DNA methylation networks underlying mammalian traits
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Abstract
Using DNA methylation profiles ( n = 15,456) from 348 mammalian species, we constructed phyloepigenetic trees that bear marked similarities to traditional phylogenetic ones. Using unsupervised clustering across all samples, we identified 55 distinct cytosine modules, of which 30 are related to traits such as maximum life span, adult weight, age, sex, and human mortality risk. Maximum life span is associated with methylation levels in HOXL subclass homeobox genes and developmental processes and is potentially regulated by pluripotency transcription factors. The methylation state of some modules responds to perturbations such as caloric restriction, ablation of growth hormone receptors, consumption of high-fat diets, and expression of Yamanaka factors. This study reveals an intertwined evolution of the genome and epigenome that mediates the biological characteristics and traits of different mammalian species.
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Comparative epigenomics links evolutionary phylogenesis and epigenetic indicators to find traits related to life span.
“A recently emerging discipline called comparative epigenomics links evolutionaryphylogenesis and epigenetic indicators to find traits related to life span [85].”
From Revisiting Epigenetics Fundamentals and Its Biomedical Implications (2024) · cites this paper as [85]
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Universal DNA methylation age across mammalian tissues
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Self-citationE5 treatment showing improved health‐span and lifespan in old Sprague Dawley rats
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Self-citationSex differences in DNA methylation in bats
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Self-citationParental kinship influences global methylation and epigenetic age estimation in Peromyscus
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Molecular signatures of longevity identify compounds that extend mouse lifespan and healthspanPreprint
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Self-citationJames German and the Quest to Understand Human RECQ Helicase Deficiencies
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SFP6 fluorescent probes for imaging SAM dynamics in living cells
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- Authors
- Haghani, A., Li, C. Z., Robeck, T. R., Zhang, J., Lu, A. T., Ablaeva, J., Acosta-Rodríguez, V. A., Adams, D. M., Alagaili, A. N., Almunia, J., Aloysius, A., Amor, N. M. S., Ardehali, R., Arneson, A., Baker, C. S., Banks, G., Belov, K., Bennett, N. C., Black, P., Blumstein, D. T., Bors, E. K., Breeze, C. E., Brooke, R. T., Brown, J. L., Carter, G., Caulton, A., Cavin, J. M., Chakrabarti, L., Chatzistamou, I., Chavez, A. S., Chen, H., Cheng, K., Chiavellini, P., Choi, O.-W., Clarke, S., Cook, J. A., Cooper, L. N., Cossette, M.-L., Day, J., DeYoung, J., Dirocco, S., Dold, C., Dunnum, J. L., Ehmke, E. E., Emmons, C. K., Emmrich, S., Erbay, E., Erlacher-Reid, C., Faulkes, C. G., Fei, Z., Ferguson, S. H., Finno, C. J., Flower, J. E., Gaillard, J.-M., Garde, E., Gerber, L., Gladyshev, V. N., Goya, R. G., Grant, M. J., Green, C. B., Hanson, M. B., Hart, D. W., Haulena, M., Herrick, K., Hogan, A. N., Hogg, C. J., Hore, T. A., Huang, T., Izpisua Belmonte, J. C., Jasinska, A. J., Jones, G., Jourdain, E., Kashpur, O., Katcher, H., Katsumata, E., Kaza, V., Kiaris, H., Kobor, M. S., Kordowitzki, P., Koski, W. R., Krützen, M., Kwon, S. B., Larison, B., Lee, S.-G., Lehmann, M., Lemaître, J.-F., Levine, A. J., Li, X., Li, C., Lim, A. R., Lin, D. T. S., Lindemann, D. M., Liphardt, S. W., Little, T. J., Macoretta, N., Maddox, D., Matkin, C. O., Mattison, J. A., McClure, M., Mergl, J., Meudt, J. J., Montano, G. A., Mozhui, K., Munshi-South, J., Murphy, W. J., Naderi, A., Nagy, M., Narayan, P., Nathanielsz, P. W., Nguyen, N. B., Niehrs, C., Nyamsuren, B., O’Brien, J. K., Ginn, P. O., Odom, D. T., Ophir, A. G., Osborn, S., Ostrander, E. A., Parsons, K. M., Paul, K. C., Pedersen, A. B., Pellegrini, M., Peters, K. J., Petersen, J. L., Pietersen, D. W., Pinho, G. M., Plassais, J., Poganik, J. R., Prado, N. A., Reddy, P., Rey, B., Ritz, B. R., Robbins, J., Rodriguez, M., Russell, J., Rydkina, E., Sailer, L. L., Salmon, A. B., Sanghavi, A., Schachtschneider, K. M., Schmitt, D., Schmitt, T., Schomacher, L., Schook, L. B., Sears, K. E., Seifert, A. W., Shafer, A. B. A., Shindyapina, A. V., Simmons, M., Singh, K., Sinha, I., Slone, J., Snell, R. G., Soltanmohammadi, E., Spangler, M. L., Spriggs, M., Staggs, L., Stedman, N., Steinman, K. J., Stewart, D. T., Sugrue, V. J., Szladovits, B., Takahashi, J. S., Takasugi, M., Teeling, E. C., Thompson, M. J., Van Bonn, B., Vernes, S. C., Villar, D., Vinters, H. V., Vu, H., Wallingford, M. C., Wang, N., Wilkinson, G. S., Williams, R. W., Yan, Q., Yao, M., Young, B. G., Zhang, B., Zhang, Z., Zhao, Y., Zhao, P., Zhou, W., Zoller, J. A., Ernst, J., Seluanov, A., Gorbunova, V., Yang, X. W., Raj, K., & Horvath, S.
