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Cited by 66Genetic and Clinical Aspects of Sex Determination and Chromosomal AbnormalitiesSexual Differentiation and DisordersChromosomal and Genetic Variations

The mole genome reveals regulatory rearrangements associated with adaptive intersexuality

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M. Real, Francisca, Haas, Stefan A., Franchini, Paolo, Xiong, Peiwen, Simakov, Oleg, Kuhl, Heiner, Schöpflin, Robert, Heller, David +21 more·2020·Science
DOI 10.1126/science.aaz2582PMC PMC8243244
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Abstract

Intersexuality in female moles: Female moles are intersexual and develop masculinizing ovotestes, a distinctive trait among mammals. Real et al. investigated the origin of this trait by sequencing the Iberian mole genome and applying comparative strategies that integrate transcriptomic, epigenetic, and chromatin interaction data. They identified mole-specific genomic rearrangements that alter the three-dimensional regulatory landscape of the androgen-converting gene CYP17A1 and the pro-testicular factor gene FGF9 , both of which show distinct expression patterns in mole gonads. The use of transgenic mice confirms the capability of these factors to increase circulating testosterone levels and to induce gonadal masculinization. This study highlights how integrative approaches can reveal the phenotypic impact of genomic variation. Science , this issue p. 208

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  • A single inversion in the mole genome has resulted in a high testosterone level in females, thought to aide in digging.

    “several recent studies demonstrated that a single inversion in the mole genome has resulted in a high testosterone level in females, thought to aide in digging (153)”

    From Topological Approaches in Animal Comparative Genomics (2026) · cites this paper as [153]

    The CYP17A1 triplication section reports high circulating androgens in female moles and links increased testosterone to the triplication’s regulatory effects, not to a single inversion. The Discussion suggests that androgen-related muscle strength may aid a burrowing lifestyle. The paper instead associates an FGF9 inversion with delayed meiosis and gonadal masculinization. (LLM, conf=0.90)

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Cited by

Sorted by citations

Authors
M. Real, F., Haas, S. A., Franchini, P., Xiong, P., Simakov, O., Kuhl, H., Schöpflin, R., Heller, D., Moeinzadeh, M.-H., Heinrich, V., Krannich, T., Bressin, A., Hartmann, M. F., Wudy, S. A., Dechmann, D. K. N., Hurtado, A., Barrionuevo, F. J., Schindler, M., Harabula, I., Osterwalder, M., Hiller, M., Wittler, L., Visel, A., Timmermann, B., Meyer, A., Vingron, M., Jiménez, R., Mundlos, S., & Lupiáñez, D. G.
Affiliations
  • RG Development & Disease, Max Planck Institute for Molecular Genetics, Berlin, Germany.
  • Max Planck Institute for Molecular Genetics (DE)
  • University of Konstanz (DE)
  • University of Vienna (AT)
  • Leibniz Institute of Freshwater Ecology and Inland Fisheries (DE)
  • Justus-Liebig-Universität Gießen (DE)
  • Universidad de Granada (ES)
  • University of Bern (CH)
  • Max Planck Institute for the Physics of Complex Systems (DE)
  • Lawrence Berkeley National Laboratory (US)
  • Berlin-Brandenburger Centrum für Regenerative Therapien (DE)
  • Max Delbrück Center (DE)
Corresponding author
  • Mundlos, Stefan
  • Lupiáñez, Darío G.
ORCID
Venue
Science
Publisher
American Association for the Advancement of Science (AAAS)
Published
2020-10-09
Volume
370
Issue
6513
Pages
208-214
ISSN
  • 0036-8075 (ISSN-L)
  • 1095-9203
DOI
10.1126/science.aaz2582
PMC
PMC8243244
OpenAlex
W3092396653
Cited by
66
References
5
Citations by year
2026: 9 · 2025: 13 · 2024: 8 · 2023: 17 · 2022: 10 · 2021: 7 · 2020: 2
FWCI
5.34
Type
journal article
Language
en
Open access
Locations
  • Science (publishedVersion)
  • PubMed (publishedVersion)
  • PubMed Central (acceptedVersion)
  • DIGITAL.CSIC (Spanish National Research Council (CSIC)) (acceptedVersion, other-oa)
  • Institutional Repository of the University of Granada (University of Granada) (submittedVersion, other-oa)
  • UnitusOpen (Tuscia University) (submittedVersion, public-domain)
  • OSTI OAI (U.S. Department of Energy Office of Scientific and Technical Information) (submittedVersion)
  • RISalud Institutional Health Repository of Andalucía (submittedVersion, other-oa)
  • Bern Open Repository and Information System (University of Bern) (submittedVersion)
  • MDC Repository (Max-Delbrueck-Center for Molecular Medicine) (submittedVersion)
  • eScholarship (California Digital Library) (submittedVersion)
  • IRIS Research product catalog (Sapienza University of Rome) (submittedVersion, other-oa)
  • KOPS (University of Konstanz) (submittedVersion)
  • MPG.PuRe (Max Planck Society) (submittedVersion, other-oa)
  • MPG.PuRe (Max Planck Society) (submittedVersion)
  • Open Access CRIS of the University of Bern
Funders
  • Fundación Alfonso Martín Escudero
  • Deutsche Forschungsgemeinschaft (MU 880/15-1, MU 880/16-1)
  • Max-Planck-Gesellschaft
  • Helmholtz Association (ERC-RA-0033)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetic and Clinical Aspects of Sex Determination and Chromosomal Abnormalities
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Sexual Differentiation and Disorders
  • Life Sciences › Agricultural and Biological Sciences › Plant Science › Chromosomal and Genetic Variations
Keywords
intersex, ovotestis, CYP17A1, FGF9, genome rearrangement, 3D genome organization, epigenetics, testosterone, adaptive evolution, comparative genomics
MeSH terms
Adaptation, Physiological, Animals, Female, Gene Expression Regulation, Chromosome Inversion, Mice, Transgenic, Moles, Sex Differentiation, Steroid 17-alpha-Hydroxylase, Testosterone, Genome, Tandem Repeat Sequences, Regulatory Elements, Transcriptional, Mice, Fibroblast Growth Factor 9, Datasets as Topic

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