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

A fundamental principle of Mendelian inheritance is random segregation of a lleles to progeny; however, examples of distorted transmission either of sp ecific alleles or of whole chromosomes have been described in a variety of species. In humans and mice, a distortion in chromosome transmission is oft en associated with a chromosome abnormality. One such example is the fertil e XO female mouse. A transmission distortion effect that results in an exce ss of XX over XO daughters among the progeny of XO females has been recogni zed for nearly four decades. Utilizing contemporary methodology that combin es immuno-fluorescence, FISH, and three-dimensional confocal microscopy, we have readdressed the meiotic segregation behavior of the single X chromoso me 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 thi s deviation from Mendelian expectations is facilitated by a spindle-mediate d mechanism. This mechanism, which appears to be a general feature of the f emale meiotic process, has implications the frequency of nondisjunction in our species.