Where We Come From
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."
Haven't got a clue? Maybe DNA will do
Regular folks and history buffs play detective
BY NANCY SHUTE
Brent Kennedy is a man with a past, and he doesn't think it lies in
the misty green hills conjured by his Celtic surname. Kennedy
believes he's a Melungeon, one of a dark-skinned clan of enigmatic
origin that has long been reviled by their Appalachian neighbors. The
Wise, Va., college administrator is so intent on finding his roots that
he's having his DNA analyzed for clues.
"I grew up learning in school that we're all Scots-Irish," says
black-haired, blue-eyed Kennedy, born and raised in this tiny town
perched high in the coal-mining country of Southwest Virginia. He
thinks the genes will reveal a different lesson-one of Turks,
Portuguese, and Sephardic Jews, who sailed to the New World in
the late 16th and early 17th centuries, stayed, and assimilated, and
whose history was expunged by the burgeoning Anglo-Saxon
majority.
Kennedy's quest is intensely personal. But around the world, the
remarkable technology that allows for DNA fingerprinting is being
deployed to answer some of history's legendary conundrums.
Indeed, DNA analysis has become so sensitive that it's possible to
identify an individual from the cellular spoor left on a discarded
cocktail napkin.
That level of specificity has made the urge to exhume the past so
overwhelming it seems no corpse can rest in peace. In 1995, George
Washington University law professor James E. Starrs used DNA to
show that the body in a Kearney, Mo., grave could be outlaw Jesse
James. It could also be a James family member, so Bud Hardcastle,
an amateur historian and used car dealer in Purcell, Okla., got a
court order to dig up the Granbury, Texas, grave of J. Frank Dalton,
who he thinks is the real Jesse. But when he unearthed the body
last month, the grave held not Dalton but Henry Holland, a solid
Granbury citizen. A chagrined Hardcastle blames erroneous grave
markers. He's going back for another court order to dig again. "We're
not done. I'm not gonna quit."
Fortunately, not all DNA quests require a corpse. Brent Kennedy's
search employs the genetic material of living relatives to reconstruct
a lost past. The 49-year-old fundraiser started his search after he fell
ill in 1988. Doctors had a hard time determining the cause of
debilitating muscle aches and fever. The eventual diagnosis,
sarcoidosis, is most common among people of black or Middle
Eastern heritage. That spurred Kennedy to delve into his roots. The
quest wasn't always welcomed-one aunt torched a stack of family
photos, and threatening messages were left on his answering
machine. Indeed, for many people, Melungeon is a past best
forgotten. Melungeons were the untouchables of Appalachian
society, described in an 1891 article as "rogues, natural born
rogues, close, suspicious, inhospitable, untruthful, cowardly, and, to
use their own word, sneaky." Appalachian children were warned the
Melungeons would get them if they didn't behave.
Turkish Presley? Historians have traditionally labeled the
Melungeons a "tri-racial isolate," a pocket of people of mixed black,
Indian, and Caucasian blood. The origins of the word itself are
obscure. But oral histories and early records describe "Portyghee" in
the hills, and a 1990 analysis of Melungeon blood types suggested
Mediterranean roots. Kennedy is convinced; his office wall sports
framed articles from Turkish newspapers headlined "Were Lincoln
and Elvis Turks?"-fruits of his work with the Melungeon Heritage
Association and Turkish cultural organizations. Some historians say
Kennedy is trying to ignore the Melungeons' black and Indian past.
Not so, Kennedy says. "We feel like we're a mix of everything, but
that the Mediterranean component was undoubtedly there."
So Kennedy and about 100 other people have given hair samples for
mitochondrial DNA analysis. Mitochondrial DNA has proved a
marvelous tool for tracing human history. Mothers pass it down to
offspring almost intact-unlike nuclear DNA, the genetic material
commonly used in criminal investigations. "We can see how many
maternal lines there are in the population," says Kevin Jones, the
Wise College biology professor who is analyzing the samples and
comparing them to mtDNA databases from around the world.
But DNA has its limits. Mitochondrial DNA reflects only the maternal
line, so if the Turkish adventurers that Kennedy seeks were all men,
there would be no trace of them in the mitochondrial record. And all
DNA is perishable. "A bloodstain that's 200 years old stored dry may
be just fine, where one two weeks old that's been wet and warm may
be useless," says Charlotte Word, deputy forensic laboratory
director for Cellmark Diagnostics, a DNA lab in Germantown, Md.
Contamination is also a problem; one sneeze can ruin a sample.
Perhaps the biggest barrier to laying history bare with DNA is not the
limits of laboratory analysis, but the vagaries of human nature. More
than a few people still believe Anna Anderson was the Russian
princess Anastasia, despite evidence to the contrary from three of
the world's best mitochondrial DNA labs. Bud Hardcastle doesn't
believe the Jesse James teeth tested in 1995 necessarily came from
the right corpse. And many people would rather not offer up their
genes for the history books, fearful that the findings could be used to
deny them medical coverage.
Indeed, when it comes to history, human belief still trumps genes.
Brent Kennedy says even if DNA evidence fails to support his
Mediterranean hypothesis, he will continue his mission to
rehabilitate Melungeon identity. He and a dozen others, including
fellow Melungeons and college officials, are heading to Turkey later
this month on a research trip.
Kennedy's not the only one tempted to take a genetic peek into the
past. At Mitotyping Technologies of State College, Pa., President
and CEO Terry Melton, who helped analyze Anderson's hair, still
gets calls from people asking for a DNA test. They're convinced they
are exiled Romanovs. "I try to talk people out of it, but they will not
be dissuaded," Melton says. She takes a blood sample, charges
$1,500, and runs the sequence. She has yet to find any lost royals.
But even in an era when the human genome is posted on the
Internet, there's room amid the molecules for a good romantic
fantasy.