- Affiliations
- University of California, Los Angeles (US)
- University of Wyoming (US)
- SeaWorld Entertainment (US)
- University of Rochester (US)
- The University of Texas Southwestern Medical Center (US)
- University of Maryland, College Park (US)
- King Saud University (SA)
- Loro Parque Fundación (ES)
- University of Kentucky (US)
- Tunis University (TN)
- Oregon State University (US)
- Mary Lyon Centre at MRC Harwell (GB)
- The University of Sydney (AU)
- University of Pretoria (ZA)
- Busch Gardens Tampa, Tampa, FL, USA.
- Altius Institute for Biomedical Sciences (US)
- Epigenetic Clock Development Foundation, Los Angeles, CA, USA.
- Smithsonian Institution (US)
- The Ohio State University (US)
- AgResearch (NZ)
- Gulf World Marine Park - Dolphin Company, Panama City Beach, FL, USA.
- University of Nottingham (GB)
- University of South Carolina (US)
- University of Tennessee Health Science Center (US)
- Biochemistry Research Institute of La Plata (AR)
- University of New Mexico (US)
- Northeast Ohio Medical University (US)
- Trent University (CA)
- Taronga Conservation Society Australia (AU)
- Duke University (US)
- National Oceanic and Atmospheric Administration (US)
- Cedars-Sinai Medical Center (US)
- Queen Mary University of London (GB)
- University of California, Riverside (US)
- Fisheries and Oceans Canada (CA)
- University of California, Davis (US)
- Mystic Aquarium, Mystic, CT, USA.
- Centre National de la Recherche Scientifique (FR)
- Grønlands Naturinstitut (GL)
- Commonwealth Scientific and Industrial Research Organisation (AU)
- Brigham and Women's Hospital (US)
- University of Auckland (NZ)
- Vancouver Aquarium (CA)
- SeaWorld San Diego (US)
- National Institutes of Health (US)
- University of Otago (NZ)
- University at Buffalo, State University of New York (US)
- Altos Labs, San Diego, CA, USA.
- University of Bristol (GB)
- Norwegian Orca Survey, Andenes, Norway.
- Tufts Medical Center (US)
- Yuvan Research, Mountain View, CA, USA.
- Kamogawa Sea World, Kamogawa, Chiba, Japan.
- University of British Columbia (CA)
- Institute of Veterinary Medicine, Nicolaus Copernicus University, Torun, Poland.
- LGL Limited, King City, Ontario, Canada.
- University of Zurich (CH)
- University of Edinburgh (GB)
- Yuyao Joywee Electrics (China) (CN)
- North Gulf Oceanic Society, Homer, AK, USA.
- National Institute on Aging (US)
- ABS Global, DeForest, WI, USA.
- Marineland of Canada, Niagara Falls, Ontario, Canada.
- University of Wisconsin–Madison (US)
- Louis Calder Center - Biological Field Station, Department of Biological Sciences, Fordham University, Armonk, NY, USA.
- Texas A&M University (US)
- Museum für Naturkunde (DE)
- German Cancer Research Center (DE)
- Mammalogical Society of Mongolia, Ulaanbaatar, Mongolia.
- Mother Infant Research Institute, Tufts Medical Center, Boston, MA, USA.
- Cornell University (US)
- University of Nebraska–Lincoln (US)
- Smithsonian Conservation Biology Institute (US)
- Salk Institute for Biological Studies (US)
- Center for Coastal Studies (US)
- Miami Seaquarium, Miami, FL, USA.
