@article {333880, title = {A global view of human centromere variation and evolution}, journal = {Nature}, year = {2026}, month = {2026/07/29}, abstract = {

Centromeres are essential chromosomal regions that ensure accurate chromosome segregation during cell division, yet their highly repetitive sequence has historically hindered their complete assembly and characterization1. 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 centromeres from diverse individuals representing 5 continental and\ 28 population groups. Using bioinformatic tools tailored for centromeres, we identify variation, including 226 centromere haplotypes and 1,870 α-satellite higher-order repeat variants. While most centromeres have a single kinetochore site, we find that\ around 6\% have di-kinetochores, and less than 1\% have tri-kinetochores, which we confirm using long-read chromatin profiling and multigenerational inheritance. We also show that kinetochore position is closely associated with the\ underlying sequence and structure of the centromere. To understand the nature of evolutionary change, we compared these centromeres to 5,747 centromeres assembled by the Human Pangenome Reference Consortium. We show that centromeres have a 20-fold variation in mutation rate, and a subset of centromeres has evidence of archaic hominin introgression. We validate these mutation rates in a 4-generation, 28-member family and show that the kinetochore site is the most rapidly mutating region in the centromere. We propose a model that reveals an \‘arms race\’ between centromeric sequence and proteins, with frequent mutations within the kinetochore\ site that lead to changes in genetic and epigenetic landscapes and, ultimately, rapid evolution of these critically important regions.

}, isbn = {0028-08361476-4687}, doi = {http://dx.doi.org/10.1038/s41586-026-10841-9}, url = {https://www.nature.com/articles/s41586-026-10841-9}, author = {Gao, Shenghan and Oshima, Keisuke K. and Chuang, Shu-Cheng and Loftus, Mark and Potapova, Tamara A. and Montanari, Annalaura and Gordon, David S. and Yang, Zikun and Ashraf, Hufsah and Audano, Peter A. and Ayllon, Marcelo and Azov, Andrey and Balachandran, Parithi and Basile, Anna O. and Beck, Christine R. and Bonder, Marc Jan and Brooks, Lucy and Byrska-Bishop, Marta and Chaisson, Mark J. P. and Chong, Zechen and Corvelo, Andr{\'e} and Crabtree, Jonathan and Devine, Scott E. and Ebert, Peter and Ebler, Jana and Eichler, Evan E. and Fairbrother-Browne, Aine and Fan, Chia-Hsuan and Freeberg, Mallory and Gerstein, Mark B. and Gu, Bida and Hallast, Pille and Hasenfeld, Patrick and Henglin, Mir and Hoekzema, Kendra and Hu, Kaili and Hunt, Sarah and Jensen, Matthew and Jiang, Yunzhe and Kim, Kwondo and Korbel, Jan O. and Kwon, Youngjun and Lansdorp, Peter M. and Lee, Charles and Leung, Tiffany and Li, Jiaqi and Li, Chong and Lin, Jiadong and Loftus, Mark and Marschall, Tobias and Martino, Gianni V. and Mills, Ryan E. and Mostovoy, Yulia and Munson, Katherine M. and Narzisi, Giuseppe and Ni, Lingbin and Paisie, Carolyn and Pani, Samarendra and Peng, Zishan and Porubsky, David and Prodanov, Timofey and Rabbani, Keon and Rausch, Tobias and Shi, Xinghua and Song, Yuwei and Sun, Kaitlyn and Surapaneni, Likhitha and Talkowski, Michael E. and Tsapalou, Vasiliki and Veidenberg, Andres and Yilmaz, Feyza and Yoo, DongAhn and Zhao, Xuefang and Zhou, Weichen and Zhu, Qihui and Zody, Michael C. and Albracht, Derek and Alexandrov, Ivan A. and Allen, Jamie and Alsheikh-Ali, Alawi A. and Altemose, Nicolas and Andrews, Casey and Antipov, Dmitry and Antonacci-Fulton, Lucinda and Asri, Mobin and Balacco, Jennifer R. and Barthel, Floris P. and Belter, Edward A. and Bender, Halle D. and Blair, Andrew P. and Bolognini, Davide and Bonini, Katherine E. and Boucher, Christina and Bourque, Guillaume