Journal article

The mole genome reveals regulatory rearrangements associated with adaptive intersexuality

  • M. Real, Francisca ORCID Institute for Medical and Human Genetics, Charité - Universitätsmedizin Berlin, Berlin, Germany.
  • Haas, Stefan A. ORCID Department of Computational Molecular Biology, Max Planck Institute for Molecular Genetics, Berlin, Germany.
  • Franchini, Paolo ORCID Chair in Zoology and Evolutionary Biology, Department of Biology, University of Konstanz, 78457 Konstanz, Germany.
  • Xiong, Peiwen ORCID Chair in Zoology and Evolutionary Biology, Department of Biology, University of Konstanz, 78457 Konstanz, Germany.
  • Simakov, Oleg ORCID Department of Molecular Evolution and Development, University of Vienna, 1090 Vienna, Austria.
  • Kuhl, Heiner ORCID Department of Ecophysiology and Aquaculture, Leibniz-Institute of Freshwater Ecology and Inland Fisheries, Berlin, Germany.
  • Schöpflin, Robert Institute for Medical and Human Genetics, Charité - Universitätsmedizin Berlin, Berlin, Germany.
  • Heller, David ORCID Department of Computational Molecular Biology, Max Planck Institute for Molecular Genetics, Berlin, Germany.
  • Moeinzadeh, M-Hossein ORCID Department of Computational Molecular Biology, Max Planck Institute for Molecular Genetics, Berlin, Germany.
  • Heinrich, Verena ORCID Department of Computational Molecular Biology, Max Planck Institute for Molecular Genetics, Berlin, Germany.
  • Krannich, Thomas ORCID Department of Computational Molecular Biology, Max Planck Institute for Molecular Genetics, Berlin, Germany.
  • Bressin, Annkatrin ORCID Department of Computational Molecular Biology, Max Planck Institute for Molecular Genetics, Berlin, Germany.
  • Hartmann, Michaela F. 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.
  • 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.
  • Dechmann, Dina K. N. ORCID Department of Biology, University of Konstanz, Konstanz, Germany.
  • Hurtado, Alicia ORCID Instituto de Biotecnología, Centro de Investigación Biomédica, Universidad de Granada, Armilla, Granada, Spain.
  • Barrionuevo, Francisco J. ORCID Instituto de Biotecnología, Centro de Investigación Biomédica, Universidad de Granada, Armilla, Granada, Spain.
  • Schindler, Magdalena ORCID Institute for Medical and Human Genetics, Charité - Universitätsmedizin Berlin, Berlin, Germany.
  • Harabula, Izabela ORCID RG Development & Disease, Max Planck Institute for Molecular Genetics, Berlin, Germany.
  • Osterwalder, Marco ORCID Department for BioMedical Research (DBMR), University of Bern, 3008 Bern, Switzerland.
  • Hiller, Michael ORCID Center for Systems Biology Dresden, 01307 Dresden, Germany.
  • Wittler, Lars Department of Developmental Genetics, Transgenic Unit, Max Planck Institute for Molecular Genetics, Berlin, Germany.
  • Visel, Axel ORCID School of Natural Sciences, University of California, Merced, CA 95343, USA.
  • Timmermann, Bernd RG Development & Disease, Max Planck Institute for Molecular Genetics, Berlin, Germany.
  • Meyer, Axel ORCID Chair in Zoology and Evolutionary Biology, Department of Biology, University of Konstanz, 78457 Konstanz, Germany.
  • Vingron, Martin ORCID Department of Computational Molecular Biology, Max Planck Institute for Molecular Genetics, Berlin, Germany.
  • Jiménez, Rafael Instituto de Biotecnología, Centro de Investigación Biomédica, Universidad de Granada, Armilla, Granada, Spain.
  • Mundlos, Stefan ORCID Berlin-Brandenburg Center for Regenerative Therapies (BCRT), Charité - Universitätsmedizin Berlin, Berlin, Germany.
  • 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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  • 2020-10-8
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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  • English
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green
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https://sonar.rero.ch/global/documents/28527
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