Cell
Volume 178, Issue 5, 22 August 2019, Pages 1132-1144.e10
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Article
Molecular Strategies of Meiotic Cheating by Selfish Centromeres

https://doi.org/10.1016/j.cell.2019.07.001Get rights and content
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Highlights

  • High microtubule-destabilizing activity makes mouse centromeres selfish in meiosis

  • Amplified BUB1 signaling enriches destabilizing activity on selfish centromeres

  • Selfish centromeres can modulate the BUB1 pathway by different mechanisms

  • Rapid progression through meiosis I can suppress centromere drive

Summary

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.

Keywords

meiotic drive
meiosis
mouse
oocyte
chromosome segregation
centromere

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