Located in the southwestern corner of Europe, the Iberian Peninsula is separated from the rest of the continent by the Pyrenees Mountains and from Africa by the Strait of Gibraltar. This geographical position may have conditioned distinct selective pressures compared to the rest of Europe and influenced differential patterns of gene flow. In this work, we analyse 704 whole-genome sequences from the GCAT reference panel to quantify gene flow into Spain from various historical sources and identify the top signatures of positive (adaptive) selection. While we found no clear evidence of a 16th-century admixture event putatively related to the French diaspora during the Wars of Religion, we detected signals of North African admixture matching the Muslim period and the subsequent Christian Reconquista. Notably, besides finding that well-known candidate genes previously described in Eurasians also seem to be adaptive in Spain, we discovered novel top candidates for positive selection putatively associated with immunity and diet (UBL7, SMYD1, VAC14 and FDFT1). Finally, local ancestry deviation analysis revealed that the MHCIII genomic region underwent post-admixture selection following the post-Neolithic admixture with Steppe ancestry.

Center of Molecular Medicine Central European Institute of Technology Masaryk University Brno Czech Republic

Department of Archaeology and Museology Masaryk University Brno Czech Republic

Genomes for Life GCAT lab CORE Program Germans Trias i Pujol Research Institute 08916 Badalona Spain

Grup de REcerca en Impacte de les Malalties Cròniques i les seves Trajectòries 08916 Badalona Spain

Institute of Evolutionary Biology Department of Medicine and Life Sciences Universitat Pompeu Fabra 08003 Barcelona Spain

Zobrazit více v PubMed

Montinaro, F., Pankratov, V., Yelmen, B., Pagani, L. & Mondal, M. Revisiting the out of Africa event with a deep-learning approach. PubMed DOI PMC

Bergström, A., Stringer, C., Hajdinjak, M., Scerri, E. M. L. & Skoglund, P. Origins of modern human ancestry. PubMed DOI

Fumagalli, M. et al. Signatures of environmental genetic adaptation pinpoint pathogens as the main selective pressure through human evolution. PubMed DOI PMC

Fumagalli, M. et al. Greenlandic Inuit show genetic signatures of diet and climate adaptation. PubMed DOI

Caro-Consuegra, R. et al. Uncovering signals of positive selection in peruvian populations from three ecological regions. PubMed DOI PMC

Irving-Pease, E. K. et al. The selection landscape and genetic legacy of ancient Eurasians. PubMed DOI PMC

Sinigaglia, B. et al. Exploring adaptive phenotypes for the human calcium-sensing receptor polymorphism R990G. PubMed DOI PMC

Rees, J. S., Castellano, S. & Andrés, A. M. The genomics of human local adaptation. PubMed DOI

Garud, N. R., Messer, P. W., Buzbas, E. O. & Petrov, D. A. Recent selective sweeps in North American drosophila melanogaster show signatures of soft sweeps. PubMed DOI PMC

Sabeti, P. C. et al. Genome-wide detection and characterization of positive selection in human populations. PubMed DOI PMC

Voight, B. F., Kudaravalli, S., Wen, X. & Pritchard, J. K. A map of recent positive selection in the human genome. PubMed DOI PMC

Akbari, A. et al. Identifying the favored mutation in a positive selective sweep. PubMed DOI PMC

Speidel, L., Forest, M., Shi, S. & Myers, S. R. A method for genome-wide genealogy estimation for thousands of samples. PubMed DOI PMC

Stern, A. J., Wilton, P. R. & Nielsen, R. An approximate full-likelihood method for inferring selection and allele frequency trajectories from DNA sequence data. PubMed DOI PMC

Field, Y. et al. Detection of human adaptation during the past 2000 years. PubMed DOI PMC

Smith, J. M. & Haigh, J. The hitch-hiking effect of a favourable gene. PubMed DOI

Kaplan, N. L., Hudson, R. R. & Langley, C. H. The ‘hitchhiking effect’ revisited. PubMed DOI PMC

