DNA methylation networks underlying mammalian traits
Amin Haghani, Caesar Z. Li, 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 Amor, Reza Ardehali, A Arneson, C. Scott Baker, Gareth Banks, Katherine Belov, Nigel C. Bennett, Peter McL. Black, Daniel T. Blumstein, Eleanor K. Bors, Charles E. Breeze, Robert T. Brooke, Janine L. Brown, Gerald G. 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 Noelle 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 Izpisúa Belmonte, Anna J. Jasinska, Gareth Jones, Eve Jourdain, Olga Kashpur, Harold L. Katcher, Etsuko Katsumata, Vimala Kaza, Hippokratis Kiaris, Michael S. Kobor, Paweł Kordowitzki, William R. Koski, Michael Krützen, Soo Bin Kwon, Brenda Larison, Sang‐Goo Lee, Marianne Lehmann, Jean‐François Lemaître, Andrew J. Levine, Xinmin Li, Cun Li, Cun Li, Andrea R. Lim, David Lin, Dana M. Lindemann, Schuyler Liphardt, Thomas J. Little, Nicholas Macoretta, Dewey Maddox, Craig O. Matkin, Julie A. Mattison
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.