宾夕法尼亚大学Michael A. Lampson课题组揭示“自私”着丝粒在减数分裂“作弊”时的分子机制。2019年8月22日，国际知名学术期刊《细胞》发表了这一成果。

研究人员鉴定了一个分子通路，其将延伸的着丝粒与组蛋白磷酸化和微管分解因子的招募联系起来，从而使得丝粒从纺锤体微管中自发脱离，导致它们进入极体。利用物种之间的着丝粒差异，研究人员发现两个杂交小鼠模型中的自私着丝粒使用相同的分子途径，但差异性地进行调控，从而富集分解因子。这些结果表明，增加微管分解活性是两种模型中的共同驱动策略，但着丝粒已经进化出不同的机制来增加该活性。此外，研究人员发现这种驱动依赖于减数分裂进展的减缓，这表明通过调控减数分裂时间可以抑制自私着丝粒。

雌性减数分裂中的不对称分裂产生选择性压力，有利于自私的着丝粒将其偏向于向卵传播。 尽管具有保守的着丝粒功能，但这种着丝粒驱动可以解释着丝粒DNA和着丝粒结合蛋白矛盾的快速进化。

Title: Molecular Strategies of Meiotic Cheating by Selfish Centromeres

Author: Takashi Akera, Emily Trimm, Michael A. Lampson

Issue&Volume: 22 August 2019

Abstract: Asymmetric division in female meiosis creates selective pressure favoring selfish centromeres that bias their transmission to the egg. This centromere drive can explain the paradoxical rapid evolution of both centromere DNA and centromere-binding proteins despite conserved centromere function. Here, we define a molecular pathway linking expanded centromeres to histone phosphorylation and recruitment of microtubule destabilizing factors, leading to detachment of selfish centromeres from spindle microtubules that would direct them to the polar body. Exploiting centromere divergence between species, we show that selfish centromeres in two hybrid mouse models use the same molecular pathway but modulate it differently to enrich destabilizing factors. Our results indicate that increasing microtubule destabilizing activity is a general strategy for drive in both models, but centromeres have evolved distinct mechanisms to increase that activity. Furthermore, we show that drive depends on slowing meiotic progression, suggesting that selfish centromeres can be suppressed by regulating meiotic timing.

DOI: https://doi.org/10.1016/j.cell.2019.07.001

Source: https://www.cell.com/cell/fulltext/S0092-8674(19)30740-8#