Enattah, N. S. et al. Identification of a variant associated with adult-type hypolactasia. PubMed DOI

Jablonski, N. G. & Chaplin, G. Epidermal pigmentation in the human lineage is an adaptation to ultraviolet radiation. PubMed DOI

Huerta-Sánchez, E. et al. Altitude adaptation in Tibetans caused by introgression of Denisovan-like DNA. PubMed DOI PMC

Farré, X. et al. Skin phototype and disease: A comprehensive genetic approach to pigmentary traits pleiotropy using PRS in the GCAT Cohort. PubMed DOI PMC

Alexander, D. H., Novembre, J. & Lange, K. Fast model-based estimation of ancestry in unrelated individuals. PubMed DOI PMC

Loh, P.-R. et al. Inferring admixture histories of human populations using linkage disequilibrium. PubMed DOI PMC

Hellenthal, G. et al. A genetic atlas of human admixture history. PubMed DOI PMC

Salter-Townshend, M. & Myers, S. Fine-scale inference of ancestry segments without prior knowledge of admixing groups. PubMed DOI PMC

Olalde, I. et al. The genomic history of the Iberian Peninsula over the past 8000 years. PubMed DOI PMC

Villalba-Mouco, V. et al. Survival of late pleistocene hunter-gatherer ancestry in the iberian peninsula. PubMed DOI

Lazaridis, I. et al. Ancient human genomes suggest three ancestral populations for present-day Europeans. PubMed DOI PMC

Moorjani, P. et al. The history of African gene flow into Southern Europeans, levantines, and jews. PubMed DOI PMC

Bycroft, C. et al. Patterns of genetic differentiation and the footprints of historical migrations in the Iberian Peninsula. PubMed DOI PMC

Hernández, C. L. et al. Human genomic diversity where the mediterranean joins the Atlantic. PubMed DOI PMC

Biagini, S. A., Ramos-Luis, E., Comas, D. & Calafell, F. The place of metropolitan France in the European genomic landscape. PubMed DOI

Salas Ausens, J. A.

Millàs i Castellví, C.

Rumech, R. S. i. Quan la terra promesa era al sud. La immigració francesa al Maresme als segles XVI i XVII. Fundació Huro.

Barquer I Cerdà, A., Congost I Colomer, R. & Mutos Xicola, C. El reto de reconstituir procesos migratorio.s Diferentes modelos de migraciones francesas en la diócesis de Girona en la época moderna.

Dopazo, J. et al. 267 spanish exomes reveal population-specific differences in disease-related genetic variation. PubMed DOI PMC

Auton, A. et al. A global reference for human genetic variation. PubMed DOI PMC

Byrska-Bishop, M. et al. High-coverage whole-genome sequencing of the expanded 1000 Genomes Project cohort including 602 trios. PubMed DOI PMC

Obón-Santacana, M. et al. GCAT|Genomes for life: A prospective cohort study of the genomes of Catalonia. PubMed DOI PMC

Galván-Femenía, I. et al. Multitrait genome association analysis identifies new susceptibility genes for human anthropometric variation in the GCAT cohort. PubMed DOI PMC

Valls-Margarit, J. et al. GCAT|Panel, a comprehensive structural variant haplotype map of the Iberian population from high-coverage whole-genome sequencing. PubMed DOI PMC

Fibla, J. et al. The power of geohistorical boundaries for modeling the genetic background of human populations: The case of the rural catalan Pyrenees. PubMed DOI PMC

Biagini, S. A. et al. People from Ibiza: An unexpected isolate in the Western Mediterranean. PubMed DOI PMC

Allentoft, M. E. et al. Population genomics of post-glacial western Eurasia. PubMed DOI PMC

Flores-Bello, A. et al. Genetic origins, singularity, and heterogeneity of Basques. PubMed DOI

