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E-GEOD-49417 - The conserved organization of the human and mouse transcriptomes
Released on 20 November 2014, last updated on 28 November 2014
, Homo sapiens, Mus musculus
We characterized by RNA-seq the transcriptional profiles of a large and heterogeneous collection of mouse tissues, augmenting the mouse transcriptome with thousands of novel transcript candidates. Comparison with transcriptome profiles obtained in human cell lines reveals substantial conservation of transcriptional programs, and uncovers a distinct class of genes with levels of expression across cell types and species, that have been constrained early in vertebrate evolution. This core set of genes capture a substantial and constant fraction of the transcriptional output of mammalian cells, and participates in basic functional and structural housekeeping processes common to all cell types. Perturbation of these constrained genes is associated with significant phenotypes including embryonic lethality and cancer. Evolutionary constraint in gene expression levels is not reflected in the conservation of the genomic sequences, but it is associated with strong and conserved epigenetic marking, as well as to a characteristic post-transcriptional regulatory program in which sub-cellular localization and alternative splicing play comparatively large roles. Comparison of human and mouse transcriptome profiles has uncovered a distinct class of genes (6600- one third of all expressed genes in both human and mouse) whose variation in expression levels have been constrained irrespective of cell types and species that they are express in. Such constraint appears to have been developed early in vertebrate evolution since it seen in multiple other species. This constraint is not associated with the conservation of the genomic sequences found in each species. Finally, this core set of genes helps in interpreting how non-human organisms like the mouse can better be used as models for human disease and why perturbation of these constrained genes is associated with significant phenotypes including embryonic lethality and cancer.
RNA-seq of coding RNA
ENCODE DCC <email@example.com>, Alessandra Breschi, Alex Dobin, Andrea Tanzer, Arif Harmanci, Baikang Pei, Carrie A Davis, Cedric Notredame, Chris Zaleski, Dmitri D Pervouchine, Giovanni Bussotti, Huaien Wang, Jean Monlong, Jorg Drenkow, Julien Lagarde, Lei-Hoon See, Mark Gerstein, Meagan Fastuca, Micheal A Beer, Pablo P Barja, Roderic Guigo, Sarah Djebali, Suganthi Balasubramanian, Thomas R Gingeras