Font-Porterias, NeusCaro Consuegra, RocioLucas Sánchez, MarcelLópez, MarieGiménez, AaronCarballo Mesa, AnnabelBosch Fusté, ElenaCalafell i Majó, FrancescQuintana Murci, LluisComas, David, 1969-2021-08-052021-08-052021Font-Porterias N, Caro-Consuegra R, Lucas-Sánchez M, Lopez M, Giménez A, Carballo-Mesa A, Bosch E, Calafell F, Quintana-Murci L, Comas D. The counteracting effects of demography on functional genomic variation: the Roma paradigm. Mol Biol Evol. 2021;38(7):2804-17. DOI: 10.1093/molbev/msab0700737-4038http://hdl.handle.net/10230/48317Demographic history plays a major role in shaping the distribution of genomic variation. Yet the interaction between different demographic forces and their effects in the genomes is not fully resolved in human populations. Here, we focus on the Roma population, the largest transnational ethnic minority in Europe. They have a South Asian origin and their demographic history is characterized by recent dispersals, multiple founder events, and extensive gene flow from non-Roma groups. Through the analyses of new high-coverage whole exome sequences and genome-wide array data for 89 Iberian Roma individuals together with forward simulations, we show that founder effects have reduced their genetic diversity and proportion of rare variants, gene flow has counteracted the increase in mutational load, runs of homozygosity show ancestry-specific patterns of accumulation of deleterious homozygotes, and selection signals primarily derive from preadmixture adaptation in the Roma population sources. The present study shows how two demographic forces, bottlenecks and admixture, act in opposite directions and have long-term balancing effects on the Roma genomes. Understanding how demography and gene flow shape the genome of an admixed population provides an opportunity to elucidate how genomic variation is modeled in human populations.application/pdfeng© The Author(s) 2021. Published by Oxford University Press on behalf of the Society for Molecular Biology and Evolution. This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://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/msab070RomaAdaptationAdmixtureDemographyExomesMutational loadinfo:eu-repo/semantics/openAccess