NEW YORK (GenomeWeb News) – An international research team has published the largest study yet of African genetics — work that they say not only offers a peek into human history but also provides the foundation for future biomedical research in Africa and beyond. The research appeared in the advanced, online issue of Science today.
The researchers assessed more than 1,300 polymorphic markers in thousands of individuals from more than 100 African populations, four African-American populations, and 60 non-African populations. The results confirmed relationships between some populations with shared language and culture, but uncovered shared ancestry in other groups that were previously thought to be unrelated.
In a conference call with reporters yesterday, lead author Sarah Tishkoff, a geneticist affiliated with the Universities of Maryland and Pennsylvania, called the work the "culmination of a nearly 10 years effort."
Tishkoff emphasized the remarkable genetic diversity both within and between the African populations they tested, noting that no single African population alone represents the overall diversity present on the continent.
Modern humans arose some 200,000 years ago in Africa. Linguistic studies have placed African populations into four main language groups: Niger-Kordofanian, Nilo-Saharan, Afroasiatic, and Khoesan. But relatively little was known about the nuclear genetic variation on the continent.
"Characterizing the pattern of genetic variation among ethnically diverse African populations is critical for reconstructing human evolutionary history, the population history of African Americans, and for the proper design and interpretation of genetic disease association studies, since sub-structure can cause spurious results," the authors explained.
To begin untangling African genetics, the researchers evaluated 848 microsatellites, 476 insertions and deletions, and three SNPs in 2,551 individuals: 2,432 Africans from 113 populations; 98 African Americans from Chicago, Baltimore, Pittsburgh, and North Carolina; and 21 Yemenites. They integrated these findings with data on 952 Human Polymorphism Study Center-Human Genome Diversity Panel individuals from around the world, as well as 432 individuals of Indian descent, and 10 Native Australians.
The researchers detected 14 main ancestral population clusters in Africa, which corresponded fairly well with language and cultural information. They speculated that genetic differences between populations likely arose through a combination of factors — from ethnicity, language, and cultural differences to geographical, environmental, and climate differences that "contributed to population size fluctuations, fragmentations, and dispersals in Africa."
The researchers also uncovered previously unrecognized relationships between geographically distinct populations. For example, their genetic analysis suggests southern African Khoesan, Hadza, Sandawe, and Pygmy populations — hunter-gatherer populations currently living in different parts of Africa — might be "remnants of an historically more widespread proto-Khoesan-Pygmy population of hunter-gatherers."
The work also provided a window on historical human migrations within and out of Africa, suggesting modern human migration originated in southern Africa near what is now the Namibia-Angola border — the current homeland of click-speaking San populations. Even so, the researchers noted, current geographic distribution of populations may not represent the population distributions present long ago.
The work provided new insights into language patterns in Africa as well. By looking at gene flow, for instance, the team could determine whether language spread into new areas via large groups of individuals or via small but influential groups. The current findings included examples of both, co-author Christopher Ehret, an African history researcher at the University of California at Los Angeles, told reporters.
By assessing particular markers, the researchers were also able to trace the ancestry of the African Americans tested. They found that, as a group, African Americans most often shared ancestry with the Niger-Kordofanian language group, mainly from different parts of western Africa. Although genetic evidence indicated that the African Americans had genetic contributions from more than one Niger-Kordofanian population, the markers used couldn't accurately pinpoint individuals' ancestry to a particular West African tribe.
"[M]ost African Americans are likely to have mixed ancestry from different regions of western Africa," the authors noted. "This observation, together with the subtle substructure observed among Niger-Kordofanian speakers, will make tracing ancestry of African Americans to specific ethnic groups challenging, unless considerably more markers are used."
Overall, the African Americans tested had a mean European ancestry of 13 percent, though this varied widely from one individual to the next, with some having no European ancestry and others having more than 50 percent European ancestry, Tishkoff said. Researchers also detected a lower degree of ancestry from other African populations as well as some East Asian and Indian ancestry in the African Americans tested.
Along with its potential for offering insights into human history, Vanderbilt University Center for Human Genetics Research molecular physiology and biophysics researcher Scott Williams, senior author on the study, said the research also has implications for biomedical research, providing a "critical piece of the puzzle" for researchers designing disease-gene and drug-response studies.
"Because of the extensive level of sub-structure in Africa, ethnically and geographically diverse populations need to be included in re-sequencing, genome-wide association (GWAS), and pharmacogenomic studies, to identify population or regional-specific functional variants associated with disease or drug response," the authors wrote.
Consequently, even though the current study has provided information about more than a hundred African populations, Tishkoff stressed the need for even more genetic research in Africa to learn more about the nearly 2,000 other ethno-linguistic populations on the continent.
"I truly hope that the study will set the stage for future research in Africa," Tishkoff said. "We don't want to see African programs left behind in this genomic revolution."