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      Genetic conflict reflected in tissue-specific maps of genomic imprinting in human and mouse

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          Abstract

          Genomic imprinting is an epigenetic process that restricts gene expression to either the maternally or paternally inherited allele 1, 2 . Many theories have been proposed to explain its evolutionary origin 3, 4 , but our understanding has been limited by a paucity of data mapping the breadth and dynamics of imprinting within any organism. We generated an atlas of imprinting spanning 33 mouse and 45 human developmental stages and tissues. Nearly all imprinted genes were imprinted in early development and either retained their parent-of-origin expression in adults, or lost it completely. Consistent with an evolutionary signature of parental conflict, imprinted genes were enriched for co-expressed pairs of maternally/paternally expressed genes, showed accelerated expression divergence between human and mouse, and were more highly expressed than their non-imprinted orthologs in other species. Our approach demonstrates a general framework for imprinting discovery in any species, and sheds light on the causes and consequences of genomic imprinting in mammals.

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          Most cited references40

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          Gene Ontology: tool for the unification of biology

          Genomic sequencing has made it clear that a large fraction of the genes specifying the core biological functions are shared by all eukaryotes. Knowledge of the biological role of such shared proteins in one organism can often be transferred to other organisms. The goal of the Gene Ontology Consortium is to produce a dynamic, controlled vocabulary that can be applied to all eukaryotes even as knowledge of gene and protein roles in cells is accumulating and changing. To this end, three independent ontologies accessible on the World-Wide Web (http://www.geneontology.org) are being constructed: biological process, molecular function and cellular component.
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            The evolution of gene expression levels in mammalian organs.

            Changes in gene expression are thought to underlie many of the phenotypic differences between species. However, large-scale analyses of gene expression evolution were until recently prevented by technological limitations. Here we report the sequencing of polyadenylated RNA from six organs across ten species that represent all major mammalian lineages (placentals, marsupials and monotremes) and birds (the evolutionary outgroup), with the goal of understanding the dynamics of mammalian transcriptome evolution. We show that the rate of gene expression evolution varies among organs, lineages and chromosomes, owing to differences in selective pressures: transcriptome change was slow in nervous tissues and rapid in testes, slower in rodents than in apes and monotremes, and rapid for the X chromosome right after its formation. Although gene expression evolution in mammals was strongly shaped by purifying selection, we identify numerous potentially selectively driven expression switches, which occurred at different rates across lineages and tissues and which probably contributed to the specific organ biology of various mammals.
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              Genomic imprinting in mammals.

              Genomic imprinting affects a subset of genes in mammals and results in a monoallelic, parental-specific expression pattern. Most of these genes are located in clusters that are regulated through the use of insulators or long noncoding RNAs (lncRNAs). To distinguish the parental alleles, imprinted genes are epigenetically marked in gametes at imprinting control elements through the use of DNA methylation at the very least. Imprinted gene expression is subsequently conferred through lncRNAs, histone modifications, insulators, and higher-order chromatin structure. Such imprints are maintained after fertilization through these mechanisms despite extensive reprogramming of the mammalian genome. Genomic imprinting is an excellent model for understanding mammalian epigenetic regulation.
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                Author and article information

                Journal
                9216904
                2419
                Nat Genet
                Nat. Genet.
                Nature genetics
                1061-4036
                1546-1718
                27 March 2015
                13 April 2015
                May 2015
                01 November 2015
                : 47
                : 5
                : 544-549
                Affiliations
                [1 ]Department of Biology, Stanford University, Stanford, CA, 94305, USA
                [2 ]UCSF School of Medicine, UCSF, San Francisco, CA, 94143, USA
                [3 ]Department of Pathology, Stanford University, Stanford, CA, 94305, USA
                [4 ]Department of Genetics, Stanford University, Stanford, CA, 94305, USA
                [5 ]Department of Molecular Genetics, University of Toronto, Toronto, ON, M5S 3E1, Canada
                Author notes
                [*]

                Current affiliation: Department of Biology, Queen's University, Kingston, ON, K7L 3N6, Canada

                [§ ]Correspondence should be addressed to: hbfraser@ 123456stanford.edu
                Article
                NIHMS672874
                10.1038/ng.3274
                4414907
                25848752
                f1757cf6-a446-42b6-9fdb-fef7270030b9
                History
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                Genetics
                Genetics

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