Maternal transmission ratio distortion at the mouse Om locus results from meiotic drive at the second meiotic division

Abstract

We have observed maternal transmission ratio distortion (TRD) in favor of DDK alleles at the Ovum mutant (Om) locus on mouse chromosome 11 among the offspring of (C57BL/6 x DDK) F(1) females and C57BL/6 males. Although significant lethality occurs in this backcross ( approximately 50%), differences in the level of TRD found in recombinant vs. nonrecombinant chromosomes among offspring argue that TRD is due to nonrandom segregation of chromatids at the second meiotic division, i.e., true meiotic drive. We tested this hypothesis directly, by determining the centromere and Om genotypes of individual chromatids in zygote stage embryos. We found similar levels of TRD in favor of DDK alleles at Om in the female pronucleus and TRD in favor of C57BL/6 alleles at Om in the second polar body. In those embryos for which complete dyads have been reconstructed, TRD was present only in those inheriting heteromorphic dyads. These results demonstrate that meiotic drive occurs at MII and that preferential death of one genotypic class of embryo does not play a large role in the TRD.

Figure 1.—

A representative enucleation series. Top left: a zygote positioned so that both maternal and paternal pronuclei are visible, with maternal pronucleus closer to the second polar body. Top right: the embryo after removal of the maternal pronucleus (maternal pronucleus is positioned in the enucleation pipette). Bottom left: the embryo after removal of the paternal pronucleus (in enucleation pipette). Bottom right: the embryo after removal of the second polar body (in enucleation pipette).

Figure 2.—

Representative agarose gel electrophoresis of nested PCR products. PCR templates are pronuclei and second polar bodies. M, maternal pronucleus; PB, polar body; P, paternal pronucleus; −ve, negative control. Genotype on each chromatid is inferred (below gel) by identity of allele (right side of gel) at D11Mit71 (for centromere) and D11Spn1 (for Om). Solid circles, C57BL/6 centromeres; open circles, DDK centromeres; wavy lines, the DDK allele; straight lines, the C57BL/6 allele.

Figure 3.—

Schematic of complete dyads scored. The dyads were reconstructed after individual testing of maternal pronuclei and second polar bodies. In each dyad, solid circles represent C57BL/6 centromeres, open circles represent DDK centromeres, and hatched circles represent instances in which the maternal pronucleus and second polar body were of different genotype at D11Mit71. (Such instances are interpreted to represent recombination between D11Mit71 and the centromere or premature separation of sister chromatids. It is not possible to infer centromere genotype in either case.) Nonrecombinant (i.e., parental—D11Mit71 and D11Spn1/D11Spn4 genotypes the same) C57BL/6 chromatids are represented as continuous straight lines, nonrecombinant DDK chromatids are represented as continuous wavy lines, recombinant chromatids (i.e., nonparental—D11Mit71 and D11Spn1/D11Spn4 genotypes differ) that carry Om^DDK are represented as straight lines adjacent to centromeres and wavy lines below, while recombinant chromatids that carry Om^C57BL/6 are represented as wavy lines adjacent to centromeres and straight lines below. The chromatid on the left of each dyad was segregated to the maternal pronucleus, and the chromatid on the right was segregated to the second polar body.