Genome-wide data from medieval German Jews show that the Ashkenazi founder event pre-dated the 14^th century

Shamam Waldman¹, Daniel Backenroth¹, Éadaoin Harney², Stefan Flohr³, Nadia C Neff⁴, Gina M Buckley⁵, Hila Fridman⁶, Ali Akbari⁷, Nadin Rohland⁸, Swapan Mallick⁹, Iñigo Olalde¹⁰, Leo Cooper¹¹, Ariel Lomes¹, Joshua Lipson¹², Jorge Cano Nistal¹³, Jin Yu¹⁴, Nir Barzilai¹⁵, Inga Peter¹⁶, Gil Atzmon¹⁷, Harry Ostrer¹⁸, Todd Lencz¹⁹, Yosef E Maruvka¹³, Maike Lämmerhirt²⁰, Alexander Beider²¹, Leonard V Rutgers²², Virginie Renson⁵, Keith M Prufer⁴, Stephan Schiffels²³, Harald Ringbauer²⁴, Karin Sczech²⁵, Shai Carmi²⁶, David Reich²⁷

Affiliations

¹ Braun School of Public Health and Community Medicine, The Hebrew University of Jerusalem, Jerusalem 9112102, Israel.
² Department of Human Evolutionary Biology, Harvard University, Cambridge, MA 02138, USA.
³ Department of Biology, University of Hildesheim, 31141 Hildesheim, Germany.
⁴ Department Anthropology, University of New Mexico, Albuquerque, NM 87131, USA; Center for Stable Isotopes, University of New Mexico, Albuquerque, NM 87106, USA.
⁵ Research Reactor Center, University of Missouri, Columbia, MO 65211, USA.
⁶ Braun School of Public Health and Community Medicine, The Hebrew University of Jerusalem, Jerusalem 9112102, Israel; Medical Genetics Institute, Shaare Zedek Medical Center, Jerusalem 9103102, Israel; Faculty of Medicine, The Hebrew University of Jerusalem, Jerusalem 9112001, Israel.
⁷ Department of Human Evolutionary Biology, Harvard University, Cambridge, MA 02138, USA; Department of Genetics, Harvard Medical School, Boston, MA 02115, USA; Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA.
⁸ Department of Genetics, Harvard Medical School, Boston, MA 02115, USA; Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA.
⁹ Department of Genetics, Harvard Medical School, Boston, MA 02115, USA; Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA; Howard Hughes Medical Institute, Harvard Medical School, Boston, MA 02115, USA.
¹⁰ Department of Human Evolutionary Biology, Harvard University, Cambridge, MA 02138, USA; Department of Zoology and Animal Cell Biology, University of the Basque Country UPV/EHU, 01006 Vitoria-Gasteiz, Spain; Ikerbasque-Basque Foundation of Science, 48009 Bilbao, Spain.
¹¹ Independent Scholar, Kalamazoo, MI 49008, USA.
¹² Independent Scholar, New York, NY 10027, USA.
¹³ Faculty of Biotechnology and Food Engineering, Technion - Israel Institute of Technology, Haifa 3200003, Israel.
¹⁴ Department of Psychiatry, Division of Research, The Zucker Hillside Hospital Division of Northwell Health, Glen Oaks, NY 11004, USA.
¹⁵ Departments of Medicine and Genetics, Albert Einstein College of Medicine, Bronx, NY 10461, USA.
¹⁶ Department of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA.
¹⁷ Departments of Medicine and Genetics, Albert Einstein College of Medicine, Bronx, NY 10461, USA; Faculty of Natural Sciences, University of Haifa, Haifa 3498838, Israel.
¹⁸ Department of Pathology, Albert Einstein College of Medicine, Bronx, NY 10461, USA.
¹⁹ Department of Psychiatry, Division of Research, The Zucker Hillside Hospital Division of Northwell Health, Glen Oaks, NY 11004, USA; Departments of Psychiatry and Molecular Medicine, Zucker School of Medicine at Hofstra/Northwell, Hempstead, NY 11550, USA; Institute for Behavioral Science, The Feinstein Institutes for Medical Research, Manhasset, NY 11030, USA.
²⁰ Department of Medieval History, University of Erfurt, 99089 Erfurt, Germany.
²¹ Independent Scholar, 92370 Chaville, France.
²² Department of History and Art History, Utrecht University, Utrecht 3512 BS, the Netherlands.
²³ Department of Archaeogenetics, Max Planck Institute for Evolutionary Anthropology, 04103 Leipzig, Germany.
²⁴ Department of Human Evolutionary Biology, Harvard University, Cambridge, MA 02138, USA; Department of Archaeogenetics, Max Planck Institute for Evolutionary Anthropology, 04103 Leipzig, Germany.
²⁵ World Heritage Coordinator, City of Erfurt, 99084 Erfurt, Germany.
²⁶ Braun School of Public Health and Community Medicine, The Hebrew University of Jerusalem, Jerusalem 9112102, Israel. Electronic address: shai.carmi@huji.ac.il.
²⁷ Department of Human Evolutionary Biology, Harvard University, Cambridge, MA 02138, USA; Department of Genetics, Harvard Medical School, Boston, MA 02115, USA; Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA; Howard Hughes Medical Institute, Harvard Medical School, Boston, MA 02115, USA. Electronic address: reich@genetics.med.harvard.edu.

