Abstract
BackgroundGenomic imprinting occurs in both marsupial and eutherian mammals. The CDKN1C and IGF2 genes are both imprinted and syntenic in the mouse and human, but in marsupials only IGF2 is imprinted. This study examines the evolution of features that, in eutherians, regulate CDKN1C imprinting.ResultsDespite the absence of imprinting, CDKN1C protein was present in the tammar wallaby placenta. Genomic analysis of the tammar region confirmed that CDKN1C is syntenic with IGF2. However, there are fewer LTR and DNA elements in the region and in intron 9 of KCNQ1. In addition there are fewer LINEs in the tammar compared with human and mouse. While the CpG island in intron 10 of KCNQ1 and promoter elements could not be detected, the antisense transcript KCNQ1OT1 that regulates CDKN1C imprinting in human and mouse is still expressed.ConclusionCDKN1C has a conserved function, likely antagonistic to IGF2, in the mammalian placenta that preceded its acquisition of imprinting. CDKN1C resides in synteny with IGF2, demonstrating that imprinting of the two genes did not occur concurrently to balance maternal and paternal influences on the growth of the placenta. The expression of KCNQ1OT1 in the absence of CDKN1C imprinting suggests that antisense transcription at this locus preceded imprinting of this domain. These findings demonstrate the stepwise accumulation of control mechanisms within imprinted domains and show that CDKN1C imprinting cannot be due to its synteny with IGF2 or with its placental expression in mammals.
Highlights
Genomic imprinting occurs in both marsupial and eutherian mammals
P57KIP2 localises to the tammar placenta While CDKN1C is imprinted in eutherians and vital for placentation, it is not imprinted in the tammar [11]
Despite its lack of imprinting, marsupial CDKN1C is expressed in the developing placenta where it may antagonise the actions of IGF2 on cell-cycle progression, as it does in eutherians
Summary
Genomic imprinting occurs in both marsupial and eutherian mammals. The CDKN1C and IGF2 genes are both imprinted and syntenic in the mouse and human, but in marsupials only IGF2 is imprinted. Eutherians and marsupials (therian mammals) diverged between 125–145 million years ago [1,2,3]. In which the monoallelic expression of certain genes depends on the parent of origin, occurs in both therian mammal lineages. This is in contrast to all other vertebrate species including monotreme mammals in which imprinting of endogenous genes has not been demonstrated [4,5,6,7]. The parental conflict hypothesis proposes that imprinting is the product of asymmetric selection on parental genomes, with selection favouring the expression of paternal genes that increase the amount of maternal nutrient transfer while expression from maternally-inherited genes will be favoured if they reduce nutritional (page number not for citation purposes)
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