The mechanism of meiotic drive in the mouse oocyte

Abstract

This thesis investigated the biased reorientation of asymmetrical bivalents and so the mechanism of meiotic drive. In the first meiotic division of oocytes, the cortically positioned spindle leads to bivalent segregation in which only the centre-facing homologues are retained. ‘Selfish’ chromosomes are known to exist, which bias their orientation in the spindle and hence retention in the egg, a process known as ‘meiotic drive’. Here this phenomenon was investigated using oocytes from F1 hybrid mice, in which parental strain differences in centromere and kinetochore sizes allowed distinction of the two homologous pairs that comprise a specific bivalent inside the F1 oocyte. With this mouse model, it is shown that the homologue with smaller major satellite DNA region, larger minor satellite DNA region, and less of the kinetochore protein Spc24, is preferentially retained in the MII oocyte. The alignment process of this distinct bivalent was recorded by real-time imaging. The selfish retention of one homologue was found to depend on bivalent rotation during prometaphase, in a process dependent on AURKB/C activity. In addition to the asymmetries within the bivalents, I also found asymmetrical tubulin and microtubule organising centres intensity between the two halves of the spindle and cortically positioned homologues appeared to be under greater stretch than their centre-facing partners. These findings reveal a crucial model in which meiotic drive is explained by the relative impact of microtubule force asymmetry on homologues with different sized centromeres and kinetochores in meiosis I.

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ORCID for Keith Jones: orcid.org/0000-0002-0294-0851

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