The history of click-speaking Khoe-San, and African populations in general, remains poorly understood. We genotyped ~2.3 million single-nucleotide polymorphisms in 220 southern Africans and found that the Khoe-San diverged from other populations ≥100,000 years ago, but population structure within the Khoe-San dated back to about 35,000 years ago. Genetic variation in various sub-Saharan populations did not localize the origin of modern humans to a single geographic region within Africa; instead, it indicated a history of admixture and stratification. We found evidence of adaptation targeting muscle function and immune response; potential adaptive introgression of protection from ultraviolet light; and selection predating modern human diversification, involving skeletal and neurological development. These new findings illustrate the importance of African genomic diversity in understanding human evolutionary history.

The quest to explain demographic history during the early part of human evolution has been limited because of the scarce paleoanthropological record from the Middle Stone Age. To shed light on the structure of the mitochondrial DNA (mtDNA) phylogeny at the dawn of Homo sapiens, we constructed a matrilineal tree composed of 624 complete mtDNA genomes from sub-Saharan Hg L lineages. We paid particular attention to the Khoi and San (Khoisan) people of South Africa because they are considered to be a unique relic of hunter-gatherer lifestyle and to carry paternal and maternal lineages belonging to the deepest clades known among modern humans. Both the tree phylogeny and coalescence calculations suggest that Khoisan matrilineal ancestry diverged from the rest of the human mtDNA pool 90,000-150,000 years before present (ybp) and that at least five additional, currently extant maternal lineages existed during this period in parallel. Furthermore, we estimate that a minimum of 40 other evolutionarily successful lineages flourished in sub-Saharan Africa during the period of modern human dispersal out of Africa approximately 60,000-70,000 ybp. Only much later, at the beginning of the Late Stone Age, about 40,000 ybp, did introgression of additional lineages occur into the Khoisan mtDNA pool. This process was further accelerated during the recent Bantu expansions. Our results suggest that the early settlement of humans in Africa was already matrilineally structured and involved small, separately evolving isolated populations.

Southern Africa is consistently placed as a potential region for the evolution of We present genome sequences, up to 13x coverage, from seven ancient individuals from KwaZulu-Natal, South Africa. The remains of three Stone Age hunter-gatherers (about 2000 years old) were genetically similar to current-day southern San groups, and those of four Iron Age farmers (300 to 500 years old) were genetically similar to present-day Bantu-language speakers. We estimate that all modern-day Khoe-San groups have been influenced by 9 to 30% genetic admixture from East Africans/Eurasians. Using traditional and new approaches, we estimate the first modern human population divergence time to between 350,000 and 260,000 years ago. This estimate increases the deepest divergence among modern humans, coinciding with anatomical developments of archaic humans into modern humans, as represented in the local fossil record.