PMID: 36455558
PMCID: PMC9793425
DOI: 10.1016/j.cell.2022.11.002

Genome-wide data from medieval German Jews show that the Ashkenazi founder event pre-dated the 14^th century

Shamam Waldman et al. Cell. 2022.

. 2022 Dec 8;185(25):4703-4716.e16.

doi: 10.1016/j.cell.2022.11.002. Epub 2022 Nov 30.

Authors

Affiliations

¹ Braun School of Public Health and Community Medicine, The Hebrew University of Jerusalem, Jerusalem 9112102, Israel.
² Department of Human Evolutionary Biology, Harvard University, Cambridge, MA 02138, USA.
³ Department of Biology, University of Hildesheim, 31141 Hildesheim, Germany.
⁴ Department Anthropology, University of New Mexico, Albuquerque, NM 87131, USA; Center for Stable Isotopes, University of New Mexico, Albuquerque, NM 87106, USA.
⁵ Research Reactor Center, University of Missouri, Columbia, MO 65211, USA.
⁶ Braun School of Public Health and Community Medicine, The Hebrew University of Jerusalem, Jerusalem 9112102, Israel; Medical Genetics Institute, Shaare Zedek Medical Center, Jerusalem 9103102, Israel; Faculty of Medicine, The Hebrew University of Jerusalem, Jerusalem 9112001, Israel.
⁷ Department of Human Evolutionary Biology, Harvard University, Cambridge, MA 02138, USA; Department of Genetics, Harvard Medical School, Boston, MA 02115, USA; Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA.
⁸ Department of Genetics, Harvard Medical School, Boston, MA 02115, USA; Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA.
⁹ Department of Genetics, Harvard Medical School, Boston, MA 02115, USA; Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA; Howard Hughes Medical Institute, Harvard Medical School, Boston, MA 02115, USA.
¹⁰ Department of Human Evolutionary Biology, Harvard University, Cambridge, MA 02138, USA; Department of Zoology and Animal Cell Biology, University of the Basque Country UPV/EHU, 01006 Vitoria-Gasteiz, Spain; Ikerbasque-Basque Foundation of Science, 48009 Bilbao, Spain.
¹¹ Independent Scholar, Kalamazoo, MI 49008, USA.
¹² Independent Scholar, New York, NY 10027, USA.
¹³ Faculty of Biotechnology and Food Engineering, Technion - Israel Institute of Technology, Haifa 3200003, Israel.
¹⁴ Department of Psychiatry, Division of Research, The Zucker Hillside Hospital Division of Northwell Health, Glen Oaks, NY 11004, USA.
¹⁵ Departments of Medicine and Genetics, Albert Einstein College of Medicine, Bronx, NY 10461, USA.
¹⁶ Department of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA.
¹⁷ Departments of Medicine and Genetics, Albert Einstein College of Medicine, Bronx, NY 10461, USA; Faculty of Natural Sciences, University of Haifa, Haifa 3498838, Israel.
¹⁸ Department of Pathology, Albert Einstein College of Medicine, Bronx, NY 10461, USA.
¹⁹ Department of Psychiatry, Division of Research, The Zucker Hillside Hospital Division of Northwell Health, Glen Oaks, NY 11004, USA; Departments of Psychiatry and Molecular Medicine, Zucker School of Medicine at Hofstra/Northwell, Hempstead, NY 11550, USA; Institute for Behavioral Science, The Feinstein Institutes for Medical Research, Manhasset, NY 11030, USA.
²⁰ Department of Medieval History, University of Erfurt, 99089 Erfurt, Germany.
²¹ Independent Scholar, 92370 Chaville, France.
²² Department of History and Art History, Utrecht University, Utrecht 3512 BS, the Netherlands.
²³ Department of Archaeogenetics, Max Planck Institute for Evolutionary Anthropology, 04103 Leipzig, Germany.
²⁴ Department of Human Evolutionary Biology, Harvard University, Cambridge, MA 02138, USA; Department of Archaeogenetics, Max Planck Institute for Evolutionary Anthropology, 04103 Leipzig, Germany.
²⁵ World Heritage Coordinator, City of Erfurt, 99084 Erfurt, Germany.
²⁶ Braun School of Public Health and Community Medicine, The Hebrew University of Jerusalem, Jerusalem 9112102, Israel. Electronic address: shai.carmi@huji.ac.il.
²⁷ Department of Human Evolutionary Biology, Harvard University, Cambridge, MA 02138, USA; Department of Genetics, Harvard Medical School, Boston, MA 02115, USA; Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA; Howard Hughes Medical Institute, Harvard Medical School, Boston, MA 02115, USA. Electronic address: reich@genetics.med.harvard.edu.

