RT Journal
A1 Chen, Jenny
A1 Swofford, Ross
A1 Johnson, Jeremy
A1 Cummings, Beryl B.
A1 Rogel, Noga
A1 Lindblad-Toh, Kerstin
A1 Haerty, Wilfried
A1 Palma, Federica di
A1 Regev, Aviv
T1 A quantitative framework for characterizing the evolutionary history of mammalian gene expression
JF Genome Research 
JO Genome Research 
YR 2019 
FD January 01 
VO 29 
IS 1 
SP 53 
OP 63 
DO 10.1101/gr.237636.118 
UL http://genome.cshlp.org/content/29/1/53.abstract 
AB 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.