East Africa is a strategic region to study human genetic diversity due to the presence of ethnically, linguistically, and geographically diverse populations. Here, we provide new insight into the genetic history of populations living in the Sudanese region of East Africa by analysing nine ethnic groups belonging to three African linguistic families: Niger-Kordofanian, Nilo-Saharan and Afro-Asiatic. A total of 500 individuals were genotyped for 200,000 single-nucleotide polymorphisms. Principal component analysis, clustering analysis using ADMIXTURE, FST statistics, and the three-population test were used to investigate the underlying genetic structure and ancestry of the different ethno-linguistic groups. Our analyses revealed a genetic component for Sudanese Nilo-Saharan speaking groups (Darfurians and part of Nuba populations) related to Nilotes of South Sudan, but not to other Sudanese populations or other sub-Saharan populations. Populations inhabiting the North of the region showed close genetic affinities with North Africa, with a component that could be remnant of North Africans before the migrations of Arabs from Arabia. In addition, we found very low genetic distances between populations in genes important for anti-malarial and anti-bacterial host defence, suggesting similar selective pressures on these genes and stressing the importance of considering functional pathways to understand the evolutionary history of populations.

M.G.N. was supported by a Vici Grant of the Netherlands Organization for Scientific Research, and an ERC Consolidator Grant (nr. 310372). J.B. was supported by grant BFU2013-43726-P awarded by Ministerio de Economía y Competitividad (Spain) and with the support of Secretaria d’Universitats i Recerca del Departament d’Economia i Coneixement de la Generalitat de Catalunya (GRC 2014 SGR 866). B.D. is supported by F.P.U. grant FPU13/06813 from the Ministerio de Educación, Cultura y Deporte (Spain). C.W. is supported by the European Research Council under the European Union’s Seventh Frame-work Programme (FP/2007-2013)/ERC Grant Agreement [n. 2012-322698]. A.Z. holds a Rosalind Franklin fellowship from the University of Groningen. We thank the National Institute of Bioinformatics (http://www.inab.org) for computational support.