Characterising genomic variation across Africa is critical to understanding human biology. Recently, there has been a shift in focus, in an attempt to fill the “missing diversity” that has plagued genomics research for years.
A recent paper discusses the findings of a large whole genome sequencing study of sub-Saharan African participants from 50 different ethnic/linguistic groups. Here we review their findings, and how they contribute to the understanding of genetic diversity, human history and health.
New Genetic Variants Discovered
The study identified many novel genetic variants, including several that may be medically relevant. Although only representing a small portion of the approximately 2000 ethnolinguistic populations on the African continent, the sample used was significantly broader than previous studies, making this study a landmark piece.
Of the >40 million genetic variants detected, ~3.4 million had not been previously identified. Most of these were found at low frequencies in the dataset but their role in phenotypic variation is yet to be explored. This opens the door to new hypotheses that would never had been generated while studying non-African populations.
From an evolutionary perspective, the data allowed inference about past migration and selection events in the African genomes. They identified 107 genes which displayed evidence of recent selection, and 62 of these had not been previously identified. Many of these novel loci were shared across several geographically distinct locations, likely due to shared common ancestry.
However, there were also significant regions of heterogeneity with respect to selection patterns. For example, several genes linked to metabolism were found to be under selection only in populations emanating from Botswana. How this links to their historical lifestyle poses an interesting question. Similarly, populations from West Africa and Cameroon uniquely displayed recent selection for genes involved in DNA maintenance. Why these genes are under unique selection patterns is a mystery worthy of exploration.
High levels of Genetic Diversity
Many alleles were highly differentiated between pairs of populations. Furthermore, ~10% of these highly differentiated variants were found near GWAS-significant loci, including variants associated with cardio-metabolic traits. Understanding the functional implications of this variation will be a major task but will inform our understanding of disease genetics in ways previously unimaginable.
The level of variation reported in this recent paper is enormous. As researchers continue to explore African genetic diversity, it will generate new hypotheses and ultimately revelations about human evolutionary history and disease risk.
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