Abstract
Sudan lies at the crossroads of Africa and the Middle East, with rich cultural, linguistic, and ecological diversity shaped by a complex demographic history. We present a whole-genome sequencing (WGS) study of Sudanese populations, analyzing high-coverage genomes (~30×) from 125 individuals representing five ethnolinguistic groups across three language families. Our results reveal deep population structure, involving Nilo-Saharan, West Eurasian, Northern African, and Western African ancestral components, as well as signatures of the Arab expansion. We report over one million novel variants, including population-specific deleterious alleles, highlighting the need for broader African genomic representation. Notably, local ancestry inference reveals a strong signal of adaptive admixture on chromosome 1 in Sudanese Copts, marked by a peak of Nilo-Saharan ancestry introduced via genetic admixture 1,000 to 1,500 y ago. At this locus, we estimate a remarkably strong selection coefficient (s = 0.0996) for SNP rs2814778 within the ACKR1 gene, which is responsible for the Duffy-null blood group that provides resistance to Plasmodium vivax malaria. These findings reveal Sudan as a genomic mosaic shaped by ancient and recent migrations and provide clear evidence of admixture-driven adaptation in an understudied region of Africa.