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“This paper shows that we share a common genetic imprinting mechanism which has been active for about 150 million years despite the differences in reproductive strategies between marsupials and humans,” said Professor Geoffrey Shaw of the Department of Zoology at the University of Melbourne, a coauthor on the paper.

Professor Marilyn Renfree who lead the University of Melbourne research team says marsupials give birth to very small young that develop mainly within the pouch while humans have more developed young at birth that undergo a large period of growth in the uterus.

“Our team provided vital samples and genetic resources from marsupials to enable this study and contributed our world-leading expertise on marsupial biology and genomics to the interpretation of the results,” Professor Renfree said.

Genomic imprinting is a mechanism that regulates gene expression in the developing fetus and plays a major role in regulating its growth.

“We all carry two copies of every gene in our DNA, one inherited from our mother and one from our father. So for each gene we have a ‘back-up’. Normally, both copies of the gene are used for development, but in some special cases the gene from either our mother or father is switched off, so we only have one active copy. This phenomenon is known as genomic imprinting,” explained Dr Andrew Pask also from the Department of Zoology.

“Because there is no back up copy, when errors occur in this process, it results in many human genetic diseases mainly affecting growth and brain function.”

Pask explains that a key gene regulating fetal growth is the Insulin-like-growth-factor-2 or IGF2 which is an imprinted gene.

“We inherit a single working copy of this gene from our fathers, while the copy we inherit from our mothers is switched off. The switch for this gene is controlled by another gene known as H19. The H19 gene is unusual gene that makes a microRNA and not a protein.”

“MicroRNA genes have been sought in marsupials for years, and now for the first time one has been discovered,” Dr Pask said.

Pask explains that the microRNA structure is virtually identical to that of mice and humans, but there was no evidence of this gene or a similar microRNA in the more distantly related platypus.

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Conservation of the H19 noncoding RNA and H19-IGF2 imprinting mechanism in therians

Comparisons between eutherians and marsupials suggest limited conservation of the molecular mechanisms that control genomic imprinting in mammals. We have studied the evolution of the imprinted IGF2-H19 locus in therians. Although marsupial orthologs of protein-coding exons were easily identified, the use of evolutionarily conserved regions and low-stringency Bl2seq comparisons was required to delineate a candidate H19 noncoding RNA sequence. The therian H19 orthologs show miR-675 and exon structure conservation, suggesting functional selection on both features. Transcription start site sequences and poly(A) signals are also conserved. As in eutherians, marsupial H19 is maternally expressed and paternal methylation upstream of the gene originates in the male germline, encompasses a CTCF insulator, and spreads somatically into the H19 gene. The conservation in all therians of the mechanism controlling imprinting of the IGF2-H19 locus suggests a sequential model of imprinting evolution.


http://www.nature.com/ng/journal/vaop/ncurrent/abs/ng.168.html