The matrilineal ancestry of Ashkenazi Jewry: portrait of a recent founder event

Abstract

Both the extent and location of the maternal ancestral deme from which the Ashkenazi Jewry arose remain obscure. Here, using complete sequences of the maternally inherited mitochondrial DNA (mtDNA), we show that close to one-half of Ashkenazi Jews, estimated at 8,000,000 people, can be traced back to only 4 women carrying distinct mtDNAs that are virtually absent in other populations, with the important exception of low frequencies among non-Ashkenazi Jews. We conclude that four founding mtDNAs, likely of Near Eastern ancestry, underwent major expansion(s) in Europe within the past millennium.

Figure 1

Most parsimonious tree of complete Hg K mtDNA sequences. The tree is rooted in Hg U* and includes 121 mtDNAs, of which 28 are novel and 93 were reported elsewhere (12 sequences from Finnila et al. [2001], 1 from Maca-Meyer et al. [2001], 47 from Herrnstadt et al. [2002] [including the control-region information that was not reported], 1 from Mishmar et al. [2003], 28 from Coble et al. [2004], 2 from Palanichamy et al. [2004], and 2 from Achilli et al. [2005]). The genotyping information from Finnila et al. (2001) included herein corrects several inaccuracies that were reported elsewhere for the control-region phylogeny. Mutations are shown on the branches and are transitions unless the base change is explicitly indicated. Deletions are indicated by a “D” following the deleted nucleotide position. Insertions are indicated by a dot followed by the number and type of inserted nucleotide(s). Underlined nucleotide positions occur at least twice in the tree. An asterisk (*) at the end of a nucleotide position denotes a reversion. The information of the reported samples is presented in table 3. Samples in blue are from Ashkenazi Jews. Nucleotide positions in red were assayed in the entire set of 789 mtDNAs belonging to K. To resolve three possible reticulations, reversions at nucleotide 7082 in sample A01 and nucleotides 10398 and 11485 in sample H510 and a homoplasy at nucleotide 7927 for subHg K1a1a and K1a8 were assumed. The tree was drawn by hand from networks constructed using program Network 4.1.0.0. We applied the reduced-median algorithm (ρ=2) followed by the median-joining algorithm (ε=2), as described at the Fluxus Engineering Web site. The control-region positions were twofold down-weighted, with respect to coding-region positions. The hypervariable nucleotides 16182 and 16183 in HVS-I and the indels at nucleotides 309, 315, and 524 in HVS-II were excluded. Coding-region mutations at nucleotides 750, 1438, 1811, 2706, 4769, 7028, 8860, 11467, 11719, and 12308 are not shown unless reverted. Ethnic designation of the sequences was available for the sequences reported by Finnila et al. (2001), Maca-Meyer et al. (2001), Palanichamy et al. (2004), and Achilli et al. (2005), and for the novel samples reported herein (table 3).

Figure 2

The location of the three Ashkenazi lineages (light blue) belonging to Hg K in a global set of complete K sequences. For the network construction, first, a topology network encompassing the 91 branches found in the total set of 121 complete K sequences was drawn using the same principles described in figure 1. For simplicity, we used only one complete mtDNA sequence per node, and we indicate only the coding-region nucleotide positions that are relevant in the context of the three Ashkenazi lineages K1a1b1a, K1a9, and K2a2a, with the exception of positions 497, 498D, and 16524, which define K1a, K1c, and K1a9, respectively. Branch lengths were sometimes distorted to increase legibility. Then, the topology network was compared with a second phylogenetic tree of the entire set of 789 K mtDNAs analyzed hierarchically for the diagnostic mutations (red). All Jews of North African, Caucasian, Near Eastern, and Spanish-exile ancestry were aggregated into the category of “non-Ashkenazi Jews.” Likewise, all non-Jewish samples from Anatolia, the Caucasus, central and southwestern Asia, and the Near East were aggregated into the category of “West Asia.” Circle sizes are proportional to the haplotype frequency in the sample.

Figure 3

Most parsimonious tree of complete Hg N1b mtDNA sequences. The tree encompasses the two complete Ashkenazi N1b sequences and one previously published sequence (Maca-Meyer et al. 2001). The same considerations detailed in figure 1 are relevant here. Nucleotide positions 11928 and 12092 (bold) were examined in all N1b mtDNAs.