A quantitative framework for characterizing the evolutionary history of mammalian gene expression
Name
Genome Res.-2019-Chen-53-63.pdf
Description
Published version
Size
2.11 MB
Format
Adobe PDF
Checksum (MD5)
7585db6241c885816f4c339bdcbde283
Author(s)
Chen, Jenny (Jennifer)
Regev, Aviv
Date Issued
December 2018
Journal
Genome research
Publisher
Cold Spring Harbor Laboratory
Citation
Chen, Jenny et al. “A quantitative framework for characterizing the evolutionary history of mammalian gene expression.” Genome research 29 (2019): 53-63 © 2019 The Author(s)
Version
Final published version
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.
MIT Department
Harvard University--MIT Division of Health Sciences and Technology
Massachusetts Institute of Technology. Department of Biology
Terms of Use
Creative Commons Attribution NonCommercial License 4.0
Persistent DSpace Link
DOI of Published Version
https://doi.org/10.1101/GR.237636.118
