Nonrandom segregation of the mouse univalent X chromosome: Evidence of spindle-mediated meiotic drive

A fundamental principle of Mendelian inheritance is random segregation of alleles to progeny; however, examples of distorted transmission either of specific alleles or of whole chromosomes have been described in a variety of species. In humans and mice, a distortion in chromosome transmission is often associated with a chromosome abnormality. One such example is the fertile XO female mouse. A transmission distortion effect that results in an excess of XX over XO daughters among the progeny of XO females has been recognized for nearly four decades. Utilizing contemporary methodology that combines immuno-fluorescence, FISH, and three-dimensional confocal microscopy, we have readdressed the meiotic segregation behavior of the single X chromosome in oocytes from XO females produced on two different inbred backgrounds. Our studies demonstrate that segregation of the univalent X chromosome at the first meiotic division is nonrandom, with preferential retention of the X chromosome in the oocyte in similar to 60% of cells. We propose that this deviation from Mendelian expectations is facilitated by a spindle-mediated mechanism. This mechanism, which appears to be a general feature of the female meiotic process, has implications the frequency of nondisjunction in our species.