Although Africa is regarded as the cradle of modern humans, only a fraction of the genetic diversity among African individuals has been surveyed. In this week’s issue, Zané Lombard, Adebowale Adeyemo, Neil Hanchard and their colleagues from the H3Africa Consortium help to redress this imbalance by presenting whole-genome sequence analyses of 426 individuals covering 50 ethnolinguistic groups. The researchers uncovered more than three million new variants, mostly among newly sampled groups, and identified 62 previously unreported genes associated with viral immunity, DNA repair and metabolism. They also observed complex patterns of ancestral mixing within and between populations, and found evidence that Zambia was a likely intermediate site along the routes of expansion for Bantu-speaking populations. The findings help to refine understanding of migration across the African continent and identify gene flow and response to disease as strong drivers of genome-level population variation. The cover shows a subset of the genetic data collected in the study translated into hand-loomed beaded necklaces by the Marigold beadwork cooperative in Zimbabwe.