*Arboretum: Reconstruction and analysis of the evolutionary history of condition-specific transcriptional modules* Sushmita Roy1,2,6,7, Ilan Wapinski1,3, Jenna Pfiffner1, Courtney French1, Amanda Socha1, Jay Konieczka1, Naomi Habib4, Manolis Kellis1,2, Dawn Thompson1 and Aviv Regev1,5,7 Abstract 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. http://genome.cshlp.org/content/23/6/1039.abstract -- Prof. Dr. Klaas Vandepoele Tel. 32 (0)9 33 13822 VIB Department of Plant Systems Biology, Ghent University Technologiepark 927, 9052 Gent, Belgium E-mail: Klaas.Vandepoele@psb.vib-ugent.be Website: http://bioinformatics.psb.ugent.be/cig/ Twitter: http://twitter.com/plaza_genomics ---------------------------------------------------------