The Wandering Gene and the Indian Princess

by Jeff Wheelwright

  Harry’s e-mail touched on a third factor at work in the Jewish genome: selection. This is the Darwinian process working at the level of genes. Simply put, natural selection means the bad stuff is weeded out because carriers of harmful mutations usually don’t do as well as their rivals in the mating game. But when individuals carry good stuff—genes that respond favorably to the environment and boost the carriers’ fitness and possibilities for finding mates—their DNA is likely to multiply in subsequent generations. As new mutations emerge at random in a population, natural selection puts them to the test. Occasionally there will be a change in the DNA that both hurts and helps an individual, as it makes her less fit in one respect but more fit in another. (The classic example is sickle-cell anemia, discussed below.) It’s not impossible that 185delAG, a dark cloud of disadvantage in the human genome, has a silver lining too. The mutation might have been beneficial in the past, when environmental conditions were different.

  The breast-cancer mutation 185delAG entered the gene pool of Judeans around the time of the Babylonian captivity, some twenty-five hundred years ago. Random and unbidden, it appeared on the chromosome of a single person, who is known as the founder. In the same sense that Abraham is said to have founded the Jewish people, scientists call the person at the top of a genetic pyramid a founder. Whether a man or a woman, this particular founder was born missing the letters A and G at the 185 site on one copy of his or her BRCA1 gene. The deletion of the two letters interrupted the genetic code and disabled the gene’s protective function. The mutation wasn’t immediately harmful to the founder because he or she had another copy of the gene that worked.

  The 185delAG mutation is very old. How do the researchers know when its founder lived? The date was deduced from historical evidence. When Jerusalem was restored to them, not all the Judean exiles returned from Babylon. The ones who stayed behind are the ancestors of Iraqi Jews, who are today much reduced in number, but for centuries they were a venerable center of the faith. In addition to the Jews living in Mesopotamia and Jerusalem, satellite communities had sprung up elsewhere in the Middle East. A decentralization of the gene pool had begun, and the distances between groups acted as barriers to the exchange of DNA, barriers that persisted into the modern era. In the 1990s, when scientists in Israel tested BRCA1 carriers from the dispersed Jewish populations, they discovered that all had the same spelling in the genetic region of 185delAG. Clearly this was a universal Jewish mutation. But some of the matches between groups were off by a letter or two, which indicated minor changes since they had split apart. Rolling back the demographic clock, the scientists inferred that the mutation’s founder must have lived before the groups divided—i.e., prior to the Babylonian watershed.

  Keep in mind that this sort of research, dating a genetic mutation, could not have been done on another people. It requires the subjects to have maintained historical records—the cultural cladding around their genes—for three millennia. Inbreeding was a helpful factor too, because it created consistent hallmarks within the hodgepodge of DNA. Even Zionism abetted the task, because it led to the state of Israel, which drew Jews from all over the world and recentralized the DNA, thereby easing the research costs. Not to be overlooked are the native interests of the researchers themselves, what sociologists delicately call the ethnic concordance. Since many of the world’s geneticists are Jewish, they naturally have been drawn to study themselves.

  The understanding is not only that 185delAG originated with Jews but also that when the mutation shows up in another ethnic or racial group, such as Shonnie Medina’s Hispanos, it’s because a Jew or a descendant of a Jew has married in. Beyond the bounds of Jewry, sightings of 185delAG are few. There are scattershot reports in the medical literature of gentile carriers in Spain, Chile, Slovakia, the Netherlands, Pakistan, India, even South Africa. Most of these countries have or used to have Jewish enclaves. By the same token, there are American carriers who are not Jewish, or so it’s reported on their orders for gene tests, but these people, like the Medinas, undoubtedly have Jewish ancestors. As an example, the mutation has affected a large and gregarious family from the Midwest named K——. Irish Catholic on the mother’s side, German Protestant on the father’s, the family suspects that the gene came in from the German side.

  A corollary theory about 185delAG is that it occurred just once in history. However, nothing about DNA prevents lightning from having struck twice at the AG site, altering the BRCA1 gene of two different founders at two different times in history. Although evidence for a twenty-five-hundred-year-old Jewish founder is overwhelming, couldn’t there be others whose descendants are not as numerous or as conspicuous? Several claims of a rival 185delAG have been put forward, only to fade when the fine print of the DNA region is analyzed and the signature of the Jewish variant emerges.

