Spindle asymmetry drives non-Mendelian chromosome segregation

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Science  03 Nov 2017:
Vol. 358, Issue 6363, pp. 668-672
DOI: 10.1126/science.aan0092

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How selfish genes get their way

At the core of Mendelian genetics is the concept that gametes are equally likely to carry either of the two parental copies of a gene. Selfish genetic elements can cheat, however, by subverting Mendelian segregation to increase their representation in the gametes. Akera et al. show how the inherent asymmetry of female meiosis is translated to an asymmetry within the spindle machinery that segregates the chromosomes (see the Perspective by McNally). Experiments in mouse eggs revealed how asymmetry is exploited by selfish genetic elements to increase their transmission to the egg.

Science, this issue p. 668; see also p. 594


Genetic elements compete for transmission through meiosis, when haploid gametes are created from a diploid parent. Selfish elements can enhance their transmission through a process known as meiotic drive. In female meiosis, selfish elements drive by preferentially attaching to the egg side of the spindle. This implies some asymmetry between the two sides of the spindle, but the molecular mechanisms underlying spindle asymmetry are unknown. Here we found that CDC42 signaling from the cell cortex regulated microtubule tyrosination to induce spindle asymmetry and that non-Mendelian segregation depended on this asymmetry. Cortical CDC42 depends on polarization directed by chromosomes, which are positioned near the cortex to allow the asymmetric cell division. Thus, selfish meiotic drivers exploit the asymmetry inherent in female meiosis to bias their transmission.

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