The mole genome reveals regulatory rearrangements associated with adaptive intersexuality
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M. Real, Francisca
ORCID
Institute for Medical and Human Genetics, Charité - Universitätsmedizin Berlin, Berlin, Germany.
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Haas, Stefan A.
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Department of Computational Molecular Biology, Max Planck Institute for Molecular Genetics, Berlin, Germany.
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Franchini, Paolo
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Chair in Zoology and Evolutionary Biology, Department of Biology, University of Konstanz, 78457 Konstanz, Germany.
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Xiong, Peiwen
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Chair in Zoology and Evolutionary Biology, Department of Biology, University of Konstanz, 78457 Konstanz, Germany.
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Simakov, Oleg
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Department of Molecular Evolution and Development, University of Vienna, 1090 Vienna, Austria.
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Kuhl, Heiner
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Department of Ecophysiology and Aquaculture, Leibniz-Institute of Freshwater Ecology and Inland Fisheries, Berlin, Germany.
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Schöpflin, Robert
Institute for Medical and Human Genetics, Charité - Universitätsmedizin Berlin, Berlin, Germany.
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Heller, David
ORCID
Department of Computational Molecular Biology, Max Planck Institute for Molecular Genetics, Berlin, Germany.
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Moeinzadeh, M-Hossein
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Department of Computational Molecular Biology, Max Planck Institute for Molecular Genetics, Berlin, Germany.
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Heinrich, Verena
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Department of Computational Molecular Biology, Max Planck Institute for Molecular Genetics, Berlin, Germany.
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Krannich, Thomas
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Department of Computational Molecular Biology, Max Planck Institute for Molecular Genetics, Berlin, Germany.
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Bressin, Annkatrin
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Department of Computational Molecular Biology, Max Planck Institute for Molecular Genetics, Berlin, Germany.
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Hartmann, Michaela F.
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Steroid Research & Mass Spectrometry Unit, Laboratory for Translational Hormone Analytics in Paediatric Endocrinology, Division of Paediatric Endocrinology & Diabetology, Center of Child and Adolescent Medicine, Justus Liebig University, Giessen, Germany.
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Wudy, Stefan A.
ORCID
Steroid Research & Mass Spectrometry Unit, Laboratory for Translational Hormone Analytics in Paediatric Endocrinology, Division of Paediatric Endocrinology & Diabetology, Center of Child and Adolescent Medicine, Justus Liebig University, Giessen, Germany.
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Dechmann, Dina K. N.
ORCID
Department of Biology, University of Konstanz, Konstanz, Germany.
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Hurtado, Alicia
ORCID
Instituto de Biotecnología, Centro de Investigación Biomédica, Universidad de Granada, Armilla, Granada, Spain.
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Barrionuevo, Francisco J.
ORCID
Instituto de Biotecnología, Centro de Investigación Biomédica, Universidad de Granada, Armilla, Granada, Spain.
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Schindler, Magdalena
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Institute for Medical and Human Genetics, Charité - Universitätsmedizin Berlin, Berlin, Germany.
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Harabula, Izabela
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RG Development & Disease, Max Planck Institute for Molecular Genetics, Berlin, Germany.
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Osterwalder, Marco
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Department for BioMedical Research (DBMR), University of Bern, 3008 Bern, Switzerland.
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Hiller, Michael
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Center for Systems Biology Dresden, 01307 Dresden, Germany.
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Wittler, Lars
Department of Developmental Genetics, Transgenic Unit, Max Planck Institute for Molecular Genetics, Berlin, Germany.
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Visel, Axel
ORCID
School of Natural Sciences, University of California, Merced, CA 95343, USA.
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Timmermann, Bernd
RG Development & Disease, Max Planck Institute for Molecular Genetics, Berlin, Germany.
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Meyer, Axel
ORCID
Chair in Zoology and Evolutionary Biology, Department of Biology, University of Konstanz, 78457 Konstanz, Germany.
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Vingron, Martin
ORCID
Department of Computational Molecular Biology, Max Planck Institute for Molecular Genetics, Berlin, Germany.
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Jiménez, Rafael
Instituto de Biotecnología, Centro de Investigación Biomédica, Universidad de Granada, Armilla, Granada, Spain.
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Mundlos, Stefan
ORCID
Berlin-Brandenburg Center for Regenerative Therapies (BCRT), Charité - Universitätsmedizin Berlin, Berlin, Germany.
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Lupiáñez, Darío G.
ORCID
Epigenetics and Sex Development Group, Berlin Institute for Medical Systems Biology, Max-Delbrück Center for Molecular Medicine, Berlin, Germany.
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Published in:
- Science. - American Association for the Advancement of Science (AAAS). - 2020, vol. 370, no. 6513, p. 208-214
English
Linking genomic variation to phenotypical traits remains a major challenge in evolutionary genetics. In this study, we use phylogenomic strategies to investigate a distinctive trait among mammals: the development of masculinizing ovotestes in female moles. By combining a chromosome-scale genome assembly of the Iberian mole, Talpa occidentalis, with transcriptomic, epigenetic, and chromatin interaction datasets, we identify rearrangements altering the regulatory landscape of genes with distinct gonadal expression patterns. These include a tandem triplication involving CYP17A1, a gene controlling androgen synthesis, and an intrachromosomal inversion involving the pro-testicular growth factor gene FGF9, which is heterochronically expressed in mole ovotestes. Transgenic mice with a knock-in mole CYP17A1 enhancer or overexpressing FGF9 showed phenotypes recapitulating mole sexual features. Our results highlight how integrative genomic approaches can reveal the phenotypic impact of noncoding sequence changes.
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Language
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Open access status
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green
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Identifiers
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Persistent URL
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https://sonar.rero.ch/global/documents/28527
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