Paternally expressed genes predominate in the placenta

Abstract

The discovery of genomic imprinting through studies of manipulated mouse embryos indicated that the paternal genome has a major influence on placental development. However, previous research has not demonstrated paternal bias in imprinted genes. We applied RNA sequencing to trophoblast tissue from reciprocal hybrids of horse and donkey, where genotypic differences allowed parent-of-origin identification of most expressed genes. Using this approach, we identified a core group of 15 ancient imprinted genes, of which 10 were paternally expressed. An additional 78 candidate imprinted genes identified by RNA sequencing also showed paternal bias. Pyrosequencing was used to confirm the imprinting status of six of the genes, including the insulin receptor ( INSR ), which may play a role in growth regulation with its reciprocally imprinted ligand, histone acetyltransferase-1 ( HAT1 ), a gene involved in chromatin modification, and lymphocyte antigen 6 complex, locus G6C, a newly identified imprinted gene in the major histocompatibility complex. The 78 candidate imprinted genes displayed parent-of-origin expression bias in placenta but not fetus, and most showed less than 100% silencing of the imprinted allele. Some displayed variability in imprinting status among individuals. This variability results in a unique epigenetic signature for each placenta that contributes to variation in the intrauterine environment and thus presents the opportunity for natural selection to operate on parent-of-origin differential regulation. Taken together, these features highlight the plasticity of imprinting in mammals and the central importance of the placenta as a target tissue for genomic imprinting.

Non-conflict theories for the evolution of genomic imprinting

“…They went on to describe a mathematical model that corroborated these ideas. The horse-donkey hybrid data in Wang et al (2013) may fit better with this version of the hypothesis.…”

“…These authors then argued that this directional bias was consistent with data from the mouse, in which all genes known to be imprinted in the placenta but not elsewhere are maternally expressed (Ferguson-Smith et al, 2006;Wagschal and Feil, 2006). More recent data from horse-donkey hybrids, however, show an overabundance of paternally expressed imprinted genes in the equine placenta (Wang et al, 2013), which clearly does not fit with this prediction. Moreover, the model implies that imprinting should be found outside mammals, in taxa with strong parent-offspring interactions, and that in taxa where paternal care was important paternal expression would be favoured for the genes involved in this interaction.…”

“…It is also unclear why so many genes appear to be imprinted: it would seem that the hypothesized protective effect would occur with just a few imprinted genes. Finally, the differences among species in the loci that are imprinted (Wang et al, 2013) would also appear to be inconsistent with this hypothesis: one might expect genes of similar function to have evolved their imprinting status early on in mammalian evolution and for this ancient pattern to have been largely conserved. Many of these criticisms are against the argument that all genes acquired imprinting by the ovarian timebomb mechanism, and these arguments pale if instead imprinting were initiated in a few genes to neutralize the ovarian time-bomb, and then subsequent addition of imprinting arose by other means.…”

“…(We consider the myriad of cases of whole-genome silencing or elimination in insects and mites to be a different phenomenon, requiring completely different evolutionary explanations.) Finally, imprinted genes generally have appeared to occur in clusters on chromosomes (Morison et al, 2005), but as more exhaustive lists of imprinted genes are compiled, the newly discovered genes more often appear to be singletons (Wang et al, 2013).…”

A review of inter- and intraspecific variation in the eutherian placenta

“…Other studies have used placenta transcriptomes of several equines to study parent of origin effects and genetic imprinting, where the fetus inherits genes from either the mother or the father [31,32]. One study compared placental transcriptomes of horses, donkeys and their crosses (mules and hinnys) and found that a majority of the genes that were significantly different were paternally expressed, showing that the father's size has some influence in determining the size of the fetus [31]. Placental transcriptomics has also identified novel splice variants that are processed differently in various eutharian species.…”