A catalogue of early diverged contemporary human genome variation reveals distinct Khoe-San populations

Creating a catalogue of early diverged genome variation is critical to determine the true extent of human diversity and associated medical impact. Generating deep whole genome data for 150 Khoe-San (12 groups, 1 unclassified), and 40 regionally comparative Southern Africans (3 groups), we identify ~30 million small-to-large variants - over 1.3 million unknown single nucleotide variants. Representing shared traditionally forager lifestyles and click-speaking languages, we identify San and Damara as separate phylogenetic lineages, contributing two admixture waves to Nama. While San represented modern humans’ deep divergence (~115 thousand years ago), Damara divergence is recent, with both showing high effective population sizes between 45–150 thousand years ago. Developing an assembly-based test we report 1,376 genes under positive selection (dN/dS = 19.46) of which 479 are significantly associated with forager peoples and, therefore, maintained ancestral alleles that differ from derived genetic variation observed in non-African biomedical resources.