RT Journal A1 Roy, Sushmita A1 Wapinski, Ilan A1 Pfiffner, Jenna A1 French, Courtney A1 Socha, Amanda A1 Konieczka, Jay A1 Habib, Naomi A1 Kellis, Manolis A1 Thompson, Dawn A1 Regev, Aviv T1 Arboretum: Reconstruction and analysis of the evolutionary history of condition-specific transcriptional modules JF Genome Research JO Genome Research YR 2013 FD June 01 VO 23 IS 6 SP 1039 OP 1050 DO 10.1101/gr.146233.112 UL http://genome.cshlp.org/content/23/6/1039.abstract AB Comparative functional genomics studies the evolution of biological processes by analyzing functional data, such as gene expression profiles, across species. A major challenge is to compare profiles collected in a complex phylogeny. Here, we present Arboretum, a novel scalable computational algorithm that integrates expression data from multiple species with species and gene phylogenies to infer modules of coexpressed genes in extant species and their evolutionary histories. We also develop new, generally applicable measures of conservation and divergence in gene regulatory modules to assess the impact of changes in gene content and expression on module evolution. We used Arboretum to study the evolution of the transcriptional response to heat shock in eight species of Ascomycota fungi and to reconstruct modules of the ancestral environmental stress response (ESR). We found substantial conservation in the stress response across species and in the reconstructed components of the ancestral ESR modules. The greatest divergence was in the most induced stress, primarily through module expansion. The divergence of the heat stress response exceeds that observed in the response to glucose depletion in the same species. Arboretum and its associated analyses provide a comprehensive framework to systematically study regulatory evolution of condition-specific responses.