U.S.News & World Report
Cover Story 1/29/01
Recent advances in genetics are starting to illuminate the wanderings of early humans
Andy Carvin is a pioneer on the strange frontier of DNA genealogy. The 29-year-old Internet policy analyst had built his family tree back to ancestors in Busk, Ukraine, but that's where the trail went cold. Then he read about research tracing the Y sex chromosome, which is passed intact from father to son, all the way back to the time of Aaron, the single progenitor of the priestly cohen caste 3,000 years ago. More than once, his father had told him their family was cohanim. "I was really curious," Carvin says, "to see if there was even a small possibility that the oral tradition was true."
On the Internet, Carvin located Family Tree DNA, a small Houston firm created to answer such questions. He mailed in a sample of his DNA, gathered by swabbing the inside of his cheek, and waited. In late October, he got a call from Bennett Greenspan, president of Family Tree DNA. Not only did his Y chromosome have the cohanim markers–small genetic variations–but other markers matched with those of another man in the database, making it likely that they share a forefather within the past 250 years.
So, just before Thanksgiving, Carvin set off on a DNA-induced family reunion. He took the train from his home in Washington, D.C., to Philadelphia and met Bill Swersky, a 59-year-old federal official. "We immediately hit it off," says Carvin. "I felt like I was visiting one of my uncles." Over smoked whitefish and bagels, they paged through family photos. Andy's dad looks like Bill's father. Bill's son looks like Andy when he was younger. "He's a hell of a lot better looking than I am," Swersky says of his new relative. "I'm jealous."
It's exceedingly unusual to find such treasure in the genetic attic. Humans are very much alike genetically, with most of the variation within–rather than between–ethnic groups. Carvin and Swersky struck gold because they're part of the small cohanim group, which is itself a subset of an insular group, Jews. Finns, Sardinians, and Basques are among other groups with small founding populations that also have highly distinctive genetic pedigrees. By contrast, most people of European origin are so genetically mixed that it's impossible to tell German from Frenchman, Bosnian from Serb.
But the tools of biotechnology have become so powerful that it's now possible to deduce ancient human history from a drop of blood or a few shed skin cells. This molecular view of the past is already being employed to trace the cause of ailments such as cancer and heart disease, as well as aiding individuals like Carvin in tracking their roots. Most significantly for scientists studying past human life and culture, it offers the best insight yet into the abiding mystery of how modern Homo sapiens arose out of archaic hominids who first left Africa about 1.7 million years ago. "It's a very exciting time," says Colin Renfrew, a professor of archaeology at the University of Cambridge. "In the next 10 years the whole course of early human history is going to become very much clearer."
Indeed, in recent months, two groups of geneticists have published sweeping chronicles of the peopling of Europe, one tracing maternal DNA lineages, the other, paternal. These findings portray the majority of European forebears arriving from the Middle East as hunter-gatherers 25,000 to 40,000 years ago. During the last Ice Age, these first Europeans fled south to Iberia, Ukraine, and the Balkans. As the ice retreated, the Ice Age survivors spread out and flourished. The last major migration from the East 9,000 years ago brought agriculture and domestic animals but did not displace the earlier settlers, as some researchers had thought.
Genetic clock. The European studies are among the first to capitalize on a new ability to compare the migrations of males and females, which don't always follow the same path through history. Over the past 20 years, researchers have been able to track women's wanderings through mitochondria–tiny energy-producing bodies that cluster by the hundreds in human cells. Mitochondria have very odd DNA. They contain genetic material only from the maternal line, unlike the cell nucleus, which is a mix of DNA from both parents. This means that all children, male and female, carry copies of their mother's mitochondrial DNA.
That peculiarity gave geneticists a key tool for learning the movements of ancient populations. That's because as mitochondrial DNA is passed along, tiny, harmless mutations occur. By comparing the mutations among people, it's possible to calculate how closely they're related. And by calculating the mutation rate, researchers can deduce how far back in time different groups split apart. Douglas Wallace, director of the center for molecular medicine at Emory University Medical School, says: "You literally have a genetic clock." Wallace proved that point in 1980, when he was able to differentiate people from Europe, Asia, and Africa by comparing their DNA.