PMID: 36455558
PMCID: PMC9793425
DOI: 10.1016/j.cell.2022.11.002

Abstract

We report genome-wide data from 33 Ashkenazi Jews (AJ), dated to the 14^th century, obtained following a salvage excavation at the medieval Jewish cemetery of Erfurt, Germany. The Erfurt individuals are genetically similar to modern AJ, but they show more variability in Eastern European-related ancestry than modern AJ. A third of the Erfurt individuals carried a mitochondrial lineage common in modern AJ and eight carried pathogenic variants known to affect AJ today. These observations, together with high levels of runs of homozygosity, suggest that the Erfurt community had already experienced the major reduction in size that affected modern AJ. The Erfurt bottleneck was more severe, implying substructure in medieval AJ. Overall, our results suggest that the AJ founder event and the acquisition of the main sources of ancestry pre-dated the 14^th century and highlight late medieval genetic heterogeneity no longer present in modern AJ.

Keywords: Ashkenazi Jews; IBD sharing; admixture; ancient DNA; demographic inference; founder event; mitochondrial DNA; pathogenic variants; population structure; runs of homozygosity.

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Conflict of interest statement

Declaration of interests S.C. is a paid consultant and holds stock options at MyHeritage. D.B. is an employee and shareholder at The Janssen Pharmaceutical Companies of Johnson & Johnson. É.H. is an employee of 23andMe.

Figures

**Figure 1.. The medieval Jewish cemetery at Erfurt**
(A) The layout of the cemetery. The inner city wall and the outer city wall are at the bottom and top of the map, respectively. Family members are marked in red ellipses (see next). (B) The pedigrees of the two families identified based on first degree relationships. Black symbols represent individuals with DNA; gray symbols represent inferred family members. Circles: females; squares: males. For each individual, we indicate the ID, the number of genotyped SNPs, the estimated age at death, and the ¹⁴C date (95.4% probability intervals). See also Figure S1.

