Continental-scale genomic analysis suggests shared post-admixture adaptation in the Americas Ongaro, Linda Alarcón Riquelme, Marta Eugenia We thank the people working at the High Performance Computing Center of the University of Tartu for the help and support provided. We thank Marco Rosario Capodiferro for useful discussions. This work was supported by the European Union through the European Regional Development Fund (Project No. 20142020.4.01.16-0030 to LO, MMe, FM; Project No. 2014-2020.4.01.160271 to RF; Project No. 2014-2020.4.01.16-0125 to RF; Project No. 2014-2020.4.01.16-0024 to DM, LP). This work was supported by the Estonian Research Council grant PUT (PRG243) (to RF, MMe, LP). This work was supported by institutional research funding IUT (IUT24-1) of the EstonianMinistry of Education and Research (to TK). This research was supported by the European Union through Horizon 2020 grant no. 810645 (to MMe). This research was supported by the European Union through the Horizon 2020 research and innovation programme under grant no 810645 and through the European Regional Development Fund project no. MOBEC008 to MMo. American populations are one of the most interesting examples of recently admixed groups, where ancestral components from three major continental human groups (Africans, Eurasians and Native Americans) have admixed within the last 15 generations. Recently, several genetic surveys focusing on thousands of individuals shed light on the geography, chronology and relevance of these events. However, even though gene f low could drive adaptive evolution, it is unclear whether and how natural selection acted on the resulting genetic variation in the Americas. In this study, we analysed the patterns of local ancestry of genomic fragments in genome-wide data for ∼6000 admixed individuals from 10 American countries. In doing so, we identified regions characterized by a divergent ancestry profile (DAP), in which a significant over or under ancestral representation is evident. Our results highlighted a series of genomic regions with DAPs associated with immune system response and relevant medical traits, with the longest DAP region encompassing the human leukocyte antigen locus. Furthermore, we found that DAP regions are enriched in genes linked to cancer-related traits and autoimmune diseases. Then, analysing the biological impact of these regions, we showed that natural selection could have acted preferentially towards variants located in coding and non-coding transcripts and characterized by a high deleteriousness score. Taken together, our analyses suggest that shared patterns of post admixture adaptation occurred at a continental scale in the Americas, affecting more often functional and impactful genomic variants. 2021-12-03T09:50:03Z 2021-12-03T09:50:03Z 2021-07-01 journal article Linda Ongaro... [et al.]. Continental-scale genomic analysis suggests shared post-admixture adaptation in the Americas, Human Molecular Genetics, Volume 30, Issue 22, 15 November 2021, Pages 2123–2134, [https://doi.org/10.1093/hmg/ddab177] http://hdl.handle.net/10481/71873 10.1093/hmg/ddab177 eng info:eu-repo/grantAgreement/EC/H2020/810645 http://creativecommons.org/licenses/by-nc/3.0/es/ open access Atribución-NoComercial 3.0 España Oxford University Press