Genetics of Ashkenazi Jews

Ashkenazi Jews (/ˌɑːʃkəˈnɑːzi, ˌæʃ-/ AHSH-kə-NAH-zee, ASH-;[18] Hebrew: יְהוּדֵי אַשְׁכְּנַז, romanizedYehudei Ashkenaz, lit. ’Jews of Germania‘; Yiddish: אַשכּנזישע ייִדן, romanizedAshkenazishe Yidn), also known as Ashkenazic Jews or Ashkenazim,[a] are a Jewish diaspora population who coalesced in the Holy Roman Empire around the end of the first millennium CE.[20] Their traditional diaspora language is Yiddish (a West Germanic language with Jewish linguistic elements, including the Hebrew alphabet),[20] which developed during the Middle Ages after they had moved from Germany and France into Northern Europe and Eastern Europe. For centuries, Ashkenazim in Europe used Hebrew only as a sacred language until the revival of Hebrew as a common language in 20th-century Israel.

Throughout their numerous centuries living in Europe, Ashkenazim have made many important contributions to its philosophy, scholarship, literatureartmusic, and science.[21][22][23][24]

The rabbinical term Ashkenazi refers to diaspora Jews who established communities along the Rhine in western Germany and northern France during the Middle Ages.[25] Upon their arrival, they adapted traditions carried over from the Holy LandBabylonia, and the western Mediterranean to their new European environment.[26] The Ashkenazi religious rite developed in cities such as MainzWorms, and Troyes. The eminent rishon from medieval France, Rashi, has had a significant influence on the interpretations of Judaism by Ashkenazim.

In the late Middle Ages, due to widespread persecution, the majority of the Ashkenazi population steadily shifted eastward,[27] moving out of the Holy Roman Empire into the areas that later became part of the Polish–Lithuanian Commonwealth; these areas today comprise parts of present-day BelarusEstoniaLatviaLithuaniaMoldovaPolandRussiaSlovakia, and Ukraine.[28][29]

Over the course of the late-18th and 19th centuries, those Jews who remained in or returned to historical German lands generated a cultural reorientation; under the influence of the Haskalah and the struggle for emancipation as well as the intellectual and cultural ferment in urban centres, they gradually abandoned the use of Yiddish and adopted German while developing new forms of Jewish religious life and cultural identity.[30]

It is estimated that in the 11th century, Ashkenazim comprised 3 percent of the global Jewish population, while an estimate made in 1930 (near the population’s peak) listed them as comprising 92 percent of the world’s Jewish population. However, the Ashkenazi population was decimated shortly after as a result of the Holocaust that was carried out by Nazi Germany during World War II, which affected almost every Jewish European family. Immediately prior to the Holocaust, the worldwide Jewish population stood at approximately 16.7 million people. Statistical figures vary for the contemporary demography of Ashkenazi Jews, ranging from 10 million[1] to 11.2 million.[2] Israeli demographer and statistician Sergio D. Pergola, in a rough calculation of Sephardi Jews and Mizrahi Jews, implies that Ashkenazi Jews made up 65–70 percent of Jews worldwide in 2000.[35] Other estimates place the Ashkenazim as comprising upwards of 75 percent of the global Jewish population.[36]

Genetic studies on Ashkenazi Jews—researching both their paternal and maternal lineages as well as autosomal DNA—indicate that they are of mixed Levantine and European (mainly western European and southern European) ancestry. These studies have arrived at diverging conclusions regarding both the degree and the sources of their European admixture, with some focusing on the extent of the European genetic origin observed in Ashkenazi maternal lineages, which is in contrast to the predominant Middle Eastern genetic origin observed in Ashkenazi paternal lineages.

Genetics Origins

Efforts to identify the origins of Ashkenazi Jews through DNA analysis began in the s. Currently, there are three types of genetic origin testing, autosomal DNA (atDNA), mitochondrial DNA (mtDNA), and Y-chromosomal DNA (Y-DNA). Autosomal DNA is a mixture from an individual’s entire ancestry, Y-DNA shows a male’s lineage only along his strict paternal line, mtDNA shows any person’s lineage only along the strict maternal line. Genome-wide association studies have also been employed to yield findings relevant to genetic origins.

Like most DNA studies of human migration patterns, the earliest studies on Ashkenazi Jews focused on the Y-DNA and mtDNA segments of the human genome. Both segments are unaffected by recombination (except for the ends of the Y chromosome – the pseudoautosomal regions known as PAR and PAR), thus allowing tracing of direct maternal and paternal lineages.