  One case of independent origin is strong, though. It comes from Yorkshire, in England. Two families there, not Jewish, share a novel spelling around the site of their AG deletion, which points to a different founder. The geneticists who study BRCA are not all in agreement that the Yorkshire mutation is truly new. Genotyping techniques have advanced in the fifteen years since the mutation was found, and if the experts were bothered enough by the uncertainty, they could undertake a closer analysis of the DNA samples in England, but as of this writing they haven’t done so.

  Harry Ostrer was in the camp that believed that 185delAG had appeared in a Jewish founder just once in history and had spread from there. Ergo, the Yorkshire carriers must be related to Jews.

  Well, I asked, why hadn’t Harry and his colleagues straightened the matter out?

  It’s not rocket science, he replied, and the work wouldn’t cost that much. Pressed again on the issue, he said, You should do a shidduch, Mr. Jewish Wannabe, and get [the Yorkshire scientists] to send the samples to [the Israeli scientists] for analysis.

  So the gene was present in the people at the time of the Babylonian Diaspora. In the five centuries preceding the birth of Christ, the people of Judea resisted the paganizing influences of their successive overlords: Persian, Greek, Syrian, Roman. Indeed, during the latter part of this period they made converts among other peoples, bringing substantial new blood into the fold without relaxing their own strict standards. But their proud state came crashing down, the Second Temple destroyed, after the Judeans rebelled against the Romans in 66 CE. The Romans killed or enslaved everyone they did not drive from Jerusalem. Judaism from that time onward was a religion in flight, never confident, wherever it set down roots, that it would not be ripped out.

  There followed a fluid period in Palestine in which pagans, Jews, and Christians jockeyed under the slackening eye of Rome. The empire, as it weakened, succumbed to Christianity. Now Christianity provides the backdrop for the Jewish Diaspora. Christianizing peoples are the broad canvas on which Jews’ tracks can be discerned after the collapse of the Roman Empire. The Jesus movement hadn’t set the Jews in motion, but its astonishing success ensured that the Jews would not come to rest. In evolutionary genetics, as opposed to medical genetics, if a new mutation with a bodily function doesn’t make its host stronger, it will fade out and be replaced by a change that does. Random and unbidden, the new, Christian variant of Judaism soon eclipsed the ancestral type, taking over Western Europe, North Africa, and Palestine.

  Until there were Christians, Jewish chosenness was not a problem. That the Jews were the chosen people of God was something they told themselves as part of their rubric of unity. The paradoxical responsibility of an insular people was to shine the light of their chosenness on all of mankind, yet this was a duty they must perform indirectly, by obeying the laws of the covenant. Chosenness was their own affair, really, until Christians objected and, flinging Christ-killer into the faces of Jews, appropriated the idea of the elect for their own believers. Ah, well. The Jews were prepared to be disliked, persecuted, exiled. Their Bible had warned them. Exile and suffering were the pr
ice of chosenness. If God intended them to be a beacon apart from humanity while lighting the way for humanity, they should not wonder that people would throw stones at them from the darkness.

  Islam was born in the seventh century and conquered Palestine, ending any hope that the Jews might be reinstated in their homeland. For a while, Muslim and Jewish clans lived together in peace in Medina, which was Muhammad’s capital city in what is now Saudi Arabia, but the peace broke down. The Jews wandered about the Mediterranean and crossed the Alps. They waxed and waned according to the tolerance of the societies in which they were embedded. Certainly tens and perhaps hundreds of thousands of Jews lived in Rome, in southern France, and along the Rhine, while a separate group migrated to the Iberian Peninsula. Carriers of the185delAG breast-cancer mutation must have been among them, but of course there are no records of the gene’s toll. Life spans were so brief that a Jewish wife would bear her children and die of other causes before fast-acting 185delAG could catch up with her.

