Haldane's rule in the placenta: Sex-biased misregulation of the Kcnq1 imprinting cluster in hybrid mice.

摘要: Hybrid phenotypes that contribute to postzygotic reproductive isolation often exhibit pronounced asymmetry, both between reciprocal crosses and the sexes in accordance with Haldane's rule. Inviability mammalian hybrids is associated parent-of-origin placental growth abnormalities for which misregulation of imprinted gene (IGs) leading candidate mechanism. However, direct evidence involvement IGs hybrid dysplasia limited. We used transcriptome reduced representation bisulfite sequencing conduct first genome-scale assessment contribution cross house mouse (Mus musculus domesticus) Algerian spretus). transgressive expression methylation were concentrated Kcnq1 cluster, contains causal genes prenatal mice humans. Hypermethylation cluster's imprinting control region, consequent misexpression Phlda2 Ascl2, a strong mechanism undergrowth. Transgressive regulatory phenotypes, including more extreme males. Although consistent rule, male-biased defects are unexpected rodent placenta because X-chromosome effectively hemizygous sexes. In search an explanation, we found leaky (paternal) inactivation female placenta, epigenetic disturbance may buffer females from effects X-linked incompatibilities males fully exposed. Sex differences chromatin structure on X sex-biased maternal nonmutually exclusive alternative explanations adherence rule placenta. The results this study understanding genetic basis inviability mammals, role speciation.