1. Academic Validation
  2. Molecular Strategies of Meiotic Cheating by Selfish Centromeres

Molecular Strategies of Meiotic Cheating by Selfish Centromeres

  • Cell. 2019 Aug 22;178(5):1132-1144.e10. doi: 10.1016/j.cell.2019.07.001.
Takashi Akera 1 Emily Trimm 1 Michael A Lampson 2
Affiliations

Affiliations

  • 1 Department of Biology, School of Arts and Sciences, University of Pennsylvania, Philadelphia, PA 19104, USA.
  • 2 Department of Biology, School of Arts and Sciences, University of Pennsylvania, Philadelphia, PA 19104, USA. Electronic address: lampson@sas.upenn.edu.
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.

Keywords

centromere; chromosome segregation; meiosis; meiotic drive; mouse; oocyte.

Figures
Products
  • Cat. No.
    Product Name
    Description
    Target
    Research Area
  • HY-103020
    99.05%, BUB1 Kinase Inhibitor