title: Correlated changes between regulatory cis elements and condition-specific expression in paralogous gene families.
abstract: Gene duplication is integral to evolution, providing novel opportunities for organisms to diversify in function. One fundamental pathway of functional diversification among initially redundant gene copies, or paralogs, is via alterations in their expression patterns. Although the mechanisms underlying expression divergence are not completely understood, transcription factor binding sites and nucleosome occupancy are known to play a significant role in the process. Previous attempts to detect genomic variations mediating expression divergence in orthologs have had limited success for two primary reasons. First, it is inherently challenging to compare expressions among orthologs due to variable trans-acting effects and second, previous studies have quantified expression divergence in terms of an overall similarity of expression profiles across multiple samples, thereby obscuring condition-specific expression changes. Moreover, the inherently inter-correlated expressions among homologs present statistical challenges, not adequately addressed in many previous studies. Using rigorous statistical tests, here we characterize the relationship between cis element divergence and condition-specific expression divergence among paralogous genes in Saccharomyces cerevisiae. In particular, among all combinations of gene family and TFs analyzed, we found a significant correlation between TF binding and the condition-specific expression patterns in over 20% of the cases. In addition, incorporating nucleosome occupancy reveals several additional correlations. For instance, our results suggest that GAL4 binding plays a major role in the expression divergence of the genes in the sugar transporter family. Our work presents a novel means of investigating the cis regulatory changes potentially mediating expression divergence in paralogous gene families under specific conditions.
authors.affiliation: Penn Center for Bioinformatics, Department of Genetics, University of Pennsylvania, Philadelphia, PA, USA. larryns@pcbi.upenn.edu
authors.forename: Larry N
authors.initials: LN
authors.lastname: Singh
authors.forename: Sridhar
authors.initials: S
authors.lastname: Hannenhalli
mesh_terms: D026905:Amino Acid Transport Systems / Q000145:classification / Q000235:genetics / Q000378:metabolism; D001665:Binding Sites; D047369:Chromatin Immunoprecipitation; D004268:DNA-Binding Proteins / Q000378:metabolism; D015966:Gene Expression Regulation, Fungal; D026341:Minichromosome Maintenance 1 Protein; D009004:Monosaccharide Transport Proteins / Q000145:classification / Q000235:genetics / Q000378:metabolism; D009707:Nucleosomes / Q000378:metabolism; D020411:Oligonucleotide Array Sequence Analysis; D011401:Promoter Regions, Genetic; D050436:Regulatory Elements, Transcriptional; D012441:Saccharomyces cerevisiae / Q000235:genetics* / Q000378:metabolism; D029701:Saccharomyces cerevisiae Proteins / Q000378:metabolism; D014157:Transcription Factors / Q000378:metabolism*
chemical_list: D026905:Amino Acid Transport Systems; D004268:DNA-Binding Proteins; C052130:GAL4 protein, S cerevisiae; C498030:MCM1 protein, S cerevisiae; D026341:Minichromosome Maintenance 1 Protein; D009004:Monosaccharide Transport Proteins; D009707:Nucleosomes; D029701:Saccharomyces cerevisiae Proteins; D014157:Transcription Factors