Methods · doi:10.1038/nmeth.1785 · Cited by 1,850 · see citing works
History and Geography of Human Genes
Piazza, A. (1994) · Advances in forensic haemogenetics · doi:10.1007/978-3-642-78782-9_1 · Cited by 1,639 · see citing works
The history and geography of human genes
Cann, R. L. (1995) · Choice Reviews Online · doi:10.5860/choice.33-0316 · Cited by 1,328 · see citing works
Human Genome Sequencing Using Unchained Base Reads on Self-Assembling DNA Nanoarrays
Drmanac, R., Sparks, A. B., Callow, M. J., Halpern, A. L., Burns, N. L., Kermani, B. G., Carnevali, P., Nazarenko, I., Nilsen, G. B., Yeung, G., et al. (2010) · Science · doi:10.1126/science.1181498 · Cited by 1,212 · see citing works
Inferring human population size and separation history from multiple genome sequences
Schiffels, S., & Durbin, R. M. (2014) · Nature Genetics · doi:10.1038/ng.3015 · Cited by 1,051 · see citing works
Self-citationReconstruction of human evolution: bringing together genetic, archaeological, and linguistic data.
Cavalli-Sforza, L. L., Piazza, A., Menozzi, P., & Mountain, J. L. (1988) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.85.16.6002 · Cited by 910 · see citing works
Campbell, M. C., & Tishkoff, S. A. (2008) · Annual Review of Genomics and Human Genetics · doi:10.1146/annurev.genom.9.081307.164258 · Cited by 847 · see citing works
Serjeant, G. R. (1997) · The Lancet · doi:10.1016/s0140-6736(97)07330-3 · Cited by 760 · see citing works
The African Genome Variation Project shapes medical genetics in Africa
Gurdasani, D., Carstensen, T., Ayele, F. T., Pagani, L., Tachmazidou, I., Hatzikotoulas, K., Karthikeyan, S., Iles, L., Pollard, M., Choudhury, A., et al. (2014) · Nature · doi:10.1038/nature13997 · Cited by 636 · see citing works
Self-citationBayesian inference of ancient human demography from individual genome sequences
Gronau, I., Hubisz, M. J., Gulko, B., Danko, C. G., & Siepel, A. C. (2011) · Nature Genetics · doi:10.1038/ng.937 · Cited by 580 · see citing works
The Southern Route “Out of Africa”: Evidence for an Early Expansion of Modern Humans into Arabia
Armitage, S. J., Jasim, S., Marks, A. E., Parker, A. G., Usik, V. I., & Uerpmann, H. (2011) · Science · doi:10.1126/science.1199113 · Cited by 546 · see citing works
Genetic evidence of an early exit of Homo sapiens sapiens from Africa through eastern Africa
Quintana-Murci, L., Semino, O., Bandelt, H., Passarino, G., McElreavey, K., & Santachiara-Benerecetti, A. (1999) · Nature Genetics · doi:10.1038/70550 · Cited by 518 · see citing works
Inferring admixture histories of human populations using linkage disequilibrium
Loh, P.-R., Lipson, M., Patterson, N., Moorjani, P., Pickrell, J. K., Reich, D., & Berger, B. (2013) · Genetics · doi:10.1534/genetics.112.147330 · Cited by 466 · see citing works
Multiple dispersals and modern human origins
Lahr, M. M., & Foley, R. (1994) · Evolutionary Anthropology Issues News and Reviews · doi:10.1002/evan.1360030206 · Cited by 425 · see citing works
Jobling, M., Hollox, E., Hurles, M., Kivisild, T., & Tyler-Smith, C. (2013) · doi:10.1201/9781317952268 · Cited by 385 · see citing works
Self-citationHaploview: Visualization and Analysis of SNP Genotype DataPreprint
Barrett, J. C. (2009) · Cold Spring Harbor Protocols · doi:10.1101/pdb.ip71 · Cited by 354 · see citing works
Neanderthals in central Asia and Siberia
Krause, J., Orlando, L., Serre, D., Viola, B., Prüfer, K., Richards, M. P., Hublin, J.-J., Hänni, C., Derevianko, A. P., & Pääbo, S. (2007) · Nature · doi:10.1038/nature06193 · Cited by 333 · see citing works
Genomic Ancestry of North Africans Supports Back-to-Africa Migrations
