PT - JOURNAL ARTICLE AU - Trevor Martin AU - Hunter B. Fraser TI - Phylogenetic expression profiling reveals widespread coordinated evolution of gene expression AID - 10.1101/045211 DP - 2016 Jan 01 TA - bioRxiv PG - 045211 4099 - http://biorxiv.org/content/early/2016/03/22/045211.short 4100 - http://biorxiv.org/content/early/2016/03/22/045211.full AB - Phylogenetic profiling, which infers functional relationships between genes based on patterns of gene presence/absence across species, has proven to be highly effective. Here we introduce a complementary approach, phylogenetic expression profiling (PEP), which detects gene sets with correlated expression levels across a phylogeny. Applying PEP to RNA-seq data consisting of 657 samples from 309 diverse unicellular eukaryotes, we found several hundred gene sets evolving in a coordinated fashion. These allowed us to predict a role of the Golgi apparatus in Alzheimer’s disease, as well as novel genes related to diabetes pathways. We also detected adaptive evolution of tRNA ligase levels to match genome-wide codon usage. In sum, we found that PEP is an effective method for inferring functional relationships—especially among core cellular components that are never lost, to which phylogenetic profiling cannot be applied—and that many subunits of the most conserved molecular machines are coexpressed across eukaryotes.