  A curving corridor from Italy to France to Germany is thought to have brought bands of Jews to the northern region they called Ashkenaz by the year 1000 CE. Many men would have brought along wives and children, but just as many, the adventuring males, traveled solo and would take local mates. Some of the genetic data suggests that male pioneers of Ashkenaz took foreign wives and literally changed them into Jews. When DNA from different ethnic or racial groups comes together, the technical term for the result is admixture. But the Jews’ admixture or outbreeding with Germanic peoples did not last long. After they established their settlements and families, they circled the wagons and resumed their endogamous practices, their rabbis hectoring them about blood purity in a new Germanic language, Yiddish. Thus did the Ashkenazim come into being. They are by far the world’s most numerous Jews today. Almost six million Americans have Ashkenazi ancestry; they represent about 90 percent of American Jews.

  Harry Ostrer and other Ashkenazi scientists debated the genetic ratio between the original Jewish migrants from the Middle East and the Europeans they eventually became. Historically, there has been a high-admixture crowd and a low-admixture crowd, Harry explained. Evidence of high admixture justified Jews’ rightful assimilation into Western society, since they were difficult to distinguish from other Europeans. Whereas findings of low genetic admixture supported their ethnic pride: the idea that Jews were a people from Palestine, as told in their Bible.

  A persistent third faction argued that the Ashkenazim were not from the Mediterranean region but rather descended from Turkic converts, the Khazars, who migrated to Europe from western Asia. The DNA evidence for the Khazar theory of origin was rather weak, however, and was dispatched for good by a paper that Ostrer and his associates published in the American Journal of Human Genetics in 2010. The latest research reaffirmed Jews’ roots in the Levant.

  But the Khazar theory has the advantage, Harry observed, of absolving the majority of Jews from Christ-killing.

  Do you mean that some Jews could say, Well, at the time of the Crucifixion my ancestors were out of the region—don’t blame me?

  Yes, he replied, because the Khazars were not talking to Pontius Pilate.

  After the year 1000, when Christian authorities in Europe banned intermarriage with Jews, isolation became a two-way street. Prohibited from farming and landowning, Jews fastened themselves to urban centers and found success in trade, medicine, and moneylending. The latter service was especially useful to Christians because the Catholic Church did not permit its own people to charge interest on loans. During this period, the Jews burnished the Talmud while Christians burnished the myth of the Wandering Jew, an ageless sinner who could not die until the promised Second Coming of Christ. A corrosive slander against Jews was that they were required to drink the blood of Christian children.

  Now come the Ashkenazi bottlenecks. Classically, in a bottleneck a population sharply contracts and then just as sharply expands. The passage through the bottleneck shears away some of the DNA—that is, it reduces the number of variants of a group’s genes. The remaining variants arrange themselves in different proportions. Mutations too scarce to make a dent on a larger population can be enriched. Thus the likes of 185delAG might come through a bottleneck not only unscathed but more prominent than before, its carriers overrepresented in the new population. Genetic drift, as noted earlier, succeeds a bottleneck. Genetic drift can happen when a people recovers from an abrupt and, in the Jews’ case, terrible constriction, as from pogroms, forced relocations, and mass murder.

  The major reason for the turn in Ashkenazi fortunes was the Crusades, beginning in the late eleventh century. Seeking to retake Jerusalem for Christianity, armies from northern Europe marched against the infidel Moors and, along the way to the Holy Land, took cruel swipes at Jewish communities. Local violence against Jews was legitimized during the feverish period of the Crusades; many Jews were killed. In the twelfth and thirteenth centuries, England, France, and Germany expelled their Jewish populations altogether. Those who filtered back to Germany a century or two later were made to wear yellow badges on their coats or caps so that the authorities could keep an eye on them. Throughout, the educated Jew would serve the local prince as treasurer, banker, doctor, scholar, well aware that he could lose all when the climate changed.

  Spurned, the mass of Ashkenazim gradually migrated east to Poland, where they felt welcome, and north to Lithuania, a land whose lakes froze black in winter, imagine, and Russia, such a far cry from the stony hills of Palestine. In their new territory the Jews rebounded from persecution. This would be the Ashkenazi homeland for five centuries. Shtetl life began, the thriving era of the Jewish village and Jewish urban quarter and busy synagogue. The village of Ostrog, from which Harry Ostrer’s name probably derives, was one such active village. Ownership of Ostrog floated among Russia, Ukraine, Poland, and Lithuania—the geopolitical title didn’t matter to Jews because they could do nothing about it. They paid their taxes and went about their business. Every now and then a Cossack raid or catastrophic fire would destroy the Jewish sector, and they would rebuild it.