- The University of Texas at San Antonio Health Science Center (US)
- University of Illinois Urbana-Champaign (US)
- Missouri State University (US)
- Institute of Molecular Biology (DE)
- Narsee Monjee Institute of Management Studies (IN)
- Applied Translational Genetics Group, School of Biological Sciences, Centre for Brain Research, The University of Auckland, Auckland, New Zealand.
- Acadia University (CA)
- Department of Pathobiology and Population Sciences, Royal Veterinary College, Hatfield, UK.
- Howard Hughes Medical Institute (US)
- University College Dublin (IE)
- Animal Care and Science Division, John G. Shedd Aquarium, Chicago, IL, USA.
- University of St Andrews (GB)
- Children's Hospital of Philadelphia (US)
- Altos Labs (US)
- Corresponding author
- Haghani, Amin
- Li, Caesar Z.
- Horvath, Steve
- ORCID
- Haghani, Amin
- Li, Caesar Z.
- Robeck, Todd R.
- Zhang, Joshua
- Lu, Ake T.
- Ablaeva, Julia
- Acosta-Rodríguez, Victoria A.
- Adams, Danielle M.
- Alagaili, Abdulaziz N.
- Almunia, Javier
- Aloysius, Ajoy
- Amor, Nabil M.S.
- Ardehali, Reza
- Arneson, Adriana
- Baker, C. Scott
- Banks, Gareth
- Belov, Katherine
- Bennett, Nigel C.
- Black, Peter
- Blumstein, Daniel T.
- Bors, Eleanor K.
- Breeze, Charles E.
- Brooke, Robert T.
- Brown, Janine L.
- Carter, Gerald
- Caulton, Alex
- Cavin, Julie M.
- Chakrabarti, Lisa
- Chatzistamou, Ioulia
- Chavez, Andreas S.
- Chen, Hao
- Cheng, Kaiyang
- Chiavellini, Priscila
- Clarke, Shannon
- Cook, Joseph A.
- Cooper, Lisa N.
- Cossette, Marie-Laurence
- Day, Joanna
- Dirocco, Stacy
- Dold, Christopher
- Dunnum, Jonathan L.
- Ehmke, Erin E.
- Emmons, Candice K.
- Emmrich, Stephan
- Erbay, Ebru
- Erlacher-Reid, Claire
- Faulkes, Chris G.
- Fei, Zhe
- Ferguson, Steven H.
- Finno, Carrie J.
- Flower, Jennifer E.
- Gaillard, Jean-Michel
- Garde, Eva
- Gerber, Livia
- Gladyshev, Vadim N.
- Goya, Rodolfo G.
- Grant, Matthew J
- Green, Carla B.
- Hanson, M. Bradley
- Hart, Daniel W.
- Haulena, Martin
- Herrick, Kelsey
- Hogan, Andrew N.
- Hogg, Carolyn J.
- Hore, Timothy A.
- Huang, Taosheng
- Jasinska, Anna J.
- Jones, Gareth
- Jourdain, Eve
- Katcher, Harold
- Kaza, Vimala
- Kiaris, Hippokratis
- Kobor, Michael S.
- Kordowitzki, Pawel
- Koski, William R.
- Krützen, Michael
- Kwon, Soo Bin
- Larison, Brenda
- Lee, Sang-Goo
- Lemaître, Jean-François
- Levine, Andrew J.
- Li, Xinmin
- Li, Cun
- Lim, Andrea R.
- Lin, David T. S.
- Lindemann, Dana M.
- Liphardt, Schuyler W.
- Little, Thomas J.
- Mattison, Julie A.
- McClure, Matthew
- Montano, Gisele A.
- Mozhui, Khyobeni
- Munshi-South, Jason
- Murphy, William J.
- Naderi, Asieh
- Nagy, Martina
- Narayan, Pritika
- Nathanielsz, Peter W.
- Nguyen, Ngoc B.
- Niehrs, Christof
- O’Brien, Justine K.
- Ginn, Perrie O’Tierney
- Odom, Duncan T
- Ophir, Alexander G.
- Ostrander, Elaine A.
- Parsons, Kim M.
- Paul, Kimberly C.
- Pedersen, Amy B.
- Pellegrini, Matteo
- Peters, Katharina J.
- Petersen, Jessica L.
- Pietersen, Darren W.
- Pinho, Gabriela M.
- Plassais, Jocelyn
- Poganik, Jesse R.
- Prado, Natalia A.
- Reddy, Pradeep
- Rey, Benjamin
- Ritz, Beate R.
- Robbins, Jooke
- Rodriguez, Magdalena
- Russell, Jennifer
- Sailer, Lindsay L.
- Salmon, Adam B.
- Sanghavi, Akshay
- Schachtschneider, Kyle M.
- Schmitt, Dennis
- Schmitt, Todd
- Schomacher, Lars
- Schook, Lawrence B.
