Abstract
The southern African indigenous Khoe-San populations harbor the most divergent lineages of all living peoples. Exploring their genomes is key to understanding deep human history. We sequenced 25 full genomes from five Khoe-San populations, revealing many novel variants, that 25% of variants are unique to the Khoe-San, and that the Khoe-San group harbors the greatest level of diversity across the globe. In line with previous studies, we found several gene regions with extreme values in genome-wide scans for selection, potentially caused by natural selection in the lineage leading to Homo sapiens and more recent in time. These gene regions included immunity-, sperm-, brain-, diet-, and muscle-related genes. When accounting for recent admixture, all Khoe-San groups display genetic diversity approaching the levels in other African groups and a reduction in effective population size starting around 100,000 years ago. Hence, all human groups show a reduction in effective population size commencing around the time of the Out-of- Africa migrations, which coincides with changes in the paleoclimate records, changes that potentially impacted all humans at the time.