17q21.31 inversion exists as H1 direct or H2 inverted haplotypes with disease and selection differences. Eight structural haplotypes arise from 1.08-1.49 Mb rearrangements. 30-kb H1-H2 double recombination event occurred. Recurrent KANSL1 partial duplications happened on both H1 and H2. KANSL1 duplications reached high frequency in Europeans. Ancestral H2' haplotype lacks duplications and enriches African hunter-gatherers. H2' haplotype essentially absent from West Africans. H1 and H2 segmental duplications arose independently before out-of-Africa migration. H1 and H2 duplications rose to high frequencies recently in Europeans. Recent European rise due to genetic drift or selective sweeps. H2' haplotype identified as likely ancestral. Complex haplotype diversity emphasized in Africans. Phylogenetic relationships distinguish H1 from H2 lineages. Historical exchanges occurred between H1 and H2 haplotypes. Evolutionary model proposes H2' persistence in hunter-gatherers.