Editors’ Note: It’s a question that sparks intense interest from scientists and the lay public alike: What causes some people to live long, healthy lives—nearly free of disease—until their deaths in their nineties and beyond? The answers have implications for all of us. If we can identify genes that extend life and stave off disease, we might be able to replicate the benefits of those genes through drug therapy—potentially improving the quality and length of life for millions.
The science is highly complex. But rapid advances in gene sequencing have helped Einstein researchers and their colleagues around the world make significant strides in understanding the genetic basis for longevity. Two studies in particular, the Einstein Aging Study, and the Longevity Genes Project , are unlocking the mysteries of healthy old age. And discoveries have also deepened the understanding of how our genes can be traced to specific regions of the world.
Over the next few months, those researchers will share their insights with The Doctor’s Tablet. We begin with medical geneticist Harry Ostrer, M.D., who explores the intersection of genetics and history—starting with his own.
About 10 years ago, my kids and I decided to identify whether males with the surname Ostrer shared a Y chromosomal type and were descended from a single progenitor male. Alas, the scions of the British film studio royalty (Maurice and Isadore Ostrer of Gaumont British Studios) declined to participate. But enough men participated for us to develop a worldview of Ostrers. We all had a Y chromosomal type known as E3b, the second most common found among Ashkenazi Jewish men, but finer mapping revealed that there was Us and there was Them. Us included my son, my cousins and me, and Them were, well, all of the other male Ostrers. So we Ostrers share a rare surname and an Ashkenazi Jewish legacy stamped into our genomes without sharing a single Y chromosomal type.
My work in population genetics since that time has delved more deeply into the ancestries and disease susceptibilities of several groups, including Jews from across the Diaspora and Hispanics and Latinos from across the Americas. During the course of my investigations of Jewish genetic diseases, so-called Jewish mutations kept popping up in Hispanic/Latino communities. The common Ashkenazi Jewish BRCA1 gene mutation (called 185delAG) was found not only among the Jews of New York, Tel Aviv and Sydney, but also among the Chicanos of the Bay Area and the Hispanos of New Mexico. The Little People of Loja, an endogamous group in Southern Ecuador with a rare form of severe short stature known as “Laron syndrome,” have the common Moroccan Jewish growth hormone receptor gene mutation. Larons, as they are called, have been identified across South America, with all of them sharing that mutation. Despite the handicap of severe short stature (adult height less than four feet), people with Laron syndrome are protected from developing cancer and tend to live a long time.
The finding of Jewish mutations in Hispanic/Latino communities reinvigorated a debate that had raged between the anthropologists Stanley Hordes and Judith Neulander about whether members of these communities were the descendants of Converso Jews, who had escaped the Inquisition on the Iberian peninsula by coming to the New World. In his book To the Ends of the Earth, Hordes wrote about the preservation of Jewish customs (Friday night candles, avoidance of pork) among certain Hispanos. He also provided compelling histories of how Converso Jews went to the end of the Camino Real and beyond in New Mexico to avoid the Catholic Church.
Prompted by the journalist Jeff Wheelwright (author of The Wandering Gene and the Indian Princess) and the endocrinologist Jaime Guevara-Aguirre (the discoverer of Laron syndrome in Ecuador), I went to Colorado and Ecuador to recruit subjects within the local communities. My collaborators and I used DNA chips to study their entire genomes, not only the BRCA1 and GHR genes. We found that Hispanos and Larons shared multiple different genomic segments with Sephardic Jews, including Y chromosomal types. This blending of Converso Jews with their neighbors has been observed in Spain itself, with 20 percent of contemporary Spanish men having typical Sephardic Y chromosomal types.
Our study was one of a spate of population genetic observations in recent years that have shed light on human history, some involving genetic admixture and others not. A few stand out. David Reich and his colleagues sequenced DNA from a tooth discovered in a cave in Denisova, Siberia, and discovered a new hominin species. They went on to observe that modern humans in New Guinea share DNA sequences with Denisovans, representing “rehybridization” mating events. The genome of a Neanderthal man found in the ice of the Tyrolean Mountains has also been sequenced. Svante Paabo and his colleagues observed rehybridized Neanderthal DNA in the genomes of contemporary Middle Easterners.
Mutations producing identical traits have occurred in different populations. Lactase persistence enables adults to drink milk and consume dairy products as a significant source of calories. This trait has arisen not only in Europe but also among East Africans. Sarah Tishkoff and her colleagues observed a distinct persistence mutation in the lactase gene among the pastoral herders in East Africa, demonstrating that it did not occur as the result of admixture with European explorers or colonists.
We can learn much about our histories not only by studying the relics and records of our pasts, but also by looking into our genomes. These DNA sequences can tell us about disease susceptibilities; it can also illuminate migrations, rehybridizations and development of new traits. Analysis of DNA blends the study of human history with the study of human biology.