By Michael Eisenstein
It is the cradle of humanity, and evidence suggests that the world’s ethnic diversity originated from a single exodus of a few thousand individuals from Africa approximately 100,000 years ago. Until very recently, however, Africa was essentially a blank spot on geneticists’ maps.
University of Pennsylvania researcher Sarah Tishkoff recalls being surprised as a graduate student by the dearth of genomic data. “Pretty much the only African populations being studied by our group… were Pygmies,” she says. “Samples just didn’t exist.” This limitation was due in part to problems of access, but there was also a strong funding bias favoring projects centered on North American or European genetics. “There had even been more work done on American Indians and Pacific Islanders, but almost nothing done in Africa,” says Tishkoff. One notable exception is the Yoruba of West Africa, who have become the standard ‘African’ sample for US genetic research due to their overrepresentation among the historic victims of slavery. “I think the estimate is that about 25% of the slave trade emanated from the coast of Nigeria, and a little bit less than 20% from Ghana,” says Scott Williams, of the Vanderbilt University School of Medicine.
Tishkoff and Williams have been collaborating with African scientists in an effort to move beyond this myopic focus, and a recent Science article from their team revealed a richness of genome sequence diversity that surpassed even their own expectations. “We identified at least 14 ancestral populations in Africa, but that’s just a minimum estimate,” says Tishkoff. “We had 121 ethnic groups—but that’s out of around 2,000 [total], so we’ve just barely scratched the surface.” Their work enabled them to reconstruct a broad history of human emergence and migration within the continent, and to identify common ancestral roots for hunter-gatherer tribes that have subsequently adopted radically different languages, cultures and lifestyles.
Initial evidence suggests that many of the genomic variations identified are not merely superficial. “For example, we identified several genetic variants associated with the ability to digest milk,” says Tishkoff. “There’s every reason to believe that there could be other genetic variants that … play a role in disease susceptibility and drug response.”
This same notion also motivated Vanessa Hayes, a South African-born researcher at the University of New South Wales in Australia, to launch her own investigations of African genomic variability. A specialist in cancer and HIV, Hayes found herself frustrated by the limited value of European genetic data for African populations. “A 32-base-pair deletion [in the CCR5 gene] that is relevant to HIV research was not even present in the populations that I was dealing with,” she says.
Working with Stephan Schuster at Penn State University and partners at the 1000 Genomes Project, Hayes compiled complete genomic sequences for five individuals from southern Africa, in a study recently published in Nature. Their subjects included four Bushmen, selected from linguistically and geographically distinct populations in Namibia, as well as a notable individual of Bantu descent—the Archbishop Desmond Tutu. “I knew the Archbishop and got him on board,” says Hayes, “and his support has just been fantastic.” As with Tishkoff’s study, Hayes and Schuster uncovered a degree of diversity in just five samples that overshadows that observed across far greater geographic distances. “Two of our individuals are as similar to each other as a European is to an Asian—and that blows me away,” says Hayes. In fact, the variability was actually greater between Bushmen, with 1.2 differences per 1,000 DNA nucleotides versus an average of 1.0 between European and Asian individuals. “To say that Africa has been covered by having Yoruba people in the database is kind of an insult,” says Hayes, who hopes that this data will help reveal ethnicity-associated risk factors for diseases such as prostate cancer, which is especially prevalent and aggressive among individuals of African ancestry.
Accordingly, there is hope that this data will also inform a better understanding of health risks among African-Americans. Recent findings from Tishkoff and Williams suggest that most African Americans share broadly similar genetic makeup from their West African ancestors, but exhibit considerable variability in their European genetic content. “Somewhere between 10 and 20 percent of the African-American genome is of European ancestry,” says Williams, “but this proportion varies substantially depending on where the sample is collected.” Nevertheless, it remains clear that certain medical conditions, such as hypertension, are significantly more common among African-Americans, and Williams is examining population-specific gene variations within ancestral populations in Africa in hopes of revealing bases for health disparities. “Pre-term birth is 1.5 to 2 times more common in African-American pregnancies than European-American pregnancies,” says Williams. ‘’The problem is, we don’t know how much of that is environmental and how much is genetic.”
Similar differences are apparent in how patients respond to certain medicines; for example, African-Americans are likely to show a different response to the commonly-used anticoagulant warfarin relative to Caucasians. Some evidence also suggests that congestive heart failure treatment BiDil, initially rejected by the Food and Drug Administration, may be effective among African Americans—although this remains controversial, as these data are based on self-reporting of race rather than genetic data.
These various projects also represent important beginnings toward focusing scientific attention on and building research infrastructure in Africa. “It happens all the time – and it’s frustrated me as a South African scientist – that people come in, take samples, and disappear and you never hear from them again,” says Hayes. “There’s not one single local person on the papers, or at least involved in the project. There’s no bringing back.” Finding local collaborators can be difficult, as many foreign-educated scientists never return to their home country to work, and Williams has co-founded the African Society of Human Genetics to help stimulate domestic scientific growth. He points out that the internet may be a great equalizer for local scientists who can’t afford the equipment that made sequencing Tutu’s genome possible. “If you’ve got a good internet connection, you can work at a supercomputer in another part of the world,” he says, “and I think there’s a realization that this could develop human infrastructure quite quickly.”
