. 2023 Apr 28;380(6643):eabn7930.

doi: 10.1126/science.abn7930. Epub 2023 Apr 28.

Mammalian evolution of human cis-regulatory elements and transcription factor binding sites

Gregory Andrews^#¹, Kaili Fan^#¹, Henry E Pratt^#¹, Nishigandha Phalke¹; Zoonomia Consortium§; Elinor K Karlsson^{1

2

3}, Kerstin Lindblad-Toh^{2

4}, Steven Gazal^{5

6}, Jill E Moore¹, Zhiping Weng¹

Collaborators, Affiliations

Collaborators

Zoonomia Consortium§:
Gregory Andrews, Joel C Armstrong, Matteo Bianchi, Bruce W Birren, Kevin R Bredemeyer, Ana M Breit, Matthew J Christmas, Hiram Clawson, Joana Damas, Federica Di Palma, Mark Diekhans, Michael X Dong, Eduardo Eizirik, Kaili Fan, Cornelia Fanter, Nicole M Foley, Karin Forsberg-Nilsson, Carlos J Garcia, John Gatesy, Steven Gazal, Diane P Genereux, Linda Goodman, Jenna Grimshaw, Michaela K Halsey, Andrew J Harris, Glenn Hickey, Michael Hiller, Allyson G Hindle, Robert M Hubley, Graham M Hughes, Jeremy Johnson, David Juan, Irene M Kaplow, Elinor K Karlsson, Kathleen C Keough, Bogdan Kirilenko, Klaus-Peter Koepfli, Jennifer M Korstian, Amanda Kowalczyk, Sergey V Kozyrev, Alyssa J Lawler, Colleen Lawless, Thomas Lehmann, Danielle L Levesque, Harris A Lewin, Xue Li, Abigail Lind, Kerstin Lindblad-Toh, Ava Mackay-Smith, Voichita D Marinescu, Tomas Marques-Bonet, Victor C Mason, Jennifer R S Meadows, Wynn K Meyer, Jill E Moore, Lucas R Moreira, Diana D Moreno-Santillan, Kathleen M Morrill, Gerard Muntané, William J Murphy, Arcadi Navarro, Martin Nweeia, Sylvia Ortmann, Austin Osmanski, Benedict Paten, Nicole S Paulat, Andreas R Pfenning, BaDoi N Phan, Katherine S Pollard, Henry E Pratt, David A Ray, Steven K Reilly, Jeb R Rosen, Irina Ruf, Louise Ryan, Oliver A Ryder, Pardis C Sabeti, Daniel E Schäffer, Aitor Serres, Beth Shapiro, Arian F A Smit, Mark Springer, Chaitanya Srinivasan, Cynthia Steiner, Jessica M Storer, Kevin A M Sullivan, Patrick F Sullivan, Elisabeth Sundström, Megan A Supple, Ross Swofford, Joy-El Talbot, Emma Teeling, Jason Turner-Maier, Alejandro Valenzuela, Franziska Wagner, Ola Wallerman, Chao Wang, Juehan Wang, Zhiping Weng, Aryn P Wilder, Morgan E Wirthlin, James R Xue, Xiaomeng Zhang

Affiliations

¹ Program in Bioinformatics and Integrative Biology, University of Massachusetts Chan Medical School, Worcester, MA, USA.
² Broad Institute of MIT and Harvard, Cambridge, MA 02139, USA.
³ Program in Molecular Medicine, UMass Chan Medical School, Worcester, MA 01605, USA.
⁴ Science for Life Laboratory, Department of Medical Biochemistry and Microbiology, Uppsala University, 75132 Uppsala, Sweden.
⁵ Department of Population and Public Health Sciences, Keck School of Medicine, University of Southern California, Los Angeles, CA 90033, USA.
⁶ Center for Genetic Epidemiology, Keck School of Medicine, University of Southern California, Los Angeles, CA 90033, USA.

^# Contributed equally.

PMID: 37104580
DOI: 10.1126/science.abn7930

Free article

Mammalian evolution of human cis-regulatory elements and transcription factor binding sites

Gregory Andrews et al. Science. 2023.

Free article

. 2023 Apr 28;380(6643):eabn7930.

doi: 10.1126/science.abn7930. Epub 2023 Apr 28.

Authors

Collaborators

Zoonomia Consortium§:
Gregory Andrews, Joel C Armstrong, Matteo Bianchi, Bruce W Birren, Kevin R Bredemeyer, Ana M Breit, Matthew J Christmas, Hiram Clawson, Joana Damas, Federica Di Palma, Mark Diekhans, Michael X Dong, Eduardo Eizirik, Kaili Fan, Cornelia Fanter, Nicole M Foley, Karin Forsberg-Nilsson, Carlos J Garcia, John Gatesy, Steven Gazal, Diane P Genereux, Linda Goodman, Jenna Grimshaw, Michaela K Halsey, Andrew J Harris, Glenn Hickey, Michael Hiller, Allyson G Hindle, Robert M Hubley, Graham M Hughes, Jeremy Johnson, David Juan, Irene M Kaplow, Elinor K Karlsson, Kathleen C Keough, Bogdan Kirilenko, Klaus-Peter Koepfli, Jennifer M Korstian, Amanda Kowalczyk, Sergey V Kozyrev, Alyssa J Lawler, Colleen Lawless, Thomas Lehmann, Danielle L Levesque, Harris A Lewin, Xue Li, Abigail Lind, Kerstin Lindblad-Toh, Ava Mackay-Smith, Voichita D Marinescu, Tomas Marques-Bonet, Victor C Mason, Jennifer R S Meadows, Wynn K Meyer, Jill E Moore, Lucas R Moreira, Diana D Moreno-Santillan, Kathleen M Morrill, Gerard Muntané, William J Murphy, Arcadi Navarro, Martin Nweeia, Sylvia Ortmann, Austin Osmanski, Benedict Paten, Nicole S Paulat, Andreas R Pfenning, BaDoi N Phan, Katherine S Pollard, Henry E Pratt, David A Ray, Steven K Reilly, Jeb R Rosen, Irina Ruf, Louise Ryan, Oliver A Ryder, Pardis C Sabeti, Daniel E Schäffer, Aitor Serres, Beth Shapiro, Arian F A Smit, Mark Springer, Chaitanya Srinivasan, Cynthia Steiner, Jessica M Storer, Kevin A M Sullivan, Patrick F Sullivan, Elisabeth Sundström, Megan A Supple, Ross Swofford, Joy-El Talbot, Emma Teeling, Jason Turner-Maier, Alejandro Valenzuela, Franziska Wagner, Ola Wallerman, Chao Wang, Juehan Wang, Zhiping Weng, Aryn P Wilder, Morgan E Wirthlin, James R Xue, Xiaomeng Zhang

