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. Beer, Cedric Notredame, Roderic Guigó () and Thomas R. Gingeras ()
Additional contact information
Dmitri D. Pervouchine: Bioinformatics and Genomics Programme, Centre for Genomic Regulation (CRG) and UPF
Sarah Djebali: Bioinformatics and Genomics Programme, Centre for Genomic Regulation (CRG) and UPF
Alessandra Breschi: Bioinformatics and Genomics Programme, Centre for Genomic Regulation (CRG) and UPF
Carrie A. Davis: Functional Genomics Group, Cold Spring Harbor Laboratory
Pablo Prieto Barja: Bioinformatics and Genomics Programme, Centre for Genomic Regulation (CRG) and UPF
Alex Dobin: Functional Genomics Group, Cold Spring Harbor Laboratory
Andrea Tanzer: Faculty of Chemistry, Institute for Theoretical Chemistry, University of Vienna
Julien Lagarde: Bioinformatics and Genomics Programme, Centre for Genomic Regulation (CRG) and UPF
Chris Zaleski: Functional Genomics Group, Cold Spring Harbor Laboratory
Lei-Hoon See: Functional Genomics Group, Cold Spring Harbor Laboratory
Meagan Fastuca: Functional Genomics Group, Cold Spring Harbor Laboratory
Jorg Drenkow: Functional Genomics Group, Cold Spring Harbor Laboratory
Huaien Wang: Functional Genomics Group, Cold Spring Harbor Laboratory
Giovanni Bussotti: Bioinformatics and Genomics Programme, Centre for Genomic Regulation (CRG) and UPF
Baikang Pei: Program in Computational Biology and Bioinformatics, Yale University
Suganthi Balasubramanian: Program in Computational Biology and Bioinformatics, Yale University
Jean Monlong: Bioinformatics and Genomics Programme, Centre for Genomic Regulation (CRG) and UPF
Arif Harmanci: Program in Computational Biology and Bioinformatics, Yale University
Mark Gerstein: Program in Computational Biology and Bioinformatics, Yale University
Michael A. Beer: Johns Hopkins University
Cedric Notredame: Bioinformatics and Genomics Programme, Centre for Genomic Regulation (CRG) and UPF
Roderic Guigó: Bioinformatics and Genomics Programme, Centre for Genomic Regulation (CRG) and UPF
Thomas R. Gingeras: Functional Genomics Group, Cold Spring Harbor Laboratory

Nature Communications, 2015, vol. 6, issue 1, 1-11

Abstract: 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.

Date: 2015
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DOI: 10.1038/ncomms6903

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