@article{9c7a21d64a6943febf060ce959f1c69a,
title = "Natural and human-driven selection of a single non-coding body size variant in ancient and modern canids",
abstract = "Domestic dogs (Canis lupus familiaris) are the most variable-sized mammalian species on Earth, displaying a 40-fold size difference between breeds.1 Although dogs of variable size are found in the archeological record,2–4 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.5 Analyses of over 200 domestic breeds have identified approximately 20 body size genes regulating insulin processing, fatty acid metabolism, TGFβ signaling, and skeletal formation.6–10 Of these, insulin-like growth factor 1 (IGF1) predominates, controlling approximately 15% of body size variation between breeds.8 The identification of a functional mutation associated with IGF1 has thus far proven elusive.6,10,11 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.",
keywords = "IGF1, ancient DNA, antisense lncRNA, body size, canid evolution, canine, dog, domestication, long non-coding RNA, wolf",
author = "Jocelyn Plassais and vonHoldt, {Bridgett M.} and Parker, {Heidi G.} and Alberto Carmagnini and Nicolas Dubos and Ilenia Papa and Kevin Bevant and Thomas Derrien and Hennelly, {Lauren M.} and Whitaker, {D. Thad} and Harris, {Alex C.} and Hogan, {Andrew N.} and Huson, {Heather J.} and Zaibert, {Victor F.} and Anna Linderholm and James Haile and Thierry Fest and Bilal Habib and Sacks, {Benjamin N.} and Norbert Benecke and Outram, {Alan K.} and Sablin, {Mikhail V.} and Mietje Germonpr{\'e} and Greger Larson and Laurent Frantz and Ostrander, {Elaine A.}",
note = "Funding Information: We thank the University of Washington Burke Museum, Museum of Vertebrate Zoology, California Academy of Science, Museum of Southwestern Biology, Denver Museum of Nature and Science, Sam Noble Oklahoma Museum of Natural History, Museum of Comparative Zoology, and Princeton University for providing access to their collection of coyotes{\textquoteright} body mass measures. We thank Pontus Skoglund and Anders Bergstr{\"o}m for facilitating access to unpublished data. We gratefully acknowledge Robert K. Wayne and Roland Kays for insightful comments on the manuscript as well as Robert K. Wayne for sharing samples; the CaniDNA biobank, which provided RNA samples for functional experiments; and the ZIN RAS (grant no. 075-15-2021-1069 ) for sharing ancient samples. The MoEFCC and the Maharashtra Forest Department provided necessary approvals for which we are also grateful. We also thank Luc Paillard, Agnes Mereau, Yann Audic, Pascale Quignon, St{\'e}phane Dreano, Marion Haas, C{\'e}dric Coulouarn, and Jenny Serra-Vinardell for constructive comments. Finally, we gratefully acknowledge the Dog10K Consortium for whole-genome sequencing a subset of samples and the many dog owners who provided samples for this study. This work was supported by funding from the 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.{\textquoteright}s research was funded by DST , the Government of India , and Maharashtra Forest Department . The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. Funding Information: We thank the University of Washington Burke Museum, Museum of Vertebrate Zoology, California Academy of Science, Museum of Southwestern Biology, Denver Museum of Nature and Science, Sam Noble Oklahoma Museum of Natural History, Museum of Comparative Zoology, and Princeton University for providing access to their collection of coyotes{\textquoteright} body mass measures. We thank Pontus Skoglund and Anders Bergstr{\"o}m for facilitating access to unpublished data. We gratefully acknowledge Robert K. Wayne and Roland Kays for insightful comments on the manuscript as well as Robert K. Wayne for sharing samples; the CaniDNA biobank, which provided RNA samples for functional experiments; and the ZIN RAS (grant no. 075-15-2021-1069) for sharing ancient samples. The MoEFCC and the Maharashtra Forest Department provided necessary approvals for which we are also grateful. We also thank Luc Paillard, Agnes Mereau, Yann Audic, Pascale Quignon, St{\'e}phane Dreano, Marion Haas, C{\'e}dric Coulouarn, and Jenny Serra-Vinardell for constructive comments. Finally, we gratefully acknowledge the Dog10K Consortium for whole-genome sequencing a subset of samples and the many dog owners who provided samples for this study. This work was supported by funding from the 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.{\textquoteright}s research was funded by DST, the Government of India, and Maharashtra Forest Department. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. J.P. and E.A.O. developed and planned the research and wrote the manuscript. J.P. conducted the experiments, performed data analyses, and created the figures. B.M.v.H. H.G.P. A.C. N.D. T.D. L.M.H. M.V.S. M.G. and L.F. performed statistical analyses. B.M.v.H. H.G.P. I.P. K.B. L.M.H. D.T.W. A.C.H. A.N.H. H.J.H. V.F.Z. A.L. J.H. T.F. B.H. B.N.S. N.B. A.K.O. M.V.S. M.G. G.L. and L.F. assisted in sample and data acquisition. All authors revised and edited the final manuscript and figures. The authors declare no competing interests. We worked to ensure sex balance in the selection of non-human subjects. While citing references scientifically relevant for this work, we also actively worked to promote gender balance in our reference list. The author list of this paper includes contributors from the location where the research was conducted who participated in the data collection, design, analysis, and/or interpretation of the work. Publisher Copyright: {\textcopyright} 2021",
year = "2022",
month = feb,
day = "28",
doi = "10.1016/j.cub.2021.12.036",
language = "English (US)",
volume = "32",
pages = "889--897.e9",
journal = "Current Biology",
issn = "0960-9822",
publisher = "Cell Press",
number = "4",
}