人类着丝粒变异和进化的全球视野
人类着丝粒变异和进化的全球视野
作者： 小柯机器人 发布时间：2026/7/30 17:41:29
本期文章：《自然》：Online/在线发表
人类着丝粒变异和进化的整体观点，这一成果由宾夕法尼亚大学Glennis A. Logsdon课题组经过不懈努力而取得。2026年7月29日出版的《自然》杂志发表了这一最新研究成果。
在这里，该团队通过组装和表征来自5个大陆和28个种群的不同个体的2,110个着丝粒来解决这一知识差距。利用为着丝粒量身定制的生物信息学工具，该研究组确定了变异，包括226个着丝粒单倍型和1870个α-卫星高阶重复变体。虽然大多数着丝粒有一个着丝点位点，但研究组发现约6%的着丝点有双着丝点，不到1%的着丝点有三着丝点，研究组证实了长读染色质谱和多代遗传。
课题组研究人员还发现着丝粒的位置与着丝粒的基本序列和结构密切相关。为了了解进化变化的本质，该课题组人员将这些着丝粒与人类泛基因组参考联盟组装的5,747个着丝粒进行了比较。小组发现着丝粒在突变率上有20倍的变异，并且着丝粒的一个子集有古人类渗入的证据。该团队在一个4代28人的家族中验证了这些突变率，并表明着丝点位点是着丝粒中突变最快的区域。课题组人员提出了一个模型，揭示了着丝粒序列和蛋白质之间的“军备竞赛”，着丝粒位点内的频繁突变导致遗传和表观遗传景观的变化，并最终导致这些至关重要区域的快速进化。
据介绍，着丝粒是确保细胞分裂过程中染色体准确分离的重要染色体区域，但其高度重复的序列历来阻碍了它们的完整组装和表征。因此，在个体、种群和进化背景中，着丝粒多样性的全谱在很大程度上仍未被探索。
附：英文原文
Title: A global view of human centromere variation and evolution
Author: Gao, Shenghan, Oshima, Keisuke K., Chuang, Shu-Cheng, Loftus, Mark, Potapova, Tamara A., Montanari, Annalaura, Gordon, David S., Yang, Zikun, Mao, Yafei, Hsieh, PingHsun, Gerton, Jennifer L., Konkel, Miriam K., Ventura, Mario, Logsdon, Glennis A.
Issue&Volume: 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.
DOI: 10.1038/s41586-026-10841-9
Source: https://www.nature.com/articles/s41586-026-10841-9