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Hominin-specific regulatory elements selectively emerged in oligodendrocytes and are disrupted in autism patients

Author

Listed:
  • Bas Castelijns

    (Hubrecht Institute-KNAW & University Medical Center Utrecht)

  • Mirna L. Baak

    (Hubrecht Institute-KNAW & University Medical Center Utrecht)

  • Ilia S. Timpanaro

    (Hubrecht Institute-KNAW & University Medical Center Utrecht)

  • Caroline R. M. Wiggers

    (Hubrecht Institute-KNAW & University Medical Center Utrecht
    University Medical Center Utrecht)

  • Marit W. Vermunt

    (Hubrecht Institute-KNAW & University Medical Center Utrecht)

  • Peng Shang

    (Hubrecht Institute-KNAW & University Medical Center Utrecht)

  • Ivanela Kondova

    (Biomedical Primate Research Center)

  • Geert Geeven

    (Hubrecht Institute-KNAW & University Medical Center Utrecht)

  • Valerio Bianchi

    (Hubrecht Institute-KNAW & University Medical Center Utrecht)

  • Wouter Laat

    (Hubrecht Institute-KNAW & University Medical Center Utrecht)

  • Niels Geijsen

    (Hubrecht Institute-KNAW & University Medical Center Utrecht)

  • Menno P. Creyghton

    (Hubrecht Institute-KNAW & University Medical Center Utrecht
    Erasmus University Medical Center)

Abstract

Speciation is associated with substantial rewiring of the regulatory circuitry underlying the expression of genes. Determining which changes are relevant and underlie the emergence of the human brain or its unique susceptibility to neural disease has been challenging. Here we annotate changes to gene regulatory elements (GREs) at cell type resolution in the brains of multiple primate species spanning most of primate evolution. We identify a unique set of regulatory elements that emerged in hominins prior to the separation of humans and chimpanzees. We demonstrate that these hominin gains perferentially affect oligodendrocyte function postnatally and are preferentially affected in the brains of autism patients. This preference is also observed for human-specific GREs suggesting this system is under continued selective pressure. Our data provide a roadmap of regulatory rewiring across primate evolution providing insight into the genomic changes that underlie the emergence of the brain and its susceptibility to neural disease.

Suggested Citation

  • Bas Castelijns & Mirna L. Baak & Ilia S. Timpanaro & Caroline R. M. Wiggers & Marit W. Vermunt & Peng Shang & Ivanela Kondova & Geert Geeven & Valerio Bianchi & Wouter Laat & Niels Geijsen & Menno P. , 2020. "Hominin-specific regulatory elements selectively emerged in oligodendrocytes and are disrupted in autism patients," Nature Communications, Nature, vol. 11(1), pages 1-12, December.
  • Handle: RePEc:nat:natcom:v:11:y:2020:i:1:d:10.1038_s41467-019-14269-w
    DOI: 10.1038/s41467-019-14269-w
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    Cited by:

    1. Xinru Zhang & Bohao Fang & Yi-Fei Huang, 2023. "Transcription factor binding sites are frequently under accelerated evolution in primates," Nature Communications, Nature, vol. 14(1), pages 1-16, December.

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