A global view of human centromere variation and evolution

作者：Shenghan Gao, Keisuke K. Oshima, Shu-Cheng Chuang, Mark Loftus, Tamara Potapova, Annalaura Montanari, David Gordon, Zikun Yang, Hufsah Ashraf, Peter A. Audano, Marcelo Ayllon, Andrey Azov, Parithi Balachandran, Anna O. Basile, Christine R. Beck, Marc Jan Bonder, Lucy Brooks, Marta Byrska-Bishop, Mark J. P. Chaisson, Zechen Chong, André Corvelo, Jonathan Crabtree, Scott E. Devine, Peter Ebert, Jana Ebler, Evan E. Eichler, Aine Fairbrother-Browne, Chia-Hsuan Fan, Mallory Freeberg, M. Gerstein, Bida Gu, Pille Hallast, Patrick Hasenfeld, Mir Henglin, Kendra Hoekzema, Kaili Hu, Sarah Hunt, Matthew Jensen, Yunzhe Jiang, Kwondo Kim, Jan O. Korbel, Youngjun Kwon, Peter M. Lansdorp, Charles Lee, Tiffany Leung, Jiaqi Li, Chong Li, Jiadong Lin, Mark Loftus, Tobias Marschall, Gianni V. Martino, Ryan E. Mills, Yulia Mostovoy, Katherine M. Munson, Giuseppe Narzisi, Lingbin Ni, Carolyn Paisie, Samarendra Pani, Zishan Peng, David Porubskỳ, Timofey Prodanov, Keon Rabbani, Tobias Rausch, Xinghua Shi, Yuwei Song, Kaitlyn Sun, Likhitha Surapaneni, Michael E. Talkowski, Vasiliki Tsapalou, Andres Veidenberg, Feyza Yilmaz, DongAhn Yoo, Xuefang Zhao, Weichen Zhou, Qihui Zhu, Michael C. Zody, Derek Albracht, Ivan A. Alexandrov, Jamie Allen, Alawi A. Alsheikh-Ali, Nicolas Altemose, Casey Andrews, Dmitry Antipov, Lucinda Antonacci-Fulton, Mobin Asri, Jennifer Balacco, Floris P. Barthel, Edward A. Belter, Halle D. Bender, Andrew P. Blair, Davide Bolognini, Katherine E. Bonini, Christina Boucher, Guillaume Bourque, Silvia Buonaiuto, Shuo Cao, Andrew Carroll, Ann M. Mc Cartney, Monika Čechová, Pi-Chuan Chang, Xian Chang, Jitender Cheema, Haoyu Cheng, Claúdio Ciofi, Hiram Clawson, Sarah Cody, Vincenza Colonna, Holland C. Conwell, Robert Cook-Deegan, Mark Diekhans, Maria Angela Diroma, Daniel Doerr, Zheng Dong, Danilo Dubocanin, Richard Durbin, Jordan M. Eizenga, Parsa Eskandar, Eddie Ferro, Anna-Sophie Fiston-Lavier, Sarah Ford, W. L. Ford, Giulio Formenti, Adam Frankish, Mallory A. Freeberg, Qichen Fu, Stephanie M. Fullerton, Robert S. Fulton, Yan Gao, Gage H. Garcia, Obed Garcia, Joshua Gardner, Shilpa Garg, Erik Garrison, Nanibaa’ A. Garrison, John Garza, Margarita Geleta, Mohammadmersad Ghorbani, Tina A. Graves-Lindsay, Richard E. Green, Cristian Groza, Andrea Guarracino, Melissa Gymrek, Maximilian Haeussler, Leanne Haggerty, Ira M. Hall, Nancy F. Hansen, Yue Hao, Mohammad Amiruddin Hashmi, David Haussler, Prajna Hebbar, Peter Heringer, Glenn Hickey, Todd Hillaker, S. Nakib Hossain, Neng Huang, Sarah E. Hunt, Toby Hunt, Alexander G. Ioannidis, Nafiseh Jafarzadeh, Nivesh Jain, Erich D. Jarvis, Maryam Jehangir, Juan Jiang, Eimear E. Kenny, Juhyun Kim, Bonhwang Koo, Sergey Koren, Milinn Kremitzki, Charles H. Langley, Ben Langmead, Heather A. Lawson, Daofeng Li, Heng Li, Wen-Wei Liao, Tianjie Liu, Ryan Lorig-Roach, Jonathan LoTempio, Hailey Loucks, Jane Loveland, Jianguo Lu, Shuangjia Lu, Julian Lucas, Walfred Ma, Juan F. Macias-Velasco, Kateryna D. Makova, Maximillian G. Marin, Christopher Markovic, Franco L. Marsico, Fergal