Three-dimensional genome rewiring in loci with human accelerated regions
Open accessPublished version of a preprint
Abstract
Abstract 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 the largest alignment of mammalian genomes to date. To facilitate exploration of accelerated evolution in other lineages, we implemented an open-source Nextflow pipeline that runs on any computing platform. 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 (TADs) containing human-specific genomic variants that change three-dimensional (3D) genome organization. Differential gene expression between humans and chimpanzees at these loci in multiple cell types 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. One-Sentence Summary Human-specific changes to 3D genome organization may have contributed to rapid evolution of mammalian-conserved loci in the human genome.
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A more recent database of 312 HARs released by the Zoonomia consortium did not detect HAR202.
“A more recent database of 312 HARs, which did not detect HAR202, has been released by the Zoonomia consortium (zooHARs) after leveraging the alignment of 241 mammalian genomes and using a novel algorithmic pipeline called AcceleratedRegionsNF (Keough et al. 2023).”
From The Human Accelerated Region HAR202 Controls <i>NPAS3</i> Expression in the Developing Forebrain Displaying Differential Enhancer Activity Between Modern and Archaic Human Sequences (2024) · cites this paper as Keough et al. 2023
The section on human and chimpanzee accelerated regions says the authors used AcceleratedRegionsNF and a Zoonomia alignment of 241 mammalian genomes to identify 312 zooHARs. Our copy does not state whether HAR202 was among them, so it does not support the claim that HAR202 was not detected. (LLM, conf=0.85)
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References 90 · Cited by 113
Research works printed but not linked: 1
- [26]Siepel A, Pollard KS, Haussler D, in Research in Computational Molecular Biology, Apostolico A, Guerra C, Istrail S, Pevzner PA, Waterman M, Eds., vol. 3909 of Lecture Notes in Computer Science (Springer, 2006), pp. 190– 205.
- Authors
- Keough, K. C., Whalen, S., Inoue, F., Przytycki, P. F., Fair, T., Deng, C., Steyert, M., Ryu, H., Lindblad-Toh, K., Karlsson, E., Zoonomia Consortium§, Nowakowski, T., Ahituv, N., Pollen, A., Pollard, K. S., Andrews, G., Armstrong, J. C., Bianchi, M., Birren, B. W., Bredemeyer, K. R., Breit, A. M., Christmas, M. J., Clawson, H., Damas, J., Di Palma, F., Diekhans, M., Dong, M. X., Eizirik, E., Fan, K., Fanter, C., Foley, N. M., Forsberg-Nilsson, K., Garcia, C. J., Gatesy, J., Gazal, S., Genereux, D. P., Goodman, L., Grimshaw, J., Halsey, M. K., Harris, A. J., Hickey, G., Hiller, M., Hindle, A. G., Hubley, R. M., Hughes, G. M., Johnson, J., Juan, D., Kaplow, I. M., Karlsson, E. K., Keough, K. C., Kirilenko, B., Koepfli, K.-P., Korstian, J. M., Kowalczyk, A., Kozyrev, S. V., Lawler, A. J., Lawless, C., Lehmann, T., Levesque, D. L., Lewin, H. A., Li, X., Lind, A., Lindblad-Toh, K., Mackay-Smith, A., Marinescu, V. D., Marques-Bonet, T., Mason, V. C., Meadows, J. R. S., Meyer, W. K., Moore, J. E., Moreira, L. R., Moreno-Santillan, D. D., Morrill, K. M., Muntané, G., Murphy, W. J., Navarro, A., Nweeia, M., Ortmann, S., Osmanski, A., Paten, B., Paulat, N. S., Pfenning, A. R., Phan, B. N., Pollard, K. S., Pratt, H. E., Ray, D. A., Reilly, S. K., Rosen, J. R., Ruf, I., Ryan, L., Ryder, O. A., Sabeti, P. C., Schäffer, D. E., Serres, A., Shapiro, B., Smit, A. F. A., Springer, M., Srinivasan, C., Steiner, C., Storer, J. M., Sullivan, K. A. M., Sullivan, P. F., Sundström, E., Supple, M. A., Swofford, R., Talbot, J.-E., Teeling, E., Turner-Maier, J., Valenzuela, A., Wagner, F., Wallerman, O., Wang, C., Wang, J., Weng, Z., Wilder, A. P., Wirthlin, M. E., Xue, J. R., & Zhang, X.
- Affiliations
- Gladstone Institutes (US)
- University of California, San Francisco (US)
- Broad Institute of MIT and Harvard, Cambridge, MA, USA.
- Broad Institute (US)
- ORCID
- Whalen, Sean
- Inoue, Fumitaka
- Przytycki, Pawel F.
