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

摘要: Mammalian hybrids often show striking asymmetries in their phenotypes both between reciprocal crosses, and sexes accordance with Haldane9s rule. Hybrid inviability is associated parent-of-origin placental growth abnormalities for which misregulation of imprinted genes a strong candidate mechanism. However, direct evidence the involvement abnormal imprinting mechanisms behind this proposed limited. We used transcriptome reduced representation bisulfite sequencing to evaluate contribution long-standing example dysplasia cross house mouse (Mus musculus domesticus) Algerian (M. spretus). found little loss biallelic expression were not misexpressed. Instead, transgressive methylation concentrated Kcnq1 cluster, contains causal prenatal mice humans. Hypermethylation cluster9s control region, consequent misexpression Phlda2 Ascl2, mechanism hybrid undergrowth. Transgressive gene regulatory phenotypes, including more extreme males. While consistent rule, male-biased defects are expected rodent placenta because maternal X chromosome effectively hemizygous sexes. In search an explanation we leaky X-chromosome inactivation females. Supplementary from paternal may buffer females effects X-linked incompatibilities males fully exposed. Sex differences chromatin structure on sex-biased non-mutually exclusive alternative explanations adherence rule placenta. The results study contribute understanding genetic basis mammals, role speciation.