Wangkumhang, P., Greenfield, M. & Hellenthal, G. An efficient method to identify, date, and describe admixture events using haplotype information. PubMed DOI PMC

Norton, H. L. et al. Genetic evidence for the convergent evolution of light skin in Europeans and East Asians. PubMed DOI

Pickrell, J. K. et al. Signals of recent positive selection in a worldwide sample of human populations. PubMed DOI PMC

Lamason, R. L. et al. SLC24A5, a putative cation exchanger, affects pigmentation in zebrafish and humans. PubMed DOI

Ginger, R. S. et al. SLC24A5 encodes a PubMed DOI

Myung, C. H., Lee, J. E., Jo, C. S., Park, J. & Hwang, J. S. Regulation of Melanophilin (Mlph) gene expression by the glucocorticoid receptor (GR). PubMed DOI PMC

Ermini, L. et al. Evolutionary selection of alleles in the melanophilin gene that impacts on prostate organ function and cancer risk. PubMed DOI PMC

Cario-André, M., Pain, C., Gauthier, Y., Casoli, V. & Taieb, A. In vivo and in vitro evidence of dermal fibroblasts influence on human epidermal pigmentation. PubMed DOI

Huff, C. D. et al. Crohn’s disease and genetic Hitchhiking at IBD5. PubMed DOI PMC

Mathieson, S. & Mathieson, I. FADS1 and the timing of human adaptation to agriculture. PubMed DOI PMC

Longo, N., Frigeni, M. & Pasquali, M. Carnitine transport and fatty acid oxidation. PubMed DOI PMC

Lam, Y. W. F. Chapter 1 - Principles of Pharmacogenomics: Pharmacokinetic, Pharmacodynamic, and Clinical Implications. In

Wang, Z. et al. Signatures of recent positive selection at the ATP-binding cassette drug transporter superfamily gene loci. PubMed DOI

Yang, X. et al. Systematic genetic and genomic analysis of cytochrome P450 enzyme activities in human liver. PubMed DOI PMC

Liu, X. et al. Detecting and characterizing genomic signatures of positive selection in global populations. PubMed DOI PMC

Han, J. et al. TMEM232 promotes the inflammatory response in atopic dermatitis via the nuclear factor-κB and signal transducer and activator of transcription 3 signalling pathways. PubMed DOI

Yahalom, V. et al. PubMed DOI

Poole, J. & Van Alphen, L. Haemophilus influenzae receptor and the AnWj antigen. PubMed DOI

van Alphen, L., van Ham, M., Geelen-van den Broek, L. & Pieters, T. Relationship between secretion of the Anton blood group antigen in saliva and adherence of PubMed DOI

Brusselmans, K. et al. Squalene synthase, a determinant of raft-associated cholesterol and modulator of cancer cell proliferation*. PubMed DOI

Weng, M. et al. Fasting inhibits aerobic glycolysis and proliferation in colorectal cancer via the Fdft1-mediated AKT/mTOR/HIF1α pathway suppression. PubMed DOI PMC

Graham, S. E. et al. The power of genetic diversity in genome-wide association studies of lipids. PubMed DOI PMC

Harrison, P. W. et al. Ensembl 2024. PubMed DOI PMC

Körner, A. et al. Sema7A is crucial for resolution of severe inflammation. PubMed DOI PMC

Ghofrani, J., Lucar, O., Dugan, H., Reeves, R. K. & Jost, S. Semaphorin 7A modulates cytokine-induced memory-like responses by human natural killer cells. PubMed DOI PMC

Gras, C. et al. Semaphorin 7A protein variants differentially regulate T-cell activity. PubMed DOI

Holmes, S. et al. Sema7A is a potent monocyte stimulator. PubMed DOI

May-Wilson, S. et al. Large-scale GWAS of food liking reveals genetic determinants and genetic correlations with distinct neurophysiological traits. PubMed DOI PMC

Secolin, R. et al. Distribution of local ancestry and evidence of adaptation in admixed populations. PubMed DOI PMC

