A quantitative framework for characterizing the evolutionary history of mammalian gene expression

Chen, Jenny, Swofford, Ross, Johnson, Jeremy, Cummings, Beryl B., Rogel, Noga, Lindblad-Toh, Kerstin, Haerty, Wilfried, Di Palma, Federica and Regev, Aviv (2019) A quantitative framework for characterizing the evolutionary history of mammalian gene expression. Genome Research, 29 (1). pp. 53-63. ISSN 1088-9051

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Abstract

The evolutionary history of a gene helps predict its function and relationship to phenotypic traits. Although sequence conservation is commonly used to decipher gene function and assess medical relevance, methods for functional inference from comparative expression data are lacking. Here, we use RNA-seq across seven tissues from 17 mammalian species to show that expression evolution across mammals is accurately modeled by the Ornstein–Uhlenbeck process, a commonly proposed model of continuous trait evolution. We apply this model to identify expression pathways under neutral, stabilizing, and directional selection. We further demonstrate novel applications of this model to quantify the extent of stabilizing selection on a gene’s expression, parameterize the distribution of each gene’s optimal expression level, and detect deleterious expression levels in expression data from individual patients. Our work provides a statistical framework for interpreting expression data across species and in disease.

Item Type: Article
Uncontrolled Keywords: genetics,genetics(clinical) ,/dk/atira/pure/subjectarea/asjc/1300/1311
Faculty \ School: Faculty of Medicine and Health Sciences > Norwich Medical School
Faculty of Science > School of Biological Sciences
Related URLs:
Depositing User: LivePure Connector
Date Deposited: 08 Apr 2019 13:30
Last Modified: 25 Jun 2020 00:32
URI: https://ueaeprints.uea.ac.uk/id/eprint/70516
DOI: 10.1101/gr.237636.118

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