Reconstruction and Analysis of the Evolution of Modular Transcriptional Regulatory Programs Using Arboretum.
Comparative functional genomics aims to measure and compare genome-wide functional data such as transcriptomes, proteomes, and epigenomes across multiple species to study the conservation and divergence patterns of such quantitative measurements. However, computational methods to systematically compare these quantitative genomic profiles across multiple species are in their infancy. We developed Arboretum, a novel algorithm to identify modules of co-expressed genes and trace their evolutionary history across multiple species from a complex phylogeny. To interpret the results from Arboretum we developed several measures to examine the extent of conservation and divergence in modules and their relationship to species lifestyle, cis-regulatory elements, and gene duplication. We applied Arboretum to study the evolution of modular transcriptional regulatory programs controlling transcriptional response to different environmental stresses in the yeast Ascomycota phylogeny. We found that modules of similar patterns of expression captured the transcriptional responses to different stresses across species; however, the genes exhibiting these patterns were not the same. Divergence in module membership was associated with changes in lifestyle and specific clades and that gene duplication was a major factor contributing to the divergence of module membership.
Wisconsin Institute for Discovery, University of Wisconsin at Madison, Madison, WI, USA.
Sara A
SA
Knaack
Broad Institute of MIT and Harvard, Cambridge, MA, USA.
Dawn A
DA
Thompson
Wisconsin Institute for Discovery, University of Wisconsin at Madison, Madison, WI, USA. sroy@biostat.wisc.edu.|Department of Biostatistics and Medical Informatics, University of Wisconsin at Madison, Madison, WI, USA. sroy@biostat.wisc.edu.
Sushmita
S
Roy
D000465:Algorithms; D019295:Computational Biology / Q000379:methods*; D020440:Gene Duplication / Q000235:genetics; D015966:Gene Expression Regulation, Fungal; D053263:Gene Regulatory Networks; D010802:Phylogeny; D012441:Saccharomyces cerevisiae / Q000145:classification / Q000235:genetics; D014157:Transcription Factors / Q000235:genetics*
D014157:Transcription Factors
Arboretum; Evolution; Gaussian mixture model (GMM); Gene tree; Multi-clustering; Phylogeny; Regulatory networks; Transcriptional module s