DNA methylation networks underlying mammalian traits

Amin Haghani, Caesar Z. Li, Todd R. Robeck, Joshua Zhang, Ake T. Lu, Julia Ablaeva, Victoria A. Acosta-Rodríguez, Danielle M. Adams, Abdulaziz N. Alagaili, Javier Almunia, Ajoy Aloysius, Nabil M.S. Amor, Reza Ardehali, Adriana Arneson, C. Scott Baker, Gareth Banks, Katherine Belov, Nigel C. Bennett, Peter Black, Daniel T. BlumsteinEleanor K. Bors, Charles E. Breeze, Robert T. Brooke, Janine L. Brown, Gerald Carter, Alex Caulton, Julie M. Cavin, Lisa Chakrabarti, Ioulia Chatzistamou, Andreas S. Chavez, Hao Chen, Kaiyang Cheng, Priscila Chiavellini, Oi Wa Choi, Shannon Clarke, Joseph A. Cook, Lisa N. Cooper, Marie Laurence Cossette, Joanna Day, Joseph DeYoung, Stacy Dirocco, Christopher Dold, Jonathan L. Dunnum, Erin E. Ehmke, Candice K. Emmons, Stephan Emmrich, Ebru Erbay, Claire Erlacher-Reid, Chris G. Faulkes, Zhe Fei, Steven H. Ferguson, Carrie J. Finno, Jennifer E. Flower, Jean Michel Gaillard, Eva Garde, Livia Gerber, Vadim N. Gladyshev, Rodolfo G. Goya, Matthew J. Grant, Carla B. Green, M. Bradley Hanson, Daniel W. Hart, Martin Haulena, Kelsey Herrick, Andrew N. Hogan, Carolyn J. Hogg, Timothy A. Hore, Taosheng Huang, Juan Carlos Izpisua Belmonte, Anna J. Jasinska, Gareth Jones, Eve Jourdain, Olga Kashpur, Harold Katcher, Etsuko Katsumata, Vimala Kaza, Hippokratis Kiaris, Michael S. Kobor, Pawel Kordowitzki, William R. Koski, Michael Krötzen, Soo Bin Kwon, Brenda Larison, Sang Goo Lee, Marianne Lehmann, Jean François Lema tre, Andrew J. Levine, Xinmin Li, Cun Li, Andrea R. Lim, David T.S. Lin, Dana M. Lindemann, Schuyler W. Liphardt, Thomas J. Little, Nicholas Macoretta, Dewey Maddox, Craig O. Matkin, Julie A. Mattison, Matthew McClure, June Mergl, Jennifer J. Meudt, Gisele A. Montano, Khyobeni Mozhui, Jason Munshi-South, William J. Murphy, Asieh Naderi, Martina Nagy, Pritika Narayan, Peter W. Nathanielsz, Ngoc B. Nguyen, Christof Niehrs, Batsaikhan Nyamsuren, Justine K. O'Brien, Perrie O.Tierney Ginn, Duncan T. Odom, Alexander G. Ophir, Steve Osborn, Elaine A. Ostrander, Kim M. Parsons, Kimberly C. Paul, Amy B. Pedersen, Matteo Pellegrini, Katharina J. Peters, Jessica L. Petersen, Darren W. Pietersen, Gabriela M. Pinho, Jocelyn Plassais, Jesse R. Poganik, Natalia A. Prado, Pradeep Reddy, Benjamin Rey, Beate R. Ritz, Jooke Robbins, Magdalena Rodriguez, Jennifer Russell, Elena Rydkina, Lindsay L. Sailer, Adam B. Salmon, Akshay Sanghavi, Kyle M. Schachtschneider, Dennis Schmitt, Todd Schmitt, Lars Schomacher, Lawrence B. Schook, Karen E. Sears, Ashley W. Seifert, Aaron B.A. Shafer, Anastasia V. Shindyapina, Melanie Simmons, Kavita Singh, Ishani Sinha, Jesse Slone, Russel G. Snell, Elham Soltanmohammadi, Matthew L. Spangler, Maria Spriggs, Lydia Staggs, Nancy Stedman, Karen J. Steinman, Donald T. Stewart, Victoria J. Sugrue, Balazs Szladovits, Joseph S. Takahashi, Masaki Takasugi, Emma C. Teeling, Michael J. Thompson, Bill Van Bonn, Sonja C. Vernes, Diego Villar, Harry V. Vinters, Ha Vu, Mary C. Wallingford, Nan Wang, Gerald S. Wilkinson, Robert W. Williams, Qi Yan, Mingjia Yao, Brent G. Young, Bohan Zhang, Zhihui Zhang, Yang Zhao, Peng Zhao, Wanding Zhou, Joseph A. Zoller, Jason Ernst, Andrei Seluanov, Vera Gorbunova, X. William Yang, Ken Raj, Steve Horvath

Research output: Contribution to journalArticlepeer-review

15 Scopus citations

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.

Original languageEnglish (US)
Article numbereabq5693
JournalScience
Volume381
Issue number6658
DOIs
StatePublished - Aug 1 2023
Externally publishedYes

ASJC Scopus subject areas

  • General

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