美国加州大学洛杉矶分校Amin Haghani等研究人员合作揭示哺乳动物性状背后的DNA甲基化网络。相关论文于2023年8月11日发表在《科学》杂志上。

利用来自348个哺乳动物物种的DNA甲基化图谱（n=15456），研究人员构建了植物表观遗传树，该树与传统的系统发育树明显相似。通过对所有样本进行无监督聚类，研究人员确定了55个不同的胞嘧啶模块，其中30个模块与最长寿命、成年体重、年龄、性别和人类死亡风险等性状有关。

最大寿命与HOXL亚类同源基因的甲基化水平和发育过程有关，并可能受多能转录因子的调控。某些模块的甲基化状态会对热量限制、生长激素受体的消减、高脂肪饮食和山中因子的表达等干扰做出反应。

这项研究揭示了基因组和表观基因组相互交织的演化过程，这种演化介导了不同哺乳动物物种的生物特征和性状。

附：英文原文

Title: DNA methylation networks underlying mammalian traits

Author: 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. Blumstein, Eleanor 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 Krützen, Soo Bin Kwon, Brenda Larison, Sang-Goo Lee, Marianne Lehmann, Jean-Franois Lematre, 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

Issue&Volume: 2023-08-11

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.

DOI: abq5693

Source: https://www.science.org/doi/full/10.1126/science.abq5693