J. Martin, Mira Mastoras, Capucine Mayoud, Brandy McNulty, Jack A Medico, J Menéndez, Karen H. Miga, Anna Minkina, Matthew W. Mitchell, Saswat K. Mohanty, Younes Mokrab, Jean Monlong, Shabir Moosa, Avelina Moreno-Ochando, Shinichi Morishita, Jonathan M. Mudge, Njagi Mwaniki, Nasna Nassir, Chiara Natali, Shloka Negi, Adam M. Novak, Faith Okamoto, Pilar N. Ossorio, Chie Owa, Sadye Paez, Benedict Paten, Clelia Peano, Adam M. Phillippy, Brandon D. Pickett, Laura Pignata, Nadia Pisanti, David Porubskỳ, Pjotr Prins, Anandi Radhakrishnan, T. Rhyker Ranallo-Benavidez, Brian J. Raney, Mikko Rautiainen, Alessandro Raveane, Luyao Ren, Arang Rhie, Fedor Ryabov, Samuel Sacco, Farnaz Salehi, Michael Schatz, Laura Scheinfeldt, Aarushi Sehgal, William Seligmann, Mahsa Shabani, Kishwar Shafin, Shadi Shahatit, Ruhollah Shemirani, Vikram S Shivakumar, Swati Sinha, Jouni Sirén, Linnéa Smeds, Steven J. Solar, Marco Sollitto, Nicole Soranzo, Andrew B. Stergachis, Marie‐Marthe Suner, Yoshihiko Suzuki, Arda Söylev, Ahmad Abou Tayoun, Jack A. S. Tierney, Chad Tomlinson, Francesca Floriana Tricomi, Mohammed Uddin, Matteo Tommaso Ungaro, Rahul Varki, Flavia Villani, Ivo Violich, Mitchell R. Vollger, Brian P. Walenz, Charles Wang, Lisa Wang, Ting Wang, Aaron M. Wenger, Conor Whelan, Zilan Xin, Zheng Xu, Kai Ye, Wenjin Zhang, Ying Zhou, Xiaoyu Zhuo, Giulia Zunino, Yafei Mao, PingHsun Hsieh, Jennifer L. Gerton, Miriam K. Konkel, Mario Ventura, Glennis A. Logsdon · 发表于：Nature · 年份：2026 · DOI：10.1038/s41586-026-10841-9 · 被引用次数：8 · 研究领域：Chromosomal and Genetic Variations、Genomics and Chromatin Dynamics、Microtubule and mitosis dynamics

ABSTRACT Centromeres are essential for accurate chromosome segregation during cell division, yet their highly repetitive sequence has historically hindered their complete assembly and characterization. Consequently, the full spectrum of centromere diversity across individuals, populations, and evolutionary contexts remains largely unexplored. Here, we address this gap in knowledge by assembling and characterizing 2,110 complete human centromeres from a diverse cohort of individuals representing 5 continental and 28 population groups. By developing a novel suite of bioinformatic tools tailored for centromeric regions, we uncover previously unknown variation within centromeres, including 226 novel centromere haplotypes and 1,870 new α-satellite higher-order repeat (HOR) variants. We find that mobile element insertions are present in 30% of centromeres, with chromosome 16 harboring Alu elements within the kinetochore site at an 11-fold higher frequency than expected. While most centromeres have a single kinetochore site, 6% of them have di-kinetochores, and <<1% have tri-kinetochores, which we confirm with long-read CENP-A CUT&RUN, DiMeLo-seq, and multi-generational inheritance. We further show that the position of the kinetochore is not random and is, instead, closely associated with the underlying sequence and structure of the centromere. To understand the nature of evolutionary change, we compared 2,110 complete human centromeres to 5,747 complete centromeres recent...