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African genetic diversity

Trends in genetic research reported during the American Society of Human Genetics meeting October 20 through 24

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Jibril Hirbo has come a long way to present his research in Honolulu at the annual meeting of the American Society of Human Genetics. Hirbo grew up in a small village on a mountain in northern Kenya. His parents immigrated to Kenya from neighboring Ethiopia.

Hirbo was one of only two children from his primary school to go to college and the only one to go to graduate school. In about a month, Hirbo will defend his Ph.D. thesis on characterizing genetic diversity in east Africa.

East Africa, especially Kenya and Tanzania, is considered the cradle of humanity. There is plenty of evidence already to suggest that the modern humans who left Africa and colonized the rest of the world, originated there. The “Out of Africa” migration has gotten much attention, and its study has shed light on human origins. But, in terms of knowledge of genetic diversity at home, Africa is still largely unexplored.

In Hirbo’s small village, (he admitted over lunch that his small village is actually larger than the small village of 300 people I come from in Nebraska. I rarely lose a game of “who came from the smallest town” unless I’m playing against another Nebraskan) people often attributed diseases such as cancer to curses placed on family for wrong-doing. That is, until a respected member of the community, who everyone knew could have done no wrong severe enough to warrant cancer, died of the disease. Then people wanted to know what, if not a curse, could cause such a horrible disease. Hirbo intended to become a doctor and find out. Instead, he ended up doing graduate work in the laboratory of Sarah Tishkoff at the University of Pennsylvania in Philadelphia.

There, Hirbo joined Tishkoff’s efforts to better understand genetic diversity in Africa and what such diversity can tell us about human evolution. The researchers also want to know, just as Hirbo’s fellow villagers do, what leads to diseases in African populations and why some drugs that do a fine job of treating people of European ancestry often don’t work well in Africans.

Geneticists have become increasingly interested in genetic diversity in Africa as well. The now-ubiquitous genome wide association studies used to find genetic variants associated with common diseases only work well when geneticists know something about the population being studied. One of the hottest tickets at the meeting on October 23 was a presentation about the first genome sequence of Bushmen from southern Africa. Usually journalists are allowed to write about things researchers present in front of hundreds to thousands of their colleagues at scientific meetings, but a threat from a major scientific journal had the researcher clamming up. Still, as interesting as that genome may prove to be, it is a picture of only one of the many, many groups of people living in Africa.

In separate work, Hirbo and Tishkoff and their colleagues journeyed to Kenya and Tanzania and some neighboring countries to collect DNA samples from 66 different populations of people living in East Africa — essentially doubling the number of African populations that scientists now have genetic information about. People from the 66 populations speak languages that fall into four major groups, and anthropologists have often used linguistics to trace the ancestry of groups.

Language classification has led to some mysteries about relationships between certain groups of people. A particularly hot debate centers on hunter-gatherer groups. Many of the hunter-gatherers speak the same language as their pastoral neighbors. One school of thought holds that the language connection means hunter-gatherers are pastoralists who have lost their wealth (in many cases that means cattle.) Another possibility is that hunter-gatherers are very ancient populations who adopt the language of their new neighbors for trade and other purposes.

Hirbo used mitochondrial DNA to trace movements of people through the genetic histories of their mothers. Mitochondria are small energy-producing centers inside of cells. Mitochondria evolved from bacteria and thus have their own circular chromosome, which is passed from mothers to their offspring. Hirbo sequenced the mitochondrial chromosomes from 222 people. He also analyzed Y chromosomes from men in the groups. Since mitochondria are inherited from mothers and Y chromosomes from fathers, Hirbo could trace the migrations of men and women. He found that women moved more than men, in a historical sense. That pattern fits with the situation he sees today in Africa, he says. Men marry women from neighboring villages, often having multiple wives that are a sampling of the women of the region. When men move, it is usually long distances and prompted by natural disasters or other huge events that would put the whole population on the move.

Data Hirbo collected may also help sort out where hunter-gatherers came from. It turns out that there is evidence that both theories about hunter-gatherers are right. Take the Watta from Kenya. This hunter-gatherer group, who call themselves the People of the Bow, now speak Borana, a Cushitic language spoken by a pastoral group who lives in the neighborhood. Genetic analysis reveals evidence that the Watta do derive some of their heritage from the Borana speakers, but that there is also something older in the Watta’s make-up. The People of the Bow’s own oral heritage holds that they are pastoralists who lost their wealth, but that they derived from the Masai, not the Borana-speakers they are associated with today. The story goes that the Watta leader was a very rich man with lots of land and many cattle. He had a certain fondness for a game, and lost everything because he kept challenging a stranger to one more game. The stranger turned out to be God. So naturally, even though God took all the land and cattle, he granted all the wild animals to the Watta.

Hirbo’s genetic analysis doesn’t weigh in on the God part of the story, but he does see genetic threads linking the Watta to the Masai. It’s nice to find evidence that corroborates oral tradition, he says, but he doesn’t think the finding will settle anything. “There will always be a debate” over the origin and identity of hunter-gatherer groups, he says.

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