Henn, B. M., Botigué, L. R., Gravel, S., Wang, W., Brisbin, A., Byrnes, J. K., Fadhlaoui-Zid, K., Zalloua, P. A., Moreno-Estrada, A., Bertranpetit, J., et al. (2012) · PLoS Genetics · doi:10.1371/journal.pgen.1002397 · Cited by 331 · see citing works
Self-citationAncient west Eurasian ancestry in southern and eastern Africa
Pickrell, J. K., Patterson, N., Loh, P.-R., Lipson, M., Berger, B., Stoneking, M., Pakendorf, B., & Reich, D. (2014) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1313787111 · Cited by 300 · see citing works
The Expansion of mtDNA Haplogroup L3 within and out of Africa
Soares, P. A., Alshamali, F., Pereira, J. B., Fernandes, V., Silva, N. M., Afonso, C., Costa, M. D., Musilová, E., Macaulay, V. A., Richards, M. B., et al. (2011) · Molecular Biology and Evolution · doi:10.1093/molbev/msr245 · Cited by 254 · see citing works
Kitchen, A., Ehret, C., Assefa, S., & Mulligan, C. J. (2009) · Proceedings of the Royal Society B Biological Sciences · doi:10.1098/rspb.2009.0408 · Cited by 247 · see citing works
The History of African Gene Flow into Southern Europeans, Levantines, and Jews
Moorjani, P., Patterson, N. J., Hirschhorn, J. N., Keinan, A., Hao, L., Atzmon, G., Burns, E. R., D, H. O. M., Price, A. L., & Reich, D. (2011) · PLoS Genetics · doi:10.1371/journal.pgen.1001373 · Cited by 240 · see citing works
ESR dates for the hominid burial site of Es Skhul in Israel
Stringer, C. B., Grün, R., Schwarcz, H. P., & Goldberg, P. S. (1989) · Nature · doi:10.1038/338756a0 · Cited by 237 · see citing works
Levantine cranium from Manot Cave (Israel) foreshadows the first European modern humans
Hershkovitz, I., Marder, O., Ayalon, A., Bar‐Matthews, M., Yasur, G., Boaretto, E., Caracuta, V., Alex, B., Frumkin, A., Goder‐Goldberger, M., et al. (2015) · Nature · doi:10.1038/nature14134 · Cited by 230 · see citing works
Pagani, L., Kivisild, T., Tarekegn, A., Ekong, R., Plaster, C., Gallego Romero, I., Ayub, Q., Mehdi, S. Q., Thomas, M. G., Luiselli, D., et al. (2012) · The American Journal of Human Genetics · doi:10.1016/j.ajhg.2012.05.015 · Cited by 230 · see citing works
Self-citationEriksson, A., & Manica, A. (2012) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1200567109 · Cited by 221 · see citing works
Petraglia, M. D., Haslam, M., Fuller, D. Q., Boivin, N. L., & Clarkson, C. (2010) · Annals of Human Biology · doi:10.3109/03014461003639249 · Cited by 183 · see citing works
Brisbin, A. G., Bryc, K., Byrnes, J., Zakharia, F., Omberg, L., Degenhardt, J. D., Reynolds, A., D, H. O. M., Mezey, J. G., & Bustamante, C. D. (2012) · Human Biology · doi:10.3378/027.084.0401 · Cited by 172 · see citing works
Seeing the Wood for the Trees: A Minimal Reference Phylogeny for the Human Y Chromosome
van Oven, M., Geystelen, A. V., Kayser, M., Decorte, R., & Larmuseau, M. (2013) · Human Mutation · doi:10.1002/humu.22468 · Cited by 169 · see citing works
HAPLOFIND: A New Method for High-Throughput mtDNA Haplogroup Assignment
Vianello, D., Sevini, F., Castellani, G., Lomartire, L., Capri, M., & Franceschi, C. (2013) · Human Mutation · doi:10.1002/humu.22356 · Cited by 149 · see citing works
Genome-Wide Diversity in the Levant Reveals Recent Structuring by Culture
Haber, M., Gauguier, D., Youhanna, S. C., Patterson, N. J., Moorjani, P., Botigué, L. R., Platt, D. E., Matisoo-Smith, E. A., Soria‐Hernanz, D. F., Wells, R. S., et al. (2013) · PLoS Genetics · doi:10.1371/journal.pgen.1003316 · Cited by 95 · see citing works
Self-citationEarly Back-to-Africa Migration into the Horn of Africa
Hodgson, J. A., Mulligan, C. J., Al‐Meeri, A., & Raaum, R. L. (2014) · PLoS Genetics · doi:10.1371/journal.pgen.1004393 · Cited by 92 · see citing works
