title: Fungal genes in context: genome architecture reflects regulatory complexity and function.
abstract: Gene context determines gene expression, with local chromosomal environment most influential. Comparative genomic analysis is often limited in scope to conserved or divergent gene and protein families, and fungi are well suited to this approach with low functional redundancy and relatively streamlined genomes. We show here that one aspect of gene context, the amount of potential upstream regulatory sequence maintained through evolution, is highly predictive of both molecular function and biological process in diverse fungi. Orthologs with large upstream intergenic regions (UIRs) are strongly enriched in information processing functions, such as signal transduction and sequence-specific DNA binding, and, in the genus Aspergillus, include the majority of experimentally studied, high-level developmental and metabolic transcriptional regulators. Many uncharacterized genes are also present in this class and, by implication, may be of similar importance. Large intergenic regions also share two novel sequence characteristics, currently of unknown significance: they are enriched for plus-strand polypyrimidine tracts and an information-rich, putative regulatory motif that was present in the last common ancestor of the Pezizomycotina. Systematic consideration of gene UIR in comparative genomics, particularly for poorly characterized species, could help reveal organisms' regulatory priorities.
authors.affiliation: Department of Genetics, University of Melbourne, Victoria, Australia.
authors.forename: Luke M
authors.initials: LM
authors.lastname: Noble
authors.forename: Alex
authors.initials: A
authors.lastname: Andrianopoulos
mesh_terms: D001230:Aspergillus / Q000235:genetics* / Q000378:metabolism; D002175:Candida / Q000235:genetics / Q000378:metabolism; D021901:DNA, Intergenic; D005656:Fungal Proteins / Q000096:biosynthesis / Q000235:genetics*; D005658:Fungi / Q000235:genetics*; D020869:Gene Expression Profiling; D015966:Gene Expression Regulation, Fungal; D005800:Genes, Fungal; D016681:Genome, Fungal; D059372:Nucleotide Motifs; D010802:Phylogeny; D012045:Regulatory Sequences, Nucleic Acid; D026801:Synteny; D020506:Untranslated Regions
chemical_list: D021901:DNA, Intergenic; D005656:Fungal Proteins; D020506:Untranslated Regions
keywords: comparative genomics; fungi; gene regulation; genome architecture; polypyrimidine; regulatory complexity