RT Journal Article SR Electronic T1 Enhanced Transcriptome Maps from Multiple Mouse Tissues Reveal Evolutionary Constraint in Gene Expression for Thousands of Genes JF bioRxiv FD Cold Spring Harbor Laboratory SP 010884 DO 10.1101/010884 A1 Dmitri D. Pervouchine A1 Sarah Djebali A1 Alessandra Breschi A1 Carrie A. Davis A1 Pablo Prieto Barja A1 Alex Dobin A1 Andrea Tanzer A1 Julien Lagarde A1 Chris Zaleski A1 Lei-Hoon See A1 Meagan Fastuca A1 Jorg Drenkow A1 Huaien Wang A1 Giovanni Bussotti A1 Baikang Pei A1 Suganthi Balasubramanian A1 Jean Monlong A1 Arif Harmanci A1 Mark Gerstein A1 Michael A. Beer A1 Cedric Notredame A1 Roderic Guigó A1 Thomas R. Gingeras YR 2014 UL http://biorxiv.org/content/early/2014/10/30/010884.abstract AB 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 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.