Abstract

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.

1. The Babraham Institute, Laboratory of Developmental Genetics and Imprinting, Cambridge CB22 3AT, UK.
2. The Wellcome Trust Sanger Institute, Cambridge CB10 1SA, UK.
3. The University of Manchester, Faculty of Life Sciences, Manchester M13 9PL, UK.
4. The University of Melbourne, Department of Zoology, Victoria 3010, Australia.
5. The Southwest Foundation for Biomedical Research, Department of Genetics, San Antonio, Texas 78227, USA.
6. The University of Texas at San Antonio, Department of Biology, San Antonio, Texas 78249, USA.
7. Present address: EMBL-European Bioinformatics Institute, Cambridge CB10 1SD, UK.
8. A full list of authors is provided in the Supplementary Note online.
9. These authors contributed equally to this work.

Correspondence to: Wolf Reik¹ e-mail: wolf.reik@bbsrc.ac.uk

Correspondence to: Ian Dunham^2,7 e-mail: dunham@ebi.ac.uk

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