Abstract:

Mendel’s Law of Segregation states that each allele has an equal chance to transmit to the gametes. However, this law can be violated by selfish genetic elements, which manipulate the production of gametes to increase their own rate of transmission. This genetic cheating in meiosis, meiotic drive, is typically associated with fitness cost to the host and has significant impacts on genetics, evolution, and reproduction. In female meiosis, selfish elements bias their transmission by preferentially segregating to the egg. We focus on selfish R2d2, a non-centromeric locus on mouse chromosome 2, which shows over 90% transmission ratio distortion with mild embryonic lethality. The underlying cell biological basis for both biased segregation and the embryonic lethality is unknown. Here, we developed a CRISPR-based strategy to live-image the R2d2 locus in mouse oocytes and found that the chromosome that harbors selfish R2d2 locus lags in anaphase. Anaphase chromosome lagging can induce biased segregation in mouse oocytes, because the majority of the cytoplasm remains in the egg after the polar body extrusion, including the lagging chromosome. Anaphase lagging would also cause aneuploidy in the egg, leading to embryonic lethality. Therefore, this simple model can explain the mechanisms underlying both the biased transmission and the associated fitness cost of this meiotic drive system.

References:

Akera T et al. Cell vol. 178,5 (2019)

Clark FE and Akera T. Open biology vol. 11,9 (2021)

Didion JP et al. PLoS genetics vol. 11,2 e1004850 (2015)