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Three-dimensional genome rewiring in loci with human accelerated regions
Gladstone Inst Data Sci & Biotechnol, San Francisco, CA 94158 USA.;Univ Calif San Francisco, Dept Bioengn & Therapeut Sci, San Francisco, CA 94143 USA.;Univ Calif San Francisco, Inst Human Genet, San Francisco, CA 94143 USA..
Gladstone Inst Data Sci & Biotechnol, San Francisco, CA 94158 USA..
Univ Calif San Francisco, Dept Bioengn & Therapeut Sci, San Francisco, CA 94143 USA.;Univ Calif San Francisco, Inst Human Genet, San Francisco, CA 94143 USA.;Kyoto Univ, Inst Adv Study Human Biol WPI ASHBi, Kyoto, Japan..
Gladstone Inst Data Sci & Biotechnol, San Francisco, CA 94158 USA.;Boston Univ, Fac Comp & Data Sci, Boston, MA 02215 USA..
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2023 (English)In: Science, ISSN 0036-8075, E-ISSN 1095-9203, Vol. 380, no 6643, article id eabm1696Article in journal (Refereed) Published
Abstract [en]

Human accelerated regions (HARs) are conserved genomic loci that evolved at an accelerated rate in the human lineage and may underlie human-specific traits. We generated HARs and chimpanzee accelerated regions with an automated pipeline and an alignment of 241 mammalian genomes. Combining deep learning with chromatin capture experiments in human and chimpanzee neural progenitor cells, we discovered a significant enrichment of HARs in topologically associating domains containing human -specific genomic variants that change three-dimensional (3D) genome organization. Differential gene expression between humans and chimpanzees at these loci suggests rewiring of regulatory interactions between HARs and neurodevelopmental genes. Thus, comparative genomics together with models of 3D genome folding revealed enhancer hijacking as an explanation for the rapid evolution of HARs.

Place, publisher, year, edition, pages
American Association for the Advancement of Science (AAAS), 2023. Vol. 380, no 6643, article id eabm1696
National Category
Medical Genetics and Genomics Genetics and Genomics Cell and Molecular Biology
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URN: urn:nbn:se:uu:diva-505571DOI: 10.1126/science.abm1696ISI: 000989260500003PubMedID: 37104607OAI: oai:DiVA.org:uu-505571DiVA, id: diva2:1773089
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Swedish Research CouncilAvailable from: 2023-06-22 Created: 2023-06-22 Last updated: 2025-02-10Bibliographically approved

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Lindblad-Toh, Kerstin

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