利用Zoonomia联盟制作的241个哺乳动物基因组的无参考比对，研究人员绘制了92万个人类候选顺式调控元件（cCRE）和1560万个人类转录因子结合点（TFBS）的演化轨迹。研究人员确定了439461个cCRE和2024062个TFBS处于演化的约束之下。靠近受限元件的基因执行基本的细胞过程，而靠近灵长类特定元件的基因参与环境互动，包括气味感知和免疫反应。
大约20%的TFBS是转座元件衍生的，在灵长类动物演化过程中表现出复杂的增益和损失模式，而与复杂性状相关的序列变体在受限TFBS中富集。这些注释阐明了人类基因组的调节功能。
据悉，了解人类基因组的调控景观是现代生物学的一个长期目标。
附：英文原文
Title: Mammalian evolution of human cis-regulatory elements and transcription factor binding sites
Author: Gregory Andrews, Kaili Fan, Henry E. Pratt, Nishigandha Phalke, Zoonomia Consortium§, Elinor K. Karlsson, Kerstin Lindblad-Toh, Steven Gazal, Jill E. Moore, Zhiping Weng, 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. Schffer, 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 Sundstrm, 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
Issue&Volume: 2023-04-28
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.
DOI: abn7930
Source: https://www.science.org/doi/10.1126/science.abn7930