Oral Presentation Society for Molecular Biology and Evolution Conference 2016

Divergent patterns of marsupial-eutherian genomic imprinting revealed from RNA-seq analysis in the opossum, Monodelphis domestica (#128)

Xu Wang 1 , Kory C Douglas 2 , John L VandeBerg 3 , Paul B Samollow 2 , Andrew G Clark 1
  1. Cornell University, Ithaca, NY, United States
  2. Texas A&M University, College Station, TX
  3. Southwest National Primate Research Center, San Antonio, TX

Among the ~150-200 imprinted genes identified in mouse and human, only 20 marsupial orthologs have been examined to date, and eight of these were found to be imprinted. Here we ask, what is the marsupial imprinting status for the remaining 130 eutherian imprinted genes, and are there any marsupial-specific imprinted genes? We profiled genome-wide allele-specific expression (RNA-seq), histone modifications (ChIP-seq) and DNA methylation (PyroMark) in fetal brain and extra-embryonic membranes from reciprocal crosses of two opossum lines, providing an unbiased survey of parent-of-origin effects. Among 68 genes known to be imprinted in eutherians (and having an opossum ortholog), 52 were covered with sufficient informative SNPs to score allelic expression. Only three (<6%) were found to be imprinted in opossum, and 48 display biallelic expression, reflecting a striking lack of conservation of imprinting status.   We also discovered and validated eight marsupial-specific imprinted genes that are not known to be imprinted in any other species. Surprisingly, three of these are non-coding lincRNA genes with no homology to any eutherian sequences, but they are present and are highly conserved in other marsupial species and non-mammalian vertebrates including chicken. Three of the rest five protein-coding imprinted genes were paralogous to eutherian genes, resulting from recent gene family expansions in opossum.  Mechanistically, our epigenetic profiles confirmed that opossum-specific imprinted genes are regulated in the same way as eutherians by differential promoter methylation, despite the evolutionary fluidity of the imprinting profile.  We estimate that opossums imprint only 30-40 genes, or about one-fifth the number imprinted by eutherian mammals. The smaller number and non-overlapping nature of imprinted genes could be due to the primitive placentation and shorter gestation time in marsupials compared to eutherians. Our study provides the first imprinting profile in a marsupial and sheds light on the regulation and evolution of genomic imprinting in mammals.