Flagged first, then by citations
Cited by
Sorted by citations
Ancient DNA and the rewriting of human history: be sparing with Occam’s razor
Haber, M., Mezzavilla, M., Xue, Y., & Tyler-Smith, C. (2016) · Genome Biology · doi:10.1186/s13059-015-0866-z · Cited by 1,924 · see citing works
Self-citationSchuenemann, V. J., Peltzer, A., Welte, B., van Pelt, W. P., Molak, M., Wang, C.-C., Furtwängler, A., Urban, C., Reiter, E., Nieselt, K., et al. (2017) · Nature Communications · doi:10.1038/ncomms15694 · Cited by 201 · see citing works
Self-citationA weakly structured stem for human origins in Africa
Ragsdale, A. P., Weaver, T. D., Atkinson, E. G., Hoal, E. G., Möller, M., Henn, B. M., & Gravel, S. (2023) · Nature · doi:10.1038/s41586-023-06055-y · Cited by 159 · see citing works
Haber, M., Doumet-Serhal, C., Scheib, C., Xue, Y., Danecek, P., Mezzavilla, M., Youhanna, S., Martiniano, R., Prado-Martinez, J., Szpak, M., et al. (2017) · The American Journal of Human Genetics · doi:10.1016/j.ajhg.2017.06.013 · Cited by 121 · see citing works
Self-citationVyas, D. N., & Mulligan, C. J. (2019) · American Journal of Physical Anthropology · doi:10.1002/ajpa.23818 · Cited by 11 · see citing works
- Authors
- Pagani, L., Schiffels, S., Gurdasani, D., Danecek, P., Scally, A., Chen, Y., Xue, Y., Haber, M., Ekong, R., Oljira, T., Mekonnen, E., Luiselli, D., Bradman, N., Bekele, E., Zalloua, P., Durbin, R., Kivisild, T., & Tyler-Smith, C.
- Affiliations
- University of Cambridge (GB)
- Wellcome Sanger Institute (GB)
- University College London (GB)
- Addis Ababa University (ET)
- University of Bologna (IT)
- Harvard University (US)
- Corresponding author
- Pagani, Luca
- ORCID
- Venue
- The American Journal of Human Genetics
- Publisher
- Elsevier BV
- Published
- 2015-06
- Volume
- 96
- Issue
- 6
- Pages
- 986-991
- ISSN
- 0002-9297 (ISSN-L)
- PMC
- PMC4457944
- OpenAlex
- W1640614960
- Cited by
- 216
- References
- 40
- Citations by year
- 2026: 7 · 2025: 47 · 2024: 11 · 2023: 19 · 2022: 14 · 2021: 21 · 2020: 17 · 2019: 16 · 2018: 20 · 2017: 16 · 2016: 17 · 2015: 11
- FWCI
- 14.58
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- The American Journal of Human Genetics (publishedVersion, cc-by-nc-nd)
- Europe PMC (PubMed Central) (publishedVersion, cc-by-nc-nd)
- PubMed Central (publishedVersion, cc-by-nc-nd)
- PubMed (publishedVersion)
- MPG.PuRe (Max Planck Society) (submittedVersion, other-oa)
- Padua Research Archive (University of Padova) (submittedVersion, cc-by-nc-nd)
- Archivio istituzionale della ricerca (Alma Mater Studiorum Università di Bologna) (submittedVersion)
- UCL Discovery (University College London) (submittedVersion)
- University of Birmingham Research Portal (University of Birmingham) (submittedVersion, other-oa)
- Funders
- Wellcome Trust (098051)
- Missouri Soybean Merchandising Council
- FP7 Ideas: European Research Council (261213, 295733)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Forensic and Genetic Research
- Social Sciences › Anthropology › Pleistocene-Era Hominins and Archaeology
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetic diversity and population structure
- Keywords
- whole genome sequencing, West African populations, East African Rift
- MeSH terms
- Egypt, Ancient, Base Sequence, Ethiopia, Biological Evolution, Geography, Haplotypes, Humans, Markov Chains, Models, Genetic, Molecular Sequence Data, Genome, Human, Principal Component Analysis, Black People, History, Ancient, High-Throughput Nucleotide Sequencing, Human Migration
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