Secolin, R. et al. Exploring a region on chromosome 8p23.1 displaying positive selection signals in brazilian admixed populations: Additional insights into predisposition to obesity and related disorders. PubMed DOI PMC

Alvarez, M. I. et al. Human genetic variation in VAC14 regulates Salmonella invasion and typhoid fever through modulation of cholesterol. PubMed DOI PMC

Gilchrist, J. J. et al. Genetic variation in VAC14 is associated with bacteremia secondary to diverse pathogens in African children. PubMed DOI PMC

Bhatia, G. et al. Genome-wide Scan of 29,141 African Americans finds no evidence of directional selection since admixture. PubMed DOI PMC

Hejase, H. A., Mo, Z., Campagna, L. & Siepel, A. A deep-learning approach for inference of selective sweeps from the ancestral recombination graph. PubMed DOI PMC

Mathieson, I. et al. Genome-wide patterns of selection in 230 ancient Eurasians. PubMed DOI PMC

Sazzini, M. et al. Genomic history of the Italian population recapitulates key evolutionary dynamics of both Continental and Southern Europeans. PubMed DOI PMC

Key, F. M. et al. Emergence of human-adapted Salmonella enterica is linked to the Neolithization process. PubMed DOI PMC

L’Hôte, L. et al. An 8000 years old genome reveals the Neolithic origin of the zoonosis Brucella melitensis. PubMed DOI PMC

Barrie, W. et al. Elevated genetic risk for multiple sclerosis emerged in steppe pastoralist populations. PubMed DOI PMC

Mendoza-Revilla, J. et al. Disentangling signatures of selection before and after European colonization in latin Americans. PubMed DOI PMC

Arezki Ferrad, M.

Blay, N. et al. Disease prevalence, health-related and socio-demographic factors in the GCAT cohort. A comparison with the general population of Catalonia. 2023.09.08.23295239 Preprint at 10.1101/2023.09.08.23295239 (2023).

Picard toolkit.

Danecek, P. et al. Twelve years of SAMtools and BCFtools. PubMed DOI PMC

Chang, C. C. et al. Second-generation PLINK: rising to the challenge of larger and richer datasets. PubMed DOI PMC

Patterson, N., Price, A. L. & Reich, D. Population structure and eigenanalysis. PubMed DOI PMC

Price, A. L. et al. Principal components analysis corrects for stratification in genome-wide association studies. PubMed DOI

Bergström, A. et al. Insights into human genetic variation and population history from 929 diverse genomes. PubMed DOI PMC

Lazaridis, I. et al. Genomic insights into the origin of farming in the ancient Near East. PubMed DOI PMC

Behr, A. A., Liu, K. Z., Liu-Fang, G., Nakka, P. & Ramachandran, S. pong: Fast analysis and visualization of latent clusters in population genetic data. PubMed DOI PMC

Delaneau, O., Zagury, J.-F., Robinson, M. R., Marchini, J. L. & Dermitzakis, E. T. Accurate, scalable and integrative haplotype estimation. PubMed DOI PMC

Lawson, D. J., Hellenthal, G., Myers, S. & Falush, D. Inference of population structure using dense haplotype data. PubMed DOI PMC

Tennessen, J. A. et al. Evolution and functional impact of rare coding variation from deep sequencing of human exomes. PubMed DOI PMC

Szpiech, Z. A. & Hernandez, R. D. selscan: An efficient multithreaded program to perform EHH-based scans for positive selection. PubMed DOI PMC

McLaren, W. et al. The ensembl variant effect predictor. PubMed DOI PMC

Scorrano, G. et al. Genomic ancestry, diet and microbiomes of Upper Palaeolithic hunter-gatherers from San Teodoro cave. PubMed DOI PMC

Maples, B. K., Gravel, S., Kenny, E. E. & Bustamante, C. D. RFMix: A discriminative modeling approach for rapid and robust local-ancestry inference. PubMed DOI PMC