- Deng, Chengyu
- Steyert, Marilyn
- Karlsson, Elinor
- Nowakowski, Tomasz
- Ahituv, Nadav
- Pollen, Alex
- Andrews, Gregory
- Armstrong, Joel C.
- Bianchi, Matteo
- Birren, Bruce W.
- Bredemeyer, Kevin R.
- Breit, Ana M.
- Christmas, Matthew J.
- Clawson, Hiram
- Damas, Joana
- Diekhans, Mark
- Dong, Michael X.
- Fan, Kaili
- Fanter, Cornelia
- Foley, Nicole M.
- Garcia, Carlos J.
- Gatesy, John
- Gazal, Steven
- Genereux, Diane P.
- Goodman, Linda
- Grimshaw, Jenna
- Hickey, Glenn
- Hiller, Michael
- Hindle, Allyson G.
- Hubley, Robert M.
- Hughes, Graham M.
- Johnson, Jeremy
- Juan, David
- Kaplow, Irene M.
- Kirilenko, Bogdan
- Koepfli, Klaus-Peter
- Korstian, Jennifer M.
- Kowalczyk, Amanda
- Kozyrev, Sergey V.
- Lawler, Alyssa J.
- Lawless, Colleen
- Lehmann, Thomas
- Levesque, Danielle L.
- Lewin, Harris A.
- Li, Xue
- Lind, Abigail
- Marinescu, Voichita D.
- Mason, Victor C.
- Meadows, Jennifer R. S.
- Meyer, Wynn K.
- Moore, Jill E.
- Moreira, Lucas R.
- Morrill, Kathleen M.
- Muntané, Gerard
- Murphy, William J.
- Navarro, Arcadi
- Nweeia, Martin
- Ortmann, Sylvia
- Osmanski, Austin
- Paten, Benedict
- Paulat, Nicole S.
- Pfenning, Andreas R.
- Phan, BaDoi N.
- Pratt, Henry E.
- Ray, David A.
- Reilly, Steven K.
- Rosen, Jeb R.
- Ruf, Irina
- Ryan, Louise
- Ryder, Oliver A.
- Sabeti, Pardis C.
- Schäffer, Daniel E.
- Shapiro, Beth
- Smit, Arian F. A.
- Springer, Mark
- Srinivasan, Chaitanya
- Steiner, Cynthia
- Storer, Jessica M.
- Sullivan, Kevin A. M.
- Sullivan, Patrick F.
- Sundström, Elisabeth
- Supple, Megan A.
- Swofford, Ross
- Talbot, Joy-El
- Teeling, Emma
- Turner-Maier, Jason
- Valenzuela, Alejandro
- Wagner, Franziska
- Wallerman, Ola
- Wang, Chao
- Weng, Zhiping
- Wilder, Aryn P.
- Wirthlin, Morgan E.
- Xue, James R.
- Zhang, Xiaomeng
- Venue
- Science
- Published
- 2023-04-28
- Volume
- 380
- Issue
- 6643
- Pages
- eabm1696-eabm1696
- ISSN
- 0036-8075 (ISSN-L)
- 1095-9203
- PMC
- PMC10999243
- OpenAlex
- W4367173670
- Cited by
- 113
- References
- 90
- Citations by year
- 2026: 33 · 2025: 36 · 2024: 30 · 2023: 14
- FWCI
- 9.98
- Type
- journal article
- Language
- en
- Open access
- green
- doi.org
- Licence
- cc-by-nc-nd
- Locations
- Science (publishedVersion)
- bioRxiv (Cold Spring Harbor Laboratory) (acceptedVersion, cc-by-nc-nd)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- DIGITAL.CSIC (Spanish National Research Council (CSIC)) (submittedVersion)
- eScholarship (California Digital Library) (submittedVersion, cc-by-nc)
- Funders
- Gladstone Institutes
- Vetenskapsrådet
- National Institutes of Health
- Japan Society for the Promotion of Science
- National Institute of Mental Health (DP2MH122400, R01MH123178, R01MH116438, R01MH109907, U01MH116438)
- National Human Genome Research Institute (R01HG010485, R01HG008742, U24HG007234)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Genomics and Chromatin Dynamics
- Life Sciences › Agricultural and Biological Sciences › Plant Science › Chromosomal and Genetic Variations
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genomic variations and chromosomal abnormalities
- Keywords
- human accelerated regions, 3D genome organization, topologically associating domains, enhancer hijacking, neural progenitor cells, deep learning, neurodevelopmental genes, regulatory evolution
- MeSH terms
- Deep Learning, Animals, Pan troglodytes, Chromatin, Humans, Genome, Human, Genomics, Neurogenesis, Genetic Loci
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