Khoisan show greatest genetic diversity worldwide. 25% of variants unique to Khoisan. Khoisan divergence from other humans 200-300 kya not due to archaic admixture. All Khoisan groups received 10-30% eastern African-Eurasian admixture ~1,500 years ago. After masking admixture, Khoisan diversity approaches other Africans but remains highest. Effective population size dropped in all humans ~100-20 kya coinciding with Out-of-Africa and paleoclimate shifts. Khoisan least affected by Ne reduction. Selection signals >300 kya target brain development genes like LPHN3 linked to ADHD and neuron connectivity. Early selection also hits immunity, sperm motility, diet, muscle genes. Local adaptation in Khoisan enriches immune genes including MHC against endemic diseases like anthrax. Southern Khoisan adapted for fat metabolism and phytic acid hydrolysis. Muscle function genes under selection in Khoisan. Functional CASP12 at 48% in Khoisan vs 5% globally protects against sepsis. Functional FMO2 at 60% in Khoisan risks toxicity from thiourea. Khoisan private alleles shared among northern/central/southern subgroups. !Xun have highest admixture from non-Khoisan Africans. Deepest PCA split: non-Africans, Khoisan, other Africans.