and Buonaiuto, Silvia and Cao, Shuo and Carroll, Andrew and Mc Cartney, Ann M. and Cechova, Monika and Chang, Pi-Chuan and Chang, Xian and Cheema, Jitender and Cheng, Haoyu and Ciofi, Claudio and Clawson, Hiram and Cody, Sarah and Colonna, Vincenza and Conwell, Holland C. and Cook-Deegan, Robert and Diekhans, Mark and Diroma, Maria Angela and Doerr, Daniel and Dong, Zheng and Dubocanin, Danilo and Durbin, Richard and Eizenga, Jordan M. and Eskandar, Parsa and Ferro, Eddie and Fiston-Lavier, Anna-Sophie and Ford, Sarah M. and Ford, Willard W. and Formenti, Giulio and Frankish, Adam and Freeberg, Mallory A. and Fu, Qichen and Fullerton, Stephanie M. and Fulton, Robert S. and Gao, Yan and Garcia, Gage H. and Garcia, Obed A. and Gardner, Joshua M. V. and Garg, Shilpa and Garrison, Erik and Garrison, Nanibaa{\textquoteright} A. and Garza, John E. and Geleta, Margarita and Ghorbani, Mohammadmersad and Graves-Lindsay, Tina A. and Green, Richard E. and Groza, Cristian and Guarracino, Andrea and Gymrek, Melissa and Haeussler, Maximilian and Haggerty, Leanne and Hall, Ira M. and Hansen, Nancy F. and Hao, Yue and Hashmi, Mohammad Amiruddin and Haussler, David and Hebbar, Prajna and Heringer, Peter and Hickey, Glenn and Hillaker, Todd L. and Hossain, S. Nakib and Huang, Neng and Hunt, Sarah E. and Hunt, Toby and Ioannidis, Alexander G. and Jafarzadeh, Nafiseh and Jain, Nivesh and Jarvis, Erich D. and Jehangir, Maryam and Jiang, Juan and Kenny, Eimear E. and Kim, Juhyun and Koo, Bonhwang and Koren, Sergey and Kremitzki, Milinn and Langley, Charles H. and Langmead, Ben and Lawson, Heather A. and Li, Daofeng and Li, Heng and Liao, Wen-Wei and Liu, Tianjie and Lorig-Roach, Ryan and LoTempio, Jonathan and Loucks, Hailey and Loveland, Jane E. and Lu, Jianguo and Lu, Shuangjia and Lucas, Julian K. and Ma, Walfred and Macias-Velasco, Juan F. and Makova, Kateryna D. and Marin, Maximillian G. and Markovic, Christopher and Marsico, Franco L. and Martin, Fergal J. and Mastoras, Mira and Mayoud, Capucine and McNulty, Brandy and Medico, Jack A. and Menendez, Julian M. and Miga, Karen H. and Minkina, Anna and Mitchell, Matthew W. and Mohanty, Saswat K. and Mokrab, Younes and Monlong, Jean and Moosa, Shabir and Moreno-Ochando, Avelina and Morishita, Shinichi and Mudge, Jonathan M. and Mwaniki, Njagi and Nassir, Nasna and Natali, Chiara and Negi, Shloka and Novak, Adam M. and Okamoto, Faith and Ossorio, Pilar N. and Owa, Chie and Paez, Sadye and Paten, Benedict and Peano, Clelia and Phillippy, Adam M. and Pickett, Brandon D. and Pignata, Laura and Pisanti, Nadia and Porubsky, David and Prins, Pjotr and Radhakrishnan, Anandi and Ranallo-Benavidez, T. Rhyker and Raney, Brian J. and Rautiainen, Mikko and Raveane, Alessandro and Ren, Luyao and Rhie, Arang and Ryabov, Fedor and Sacco, Samuel and Salehi, Farnaz and Schatz, Michael C. and Scheinfeldt, Laura B. and Sehgal, Aarushi and Seligmann, William E. and Shabani, Mahsa and Shafin, Kishwar and Shahatit, Shadi and Shemirani, Ruhollah and Shivakumar, Vikram S. and Sinha, Swati and Sir{\'e}n, Jouni and Smeds, Linn{\'e}a and Solar, Steven J. and Sollitto, Marco and Soranzo, Nicole and Stergachis, Andrew B. and Suner, Marie-Marthe and Suzuki, Yoshihiko and S{\"o}ylev, Arda and Tayoun, Ahmad Abou and Tierney, Jack A. S. and Tomlinson, Chad and Tricomi, Francesca Floriana and Uddin, Mohammed and Ungaro, Matteo Tommaso and Varki, Rahul and Villani, Flavia and Violich, Ivo and Vollger, Mitchell R. and Walenz, Brian P. and Wang, Charles and Wang, Lisa E. and Wang, Ting and Wenger, Aaron M. and Whelan, Conor V. and Xin, Zilan and Xu, Zheng and Ye, Kai and Zhang, Wenjin and Zhou, Ying and Zhuo, Xiaoyu and Zunino, Giulia and Mao, Yafei and Hsieh, Pinghsun and Gerton, Jennifer L. and Konkel, Miriam K. and Ventura, Mario and Logsdon, Glennis A.} }