The realization that there is a map and a clock of human history in every cell completely transformed the small, highly technical field of population genetics. Scientists had been searching for human history in the genes at least since World War I, when two Polish immunologists discovered that different armies had very different proportions of various blood types. (Type B blood, for example, is more common in East Asians and Africans than it is in Europeans. Since blood type is hereditary, controlled by a single gene, a blood type can be used as a crude form of genealogy.) Blood types were used to prove that the Romany, or Gypsies, were correct when they claimed they originally came from the Indian subcontinent, not Europe.
But although researchers kept cataloging genetic markers in blood proteins, the number identified was far fewer than the millions of inherited mutations that must exist. "There just weren't enough data to answer the interesting questions," says Kenneth Kidd, a genetics professor at Yale University School of Medicine.
Times changed. Since the mid-1980s, technology has unleashed a flood of new data, so much that researchers struggle to keep pace. Restriction enzymes allow scientists to snip DNA into tiny, easy-to-read bits. The 1983 invention of the polymerase chain reaction, or PCR, made it possible to make unlimited copies of a DNA strand in a test tube. PCR made it possible to decode the human genome. And for students of human history, it is opening the window to the past further than anyone imagined.
Enter Eve. In 1987, Allan Wilson, Rebecca Cann, and Mark Stoneking, researchers at the University of California-Berkeley, catapulted mitochondrial DNA into the headlines worldwide when they announced that they had traced it back 200,000 years to the oldest female ancestor of living humans–an African woman quickly dubbed Eve. Eve's debut rocked the archaeological community, which had been arguing for decades over whether modern humans evolved on more than one continent or instead swept out of Africa to replace more archaic hominids around the world. Wilson's group was attacked for sloppy science, and in fact there were problems with the original calculations. But genetic data from dozens of researchers have since almost universally supported the "Out of Africa" theory. "History has made a pretty consistent stamp on populations," says Lynn Jorde, a geneticist at the University of Utah, who has found African roots in nuclear DNA as well as in mitochondria and the Y. "Looking at more and more of the nuclear DNA is going to clarify the picture."
Questions remain about the nature of the early human diaspora. For instance, lively debate continues over whether Neanderthals and modern humans mated [box, Page 41]. And some remain skeptical about the Out of Africa theory itself. This month researchers at Australian National University published the results of mitochondrial DNA testing on a 60,000-year-old skeleton called Lake Mungo 3. The DNA didn't match that of living humans, suggesting that the Mungo lineage evolved in Australia, not Africa. But it could simply mean that the Mungo lineage went extinct, as have many others.
Indeed, there have been many Adams, and many Eves. The genetic record reflects only those whose offspring survived and reproduced. For instance, the earli-est forefather identified so far is 20,000 to 30,000 years younger than Eve. "It's rather distressing to find that Eve could not be the wife of Adam," says Luigi Luca Cavalli-Sforza, a professor emeritus at Stanford University and pioneer of population genetics. The bulk of the genetic data suggests that a small population of modern humans, as few as 10,000, left Africa 100,000 or so years ago, wandering into the Middle East and on to Asia and Europe. Their genetic footprints lead all the way to Tierra del Fuego.
Emory's Wallace has spent the past decade tracking mitochondrial markers from Africa to Asia and the Americas–and fueling a robust dispute over just when humans first arrived in the New World. For much of the past 50 years, archaeologists thought that people tramped across the Bering Land Bridge and through a gap in the glaciers about 14,000 years ago. But Wallace thinks there were other migrations, one as early as 30,000 years ago. Archaeological sites in Pennsylvania, Virginia, and Chile support this earlier migration, although the notion remains hotly contested. Wallace's newest and most surprising discovery is a set of genetic markers found only in the Ojibwa and other tribes living near the Great Lakes; the markers are not found in any other native Americans or in Asia. "We just don't know how it got there," Wallace says, "but it's clearly related to the European population." The simple answer would be that the DNA arrived with European colonists, but the strain is different enough from the existing European lineage that it must have left the Old World long before Columbus. The lineage could have passed through Asia and later died out there. But Dennis Stanford, a paleoarchaeologist at the Smithsonian Institution, says this mystery strain, dubbed Haplogroup X, bolsters his theory that a hardy band of Europeans left Iberia and navigated the North Atlantic ice pack 15,000 years ago. "During colder time periods the sea ice was as far south as the Bay of Biscay," Stanford says, adding that the ice edge would have been ideal for hunting and fishing, just as it is in the Arctic today.
