The Saudi Arabian Genome Reveals a Two Step Out-of-Africa Migration. J. J. Farrell1, A. K. Al-Ali2, L. A. Farrer1, A. N. Al-Nafaie3, A. M. Al-Rubaish4, E. Melista1, Z. Naserullah5, A. Alsuliman6, P. Sebastiani7, M. H. Steinberg1, C. T. Baldwin1 1) Department of Medicine, Boston University School of Medicine, Boston, MA; 2) Department of Clinical Biochemistry, College of Medicine, University of Dammam, Dammam, Kingdom of Saudi Arabia; 3) Department of Hematology, College of Medicine, University of Dammam, Dammam, Kingdom of Saudi Arabia; 4) Department of Internal Medicine, College of Medicine, University of Dammam Dammam, Kingdom of Saudi Arabia; 5) Department of Pediatrics, Maternity & Child Hospital, Dammam, Kingdom of Saudi Arabia; 6) Department of Hematology, King Fahd Hospital, Hafof, Al-Ahsa, Kingdom of Saudi Arabia; 7) Department of Biostatistics, Boston University School of Public Health, Boston, MA.

   Here we present the first high-coverage whole genome sequences from a Middle Eastern population consisting of 14 Eastern Province Saudi Arabians. Genomes from this region are of interest to further answer questions regarding Out-of-Africa human migration. Applying a pairwise sequentially Markovian coalescent model (PSMC), we inferred the history of population sizes between 10,000 years and 1,000,000 years before present (YBP) for the Saudi genomes and an additional 11 high-coverage whole genome sequences from Africa, Asia and Europe.
   The model estimated the initial separation from Africans at approximately 110,000 YBP. This intermediate population then underwent a long period of decreasing population size culminating in a bottleneck 50,000 YBP followed by an expansion into Asia and Europe. The split and subsequent bottleneck were thus two distinct events separated by a long intermediate period of genetic drift in the Middle East. The two most frequent mitochondria haplogroups (30% each) were the Middle Eastern U7a and the African L. The presence of the L haplogroup common in Africa was unexpected given the clustering of the Saudis with Europeans in the phylogenetic tree and suggests some recent African admixture. To examine this further, we performed formal tests for a history of admixture and found no evidence of African admixture in the Saudi after the split. Taken together, these analyses suggest that the L3 haplogroup found in the Saudi were present before the bottleneck 50,000 YBP. Given the TMRCA estimates for the L3 haplogroup of approximately 70,000 YBP and the timing of the Out-of-Africa split, these analyses suggest that L3 haplogroup arose in the Middle East with a subsequent back migration and expansion into Africa over the Horn-of-Africa during the lower sea levels found during the glacial period bottleneck.
    These results are consistent with the hypothesis that modern humans populated the Middle East before a split 110,000 YBP, underwent genetic drift for 60,000 years before expanding to Asia and Europe as well as back-migration into Africa. Examination of genetic variants discovered by Saudi whole genome sequencing in ancestral African populations and European/Asian populations will contribute to the understanding human migration patterns and the origin of genetic variation in modern humans.

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