- Sears, Karen E.
- Seifert, Ashley W.
- Shafer, Aaron B.A.
- Shindyapina, Anastasia V.
- Simmons, Melanie
- Singh, Kavita
- Slone, Jesse
- Snell, Russel G.
- Soltanmohammadi, Elham
- Spangler, Matthew L.
- Spriggs, Maria
- Staggs, Lydia
- Stedman, Nancy
- Steinman, Karen J.
- Stewart, Donald T
- Sugrue, Victoria J.
- Szladovits, Balazs
- Takahashi, Joseph S.
- Takasugi, Masaki
- Teeling, Emma C.
- Thompson, Michael J.
- Vernes, Sonja C.
- Villar, Diego
- Vinters, Harry V.
- Vu, Ha
- Wallingford, Mary C.
- Wang, Nan
- Wilkinson, Gerald S.
- Williams, Robert W.
- Yan, Qi
- Yao, Mingjia
- Young, Brent G.
- Zhang, Bohan
- Zhang, Zhihui
- Zhao, Yang
- Zhao, Peng
- Zhou, Wanding
- Zoller, Joseph A.
- Ernst, Jason
- Seluanov, Andrei
- Gorbunova, Vera
- Yang, X. William
- Raj, Ken
- Horvath, Steve
- Venue
- Science
- Published
- 2023-08-11
- Volume
- 381
- Issue
- 6658
- Pages
- eabq5693-eabq5693
- ISSN
- 0036-8075 (ISSN-L)
- 1095-9203
- PMC
- PMC11180965
- OpenAlex
- W4385726857
- Cited by
- 128
- References
- 90
- Citations by year
- 2026: 29 · 2025: 45 · 2024: 45 · 2023: 8 · 2021: 1
- FWCI
- 11.41
- Type
- journal article
- Language
- en
- Open access
- Licence
- cc-by
- Locations
- Science (publishedVersion)
- PubMed (publishedVersion)
- Bristol Research (University of Bristol) (publishedVersion, cc-by)
- PubMed Central (acceptedVersion)
- eScholarship (California Digital Library) (submittedVersion)
- Research Online (University of Wollongong) (submittedVersion)
- HAL (submittedVersion)
- Repository@Nottingham (University of Nottingham) (submittedVersion)
- NOAA Institutional Repository (submittedVersion, public-domain)
- Edinburgh Research Explorer (University of Edinburgh) (submittedVersion, cc-by)
- Queen Mary Research Online (Queen Mary University of London) (submittedVersion)
- Radboud Repository (Radboud University) (submittedVersion)
- Explore Bristol Research (submittedVersion, cc-by)
- Zurich Open Repository and Archive (University of Zurich) (submittedVersion)
- Funders
- National Science Foundation (1854469, 2017803)
- National Geographic Society
- University of Maryland
- Wellcome Trust
- UK Research and Innovation (MR/T021985/1)
- Open Philanthropy Project
- Cancer Research UK (20412)
- British Heart Foundation (FS/18/39/33684)
- Leverhulme Trust (RPG-2019-404)
- Department of Science and Technology, Ministry of Science and Technology, India (64756)
- Science Foundation Ireland (19/FFP/6790)
- King Saud University (64756)
- Universität Zürich
- A.H. Schultz-Stiftung zur Förderung Primatologischer Forschung
- Taronga Conservation Society Australia
- National Institutes of Health (AG047200, AG065403, R21OD022988)
- University of California, Los Angeles
- Natural Environment Research Council (NE/R011397/1, NE/X001423/1)
- National Institute on Aging (R56AG076607, R01AG050797, R01AG067782, AG043930, U34AG068482, R01AG045795, R21AG055841, AG047200, AG065403, R56AG072736, AG076607, R01AG027237, R01AG043930, U01AG060908, U19AG057758, AG045795, R21AG078784, AG067782, R01AG065403, P30AG013319, R01AG072736, P01AG047200, R37AG046320)
- National Institute of Environmental Health Sciences (R21ES024356)
- National Institute of Dental and Craniofacial Research (R21DE028271)
- Jonsson Comprehensive Cancer Center
- H2020 European Research Council (788937)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Epigenetics and DNA Methylation
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetic Syndromes and Imprinting
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Genomics and Chromatin Dynamics
- Keywords
- DNA methylation, mammalian evolution, maximum lifespan, mature weight, mortality risk, homeobox genes, pluripotency transcription factors, caloric restriction, growth hormone receptor, high-fat diet, Yamanaka factors
- MeSH terms
- Epigenome, Adult, Animals, Humans, Mammals, Phylogeny, Genome, DNA Methylation, Epigenesis, Genetic
About these checks
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