Arboretum: Reconstruction and analysis of the evolutionary history of condition-specific transcriptional modules

• Main Authors: Kellis, Manolis (Contributor), Regev, Aviv (Contributor), Roy, Sushmita (Author), Wapinski, Ilan (Author), Pfiffner, Jenna (Author), French, Courtney (Author), Socha, Amanda (Author), Konieczka, Jay (Author), Habib, Naomi (Author), Thompson, Dawn (Author)
• Other Authors: Massachusetts Institute of Technology. Computer Science and Artificial Intelligence Laboratory (Contributor), Massachusetts Institute of Technology. Department of Biology (Contributor), Massachusetts Institute of Technology. Department of Electrical Engineering and Computer Science (Contributor)
• Format: Article
• Language: English
• Published: Cold Spring Harbor Laboratory Press, 2014-02-14T16:59:33Z.
• Subjects: Article
• Online Access: Get fulltext

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.
Howard Hughes Medical Institute
Broad Institute of MIT and Harvard
National Institutes of Health (U.S.) (Pioneer Award)
National Institutes of Health (U.S.) (R01 2R01CA119176-01)
Burroughs Wellcome Fund (Career Award at the Scientific Interface)
Alfred P. Sloan Foundation