Highlight Publication June 2008

Smits G#, Mungall AJ#, Griffiths-Jones S, Smith P, Beury D, Matthews L, Rogers J, Pask AJ, Shaw G, VandeBerg JL, McCarrey JR, SAVOIR Consortium, Renfree MB, Reik W, Dunham I (In press)
Conservation of the H19 noncoding RNA and H19-IGF2 imprinting mechanism in therians.
Nature Genetics
http://dx.doi.org/10.1038/ng.168

For further information, please click here to refer to the press release relating to these findings (link opens in a new window).

Lay description

This paper reports that a highly conserved and extremely important mechanism of controlling genes is over 150 million years old. The findings have provided new insights into the evolution of genomic or parental imprinting and epigenetic regulation in mammals. A failure of these sophisticated processes is associated with many human genetic diseases, psychiatric and autoimmune disorders and ageing.

The control of gene expression by epigenetic imprinting mechanisms has been observed in placental mammals (eutherians) and marsupials (metatherians) where the majority of imprinted genes are associated with controlling embryonic growth and development, including the development of the placenta. Other imprinted genes are involved in post-natal development; processes like suckling and metabolism.

Imprinting is thought to have evolved because of genetic conflict that influences the allocation of resources from parents to offspring. The origin of this seems to stem from there being different developmental priorities for each parent - the father desires one large, strong offspring from each possible mother whereas the mother prefers to distribute resources equally among all her young

The apparent absence of genomic imprinting in monotremes and presence in eutherians and marsupials now reported suggests that imprinting has evolved at the boundary of monotremes and therians’ divergence. Interestingly, imprinting evolution paralleled the appearance of the placenta and implantation. Indeed, eutherians have a developed placenta that transfers a lot of nutrients to the fetus over a long gestation period while marsupials have a rudimentary placenta and give birth to very immature young that spend a long time in a pouch where they suckle milk. Both eutherians and marsupials having a placenta implies that the therian ancestor was a placental mammal; it is thus possible that imprinting and placentation co-evolved in this ancestor.

#About the lead authors

Guillaume Smits is a Medical Doctor who specialised in clinical chemistry at the Universite Libre de Bruxelles, Belgium. He obtained his PhD from the same university and joined Wolf Reik’s group at the Babraham Institute as a postdoc in 2004 to work on the IGF2-H19 locus. During his time at Babraham, Guillaume developed the fruitful Anglo-Australian-American ‘SAVOIR’ collaboration which has led to the findings now reported.  He has recently left the institute for a new postdoctoral position in the Human Genetics laboratory of Dr Peltonen at the Sanger Institute, Cambridge.

The co-lead author of this paper, Andrew Mungall, was a Sanger Institute researcher who has now moved to the Michael Smith Genome Sciences Centre in Vancouver, Canada.