  Twenty thousand Ashkenazim increased to two million. In 1791, Russia, confining Jews behind the Pale of Settlement, closed the borders of the eastern Ashkenazi homeland. It resulted in overcrowding, poverty, and additional genetic concentration. When, as part of a move to Russify the Jews, the czars instituted a military draft, many young men went on the move. The rovers included one Shmuel Ostrer, who was Harry Ostrer’s great-grandfather. Shmuel’s unsettled descendants continued to migrate, first to Vilnius, the Jewish hub in Lithuania, and thence to Boston, Massachusetts, early in the twentieth century.

  Despite its stops and starts, the world’s Ashkenazi population attained ten million by 1900. The geneticists who study the group often comment on its steep growth curve—they use the term demographic miracle. They can tell that the population grew fast because harmful mutations emerged from the bottlenecks, a downside of the miracle. For example, 185delAG, occurring in one in a hundred Ashkenazim today, could not have become so prevalent if the population hadn’t formerly been so small. The principal mutation for Tay-Sachs disease, which is carried by one in twenty-five Ashkenazim, arose from a handful of founders. All told, Jews of Central and Eastern European extraction are host to forty or more genetic disorders, according to research by Ostrer and other scientists. These are medical conditions that larger ethnic groups do not have, or do not share to the same extent.

  Whether your name is Cohen or Wheelwright, you could have one of these disorders, Harry said tartly.

  True, I said, but almost certainly the mutation behind it would be spelled differently from the Jewish form, and the probability of my inheriting or transmitting the disorder would be lower.

  To be very clear, the Jewish genetic diseases are rare. They’re asterisks when compared with the diabetes, hypertension, heart disease, cancer, etc., afflicting all population grou
ps. Also, it is important to distinguish the dominant disorders, such as heritable breast and ovarian cancer, HBOC, which is transmitted by one parent, from the more numerous recessive disorders, such as Tay-Sachs disease, which entail two parental carriers and a one-in-four chance of inheritance. The genotypes outnumber the phenotypes, a short way of saying that healthy Jewish carriers of a recessive mutation greatly exceed the number of those who actually get sick. The point to return to is that inbreeding, founder effects, population bottlenecks, and genetic drift, the instruments of inherited disease, happen to be the very elements of Jewish struggle and survival.

  The situation improved when the Jews of Western Europe were let out of their urban ghettos in the nineteenth century. The assimilated branch of Jewry met European societies halfway, embracing and enhancing the secular cultures. The same accommodation happened in the United States. It was the immigration of the poorer, more insular Ashkenazim, arriving by the millions from the East, that prompted the so-called Jewish problem in Western societies at the turn of the twentieth century. The debate in the West focused on how many to let in and how to absorb them. This time, Jews rankled not so much because of their religion but because of their race.

  Current thinking regards race as a hollow category, a grab bag of traits that distract human beings from their commonality. Dismissing biology altogether, some academics call race a social construction tacked together from cultural traits and maintained by cultural expectations. Race begets only racism, in this view. At most, race should be about identity, critics say, and they brandish genetic studies: If you take two people of different races, any two people from anywhere on the globe, and compare the several billion bases of DNA that make up their respective genomes, you will find the two genomes 99 percent the same.

  At the beginning of the twentieth century, however, most of the best minds in science, religion and politics, Jewish minds not least, believed that the human races were as separate as feudal castles in the medieval countryside. It was a long-standing medieval idea. What you saw on the outside of different peoples, be it skin color or behavior, reflected the innate, blood-borne indicators of their race. You could, by interbreeding, cross the moats that nature had built around racial castles, but the results were usually bad. Darker peoples were held to be less fit than the Caucasian standard-bearers. Whether the basic human types had been set in stone by God or had diverged or degenerated from whites because of environmental factors, the divisions of mankind were believed to be grave and deep.