Genomic imprinting, disrupted placental expression, and speciation

The importance of regulatory incompatibilities to the early stages of speciation remains unclear. Hybrid mammals often show extreme parent-of-origin growth effects that are thought to be a consequence of disrupted genetic imprinting (parent-specific epigenetic gene silencing) during early development. Here we test the long-standing hypothesis that abnormal hybrid growth reflects disrupted gene expression due to loss of imprinting (LOI) in hybrid placentas, resulting in dosage imbalances between paternal growth factors and maternal growth repressors. We analyzed placental gene expression in reciprocal dwarf hamster hybrids that show extreme parent-of-origin growth effects relative to their parental species. In massively enlarged hybrid placentas, we observed both extensive transgressive expression of growth-related genes and bi-allelic expression of many genes that were paternally silenced in normal sized hybrids. However, the apparent widespread disruption of paternal silencing was coupled with reduced gene expression levels overall. These patterns are contrary to the predictions of the LOI model and indicate that hybrid misexpression of dosage sensitive genes is caused by other regulatory mechanisms in this system. Collectively, our results support a central role for disrupted gene expression and imprinting in the evolution of mammalian hybrid inviability, but call into question the generality of the widely invoked LOI model.

调控不相容性（regulatory incompatibilities）对物种形成早期阶段的重要性至今仍不明确。哺乳类杂交后代常表现出极端的亲本起源生长效应（parent-of-origin growth effects），该现象被认为是早期发育过程中遗传印记（genetic imprinting，即亲本特异性表观遗传基因沉默）紊乱所致。本研究针对长期存在的假说展开验证：异常的杂交生长反映了杂交胎盘中印记丢失（loss of imprinting, LOI）引发的基因表达紊乱，进而导致父本生长因子与母本生长抑制因子之间的剂量失衡。我们对互交矮仓鼠杂交种进行了分析，相较于其亲本物种，该杂交种表现出极端的亲本起源生长效应，并检测了其胎盘的基因表达情况。在显著增大的杂交胎盘中，我们既观察到生长相关基因的广泛超亲表达（transgressive expression），也发现了许多在正常体型个体中父本沉默的基因出现双等位基因表达（bi-allelic expression）。不过，这种看似广泛的父本沉默紊乱，同时伴随整体基因表达水平的下调。这些模式与印记丢失模型的预测相悖，表明在该系统中，剂量敏感基因（dosage sensitive genes）的杂交表达异常是由其他调控机制造成的。综合来看，我们的研究结果支持基因表达紊乱与印记紊乱在哺乳类杂交致死性（hybrid inviability）演化中发挥核心作用，但对被广泛引用的印记丢失模型的普适性提出了质疑。