These studies revealed that Ashkenazi Jews originate from an ancient (– BCE) population of the Middle East who had spread to Europe. Ashkenazic Jews display the homogeneity of a genetic bottleneck, meaning they descend from a larger population whose numbers were greatly reduced but recovered through a few founding individuals. Although the Jewish people, in general, were present across a wide geographical area as described, genetic research done by Gil Atzmon of the Longevity Genes Project at Albert Einstein College of Medicine suggests “that Ashkenazim branched off from other Jews around the time of the destruction of the First Temple, , years ago … flourished during the Roman Empire but then went through a ‘severe bottleneck’ as they dispersed, reducing a population of several million to just families who left Northern Italy around the year for Central and eventually Eastern Europe.”

Various studies have arrived at diverging conclusions regarding both the degree and the sources of the non-Levantine admixture in Ashkenazim, particularly with respect to the extent of the non-Levantine genetic origin observed in Ashkenazi maternal lineages, which is in contrast to the predominant Levantine genetic origin observed in Ashkenazi paternal lineages. All studies nevertheless agree that genetic overlap with the Fertile Crescent exists in both lineages, albeit at differing rates. Collectively, Ashkenazi Jews are less genetically diverse than other Jewish ethnic divisions, due to their genetic bottleneck.

Male lineages: Y-chromosomal DNA
The majority of genetic findings to date concerning Ashkenazi Jews conclude that the male lines were founded by ancestors from the Middle East.

A study of haplotypes of the Y-chromosome, published in , addressed the paternal origins of Ashkenazi Jews. Hammer et al. found that the Y-chromosome of Ashkenazi and Sephardic Jews contained mutations that are also common among other Middle Eastern peoples, but uncommon in the autochthonous European population. This suggested that the male ancestors of the Ashkenazi Jews could be traced mostly to the Middle East. The proportion of male genetic admixture in Ashkenazi Jews amounts to less than .% per generation over an estimated generations, with “relatively minor contribution of European Y chromosomes to the Ashkenazim,” and a total admixture estimate “very similar to Motulsky’s average estimate of .%.” This supported the finding that “Diaspora Jews from Europe, Northwest Africa, and the Near East resemble each other more closely than they resemble their non-Jewish neighbors.” “Past research found that – percent of DNA from the Ashkenazi Y chromosome, which is used to trace the male lineage, originated in the Near East,” Richards said. The population has subsequently spread out.

A study by Nebel et al. showed that both Ashkenazi and Sephardic Jewish populations share the same overall paternal Near Eastern ancestries. In comparison with data available from other relevant populations in the region, Jews were found to be more closely related to groups in the north of the Fertile Crescent. The authors also report on Eu (Ra) chromosomes, which are very frequent in Central and Eastern Europeans (–%) at elevated frequency (%) in Ashkenazi Jews. They hypothesized that the differences among Ashkenazim Jews could reflect low-level gene flow from surrounding European populations or genetic drift during isolation. A later study by Nebel et al., found a similar level of .% of male Ashkenazim belonging to Raa (M+), the dominant Y-chromosome haplogroup in Central and Eastern Europeans. However, a study, concentrating on the Ashkenazi Levites where the proportion reaches %, while signalling that there’s a “rich variation of haplogroup Ra outside of Europe which is phylogenetically separate from the typically European Ra branches”, precises that the particular Ra-Y sub-clade testifies for a local origin, and that the “Middle Eastern origin of the Ashkenazi Levite lineage based on what was previously a relatively limited number of reported samples, can now be considered firmly validated.”

Female lineages: Mitochondrial DNA
Before , geneticists had largely attributed the ethnogenesis of most of the world’s Jewish populations, including Ashkenazi Jews, to Israelite Jewish male migrants from the Middle East and “the women from each local population whom they took as wives and converted to Judaism.” Thus, in , in line with this model of origin, David Goldstein, now of Duke University, reported that unlike male Ashkenazi lineages, the female lineages in Ashkenazi Jewish communities “did not seem to be Middle Eastern”, and that each community had its own genetic pattern and even that “in some cases the mitochondrial DNA was closely related to that of the host community.” In his view, this suggested, “that Jewish men had arrived from the Middle East, taken wives from the host population and converted them to Judaism, after which there was no further intermarriage with non-Jews.”

