The study reveals the complex and vast diversity of African genetic variation

Reviewed by Emily Henderson, B.Sc.October 29, 2020

The study, in which six Wits researchers were involved, shows that these newly discovered variants were found mainly among newly sampled ethnolinguistic groups.

Researchers identified new evidence for natural selection in and around 62 previously unreported genes associated with viral immunity, DNA repair and metabolism.

They observed complex patterns of ancestral mixing within and between populations, coupled with evidence that Zambian populations were a likely intermediate site along the expansion routes of Bantu-speaking populations.

These findings 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 study provides an important new source of African genomic data, showing the complex and vast diversity of African genetic variation and which will support research for decades to come.

Africa is the continent with the greatest genetic diversity and this study shows the importance of African genomic data for advancing scientific and health research. It is an important step to correct the existing biases in the data available for research, which hinder the study of African health problems and restrict global research. “

Zané Lombard, Senior Study Author and Associate Professor, Division of Human Genetics at the Faculty of Health Sciences, University of the Witwatersrand and National Health Laboratory Service

Lombard conducted the study under the auspices of the Human Heredity and Health in Africa Consortium (H3Africa) in association with Dr Neil Hanchard, Baylor College of Medicine, Texas, USA, and Dr Adebowale Adeyemo, National Human Genome Research Institute, Maryland, USA

The members of the H3Africa consortium who contributed to this work include people from 24 institutions across Africa, including the Sydney Brenner Institute for Molecular Bioscience (SBIMB) at Wits University’s Faculty of Health Sciences.

SBIMB’s Dr Ananyo Choudhury, Dr Dhriti Sengupta, Professor Scott Hazelhurst and Mr Shaun Aron conducted the analyzes and wrote the article, while SBIMB Director Professor Michèle Ramsay participated in the development of the design. of the study and was a principal investigator who contributed samples to this large-scale sequencing effort.

426 individuals, 13 African countries, 50 etonlinguistic groups

The study found a wide range of genomic diversity among these genomes, with each ethnolinguistic group hosting thousands of unique genetic variants.

Not only populations of the same geographic region, but also those of the same country have shown a great deal of variation among them, reflecting the deep history and rich genomic diversity across Africa.

“We used a wide variety of computational techniques to obtain information on population history, environmental adaptation and disease susceptibility from these genomes,” says Choudhury, first author of the study and senior scientist at SBIMB.

“We were able to discover over 3 million new variants within these genomes. This was after comparison with more than 1000 African genomes in public archives, suggesting that the potential for discovering new genetic variants by sequencing African populations is still far from saturation “.

First evidence of migration from East Africa to Nigeria over 50 generations ago

In addition to contributing to the large amount of new variation observed in African populations, the inclusion of previously untested population groups in the study allowed scientists to add jigsaw pieces to the puzzle of established historical interactions and migratory events on the continent.

“The inclusion of new African genomes in our study strongly supported Zambia as an intermediate site in the migration route of the Bantu to the south and east of the continent,” said Shaun Aron, chief analyst of the genetic component of the study’s population. and teacher in SBIMB.

Evidence supporting the 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 ancestry from Chad, in a Nigerian ethnolinguistic group central, the Berom.

“This highlights the complex historical movement of people on the continent and the diversity of African groups even in the near future,” says Aron.

Viral infections could shape genomic differences

The researchers found more than 100 areas of the genome that had probably been under natural selection; a considerable part of which was associated with genes related to immunity.

Natural selection – “selected by nature” – comes from Charles Darwin’s work for the survival of the fittest. It means that when individuals are exposed to certain environmental factors (diet, viral infections, etc.) certain genetic variants can give the humans who carry them in their genome an added advantage to survive.

“While genes involved in resistance to insect-borne diseases such as malaria and sleeping sickness have long been known to be positively selected, our study shows that other viral infections may also have helped shape genomic differences between people and groups. by altering the frequency of genes that influence individuals’ susceptibility to disease, “says Dr. Dhriti Sengupta of SBIMB and one of the principal analysts.

Furthermore, the selection signals were not homogeneous across the continent. Sengupta says, “There have been considerable variations in selection signals between different parts of the continent, indicating that large-scale local adaptations may have accompanied the migration of populations to new geographies and subsequent exposure to new diets and pathogens.”

Selection signals are parts of the genome that give us a signature (signal) that the specific part of the genome was under selection pressure at some point.

African access to precision medicine

Lombard, senior author of the article and associate professor in the Division of Human Genetics at Wits, says, “The findings have broad relevance, from population genetics research on human history and migration, to clinical research on the impact of specific variants. on health outcomes “.

The immediate next steps include further examination of the initial results and using the data to represent multiple African populations.

The researchers hope their work will lead to a broader recognition of the extent of uncataloged genomic variation across the African continent and the need for continued inclusion of the numerous and diverse African populations in genomic research.

“The addition of genomic data from all global populations, including Africa, is essential to ensure that everyone can benefit from the health advances offered by precision medicine,” says Lombard. Precision medicine – or “personalized” medicine – refers to the treatment and prevention of disease that takes into account the individual variability in each person’s genes, environment and lifestyle.

African genomic research in Africa by Africans

The study represents a milestone in advancing African genomics research capacity. Instead of analyzing African data elsewhere – as has been the general trend over the past decade – this research was conducted predominantly by local African researchers using local computational facilities.

Studies like this highlight the importance of IT infrastructure and storage capacity for large data projects in Wits and South Africa.

Infrastructure such as the Wits IT cluster, created and managed by Professor Scott Hazelhurst, Director of Wits Bioinformatics, is essential to support genomic research and the growth of African datasets. He says: “Initiatives such as the H3Africa Consortium have laid the groundwork to promote and encourage collaborative research in Africa, which has made studies like these possible.”

Professor Michèle Ramsay, director of SBIMB, says: ‘This study, in a sense, heralds the availability of infrastructure and analytical capabilities for large-scale genomic research on the continent.’