Molecular and evolutionary strategies of meiotic cheating by selfish centromeres

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 in an intraspecific hybrid, leading to detachment of selfish centromeres from spindle microtubules that would direct them to the polar body. We also introduce a second hybrid model, exploiting centromere divergence between species, and show that winning centromeres in one hybrid become losers in the other. Our results indicate that increasing destabilizing activity is a general strategy for drive, but centromeres have evolved distinct strategies to increase that activity. Furthermore, we show that drive depends on slowing meiotic progression, suggesting that a weakened meiotic spindle checkpoint evolved as a mechanism to suppress selfish centromeres.

ProTAME Arrest in Mammalian Oocytes and Embryos Does Not Require Spindle Assembly Checkpoint Activity

“…It was shown previously that anaphase in somatic cells and also in mouse embryos is delayed or completely prevented by the addition of small molecule proTAME into the culture media [6,12,13]. In our experiments, we first tested various concentrations of proTAME and their impact on metaphase to anaphase transition in mouse meiosis I oocytes.…”

Fertility Costs of Meiotic Drivers

“…Drive loci, however, can manipulate asymmetric meiosis to increase their transmission into up to 100% of gametes. For example, in mice heterozygous for a 'strong' and a 'weak' centromere, the strong centromere exploits spindle asymmetry in the first meiotic division to promote its preferential transmission into eggs (Figure 2) [10,[12][13][14].…”

“…Recent work in mice [14] shows how evolutionary tradeoffs can arise due to the fact that variants that can suppress selfish alleles may be suboptimal for other facets of gametogenesis. A selfish centromere can exploit a delay between metaphase and anaphase of meiosis I to gain a transmission advantage into oocytes [14]. The authors suggest that an organism could suppress these selfish centromeres by weakening the spindle checkpoint to speed up the onset of meiosis I.…”

Unravelling the mystery of female meiotic drive: where we are

“…One hypothesis is that there is a constraint on kinetochore size, and that exceeding the upper size limit results in fitness costs (e.g. errors in mitosis and meiosis), creating a selective force that eliminates fusions except those that decrease kinetochore size, in species with bigger kinetochores [36,38].…”