title: Enhanced transcriptome maps from multiple mouse tissues reveal evolutionary constraint in gene expression.
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.
authors.affiliation: 1] Bioinformatics and Genomics Programme, Centre for Genomic Regulation (CRG) and UPF, Doctor Aiguader, 88, Barcelona 08003, Spain [2] Faculty of Bioengineering and Bioinformatics, Moscow State University, Leninskie Gory 1-73, 119992 Moscow, Russia.
authors.forename: Dmitri D
authors.initials: DD
authors.lastname: Pervouchine
authors.affiliation: Bioinformatics and Genomics Programme, Centre for Genomic Regulation (CRG) and UPF, Doctor Aiguader, 88, Barcelona 08003, Spain.
authors.forename: Sarah
authors.initials: S
authors.lastname: Djebali
authors.affiliation: Bioinformatics and Genomics Programme, Centre for Genomic Regulation (CRG) and UPF, Doctor Aiguader, 88, Barcelona 08003, Spain.
authors.forename: Alessandra
authors.initials: A
authors.lastname: Breschi
authors.affiliation: Functional Genomics Group, Cold Spring Harbor Laboratory, 1 Bungtown Road, Cold Spring Harbor, New York 11724, USA.
authors.forename: Carrie A
authors.initials: CA
authors.lastname: Davis
authors.affiliation: Bioinformatics and Genomics Programme, Centre for Genomic Regulation (CRG) and UPF, Doctor Aiguader, 88, Barcelona 08003, Spain.
authors.forename: Pablo Prieto
authors.initials: PP
authors.lastname: Barja
authors.affiliation: Functional Genomics Group, Cold Spring Harbor Laboratory, 1 Bungtown Road, Cold Spring Harbor, New York 11724, USA.
authors.forename: Alex
authors.initials: A
authors.lastname: Dobin
authors.affiliation: Faculty of Chemistry, Institute for Theoretical Chemistry, University of Vienna, Waehringerstrasse 17, 1090 Vienna, Austria.
authors.forename: Andrea
authors.initials: A
authors.lastname: Tanzer
authors.affiliation: Bioinformatics and Genomics Programme, Centre for Genomic Regulation (CRG) and UPF, Doctor Aiguader, 88, Barcelona 08003, Spain.
authors.forename: Julien
authors.initials: J
authors.lastname: Lagarde
authors.affiliation: Functional Genomics Group, Cold Spring Harbor Laboratory, 1 Bungtown Road, Cold Spring Harbor, New York 11724, USA.
authors.forename: Chris
authors.initials: C
authors.lastname: Zaleski
authors.affiliation: Functional Genomics Group, Cold Spring Harbor Laboratory, 1 Bungtown Road, Cold Spring Harbor, New York 11724, USA.
authors.forename: Lei-Hoon
authors.initials: LH
authors.lastname: See
authors.affiliation: Functional Genomics Group, Cold Spring Harbor Laboratory, 1 Bungtown Road, Cold Spring Harbor, New York 11724, USA.
authors.forename: Meagan
authors.initials: M
authors.lastname: Fastuca
authors.affiliation: Functional Genomics Group, Cold Spring Harbor Laboratory, 1 Bungtown Road, Cold Spring Harbor, New York 11724, USA.
authors.forename: Jorg
authors.initials: J
authors.lastname: Drenkow
authors.affiliation: Functional Genomics Group, Cold Spring Harbor Laboratory, 1 Bungtown Road, Cold Spring Harbor, New York 11724, USA.
authors.forename: Huaien
authors.initials: H
authors.lastname: Wang
authors.affiliation: Bioinformatics and Genomics Programme, Centre for Genomic Regulation (CRG) and UPF, Doctor Aiguader, 88, Barcelona 08003, Spain.
authors.forename: Giovanni
authors.initials: G
authors.lastname: Bussotti
authors.affiliation: Program in Computational Biology and Bioinformatics, Yale University, 266 Whitney Avenue, New Haven, Connecticut 06520, USA.
authors.forename: Baikang
authors.initials: B
authors.lastname: Pei
authors.affiliation: 1] Program in Computational Biology and Bioinformatics, Yale University, 266 Whitney Avenue, New Haven, Connecticut 06520, USA [2] Department of Molecular Biophysics and Biochemistry, Yale University, 266 Whitney Avenue, New Haven, Connecticut 06520, USA.
authors.forename: Suganthi
authors.initials: S
authors.lastname: Balasubramanian
authors.affiliation: 1] Bioinformatics and Genomics Programme, Centre for Genomic Regulation (CRG) and UPF, Doctor Aiguader, 88, Barcelona 08003, Spain [2] Department of Human Genetics, McGill University, Montreal, Canada H3A 1B.
authors.forename: Jean
authors.initials: J
authors.lastname: Monlong
authors.affiliation: 1] Program in Computational Biology and Bioinformatics, Yale University, 266 Whitney Avenue, New Haven, Connecticut 06520, USA [2] Department of Molecular Biophysics and Biochemistry, Yale University, 266 Whitney Avenue, New Haven, Connecticut 06520, USA.
authors.forename: Arif
authors.initials: A
authors.lastname: Harmanci
authors.affiliation: 1] Program in Computational Biology and Bioinformatics, Yale University, 266 Whitney Avenue, New Haven, Connecticut 06520, USA [2] Department of Molecular Biophysics and Biochemistry, Yale University, 266 Whitney Avenue, New Haven, Connecticut 06520, USA [3] Department of Computer Science, Yale University, 51 Prospect Street, New Haven, Connecticut 06511, USA.
authors.forename: Mark
authors.initials: M
authors.lastname: Gerstein
authors.affiliation: Department of Biomedical Engineering and McKusick-Nathans Institute of Genetic Medicine, Johns Hopkins University, Broadway Research Building 573, Baltimore, Maryland 21205, USA.
authors.forename: Michael A
authors.initials: MA
authors.lastname: Beer
authors.affiliation: Bioinformatics and Genomics Programme, Centre for Genomic Regulation (CRG) and UPF, Doctor Aiguader, 88, Barcelona 08003, Spain.
authors.forename: Cedric
authors.initials: C
authors.lastname: Notredame
authors.affiliation: Bioinformatics and Genomics Programme, Centre for Genomic Regulation (CRG) and UPF, Doctor Aiguader, 88, Barcelona 08003, Spain.
authors.forename: Roderic
authors.initials: R
authors.lastname: Guigó
authors.affiliation: Functional Genomics Group, Cold Spring Harbor Laboratory, 1 Bungtown Road, Cold Spring Harbor, New York 11724, USA.
authors.forename: Thomas R
authors.initials: TR
authors.lastname: Gingeras
mesh_terms: D017398:Alternative Splicing; D000818:Animals; D005075:Biological Evolution; D002460:Cell Line; D044127:Epigenesis, Genetic; D019143:Evolution, Molecular; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation; D015723:Gene Library; D016678:Genome; D006657:Histones / Q000737:chemistry; D006801:Humans; D051379:Mice; D008810:Mice, Inbred C57BL; D008957:Models, Genetic; D016376:Oligonucleotides, Antisense; D010641:Phenotype; D017423:Sequence Analysis, RNA; D059467:Transcriptome
chemical_list: D006657:Histones; D016376:Oligonucleotides, Antisense