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Drylands are extensive across sub-Saharan Africa, socio-economically and ecologically important yet highly sensitive to environmental changes. Evolutionary history, as revealed by contemporary intraspecific genetic variation, can provide valuable insight into how species have responded to past environmental and population changes and guide strategies to promote resilience to future changes. The gum arabic tree (Acacia senegal) is an arid-adapted, morphologically diverse species native to the sub-Saharan drylands. We used variation in nuclear sequences (internal transcribed spacer (ITS)) and two types of chloroplast DNA (cpDNA) markers (PCR-RFLP, cpSSR) to study the phylogeography of the species with 293 individuals from 66 populations sampled across its natural range. cpDNA data showed high regional and rangewide haplotypic diversity (h(T(cpSSR)) = 0.903-0.948) and population differentiation (G(ST(RFLP)) = 0.700-0.782) with a phylogeographic pattern that indicated extensive historical gene flow via seed dispersal. Haplotypes were not restricted to any of the four varieties, but showed significant geographic structure (G(ST(cpSSR)) = 0.392; R-ST = 0.673; R-ST > R-ST (permuted)), with the major division separating East and Southern Africa populations from those in West and Central Africa. Phylogenetic analysis of ITS data indicated a more recent origin for the clade including West and Central African haplotypes, suggesting range expansion in this region, possibly during the Holocene humid period. In conjunction with paleobotanical evidence, our data suggest dispersal to West Africa, and across to the Arabian Peninsula and Indian subcontinent, from source populations located in the East African region during climate oscillations of the Plio-Pleistocene. Heredity (2012) 109, 372-382; doi:10.1038/hdy.2012.52; published online 29 August 2012