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Evolution of imprinting mechanisms: the battle of the sexes begins in the zygote

Nature Genetics volume 27, pages 255–256 (2001)Cite this article

Table 1 lists imprinted genes together with their antisense transcripts (if identified) and the methylation patterns that most likely reflect their germline imprint3. It is striking that all antisense transcripts discovered so far (seven) are maternally repressed (this excludes the X-linked gene Xist, which has a paternally repressed antisense transcript7). By contrast, with two exceptions (H19 and Rasgrf1), the currently known germline methylation imprints are imposed in the maternal germ line (12 maternal, 2 paternal). Thus, maternally repressed genes are mostly 'epigenetically' silenced by maternal methylation (Fig. 1). By contrast, of the seven paternally repressed genes (Table 1), five have maternally repressed antisense transcripts, and four have maternal methylation patterns that are thought to be germline imprints. Significantly, no protein-coding gene has been found that is paternally repressed and paternally methylated (Table 1). It is evidently more common for paternally repressed genes to be silenced 'genetically' by means of paternal antisense (or other mechanisms) than 'epigenetically' by paternal methylation (Fig. 1). Functional analyses using nuclear transplantation confirm that the acquisition of maternal imprints in oocytes is important for the silencing of maternally repressed genes (Peg1, Peg3, Snrpn) as well as for the expression of maternally expressed genes8 (Igf2r, p57Kip2), but the acquisition of paternal imprints is important only for the repression of the paternal copy of H19 (ref. 9).

Table 1 Methylation and antisense transcripts in imprinted genes
Full size table

We suggest that this asymmetry has arisen because of the active and genome-wide demethylation of the paternal genome in the mouse zygote10,11. This would make difficult the inheritance of paternal methylation in DMRs, as observed for Igf2 (ref. 10). Paternal demethylation does not occur in the zebrafish12 (which does not have imprinting), but occurs in other mammalian species with imprinting (W. Dean et al., unpublished data). Demethylation of the paternal genome can be viewed as a reprogramming mechanism by which the egg (that is, the maternal genome) strips off paternal imprints when the paternal genome is at its most vulnerable, consistent with proposals of the genetic conflict theory of imprinting13. One can therefore speculate that if paternal demethylation evolved after imprinting, the primordial imprinting mechanism might have been a simple one in which maternal methylation led to maternal repression (as it does now) and paternal methylation led to paternal repression. Alternatively, imprinting might have arisen after paternal demethylation. Subsequent to the emergence of paternal demethylation, paternally repressed genes evolved the 'genetic' mechanisms of silencing and the 'epigenetic' mechanism of activation. That there is significant evolution of imprinting mechanisms is supported by the recent finding in the opossum that the Igf2r gene is paternally repressed (as in the mouse), but the mechanism does not involve a maternally methylated DMR in intron 2 (ref. 14).

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Figure 1: Epigenetic silencing and epigenetic activation.

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Authors and Affiliations

  1. Laboratory of Developmental Genetics and Imprinting, The Babraham Institute, Cambridge, UK

    Wolf Reik & Jörn Walter

  2. Max Planck Institute for Molecular Genetics, Berlin, Germany and Universität des Saarlandes, Genetik, Saarbrücken, Germany

    Jörn Walter

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Correspondence to Wolf Reik.

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Reik, W., Walter, J. Evolution of imprinting mechanisms: the battle of the sexes begins in the zygote. Nat Genet 27, 255–256 (2001). https://doi.org/10.1038/85804

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