Eve's Secret

Genetics and the Origin of Women

Does the human mitochondria reveal when and where human beings arrived on the scene of history?

Dr. Douglas C. Wallace, whose research into the mitochondria has been probing for answers, says the evidence is there, passed along from mother to daughter throughout the centuries.

Wallace's study of the human mitochondria has triggered the "Eve" controversy. He and other geneticists assert human beings may be descended from one female who lived only about 200,000 years ago. It's a shocking statement to paleoanthropologists, who insist that the fossil record shows the human species to be far more ancient.

The debate is a case of bugs versus bones; so far, the bugs appear to be winning.

The excitement surrounding the research led to Wallace being the inaugural lecturer for Georgia Tech's recently-established New Century Lecture Series. Speaking on "Mitochondrial Genes and the Origins of Women," he began a series in which Tech will invite up to four outstanding researchers a year to give public talks. Wallace's relentless curiosity about mitochondria has brought him other honors as well. At age 43, he is a professor of biochemistry and associate professor of pediatrics, neurology and anthropology at Emory University, and one of the country's outstanding molecular biologists.

Wallace's work has revealed many surprises about human mitochondria. Until the last three decades, little was known about mitochondria beyond biology class cliches: they are the energy "factories" of the cell while DNA is the "blueprint" of life.

When Wallace was a Yale graduate student in the early 1970s, mitochondrial DNA had been discovered but little characterized. Many assumed this DNA was relatively unimportant because it was so small.

Intrigued by the idea that the mitochondrion was simple enough to be completely understandable, Wallace began studying it.

"It outwitted me, that's for sure," he said. "I did not learn what I thought I was going to learn."

He and his collaborators at Stanford University unwrapped a profound surprise about mitochondria; all the mitochondria a human inherits comes from the mother's egg. The mitochondria is passed from mother to daughter, but not to sons.

he evolutionary implications of this discovery excited Wallace and his co-workers, especially since mitochondrial DNA has a rapid mutation rate, making historical analysis feasible. Nuclear DNA averages a mutation only once approximately every 50,000 years, but mitochondrial DNA averages a fixed mutation approximately every 4,000 years--lightning transformations in evolutionary terms.

"We showed in the late '70s that the mitochondrial DNA in humans was maternally inherited," he said, "then started surveying different human populations to characterize the naturally occurring variation."

Collaborating with Luigi Cavalli-Sforza of Stanford University, Wallace analyzed mitochondrial mutations in human blood samples collected worldwide. They found a high correlation between the nature of the mutations, ethnic groups, and geographic locations, indicating that all humans are descended from a small group of proto-humans originating in either south Asia or sub-Saharan Africa about 200,000 years ago.

These early humans passed down only one strain of mitochondria, which possibly originated in a single female whom researchers dubbed "Eve." Wallace and Cavalli-Sforza's evidence, which they published in 1983, initiated the Eve controversy.

he geneticist's theory that Homo sapiens evolved fairly recently from a small group triggered howls from proponents of one major evolutionary theory that different groups of Homo erectus split up about a million years ago and went their separate ways, independently evolving into modern humans of different races.

"Some are still upset about it. Some are not," he said. "I think my data's more compelling than theirs, but I'm not very aggressive in trying to proselytize my theories."

Wallace does not say Eve was the only Hominid female alive--she may have had thousands of contemporaries, but their mitochondrial strains died out. Authorities say such losses could easily occur. If a woman has only sons, her mitochondrial line ends. If her daughters have no children or only sons, again the line ends. With generations spanning about 200,000 years, one line might easily propagate as others fade out.

Wallace notes that "Eve" could have been a mother-daughter combination, sisters, or a few dozen closely related females. However many women were "Eve," we are all their descendants.

Some speculate that Eve's mitochondria gave early humans a survival edge, an idea Wallace dismisses, saying the mitochondria just got lucky on their evolutionary ride.

"My view is that there was a population of individuals that was isolated and did accumulate mutations that increased cerebral cortex capacity," he says. "For whatever reason, it was advantageous, but it occurred slowly, through a series of mutations, until there was a time when those individuals were so different that they could no longer cross-breed with other Hominids. They were a separate species."

He and scientists Theodore Schurr and Scott Ballinger of Wallace's lab recently completed a study of mitochondrial lines in American Indians that further supports the correlation between different mitochondrial strains and different cultural or ethnic groups. Their study of three American Indian groups in North, Central and South America suggests that the groups descended from four primary maternal lineages migrating from Siberia to Alaska. He thinks further research could answer enigmas such as the ancestral origins of Pacific islanders. Subtle mitochondrial variations might even give insights about how various groups adapted to their ancestral environments.

"I wouldn't be at all surprised if there aren't polymorphisms in the mitochondrial DNA of arctic people and tropical people that give them different capabilities in cold-versus-warm climates, in high-fat versus low-fat diets, and in high-versus-low altitudes," he says.

allace thinks that the mitochondrial energy production has a role to play in such diverse kinds of neurological disease as Parkinson's, Huntington's, and certain kinds of heart, muscle and renal diseases.

"Probably most important is that mitochondrial energy production seems to decline with age, and one possibility is that it plays a major role in aging," says Wallace. "The question is, what's the molecular basis of that? So if aging is the most common mitochondrial disease, then mitochondrial genetics might prove to be very important in medicine."

Those are the words of a man who, after decades of unraveling mitochondrial mysteries, remains fascinated by secrets yet to be told.