Out of Africa: Penn Geneticist Publishes Largest-Ever Study on African Genetics Revealing Origins, Migration

PHILADELPHIA –- African, American, and European researchers working in a 10-year collaboration have released the largest-ever study of African genetic data — more than 4 million genotypes — providing a library of new information on the continent which is thought to be the source of the oldest settlements of modern humans. The study was led by Sarah Tishkoff, the David and Lyn Silfen University Associate Professor of the University of Pennsylvania.

The study demonstrates startling diversity, shared ancestry among geographically diverse groups and traces the origins of Africans and African-Americans. It will appear in the April 30 issue of the journal Science Express. Reporters can reach the Science Press Package office at 202-326-6440 or scipak@aaas.org for dial-in instructions and a passcode.

Researchers studied 121 African populations, four African-American populations and 60 non-African populations for patterns of variation at 1327 DNA markers. The study traced the genetic structure of Africans to 14 ancestral population clusters that correlated with ethnicity and shared cultural and/or linguistic properties. The research team demonstrated that there is more genetic diversity in Africa than anywhere else on earth.

A slide show of the team’s fieldwork, with audio, is available at www.sas.upenn.edu/home/SASFrontiers/tishkoff.html.

The researchers also determined that the ancestral origin of humans was probably located in southern Africa, near the South Africa-Namibia border. Extrapolating the data, scientists were able to map ancient migrations of populations and determined that the exit point of modern humans out of Africa was near the middle of the Red Sea in East Africa. They also provide evidence for ancient common ancestry of geographically diverse hunter-gatherer populations in Africa, including Pygmies from central Africa and click-speaking populations from southern and eastern Africa, suggesting the possibility that the original Pygmy language may have contained clicks. Overall, they demonstrate remarkable correspondence between cultural, linguistic and genetic diversity in Africa.

“This is the largest study to date of African genetic diversity in the nuclear genome,” said Tishkoff, a geneticist with joint appointments in the School of Arts and Sciences and the School of Medicine at Penn. “This long term collaboration, involving an international team of researchers and years of research expeditions to collect samples from populations living in remote regions of Africa, has resulted in novel insights about levels and patterns of genetic diversity in Africa, a region that has been underrepresented in human genetic studies.

“Our goal,” she said, “has been to do research that will benefit Africans, both by learning more about their population history and by setting the stage for future genetic studies, including studies of genetic and environmental risk factors for disease and drug response.”

Tishkoff said there is no single African population that is representative of the diversity on the continent. Therefore, many ethnically diverse African populations should be included in studies of human genetic variation, disease susceptibility and drug response.

Anthropologists, historians and linguists now have at their disposal a completely new volume of research with which to test theories of human migration, cultural evolution and population history in Africa. Basic scientists, physicians and public-health officials now have a foundation for illuminating the complex history of Africans and African-Americans, with implications for studies aimed at finding disease genes in these populations and learning which genetic differences make some individuals more susceptible to diseases like HIV, cancer or malaria.

This study also sheds light on African-American ancestry, which they find originates predominantly from western African Niger-Kordofanian (~71 percent), European (~13 percent) and other African (~8 percent) populations, although admixture levels varied considerably among individuals. These results could have important implications for the design and interpretation of studieswhich aim to identify genetic and environmental risk factors for diseases common among African-Americans, including prostate cancer, hypertension and diabetes.

The study was funded by the National Cancer Institute, the National Institutes of Health and the Advanced Computing Center for Research and Education at Vanderbilt University and by awards to Tishkoff from the L.S.B. Leakey and Wenner Gren Foundation, the National Science Foundation, David and Lucile Packard and a Burroughs Wellcome Foundation Career Award. Genotyping costs were supported by the National Heart, Lung and Blood Institute Mammalian Genotyping Service.

The study was conducted by Tishkoff, Alessia Ranciaro and Jibril B. Hirbo, formerly with the University of Maryland and now with the departments of Genetics and Biology at Penn; Floyd A. Reed, formerly with the University of Maryland and now with Department of Evolutionary Genetics at the Max Planck Institute of Evolutionary Biology; Françoise R. Friedlaender, an independent researcher; Christopher Ehret of the Department of History at the University of California, Los Angeles; Alain Froment of the Musée de l'Homme in Paris; Agnes. A. Awomoyi, formerly of the University of Maryland and currently with the Department of Internal Medicine at Ohio State University; Ogobara Doumbo and Mahamadou A. Thera of the Malaria Research and Training Center, University of Bamako, Mali; Muntaser Ibrahim and Abdalla T. Juma of the Department of Molecular Biology at the University of Khartoum, Sudan; Maritha J. Kotze of the Department of Pathology at the University of Stellenbosch, South Africa; Godfrey Lema and Thomas B. Nyambo of the Department of Biochemistry at Muhimbili University of Health and Allied Sciences, Tanzania; Jason H. Moore of the Departments of Genetics and Community and Family Medicine, Dartmouth Medical School; Holly Mortensen, formerly with the University of Maryland and now with the National Center for Computational Toxicology in the Office of Research and Development, U.S. Environmental Protection Agency; Sabah A. Omar of the Kenya Medical Research Institute; Kweli Powell of the University of Maryland; Gideon S Pretorius of the Division of Human Genetics, University of Stellenbosch; Michael W. Smith of the Laboratory of Genomic Diversity, National Cancer Institute; Charles Wambebe of International Biomedical Research in Africa, Nigeria; James L. Weber of the Marshfield Clinic Research Foundation, Wisc.; and Scott M. Williams of the Department of Molecular Physiology and Biophysics, Center for Human Genetics Research, Vanderbilt University.

The researchers acknowledge the indigenous populations who donated the DNA samples used in this study.