Enhanced transcriptome maps from multiple mouse tissues reveal evolutionary constraint in gene expression

Dmitri D. Pervouchine, Sarah Djebali, Alessandra Breschi, Carrie A. Davis, Pablo Prieto Barja, Alex Dobin, Andrea Tanzer, Julien Lagarde, Chris Zaleski, Lei Hoon See, Meagan Fastuca, Jorg Drenkow, Huaien Wang, Giovanni Bussotti, Baikang Pei, Suganthi Balasubramanian, Jean Monlong, Arif Harmanci, Mark Gerstein, Michael A. BeerCedric Notredame, Roderic Guigó, Thomas R. Gingeras

Research output: Contribution to journalArticlepeer-review

Abstract

Mice have been a long-standing model for human biology and disease. Here we characterize, by RNA sequencing, 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 in human cell lines reveals substantial conservation of transcriptional programmes, and uncovers a distinct class of genes with levels of expression that have been constrained early in vertebrate evolution. This core set of genes captures a substantial 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 conserved epigenetic marking, as well as with characteristic post-transcriptional regulatory programme, in which sub-cellular localization and alternative splicing play comparatively large roles.

Original languageEnglish (US)
Article number5903
JournalNature communications
Volume6
DOIs
StatePublished - Jan 2015

ASJC Scopus subject areas

  • Chemistry(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Physics and Astronomy(all)

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