Lucas-Sánchez, MarcelAbdeli, AmineBekada, AsmahanCalafell i Majó, FrancescBenhassine, TrakiComas, David, 1969-2024-04-122024-04-122024Lucas-Sánchez M, Abdeli A, Bekada A, Calafell F, Benhassine T, Comas D. The impact of recent demography on functional genetic variation in north african human groups. Mol Biol Evol. 2024 Jan 3;41(1):msad283. DOI: 10.1093/molbev/msad2830737-4038http://hdl.handle.net/10230/59744The strategic location of North Africa has made the region the core of a wide range of human demographic events, including migrations, bottlenecks, and admixture processes. This has led to a complex and heterogeneous genetic and cultural landscape, which remains poorly studied compared to other world regions. Whole-exome sequencing is particularly relevant to determine the effects of these demographic events on current-day North Africans' genomes, since it allows to focus on those parts of the genome that are more likely to have direct biomedical consequences. Whole-exome sequencing can also be used to assess the effect of recent demography in functional genetic variation and the efficacy of natural selection, a long-lasting debate. In the present work, we use newly generated whole-exome sequencing and genome-wide array genotypes to investigate the effect of demography in functional variation in 7 North African populations, considering both cultural and demographic differences and with a special focus on Amazigh (plur. Imazighen) groups. We detect genetic differences among populations related to their degree of isolation and the presence of bottlenecks in their recent history. We find differences in the functional part of the genome that suggest a relaxation of purifying selection in the more isolated groups, allowing for an increase of putatively damaging variation. Our results also show a shift in mutational load coinciding with major demographic events in the region and reveal differences within and between cultural and geographic groups.application/pdfeng© The Author(s) 2023. Published by Oxford University Press on behalf of Society for Molecular Biology and Evolution. This is an Open Access article distributed under the terms of the Creative Commons Attribution-NonCommercial License (https://creativecommons.org/licenses/by-nc/4.0/), which permits non-commercial re-use, distribution, and reproduction in any medium, provided the original work is properly cited. For commercial re-use, please contact journals.permissions@oup.cominfo:eu-repo/semantics/articlehttp://dx.doi.org/10.1093/molbev/msad283North AfricaFunctional variationHuman population diversityWhole exomesinfo:eu-repo/semantics/openAccess