Genome studies show humans are all mixed up

For years, scientists have described the human genome using words that suggest a master genetic code representing everyone from the Arctic to New Zealand.

In fact, some researchers have estimated that they would need to sample members of perhaps 6,000 ethnic groups to truly represent the human race. Today a team reports analyzing DNA from more than 50 of those groups - still 10 times more than anyone had studied before.

Scientists say the new information should help ensure that minority groups benefit from the continuing revolution in genetic medicine. It will also open the door to an unprecedented ability to trace deep human ancestry - going back thousands of years.

Finally, it completes a gradual reversal in thinking of recent years, confirming that people do not divide neatly into a handful of races. There are far more branches on the family tree that first grew in Africa, and some of them curve back on themselves and intermingle at one time or another.

People all over the world turn out to be more genetically mixed up than anyone had thought.

In papers published today in the journal Science and yesterday in Nature, two competing teams of researchers report work that represents the culmination of an ambitious but troubled undertaking known as the Human Genome Diversity Project, started in the 1990s in parallel with the better-known $3 billion government Human Genome Project.

While genome scientists did use a small handful of volunteers in the major government effort, the newly reported effort sampled a much more diverse cross-section of humanity.

"These genetic markers we deal with have very little to do with what your eyes tell you," said Stanford University geneticist Marcus Feldman, a coauthor of today's study, which evolved from the diversity project. Skin color, he said, is a particularly misleading clue to relatedness.

Back in the 1990s, Feldman said, the researchers used the diversity of global languages to estimate their goal of sampling 6,000 distinct ethnic groups.

A few of those groups cooperated, while others resisted either on religious grounds or fears that research would exploit them. Eventually, the project lost much of its funding.

Its successor, however, managed to sample DNA from Basques, Russians, Cambodians, Yorubans, Senegalese, Papuans, Native Colombians, Palestinians, Bedouins and others, a total of more than 900 people in more than 50 groups from diverse corners of the world.

The largest previous attempt to capture human genetic variation, called HapMap, studied just Africans, Europeans and Asians.

To trace differences, researchers search for what are known as markers - places in the DNA where people tend to differ from one another.

What the Stanford-led team found by examining roughly 500,000 markers on the DNA it collected was that most people are more genetically heterogeneous than had been thought. And there was more variation within what have traditionally been called races.

If a variant shows up in people from one place, scientists say, it will show up in others from some other part of the world.

This has big implications for the increasingly popular industry in genetic genealogy, a fast-growing field that some researchers say is overshadowing consumers' quest for health-related genetic information.

"It's the major thing they're interested in," said George Church, a geneticist at Harvard Medical School.

"People want a sense of identity - of who came before them," said Pennsylvania State University geneticist Mark Shriver, who consults for DNAPrint Genomics Inc. "Genetic testing is just another angle on that."

The Sarasota, Fla.-based company is one of a handful that will test customers' DNA and break down the percentages of their ancestry from Africa, Asia, the Americas and Europe for about $250. The conclusions combine the results of many different markers - none of them particularly informative in themselves.

"You look at thousands and thousands of markers of that sort and gradually you gain more certainty," said Kari Stefansson, chief executive of deCODE Genetics in Iceland.

But they often cannot tell the whole story behind the results. In December, for example, deCODE announced it had analyzed the DNA of James Watson and determined that the fair-skinned genetics pioneer was about 16 percent African. The announcement was greeted with skepticism.

Several different ancestral stories might explain the finding, Shriver said. One is that African-associated markers drifted up from Africa to Southern Europe to Northern Europe, where Watson's family is from, through slow mixing over the eons.

Another possibility is that his relatively recent ancestors include Africans who traveled to Europe.

Customers are often shocked to find that they have more European, or more African, ancestry than they can explain easily, representatives of other companies said.

Noah Rosenberg, a geneticist at the University of Michigan and an author of the paper published yesterday, says that the new, more diverse data may help people start to untangle their lineages, which are now confused by an outdated view of race.

Obviously, scientists say, people's appearance varies as you move around the globe. But they argue that race is not nearly that simple.

"There is no natural single clear subdivision of human populations," Rosenberg said. People from different regions look somewhat different, but there are no clear-cut boundaries.

Instead, he said, human diversity looks more like tree branching from Africa, where human beings emerged. Over time, mutations accumulated, building up a number of different variations in human genes.

"The farther a population is from Africa," Rosenberg said, "the smaller the level of genetic diversity." Each group of migrants setting off to new territory took a subset of the range of genetic combinations that were available in the ancestral populations, he said.

Some differences came about through adaptation to varying environments - genes that confer light skin, for example, are favored in places with little sunlight, and those that impart an ability to digest milk may take over in regions where it is needed as a major source of food.

But most variation remains hidden.

The theory that humans originated in Africa has become almost universally accepted by scientists.

"Ultimately everyone has deep ancestors tracing back to Africa," said Theodore Schurr, an anthropologist at the University of Pennsylvania Museum. Over the last 60,000 or so years, people started dispersing.

The human race was probably most spread out around 1500, Schurr said. Long-distance travel then started allowing them to meet again. "That's when things started to get mixed up."

Fleshing out the story will help scientists better use genetics to advance medicine. Being more diverse, the genes of one African may say little about those of another, said Feldman, so lumping them all into one group may be misleading.

And many smaller groups haven't been counted at all. "Just on moral grounds," Feldman said, "we should be doing more about these international minorities in what you might call genetic medicine."