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

Pervouchine, D. D., Djebali, S., Breschi, A., Davis, C. A., Barja, P. P., Dobin, A., Tanzer, A., Lagarde, J., Zaleski, C., See, L. H., Fastuca, M., Drenkow, J., Wang, H., Bussotti, G., Pei, B., Balasubramanian, S., Monlong, J., Harmanci, A., Gerstein, M., Beer, M. A., Notredame, C., Guigo, R., Gingeras, T. R. (January 2015) Enhanced transcriptome maps from multiple mouse tissues reveal evolutionary constraint in gene expression. Nat Commun, 6. p. 5903. ISSN 2041-1723

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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.

Item Type: Paper
Subjects: bioinformatics > genomics and proteomics > genetics & nucleic acid processing > DNA, RNA structure, function, modification > genes, structure and function > gene expression
bioinformatics > genomics and proteomics > genetics & nucleic acid processing > DNA, RNA structure, function, modification > genes, structure and function
organism description > animal > mammal > rodent > mouse
bioinformatics > genomics and proteomics > genetics & nucleic acid processing > transcriptomes
CSHL Authors:
Communities: CSHL Cancer Center Program > Gene Regulation and Cell Proliferation
CSHL Cancer Center Shared Resources > Bioinformatics Service
CSHL Cancer Center Shared Resources > Functional Genomics and Genetics Service
CSHL labs > Gingeras lab
CSHL labs > Dobin Lab
Depositing User: Matt Covey
Date: 13 January 2015
Date Deposited: 30 Jan 2015 20:37
Last Modified: 08 Jul 2020 18:16
PMCID: PMC4308717
Related URLs:
URI: https://repository.cshl.edu/id/eprint/31166

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