Affiliations

¹ Program in Bioinformatics and Integrative Biology, University of Massachusetts Chan Medical School, Worcester, MA, USA.
² Broad Institute of MIT and Harvard, Cambridge, MA 02139, USA.
³ Program in Molecular Medicine, UMass Chan Medical School, Worcester, MA 01605, USA.
⁴ Science for Life Laboratory, Department of Medical Biochemistry and Microbiology, Uppsala University, 75132 Uppsala, Sweden.
⁵ Department of Population and Public Health Sciences, Keck School of Medicine, University of Southern California, Los Angeles, CA 90033, USA.
⁶ Center for Genetic Epidemiology, Keck School of Medicine, University of Southern California, Los Angeles, CA 90033, USA.

^# Contributed equally.

PMID: 37104580
DOI: 10.1126/science.abn7930

Abstract

Understanding the regulatory landscape of the human genome is a long-standing objective of modern biology. Using the reference-free alignment across 241 mammalian genomes produced by the Zoonomia Consortium, we charted evolutionary trajectories for 0.92 million human candidate cis-regulatory elements (cCREs) and 15.6 million human transcription factor binding sites (TFBSs). We identified 439,461 cCREs and 2,024,062 TFBSs under evolutionary constraint. Genes near constrained elements perform fundamental cellular processes, whereas genes near primate-specific elements are involved in environmental interaction, including odor perception and immune response. About 20% of TFBSs are transposable element-derived and exhibit intricate patterns of gains and losses during primate evolution whereas sequence variants associated with complex traits are enriched in constrained TFBSs. Our annotations illuminate the regulatory functions of the human genome.

PubMed Disclaimer

Cited by

Enrichment of Cis-Acting Regulatory Elements in Differentially Methylated Regions Following Lipopolysaccharide Treatment of Bovine Endometrial Epithelial Cells.
Jhamat N, Guo Y, Han J, Humblot P, Bongcam-Rudloff E, Andersson G, Niazi A. Jhamat N, et al. Int J Mol Sci. 2024 Sep 11;25(18):9832. doi: 10.3390/ijms25189832. Int J Mol Sci. 2024. PMID: 39337320 Free PMC article.
CADD v1.7: using protein language models, regulatory CNNs and other nucleotide-level scores to improve genome-wide variant predictions.
Schubach M, Maass T, Nazaretyan L, Röner S, Kircher M. Schubach M, et al. Nucleic Acids Res. 2024 Jan 5;52(D1):D1143-D1154. doi: 10.1093/nar/gkad989. Nucleic Acids Res. 2024. PMID: 38183205 Free PMC article.
Strategies for Dissecting the Genetic Driving of Conserved Noncoding-Elements for Evolutionary Development of the Corpus Callosum.
Ye Y, Jin B, Zhang HW, Sheng N. Ye Y, et al. Neurosci Bull. 2024 Jul;40(7):1025-1027. doi: 10.1007/s12264-024-01198-y. Epub 2024 Apr 3. Neurosci Bull. 2024. PMID: 38568390 No abstract available.
Understanding and modeling human traits and diseases: Insights from the comparative genomics resources of Zoonomia.
Ye M, Zhang DF. Ye M, et al. Innovation (Camb). 2023 May 20;4(4):100444. doi: 10.1016/j.xinn.2023.100444. eCollection 2023 Jul 10. Innovation (Camb). 2023. PMID: 37305857 Free PMC article. Review. No abstract available.
Parallel Evolution at the Regulatory Base-Pair Level Contributes to Mammalian Interspecific Differences in Polygenic Traits.
Okamoto AS, Capellini TD. Okamoto AS, et al. Mol Biol Evol. 2024 Aug 2;41(8):msae157. doi: 10.1093/molbev/msae157. Mol Biol Evol. 2024. PMID: 39073613 Free PMC article.

See all "Cited by" articles

MeSH terms

Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions

Substances

Actions
Actions

Grants and funding

R01 HG008742/HG/NHGRI NIH HHS/United States

LinkOut - more resources

Full Text Sources
- Atypon
- Ovid Technologies, Inc.

Save citation to file

Email citation

Add to Collections

Add to My Bibliography

Your saved search

Create a file for external citation management software

Your RSS Feed

Mammalian evolution of human cis-regulatory elements and transcription factor binding sites

Collaborators

Affiliations

Mammalian evolution of human cis-regulatory elements and transcription factor binding sites

Authors

Collaborators

Affiliations

Abstract

Similar articles

Cited by

MeSH terms

Substances

Grants and funding

LinkOut - more resources

Full Text Sources

Abstract

Similar articles

Cited by

MeSH terms

Substances

Related information

Grants and funding

LinkOut - more resources

Full Text Sources