While Wallace and others were finding remarkable stories in mitochondrial DNA, scientists seeking similar tales in the Y chromosome were met with silence. It was particularly frustrating because the Y–passed intact from father to son–seemed like an ideal tool for tracking human origins. But unlike mitochondrial DNA, the male chromosome shows little variation, and searching for markers was excruciating work. Michael Hammer, a geneticist at the University of Arizona who first identified key Y markers, started looking for a cohanim marker in 1995, after he got a call from Karl Skorecki, an Israeli physician. Skorecki was wondering if the very different looking men he saw reading the Torah in shul could possibly all be sons of Aaron, as the Bible said. Intrigued, Hammer started searching the DNA of Skorecki and other Jewish men who according to oral tradition were cohanim, the priest caste. Hammer identified markers that are often shared by men who think they are cohanim, including Andy Carvin and Bill Swersky. By comparing the variations, Hammer determined that the cohanim had a common male ancestor 84 to 130 generations ago–which includes the time of the exodus from Egypt and the original cohen, Aaron.
Brothers and enemies. Since then, other researchers have used the cohanim markers to ascertain that the Lemba, a Bantu-speaking people in Southern Africa who have traditionally claimed Jewish ancestry, do indeed have Semitic roots. And last June, Hammer published results showing that although Palestinian and Jewish men may be political foes, they are also brethren, so closely related as to be genetically indistinguishable.
The Y chromosome is starting to yield other intriguing tales as well. Last November, Peter Underhill, a Stanford University researcher, published a list of 87 new Y markers, which he used to draw a tree that sorts all the world's men into just 10 branches. Indeed, men's lineages have much crisper divisions than women's, perhaps because men move into an area and kill or expel the men already there. "You get this alpha male effect," Underhill says.
Women, by contrast, move because they've married into a new family and village. Generation after generation, daughters marry and move out, while sons stay put, making women's DNA often more well traveled than men's. People living near Medellín, Colombia, have almost exclusively Native American mitochondrial DNA and European–specifically, Spanish–Y chromosome DNA. The story is familiar, and tragic: The Spanish colonists killed or supplanted the native men and married the native women.
For all its dazzle–or perhaps because of it–molecular anthropology is not without critics. "The molecular stuff has been very important," says Milford Wolpoff, an anthropology professor at the University of Michigan and a leading critic of the Out of Africa theory of human origins. "But in the end it has the same problem fossils have–the sample size is very small." Earlier this month, the journal Science published a Wolpoff study of early human skulls, which suggests that Africans may have mixed with earlier hominids rather than supplanting them. The small number of living humans sampled by geneticists, Wolpoff says, and the effects of natural selection over the millennia, make it foolhardy to say with assurance that Out of Africa is right. The geneticists, for their part, readily admit that they need more samples, more markers, and more precise calculations. But they also say that even with today's imperfect science, the DNA is right. And in places like India and China, where the fossil record is scanty, the genetic history will be the only history. "Genetics is moving so fast," says Chris Stringer, a paleoanthropologist at the Natural History Museum in London. "It's well ahead of the fossil and historical record."
Gene-based anthropology also struggles with the specter of racism. Australia has banned researchers from publishing work involving Aboriginal DNA, and India bars the export of its citizens' genetic matter. Geneticists are dismayed by these attitudes; if there's one thing the genes show, they say, it is that there is no such thing as race. The external differences that most people would use in defining race–skin color, eye shape, height–are genetically inconsequential, minor variations that evolved in response to the environment, the genetic equivalent of a sunburn. For instance, a change in just one gene accounts for Northern Europeans' fair skin, which may have developed to better absorb sunlight and synthesize vitamin D. "We are all brothers," says Stanford's Underhill, "and we're all different."
