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

Chen, JennyBroad Inst MIT & Harvard, Cambridge, MA 02142 USA;MIT, Div Hlth Sci & Technol, Cambridge, MA 02139 USA (author)

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.

Swofford, RossBroad Inst MIT & Harvard, Cambridge, MA 02142 USA (author)
Johnson, JeremyBroad Inst MIT & Harvard, Cambridge, MA 02142 USA (author)
Cummings, Beryl B.Broad Inst MIT & Harvard, Cambridge, MA 02142 USA;Harvard Med Sch, Program Biol & Biomed Sci, Boston, MA 02115 USA (author)
Rogel, NogaBroad Inst MIT & Harvard, Klarman Cell Observ, Cambridge, MA 02142 USA (author)
Lindblad-Toh, KerstinUppsala universitet,Institutionen för medicinsk biokemi och mikrobiologi,Science for Life Laboratory, SciLifeLab,Broad Inst MIT & Harvard, Cambridge, MA 02142 USA(Swepub:uu)kerli865 (author)
Haerty, WilfriedEarlham Inst, Norwich NR4 7UZ, Norfolk, England (author)
di Palma, FedericaEarlham Inst, Norwich NR4 7UZ, Norfolk, England;Univ East Anglia, Dept Biol & Med Sci, Norwich NR4 7TJ, Norfolk, England (author)
Regev, AvivBroad Inst MIT & Harvard, Klarman Cell Observ, Cambridge, MA 02142 USA;MIT, Dept Biol, Cambridge, MA 02142 USA;MIT, Koch Inst, Cambridge, MA 02142 USA;Howard Hughes Med Inst, Chevy Chase, MD 20815 USA (author)
Broad Inst MIT & Harvard, Cambridge, MA 02142 USA;MIT, Div Hlth Sci & Technol, Cambridge, MA 02139 USABroad Inst MIT & Harvard, Cambridge, MA 02142 USA (creator_code:org_t)

In:Genome Research: Cold Spring Harbor Laboratory29:1, s. 53-631088-90511549-5469

By the author/editor: Chen, Jenny; Swofford, Ross; Johnson, Jeremy; Cummings, Beryl ...; Rogel, Noga; Lindblad-Toh, Ke ...; show more...; Haerty, Wilfried; di Palma, Federi ...; Regev, Aviv; show less...

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