The time and place of European admixture in Ashkenazi Jewish history

The Ashkenazi Jewish (AJ) population is important in genetics due to its high rate of Mendelian disorders. AJ appeared in Europe in the 10th century, and their ancestry is thought to comprise European (EU) and Middle-Eastern (ME) components. However, both the time and place of admixture are subject to debate. Here, we attempt to characterize the AJ admixture history using a careful application of new and existing methods on a large AJ sample. Our main approach was based on local ancestry inference, in which we first classified each AJ genomic segment as EU or ME, and then compared allele frequencies along the EU segments to those of different EU populations. The contribution of each EU source was also estimated using GLOBETROTTER and haplotype sharing. The time of admixture was inferred based on multiple statistics, including ME segment lengths, the total EU ancestry per chromosome, and the correlation of ancestries along the chromosome. The major source of EU ancestry in AJ was found to be Southern Europe (≈60–80% of EU ancestry), with the rest being likely Eastern European. The inferred admixture time was ≈30 generations ago, but multiple lines of evidence suggest that it represents an average over two or more events, pre- and post-dating the founder event experienced by AJ in late medieval times. The time of the pre-bottleneck admixture event, which was likely Southern European, was estimated to ≈25–50 generations ago.Author summary: The Ashkenazi Jewish population has resided in Europe for much of its 1000-year existence. However, its ethnic and geographic origins are controversial, due to the scarcity of reliable historical records. Previous genetic studies have found links to Middle-Eastern and European ancestries, but the admixture history has not been studied in detail yet, partly due to technical difficulties in disentangling signals from multiple admixture events. Here, we present an in-depth analysis of the sources of European gene flow and the time of admixture events by using multiple new and existing methods and extensive simulations. Our results suggest a model of at least two events of European admixture. One event slightly pre-dated a late medieval founder event and was likely from a Southern European source. Another event post-dated the founder event and likely occurred in Eastern Europe. These results, as well as the methods introduced, will be highly valuable for geneticists and other researchers interested in Ashkenazi Jewish origins.