Three-dimensional genome rewiring in loci with human accelerated regionsUniv Calif San Francisco, Dept Neurol Surg, San Francisco, CA USA.;Univ Calif San Francisco, Dept Anat, San Francisco, CA 94143 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..
Univ Calif San Francisco, Dept Neurol Surg, San Francisco, CA USA.;Univ Calif San Francisco, Dept Anat, San Francisco, CA 94143 USA.;Univ Calif San Francisco, Dept Psychiat & Behav Sci, San Francisco, CA 94143 USA.;Univ Calif San Francisco, Eli & Edythe Broad Ctr Regenerat Med & Stem Cell, San Francisco, CA 94143 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..
Broad Inst MIT & Harvard, Cambridge, MA USA.;UMass, Chan Med Sch, Program Bioinformat & Integrat Biol, Worcester, MA USA.;UMass, Chan Med Sch, Program Mol Med, Worcester, MA USA..
Univ Calif San Francisco, Dept Neurol Surg, San Francisco, CA USA.;Univ Calif San Francisco, Dept Anat, San Francisco, CA 94143 USA.;Univ Calif San Francisco, Dept Psychiat & Behav Sci, San Francisco, CA 94143 USA.;Univ Calif San Francisco, Eli & Edythe Broad Ctr Regenerat Med & Stem Cell, San Francisco, CA 94143 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..
Univ Calif San Francisco, Dept Neurol, San Francisco, CA USA..
Gladstone Inst Data Sci & Biotechnol, San Francisco, CA 94158 USA.;Univ Calif San Francisco, Inst Human Genet, San Francisco, CA 94143 USA.;Univ Calif San Francisco, Dept Epidemiol & Biostat, San Francisco, CA 94143 USA.;Univ Calif San Francisco, Bakar Inst Comp Hlth Sci, San Francisco, CA 94143 USA.;Chan Zuckerberg Biohub, San Francisco, CA 94158 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
Identifiers
URN: urn:nbn:se:uu:diva-505571DOI: 10.1126/science.abm1696ISI: 000989260500003PubMedID: 37104607OAI: oai:DiVA.org:uu-505571DiVA, id: diva2:1773089
Funder
Swedish Research Council2023-06-222023-06-222025-02-10Bibliographically approved