Six Wits geneticists and their African counterparts have published a pioneering study that gives insights into African population history, environmental adaptation, and susceptibility to disease.
The project uncovered more than three million new genetic variants in what is considered one of the most extensive studies of “high-depth-sequenced African genomes reported to date”.
The findings are based on the analyses of the whole genomes of 426 individuals from 13 African countries, whose ancestries represent 50 ethno-linguistic groups from across the continent.
The study also sheds lights into ancient migrations along the routes of populations who speak Bantu languages. They observed complex patterns of ancestral mixing within and between populations, and also reveals that populations from Zambia was a likely intermediate site along the routes of expansion of Bantu-speaking populations.
It is believed these observations improve the current understanding of migration across the continent, and identify responses to human disease and gene flow as strong determinants of population variation.
The researchers also show that these newly discovered variants were found mostly among newly sampled ethno-linguistic groups. Researchers identified new evidence for natural selection in and around 62 previously unreported genes associated with viral immunity, DNA repair and metabolism.
The study also contributes a new major source of African genomic data, which showcases the complex and vast diversity of African genetic variation and which will support research for decades to come.
Zané Lombard, a senior author of the study and an associate professor in the division of Human Genetics in the Faculty of Health Sciences at Wits and at the National Health Laboratory Service said: “Africa is the continent with greatest genetic diversity and this study shows the importance of African genomic data for taking science and health research forward. It is an important step in redressing existing biases in available data for research, which hamper the study of African health problems and narrows global research.”
Lombard headed the study sponsored by the Human Heredity and Health in Africa (H3Africa) Consortium in association with Dr Neil Hanchard, Baylor College of Medicine, Texas, U.S.A, and Dr Adebowale Adeyemo, National Human Genome Research Institute, Maryland, U.S.A.
Members of the H3Africa Consortium who were part of the project comprise people from 24 institutions across Africa, including the Sydney Brenner Institute for Molecular Bioscience (SBIMB) in the Faculty of Health Sciences at Wits University.
The SBIMB’s Dr Ananyo Choudhury, Dr Dhriti Sengupta, Professor Scott Hazelhurst and Mr Shaun Aron led analyses and writing the paper, while Professor Michèle Ramsay, director of the SBIMB, participated in developing the study design and was a principal investigator who contributed samples towards this large-scale sequencing effort.
The study found a vast amount of genomic diversity among these genomes, with each ethno-linguistic group having thousands of unique genetic variants.
For instance, it revealed that “not only populations from the same geographic region but even those from the same country showed a great deal of variation among themselves”. This is a reflection of a deep history and rich genomic diversity across Africa, the study showed.
Said Choudhury, first author of the study and a senior scientist at the SBIMB: “We used a wide variety of computational techniques to gain insights into population history, environmental adaptation, and susceptibility to diseases from these genomes.”
“Inclusion of novel African genomes in our study strongly supported Zambia as an intermediate site in the Bantu-migration route to the South and East of the continent,” said Shaun Aron, lead analyst on the population genetics component of the study and a lecturer in the SBIMB.
Evidence supporting movement from East Africa to central Nigeria between 1500 and 2000 years ago was revealed through the identification of a substantial amount of East African ancestry, particularly Nilo-Saharan from Chad, in a central Nigerian ethno-linguistic group, the Berom. “This highlights the complex historical movement of people on the continent and diversity of even proximally close African groups,” said Aron.
The researchers found more than 100 areas of the genome that had probably been under natural selection; a sizable proportion of which were associated with immunity related genes.
“While genes involved in resistance to insect-transmitted diseases like malaria and sleeping sickness have long been known to be positively selected, our study shows that other viral infections could have also helped to shape genomic differences between people and groups by altering the frequency of genes that affect individuals’ disease susceptibility,” said Dr Dhriti Sengupta of the SBIMB and one of the lead analysts.
Lombard said: “The findings have broad relevance, from population genetics research into human history and migration, to clinical research into the impact of specific variants on health outcomes.” The next important steps include further assessment of the initial findings and leveraging the data to represent more African populations.
It is hoped this work will lead to wider recognition of the extent of un-catalogued genomic variation across the African continent and the need for continued inclusion of the many diverse populations in Africa in genomics research.
Researchers hail the study as a “major milestone in advancing African genomics research capacity”. They said that African data will no longer be analysed elsewhere, which has been an established trend over the years – as this study was conducted predominantly by local African researchers using local computational facilities.
This represents a major development as it highlights the importance of computing infrastructure and storage capacity for large data projects at Wits and in South Africa.
According to Professor Scott Hazelhurst, director of Wits Bioinformatics, who established and also manages the computing cluster at Wits, said such an infrastructure is vital in supporting genomics research and growing African datasets. “Initiatives such as the H3Africa Consortium have laid the foundation to foster and encourage collaborative research in Africa, which has made studies like these possible,” he said.