Custom medicine. The differences may be minor, but they matter a lot to medical researchers. African-Americans are more apt to get sickle-cell anemia; some people with Eastern European roots have a gene that confers resistance to AIDS; women with Scottish ancestry are predisposed to one form of breast cancer. So researchers are using molecular anthropology to seek the origins of disease and then using that knowledge to create customized treatments. They're looking increasingly at nuclear DNA–the DNA of genes and inherited traits–which mingles with every generation. "Go back five generations," says Yale's Kidd. "You have 32 ancestors. At each nuclear locus you may have a gene from a different set of two of those ancestors." Thus nuclear DNA paints a much fuller picture of the past than mitochondrial and Y, which represent only two ancestors in any generation. Kidd is now studying nuclear DNA in 33 populations around the world, seeking a better understanding of schizophrenia, Tourette's syndrome, and alcoholism. Science is far from being able to simply scan the human genome to find the causes of complex diseases like these. But the day will come, and soon, when it will be possible to pinpoint the genetic roots of disease without the geographic history. "Who cares where patients come from?" asks Aravinda Chakravarti, head of the institute of genetic medicine at Johns Hopkins University. "We'll be looking at what kind of diabetes is there, not whether they came from Timbuktu or Thailand or Towson."
But for some people, knowing where they came from matters a lot. Alice Petrovilli, a 71-year-old Aleut living in Anchorage, says she was eager to participate in a University of Kansas study on Aleut origins, even though other Aleut elders refused. "I think it's important. People always acted like because we were so far away we were a substandard species. It proves we were out here for a long, long time." Her DNA helps establish the Aleuts as people who migrated through Alaska and arrived in the Aleutian Islands 4,000 to 6,000 years ago and are genetically related to the Chukchi of northeast Russia.
Pearl Duncan is also interested in where her genes have been. The 51-year-old Jamaica-born writer had exhaustively researched her family history through genealogical records and traced several nicknames to Ghanaian dialects. But the trail ended there, lost in the Middle Passage when her slave ancestors were brought from Africa to the New World. So she tested her father's Y against DNA she gathered from members of Ghanaian churches in New York, where she lives, and found a match. "I really traced a cultural voice that is missing from the African-American narrative," says Duncan, who is writing a book about her search. She is incorporating her Ghanaian history with that of John Smellie, her Scottish ancestor 12 generations back.
No lifeguards. But geneticists fear that for every Pearl Duncan who boldly dives into the gene pool, at home with her mixed racial history, other more naive searchers may be dismayed at what they find. "Five percent of the people in America are sending Father's Day cards to the wrong guy," says Martin Tracey, a professor of genetics at Florida International University in Miami. What's more, mitochondrial and Y DNA reveal just a tiny slice of family history. Only one out of four great-grandfathers is represented on the Y, for instance, and only one great-grandmother in mitochondrial DNA. Go back just five generations, and only one of 16 forefathers is revealed. Thus someone seeking African roots could have DNA tests come back purely European, even though the person has largely African ancestors. "It's really dangerous to market a single locus as a statement of identity," says Emory's Wallace, who counsels patients with devastating genetic diseases. "I don't want to say to someone, 'I believe you're a Native American, but your mitochondria are European.' "
Indeed, few genetic genealogists will experience the same thrill as Adrian Targett, a schoolteacher in Cheddar, England, who discovered through DNA testing that he's a blood relative of Cheddar Man, a 9,000-year-old skeleton found in a nearby cave. But some people, those who seek answers to very specific questions, say they get their money's worth (box, Page 40). Doug Mumma, a 65-year-old retired nuclear physicist in Livermore, Calif., searched out strangers with his surname all over the world and paid $170 per sample to have their Y chromosomes tested. Many turned out to have no genetic link to Mumma, but he did locate several blood relatives in Germany. Mumma says, "To me it's cheap for what I want to do."
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