The Molecular Genetic Basis of Jewish Geography

Even before Facebook, LinkedIn and other social media outlets, Jews have long participated in and understood the value of social networking with other Jews. It is amazing how often and how quickly two Jews who do not otherwise know one another can identify the threads that connect them to Jewish individuals that they have in common. This “game” of Jewish geography presumably developed as a social custom among a people who is relatively small in number and yet widely distributed around the world. It is an example of the broader phenomenon known as six degrees of separation proposed by Hungarian writer Frigyes Karinthy in 1929 and further explored in the small world experiment by social psychologist Stanley Milgram in 1967.

For Jews, however, the game is more than a social phenomenon – it is a testament to the belief, in some cases literally and in others metaphorically, that the Jews share a common ancestry, even going all the way back to the patriarchs and to Joseph, Moses, Aaron and the tribal leaders described in the Biblical narrative. Thus, Judaism is as much about peoplehood, shared ancestry and community as it is about religion, it’s rituals and creed.

The recent advances in genetics, especially DNA sequencing, are beginning to reveal the underlying biological relationships among the Jewish people and their history. The advances also provide information of the interaction between Jews and other population groups. The resulting evidence-based data and information puts to the test our understanding of an individual’s Jewishness as well as our ability to define genetically Jews as a population group. Of course, such derived knowledge is not without social, cultural, ethical and clearly religious implications and consequences.

Advances in genetics and DNA sequencing.
An organism’s genes are encoded in DNA – a large molecule that consists of four different subunit compounds, also known as bases and commonly referred to by the letters A, T, G and C. These bases/letters are chemically linked together in a linear sequence. An organism’s entire complement of genes and corresponding DNA sequences is referred to as the organism’s genome. The human genome, encoding some 20 to 30,000 genes, is made up of 3,000,000,000 (3 Billion!) bases. With the exception of identical twins, what distinguishes us genetically from one another is that there are, on average, 3 million bases in the genome where we differ. In short, it’s the 99.9% of the genome that are identical that makes us human, but it’s the 0.1% of the genome that make us different from one another.

Reduction in cost of human genome sequencing (green line) over the first 15 years of the 21^st century, compared to reduction in cost and increased capacity of computer chips (Moore’s law) over the same time period.

As the costs of determining DNA sequences have come down dramatically, even faster than the costs for manufacturing increasingly powerful computer chips (see above), there is increasing opportunity to compare sequence information across living individuals and even across humans who lived hundreds and even thousands of years ago. And because mating is not random, it is possible to group subpopulations of humans based on comparing shared sequences. As a result of the availability of an ever-increasing amount of sequence data and of more sophisticated computational methods for comparing sequences, a genetic map of the worldwide Jewish population is coming into view.

Historical significance of Jewish population genetic associations.
While not everyone may agree with all of the findings, the emerging picture ¹see for example Ostrer, H. 2012. Legacy, A genetic history of the Jewish people. Oxford University Press;  Flegontov, P. 2016. Pitfalls of the geographic population structure approach applied to human genetic history: A case study of Ashkenazi Jews. Genome Biol. Evol. 8: 2259-2265 of the genetic history of the Jews begins in antiquity, with small founding populations in the Middle East, and develops through centuries of mating choices, population bottlenecks, global migrations and admixtures with other populations. Tracking populations genetically leads to more informed historical hypotheses about the experience of Jews throughout the ages. As an example, genetic relationships suggest that some individuals living in the Americas today may be the descendants of Jews exiled from the Iberian Peninsula during the Inquisition; however, often such individuals are unaware of their connection to the Jewish community.

Genetic basis of Jewish religious identity.
DNA sequencing is also helpful as a complement to other genealogical approaches for individuals trying to determine their ancestry and genetic relationships. Given the availability of the genetic data, there are some who seek to identify and use a genetic test to assess an individual’s claim of Jewish identity. Although non-Jews may gain entry to the Jewish community through a conversion process that includes education and participation in rituals (e.g. brit milah circumcision for males and ritual mikvah bathing), some rabbinical authorities seem willing to accept genetic data alone ²“Who is a Jew?” can now be answered by genetic testing. Jerusalem Post. Oct. 3, 2017. If such data were verified and more widely accepted, individuals with the “approved” gene sequences would be able to perform and participate in rituals from which non-Jews are excluded. For example, some people from the former Soviet Union could be considered Jewish in the absence of other evidence, including proof of matrilineal descent from a Jewish mother and rabbinically supervised and sanctioned conversion.

