Natural and human-driven selection of a single non-coding body size variant in ancient and modern canids

• Published in: Current Biology
• Main Authors: Plassais, Jocelyn, Vonholdt, Bridgett M, Parker, Heidi G, Carmagnini, Alberto, Dubos, Nicolas, Papa, Ilenia, Bevant, Kevin, Derrien, Thomas, Hennelly, Lauren M, Whitaker, D Thad, Harris, Alex C, Hogan, Andrew N, Huson, Heather J, Zaibert, Victor F, Linderholm, Anna, Haile, James, Fest, Thierry, Habib, Bilal, Sacks, Benjamin N, Benecke, Norbert, Outram, Alan K, Sablin, Mikhail V, Germonpré, Mietje, Larson, Greger, Frantz, Laurent, Ostrander, Elaine A
• Other Authors: National Human Genome Research Institute (NHGRI), Princeton University, Queen Mary University of London (QMUL), Territoires, Environnement, Télédétection et Information Spatiale (UMR TETIS), Centre de Coopération Internationale en Recherche Agronomique pour le Développement (Cirad)-AgroParisTech-Centre National de la Recherche Scientifique (CNRS)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Microenvironment and B-cells: Immunopathology,Cell Differentiation, and Cancer (MOBIDIC), Université de Rennes (UR)-Etablissement français du sang Rennes (EFS Bretagne)-Institut National de la Santé et de la Recherche Médicale (INSERM), Microenvironment, Cell Differentiation, Immunology and Cancer (MICMAC), Université de Rennes (UR)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), Hôpital Sud CHU Rennes, Centre Hospitalier Universitaire de Rennes CHU Rennes = Rennes University Hospital Ponchaillou, Chemistry, Oncogenesis, Stress and Signaling (COSS), Université de Rennes (UR)-CRLCC Eugène Marquis (CRLCC), UNICANCER-UNICANCER-Institut National de la Santé et de la Recherche Médicale (INSERM), CRLCC Eugène Marquis (CRLCC), UNICANCER, Institut de Génétique et Développement de Rennes (IGDR), Université de Rennes (UR)-Centre National de la Recherche Scientifique (CNRS)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), University of California Davis (UC Davis), University of California (UC), Cornell University New York, Al-Farabi Kazakh National University Almaty (KazNU), Stockholm University, University of Oxford, German Archaeological Institute (DAI), University of Exeter, Zoological Institute of Russian Academy of Sciences, Russian Academy of Sciences Moscow (RAS), Royal Belgian Institute of Natural Sciences (RBINS), Ludwig Maximilian University Munich = Ludwig Maximilians Universität München (LMU), Intramural Program of the National Human Genome Research Institute (J.P., H.G.P., A.N.H., and E.A.O.). J.P. is also funded by Region Bretagne and Ligue Contre le Cancer. B.M.v.H. is funded by Princeton University. L.F., J.H., and G.L. were supported by the ERC (grant ERC-2013-StG-337574-UNDEAD and ERC-2019-StG-853272-PALAEOFARM) and Natural Environment Research Council grants (NE/K005243/1 and NE/K003259/1). L.F. and A.C. were supported by the Wellcome Trust (210119/Z/18/Z). B.H.’s research was funded by DST, the Government of India, and Maharashtra Forest Department.
• Format: Article in Journal/Newspaper
• Language: English
• Published: HAL CCSD 2022
• Subjects: IGF1; ancient DNA; antisense lncRNA; body size; canid evolution; canine; dog; domestication; long non-coding RNA; wolf; [SDV.BID.EVO]Life Sciences [q-bio]/Biodiversity/Populations and Evolution [q-bio.PE]; [SDV.GEN.GA]Life Sciences [q-bio]/Genetics/Animal genetics; Canis lupus
• Online Access: https://hal.science/hal-03555249; https://hal.science/hal-03555249/document; https://hal.science/hal-03555249/file/Plassais_Current%20Biology_2022.pdf; https://doi.org/10.1016/j.cub.2021.12.036

International audience Domestic dogs (Canis lupus familiaris) are the most variable-sized mammalian species on Earth, displaying a 40-fold size difference between breeds. Although dogs of variable size are found in the archeological record, the most dramatic shifts in body size are the result of selection over the last two centuries, as dog breeders selected and propagated phenotypic extremes within closed breeding populations. Analyses of over 200 domestic breeds have identified approximately 20 body size genes regulating insulin processing, fatty acid metabolism, TGFβ signaling, and skeletal formation. Of these, insulin-like growth factor 1 (IGF1) predominates, controlling approximately 15% of body size variation between breeds. The identification of a functional mutation associated with IGF1 has thus far proven elusive. Here, to identify and elucidate the role of an ancestral IGF1 allele in the propagation of modern canids, we analyzed 1,431 genome sequences from 13 species, including both ancient and modern canids, thus allowing us to define the evolutionary history of both ancestral and derived alleles at this locus. We identified a single variant in an antisense long non-coding RNA (IGF1-AS) that interacts with the IGF1 gene, creating a duplex. While the derived mutation predominates in both modern gray wolves and large domestic breeds, the ancestral allele, which predisposes to small size, was common in small-sized breeds and smaller wild canids. Our analyses demonstrate that this major regulator of canid body size nearly vanished in Pleistocene wolves, before its recent resurgence resulting from human-imposed selection for small-sized breed dogs.