**Figure 2.. Principal components analysis**
We learned the principal components (PCs) using West Eurasian populations (Lazaridis et al., 2014) and projected the Erfurt individuals (filled red circles) onto the inferred axes. Modern Ashkenazi Jews (green squares), Jews of non-Ashkenazi origin (pink shapes), and Mediterranean populations (teal shapes) are highlighted. The inset zooms in on the region that contains AJ individuals. See also Figure S2.

**Figure 3.. Models for the ancestry of Erfurt Ashkenazi Jews**
(A) Each qpAdm model for the ancestry of Erfurt Jews includes a Middle Eastern, a Southern European, and an Eastern European (Russians) source. The Southern European source was either South or North Italians, as indicated at the top of each panel. The Middle Eastern source is indicated in the x axis labels. Only models with qpAdm p value >0.05 in the main analysis and in the robustness tests are shown (Table S3). Error bars represent one standard error in each direction. qpAdm p values are presented above each model. (B) The ancestry of single Erfurt individuals, labeled by their IDs. We used qpAdm with Russian, Lebanese, and South Italian sources. The individuals are labeled by their Erfurt subgroup (EU/ME). qpAdm p values are shown for each individual. Results are not shown for low-coverage individuals (<50k SNPs), and for an additional individual who could not be modeled using these sources (p < 0.05). (C) A plot of δ¹³C_enamel and δ¹⁸O_enamel stable isotope ratios for a subset of 20 Erfurt individuals with >200k SNPs. The Erfurt subgroup affiliation (EU/ME) is color-coded (legend). See also Figure S3.

**Figure 4.. Models for AJ demographic history based on ancient and modern haplotypes**
(A) A single-population model for the demographic history of AJ, inferred based on modern IBD sharing (Table S5, model [A]). In the diagram, the y axis represents the time in generations before present (gbp) and the width is (schematically) proportional to the effective population size. The 95% confidence intervals (CI) were computed using bootstrapping and are indicated near each parameter. (B) The mean number of IBD and ROH segments (per pair of haploid autosomal genomes) in modern AJ vs. segment length (11 bins between 4 and 15 cM). Each symbol (circles for IBD, triangles for ROH) is placed at the middle of its corresponding bin. The red line shows the expected number of segments per bin based on the demographic model of (A). (C) The total length of ROH segments in 16 EAJ individuals with >400k SNPs. The bars are colored proportionally to the contribution of segments of different lengths (legend). (D) ROH counts in EAJ (circles) and the expected number based on various models (lines). The model inferred using modern IBD (panel [A]) is in red. The same model but allowing consanguinity in EAJ (Table S5, model [D]) is in green. Both models fit poorly to short ROH segments. A model similar to (A) but with either a narrower or a longer bottleneck (Table S5, models [E] and [F], respectively) are in purple and teal, respectively. (E) A two-population model inferred jointly using IBD in MAJ and ROH in EAJ (Table S5, model [H]). According to the model, the ancestral population split T_b = 46 generations ago into one population of effective size N_b = 627 (representing Erfurt, indicated in red) and another of size N_a − N_b. At the end of the bottleneck, the two populations merged with proportions f = 52% and 1 − f, respectively, and expanded exponentially as in the single-population model. The time of sampling of the Erfurt population is shown at 26 generations ago (assuming 25 years per generation). (F) Counts of IBD segments in MAJ (green circles; same data as in [B]) and ROH in EAJ (black circles; same data as in [D]), and the expectations (lines) based on the two-population model of (E) (MAJ, red; EAJ, pink). See also Figures S4 and S5.

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Genome-wide data from medieval German Jews show that the Ashkenazi founder event pre-dated the 14^th century

Affiliations

Genome-wide data from medieval German Jews show that the Ashkenazi founder event pre-dated the 14^th century

Authors

Affiliations

Abstract

Conflict of interest statement

Figures

References

MeSH terms

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