ARC Centre of Excellence for Kangaroo Genomics, The University of Melbourne, Parkville, Victoria 3010, Australia.
BMC Evol Biol. 2011 Aug 19;11:244. doi: 10.1186/1471-2148-11-244.
Genomic imprinting causes parent-of-origin specific gene expression by differential epigenetic modifications between two parental genomes. We previously reported that there is no evidence of genomic imprinting of CDKN1C in the KCNQ1 domain in the placenta of an Australian marsupial, the tammar wallaby (Macropus eugenii) whereas tammar IGF2 and H19, located adjacent to the KCNQ1 domain in eutherian mammals, are imprinted. We have now identified and characterised the marsupial orthologue of PHLDA2, another gene in the KCNQ1 domain (also known as IPL or TSSC3) that is imprinted in eutherians. In mice, Phlda2 is a dose-sensitive negative regulator of placental growth, as Cdkn1c is for embryonic growth.
Tammar PHLDA2 is highly expressed in the yolk sac placenta compared to other fetal tissues, confirming a similar expression pattern to that of mouse Phlda2. However, tammar PHLDA2 is biallelically expressed in both the fetus and yolk sac placenta, so it is not imprinted. The lack of imprinting in tammar PHLDA2 suggests that the acquisition of genomic imprinting of the KCNQ1 domain in eutherian mammals, accompanied with gene dosage reduction, occurred after the split of the therian mammals into the marsupials and eutherians.
Our results confirm the idea that acquisition of genomic imprinting in the KCNQ1 domain occurred specifically in the eutherian lineage after the divergence of marsupials, even though imprinting of the adjacent IGF2-H19 domain arose before the marsupial-eutherian split. These data are consistent with the hypothesis that genomic imprinting of the KCNQ1 domain may have contributed to the evolution of more complex placentation in the eutherian lineage by reduction of the gene dosage of negative regulators for both embryonic and placental growth.
基因组印记通过两个亲本基因组之间的差异表观遗传修饰导致亲本特异性基因表达。我们之前报道过，在澳大利亚有袋动物袋鼹（Macropus eugenii）的胎盘的 KCNQ1 结构域中，没有证据表明 CDKN1C 存在基因组印记，而与 KCNQ1 结构域相邻的袋鼹 IGF2 和 H19 在真兽亚纲动物中是印记的。我们现在已经鉴定并描述了 KCNQ1 结构域中另一个基因 PHLDA2 的有袋动物同源物（也称为 IPL 或 TSSC3），该基因在真兽亚纲动物中是印记的。在小鼠中，Phlda2 是胎盘生长的剂量敏感负调节因子，就像 Cdkn1c 是胚胎生长的负调节因子一样。
与其他胎儿组织相比，袋鼹 PHLDA2 在卵黄囊胎盘中有高度表达，这证实了与小鼠 Phlda2 相似的表达模式。然而，袋鼹 PHLDA2 在胎儿和卵黄囊胎盘中均为双等位基因表达，因此它不是印记的。袋鼹 PHLDA2 的非印记表明，KCNQ1 结构域的基因组印记的获得伴随着基因剂量减少，发生在有胎盘哺乳动物和有袋动物的分化之后。
我们的结果证实了这样一种观点，即在有胎盘哺乳动物的分化之后，KCNQ1 结构域中的基因组印记的获得专门发生在真兽亚纲中，即使相邻的 IGF2-H19 结构域的印记发生在有袋动物和真兽亚纲的分化之前。这些数据与以下假设一致，即 KCNQ1 结构域的基因组印记可能通过减少胚胎和胎盘生长的负调节因子的基因剂量，促进了真兽亚纲中更复杂胎盘的进化。
