Sudan's complex genetic admixture history drives adaptation to malaria in Sudanese Copts

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.

This work was supported by grants PID2022-138755NB-I00 and PID2023-147621NB-I00 funded by MCIN/AEI/10.13039/501100011033 and "ERDF A way of making Europe," by the European Union. We also thank the Unidad de Excelencia María de Maeztu CEX2024-001431-M, funded by MICIU/AEI/10.13039/501100011033. We thank the Scientific Computing Core Facility (MELIS-UPF) for technical support.