title: Tracing the route of modern humans out of Africa by using 225 human genome sequences from Ethiopians and Egyptians.
abstract: 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.
authors.affiliation: The Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Hinxton CB10 1SA, UK; Department of Archaeology and Anthropology, University of Cambridge, Cambridge CB2 1QH, UK; Department of Biological, Geological, and Environmental Sciences, University of Bologna, 40126 Bologna, Italy. Electronic address: lp.lucapagani@gmail.com.
authors.forename: Luca
authors.initials: L
authors.lastname: Pagani
authors.affiliation: The Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Hinxton CB10 1SA, UK.
authors.forename: Stephan
authors.initials: S
authors.lastname: Schiffels
authors.affiliation: The Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Hinxton CB10 1SA, UK.
authors.forename: Deepti
authors.initials: D
authors.lastname: Gurdasani
authors.affiliation: The Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Hinxton CB10 1SA, UK.
authors.forename: Petr
authors.initials: P
authors.lastname: Danecek
authors.affiliation: Department of Genetics, University of Cambridge, Cambridge CB2 3EH, UK.
authors.forename: Aylwyn
authors.initials: A
authors.lastname: Scally
authors.affiliation: The Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Hinxton CB10 1SA, UK.
authors.forename: Yuan
authors.initials: Y
authors.lastname: Chen
authors.affiliation: The Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Hinxton CB10 1SA, UK.
authors.forename: Yali
authors.initials: Y
authors.lastname: Xue
authors.affiliation: The Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Hinxton CB10 1SA, UK; The Lebanese American University, Chouran, Beirut 1102 2801, Lebanon.
authors.forename: Marc
authors.initials: M
authors.lastname: Haber
authors.affiliation: Department of Genetics, Evolution, and Environment, University College London, London WC1E 6BT, UK.
authors.forename: Rosemary
authors.initials: R
authors.lastname: Ekong
authors.affiliation: University of Addis Ababa and Center of Human Genetic Diversity, PO Box 1176, Ethiopia.
authors.forename: Tamiru
authors.initials: T
authors.lastname: Oljira
authors.affiliation: University of Addis Ababa and Center of Human Genetic Diversity, PO Box 1176, Ethiopia.
authors.forename: Ephrem
authors.initials: E
authors.lastname: Mekonnen
authors.affiliation: Department of Biological, Geological, and Environmental Sciences, University of Bologna, 40126 Bologna, Italy.
authors.forename: Donata
authors.initials: D
authors.lastname: Luiselli
authors.affiliation: Henry Stewart Group, 28/30 Little Russell Street, London WC1A 2HN, UK.
authors.forename: Neil
authors.initials: N
authors.lastname: Bradman
authors.affiliation: University of Addis Ababa and Center of Human Genetic Diversity, PO Box 1176, Ethiopia.
authors.forename: Endashaw
authors.initials: E
authors.lastname: Bekele
authors.affiliation: The Lebanese American University, Chouran, Beirut 1102 2801, Lebanon; Harvard T.H. Chan School of Public Health, Boston, MA 02115, USA.
authors.forename: Pierre
authors.initials: P
authors.lastname: Zalloua
authors.affiliation: The Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Hinxton CB10 1SA, UK.
authors.forename: Richard
authors.initials: R
authors.lastname: Durbin
authors.affiliation: Department of Archaeology and Anthropology, University of Cambridge, Cambridge CB2 1QH, UK.
authors.forename: Toomas
authors.initials: T
authors.lastname: Kivisild
authors.affiliation: The Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Hinxton CB10 1SA, UK.
authors.forename: Chris
authors.initials: C
authors.lastname: Tyler-Smith
mesh_terms: D001483:Base Sequence; D005075:Biological Evolution; D044383:Black People / Q000235:genetics*; D000076144:Egypt, Ancient; D005002:Ethiopia; D015894:Genome, Human / Q000235:genetics*; D005843:Geography; D006239:Haplotypes / Q000235:genetics; D059014:High-Throughput Nucleotide Sequencing / Q000379:methods; D049690:History, Ancient; D063426:Human Migration / Q000266:history*; D006801:Humans; D008390:Markov Chains; D008957:Models, Genetic; D008969:Molecular Sequence Data; D025341:Principal Component Analysis