The origins of genomic imprinting in mammals.

Carol A Edwards,Jennifer A Corish,Anne C Ferguson-Smith,Nozomi Takahashi

doi:10.1071/rd18176

Carol A Edwards, Jennifer A Corish + Show 2 more

Open Access

https://doi.org/10.1071/rd18176

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Abstract

Genomic imprinting is a process that causes genes to be expressed according to their parental origin. Imprinting appears to have evolved gradually in two of the three mammalian subclasses, with no imprinted genes yet identified in prototheria and only six found to be imprinted in marsupials to date. By interrogating the genomes of eutherian suborders, we determine that imprinting evolved at the majority of eutherian specific genes before the eutherian radiation. Theories considering the evolution of imprinting often relate to resource allocation and recently consider maternal-offspring interactions more generally, which, in marsupials, places a greater emphasis on lactation. In eutherians, the imprint memory is retained at least in part by zinc finger protein 57 (ZFP57), a Kruppel associated box (KRAB) zinc finger protein that binds specifically to methylated imprinting control regions. Some imprints are less dependent on ZFP57invivo and it may be no coincidence that these are the imprints that are found in marsupials. Because marsupials lack ZFP57, this suggests another more ancestral protein evolved to regulate imprints in non-eutherian subclasses, and contributes to imprinting control in eutherians. Hence, understanding the mechanisms acting at imprinting control regions across mammals has the potential to provide valuable insights into our understanding of the origins and evolution of genomic imprinting.

Highlights

Genomic imprinting is an epigenetic process whereby genes are expressed from one of the two chromosome homologues in a parent-of-origin-specific manner
Six imprinted genes have been identified in marsupials, namely insulin-like growth factor 2 (IGF2), the non-coding RNA gene H19, insulin (INS), IGF2 receptor (IGF2R), paternally expressed 10 (PEG10) and mesoderm specific transcript/paternally expressed 1
When we look at marsupial imprinted genes we see that they do not fall into the category associated with brain and behaviour, but rather most of them have a role in placentation and all are known to be expressed in the marsupial yolk sac membrane (YSM) placenta (Fig. 3; Suzuki et al 2005, 2007; Ager et al 2007, 2008b; Smits et al 2008; Stringer et al 2012b)

Summary

Introduction

Genomic imprinting is an epigenetic process whereby genes are expressed from one of the two chromosome homologues in a parent-of-origin-specific manner. The maternal–offspring coadaptation model is harder to reconcile with the marsupial data This theory predicts genes involved in placentation would be maternally expressed; only two maternally expressed genes have been identified in the marsupial placenta, IGF2R and H19, and major functions of both these genes are in modulating IGF2 levels in the fetus (Filson et al 1993; Ripoche et al 1997; Wilkin et al 2000; Gabory et al 2009). When the pup is lacking a functional copy of the gene, it has impaired suckling efficiency compared with wild-type litter mates (Curley et al 2004) These observations led to the proposal of a modified coadaptation model suggesting that genes that are simultaneously expressed in the maternal hypothalamus, placenta and fetal hypothalamus, such as Peg, would tend to be switched off on the maternal allele (Keverne and Curley 2008). A more in-depth study is required to identify conserved KZFPs that could bind and protect gDMRs at eutherian and marsupial imprinted domains

Concluding remarks

Findings

Materials and methods