The genetic basis of such a Jewish genetic test relies on the identification of specific sequences found in mitochondrial DNA that is transmitted to the child only from the mother. Some specific mitochondrial DNA sequences occur at greater frequency, but not exclusively, in Jews than non-Jewish populations. Further complicating the picture is that very recently rare exceptions to the exclusive inheritance of mitochondrial DNA from the maternal parent have been demonstrated; i.e. a few children have mitochondrial DNA from their fathers.

Similarly, there have been efforts to look at DNA sequence data to address the issue of patrilineal descent. In terms of its religious relevance, patrilineal descent has been the determining factor in assigning Cohanim status to a subset of Jewish individuals who are considered to be of the Levitical line (descendants of Aaron). Traditionally, these individuals are eligible to perform certain priestly functions not given to non-priestly Jews. As this status is patrilineal, the search for Cohanim-specific DNA markers focuses on the inheritance of DNA contained on the Y (male sex-determining) chromosome. It has been found that though certain Y chromosome DNA markers are more frequently associated with individuals who identify as Cohanim, there are no markers that are restricted and exclusive to them. It should be noted that in some communities and denominations the female children of Cohanim are permitted to perform priestly duties.

Given all of the challenges and caveats in analyzing and interpreting the data, genetic testing of Jewish identity with respect to participation in religious ritual is controversial and complicated. Given the lack of what in the industry are called product specifications, we must be exceedingly careful and constrained in ascribing a DNA-encoded specification for who is a Jew ³Lewontin, R.C., Is there a Jewish Gene?, Dec 6, 2012.

Jews, health and race issues
It has been known for quite some time that certain diseases occur in Jews, or certain Jewish subpopulations, more frequently than in other human groups. For example, Tay-Sachs disease is one of a number of clinical so-called inborn errors of metabolism that occurs at much greater frequency in Ashkenazi Jews than in other groups, including other Jewish groups. In many cases, the genes associated with these diseases have been identified, leading to diagnostic tests and services to reduce the risk of these diseases and their inheritance.(In comparison to the Ashkenazi situation, Sephardi and Mizrahi Jews are more genetically diverse and are less well-studied. Thus, the medical genetics of these latter populations are more complicated and less well understood).

Importantly, in addition to its more limited relevance to Jews and their diseases, there is an intense research effort in the United States and around the world to identify specific genes associated with clinical disease outcomes. These efforts are often described as “personalized” and “precision” medicine, and are focused on developing prevention and treatment methods with more specific and individualized benefit. Although there is great potential benefit in such genetic association studies, there is a risk that population level findings will be misinterpreted and used to make associations with certain groups rather than with individuals. This is especially true when efforts are made to identify genetic associations with complex traits, such as intelligence and related cognitive abilities, as well as athletic aptitude, that are associated with many different genes, and whose expression is affected by environmental and cultural conditions.

Currently, there is an active debate among social and biological scientists regarding population-level genetic associations and the use of the term race. Is race a social construct, or a biologically defined grouping? Given the long and most often negative history (eugenics movement, Nazism, antisemitism) of studying Jews’ biological origins, we must be especially sensitive to how race and related terms are applied. The question remains, how do/should Jews collectively describe themselves in terms of community, peoplehood and religion?

In conclusion, the revolution in genetics and genomics is telling us a lot about ourselves as the Jewish people, including our documented history, our migration patterns in the diaspora, our biology and clinical conditions, and, questionably, our relationship to Judaism. It’s a complicated and presently incomplete story, although efforts are being made to collect, store and analyze larger numbers of “Jewish” DNA samples to address some of these questions and hypotheses already raised from available data and analyses.

Regardless, we must be wise in interpreting and using the data and information gained from the available cumulative results. It is one thing to accept on faith the biblical and especially the Exodus narrative as our origin story; it is quite another to link that narrative with what the DNA sequence data reveals. As Jews by choice often remind us, one can feel Jewish and identify as Jews even if one is not descended from the matriarchs and patriarchs.

(This post is part of Sinai and Synapses’ project Scientists in Synagogues, a grass-roots program to offer Jews opportunities to explore the most interesting and pressing questions surrounding Judaism and science. Michael Gottlieb, Ph.D is the retired Director, of Science at the Foundation for the National Institutes of Health (FNIH), where he managed and led research projects, funded by the Bill & Melinda Gates Foundation, on global infectious diseases. He is also a member of Sutton Place Synagogue in New York, NY).