In , a study by Behar et al., based on what was at that time high-resolution analysis of haplogroup K (mtDNA), suggested that about % of the current Ashkenazi population is descended matrilineally from just four women, or “founder lineages”, that were “likely from a Hebrew/Levantine mtDNA pool” originating in the Middle East in the st and nd centuries CE. Additionally, Behar et al. suggested that the rest of Ashkenazi mtDNA is originated from ~ women, and that most of those were also likely of Middle Eastern origin. In reference specifically to Haplogroup K, they suggested that although it is common throughout western Eurasia, “the observed global pattern of distribution renders very unlikely the possibility that the four aforementioned founder lineages entered the Ashkenazi mtDNA pool via gene flow from a European host population”.

In , a study of Ashkenazi mitochondrial DNA by a team led by Martin B. Richards of the University of Huddersfield in England reached different conclusions, in line with the pre- origin hypothesis. Testing was performed on the full , DNA units composing mitochondrial DNA (the Behar study had only tested , units) in all their subjects, and the study found that the four main female Ashkenazi founders had descent lines that were established in Europe , to , years in the past while most of the remaining minor founders also have a deep European ancestry. The study argued that the great majority of Ashkenazi maternal lineages were not brought from the Near East or the Caucasus, but instead assimilated within Europe, primarily of Italian and Old French origins. The Richards study estimated that more than percent of Ashkenazi maternal ancestry comes from women indigenous to (mainly prehistoric Western) Europe, and only percent from the Near East, while the origin of the remainder is undetermined. According to the study these findings “point to a significant role for the conversion of women in the formation of Ashkenazi communities.” Karl Skorecki criticized the study for perceived flaws in phylogenetic analysis. “While Costa et al have re-opened the question of the maternal origins of Ashkenazi Jewry, the phylogenetic analysis in the manuscript does not ‘settle’ the question.”

A study by Fernández et al. found that Ashkenazi Jews display a frequency of haplogroup K in their maternal DNA, suggesting an ancient Near Eastern matrilineal origin, similar to the results of the Behar study in . Fernández noted that this observation clearly contradicts the results of the study led by Richards that suggested a European source for exclusively Ashkenazi K lineages.

Association and linkage studies (autosomal dna)
In genetic epidemiology, a genome-wide association study (GWA study, or GWAS) is an examination of all or most of the genes (the genome) of different individuals of a particular species to see how much the genes vary from individual to individual. These techniques were originally designed for epidemiological uses, to identify genetic associations with observable traits.

A study by Seldin et al. used over five thousand autosomal SNPs to demonstrate European genetic substructure. The results showed “a consistent and reproducible distinction between ‘northern’ and ‘southern’ European population groups”. Most northern, central, and eastern Europeans (Finns, Swedes, English, Irish, Germans, and Ukrainians) showed >% in the “northern” population group, while most individual participants with southern European ancestry (Italians, Greeks, Portuguese, Spaniards) showed >% in the “southern” group. Both Ashkenazi Jews as well as Sephardic Jews showed >% membership in the “southern” group. Referring to the Jews clustering with southern Europeans, the authors state the results were “consistent with a later Mediterranean origin of these ethnic groups”.

A study by Bauchet et al. found that Ashkenazi Jews were most closely clustered with Arabic North African populations when compared to Global population, and in the European structure analysis, they share similarities only with Greeks and Southern Italians, reflecting their east Mediterranean origins.

A study on Jewish ancestry by Atzmon-Ostrer et al. stated “Two major groups were identified by principal component, phylogenetic, and identity by descent (IBD) analysis: Middle Eastern Jews and European/Syrian Jews. The IBD segment sharing and the proximity of European Jews to each other and to southern European populations suggested similar origins for European Jewry and refuted large-scale genetic contributions of Central and Eastern European and Slavic populations to the formation of Ashkenazi Jewry”, as both groups – the Middle Eastern Jews and European/Syrian Jews – shared common ancestors in the Middle East about years ago. The study examines genetic markers spread across the entire genome and shows that the Jewish groups (Ashkenazi and non-Ashkenazi) share large swaths of DNA, indicating close relationships and that each of the Jewish groups in the study (Iranian, Iraqi, Syrian, Italian, Turkish, Greek and Ashkenazi) has its own genetic signature but is more closely related to the other Jewish groups than to their fellow non-Jewish countrymen. Atzmon’s team found that the SNP markers in genetic segments of million DNA letters or longer were times more likely to be identical among Jews than non-Jews. Results of the analysis also tally with biblical accounts of the fate of the Jews. The study also found that with respect to non-Jewish European groups, the population most closely related to Ashkenazi Jews are modern-day Italians. The study speculated that the genetic-similarity between Ashkenazi Jews and Italians may be due to inter-marriage and conversions in the time of the Roman Empire. It was also found that any two Ashkenazi Jewish participants in the study shared about as much DNA as fourth or fifth cousins.

A study by Bray et al., using SNP microarray techniques and linkage analysis found that when assuming Druze and Palestinian Arab populations to represent the reference to world Jewry ancestor genome, between and percent of the modern Ashkenazi genome can possibly be of European origin, and that European “admixture is considerably higher than previous estimates by studies that used the Y chromosome” with this reference point. Assuming this reference point the linkage disequilibrium in the Ashkenazi Jewish population was interpreted as “matches signs of interbreeding or ‘admixture’ between Middle Eastern and European populations”. On the Bray et al. tree, Ashkenazi Jews were found to be a genetically more divergent population than Russians, Orcadians, French, Basques, Sardinians, Italians and Tuscans. The study also observed that Ashkenazim are more diverse than their Middle Eastern relatives, which was counterintuitive because Ashkenazim are supposed to be a subset, not a superset, of their assumed geographical source population. Bray et al. therefore postulate that these results reflect not the population antiquity but a history of mixing between genetically distinct populations in Europe. However, it is possible that the relaxation of marriage prescription in the ancestors of Ashkenazim drove their heterozygosity up, while the maintenance of the FBD rule in native Middle Easterners has been keeping their heterozygosity values in check. Ashkenazim distinctiveness as found in the Bray et al. study, therefore, may come from their ethnic endogamy (ethnic inbreeding), which allowed them to “mine” their ancestral gene pool in the context of relative reproductive isolation from European neighbors, and not from clan endogamy (clan inbreeding). Consequently, their higher diversity compared to Middle Easterners stems from the latter’s marriage practices, not necessarily from the former’s admixture with Europeans.

The genome-wide genetic study carried out in by Behar et al. examined the genetic relationships among all major Jewish groups, including Ashkenazim, as well as the genetic relationship between these Jewish groups and non-Jewish ethnic populations. The study found that contemporary Jews (excluding Indian and Ethiopian Jews) have a close genetic relationship with people from the Levant. The authors explained that “the most parsimonious explanation for these observations is a common genetic origin, which is consistent with an historical formulation of the Jewish people as descending from ancient Hebrew and Israelite residents of the Levant”.

A study by Behar et al. () found evidence in Ashkenazim of mixed European and Levantine origins. The authors found the greatest affinity and shared ancestry of Ashkenazi Jews to be firstly with other Jewish groups from southern Europe, Syria, and North Africa, and secondly with both southern Europeans (such as Italians) and modern Levantines (such as the Druze, Cypriots, Lebanese and Samaritans). In addition to finding no affinity in Ashkenazim with northern Caucasus populations, the authors found no more affinity in Ashkenazi Jews to modern south Caucasus and eastern Anatolian populations (such as Armenians, Azerbaijanis, Georgians, and Turks) than found in non-Ashkenazi Jews or non-Jewish Middle Easterners (such as the Kurds, Iranians, Druze and Lebanese).

A autosomal study by Xue, Shai Carmi et al. found an admixture of Middle-Eastern and European ancestry in Ashkenazi Jews: with the European component comprising ≈%-% (estimated at “possibly %”) and largely being of a Southern European source with a minority being Eastern European, and the remainder (estimated at possibly ≈%) being Middle Eastern ancestry showing the strongest affinity to Levantine populations such as the Druze and Lebanese.

A study, referencing the popular theory of Ashkenazi Jewish (AJ) origins in “an initial settlement in Western Europe (Northern France and Germany), followed by migration to Poland and an expansion there and in the rest of Eastern Europe”, tested “whether Ashkenazi Jews with recent origins in Eastern Europe are genetically distinct from Western European Ashkenazi”. The study concluded that “Western AJ consist of two slightly distinct groups: one that descends from a subset of the original founders [who remained in Western Europe], and another that migrated there back from Eastern Europe, possibly after absorbing a limited degree of gene flow”.