title: Polygenic and directional regulatory evolution across pathways in Saccharomyces.
abstract: The search to understand how genomes innovate in response to selection dominates the field of evolutionary biology. Powerful molecular evolution approaches have been developed to test individual loci for signatures of selection. In many cases, however, an organism's response to changes in selective pressure may be mediated by multiple genes, whose products function together in a cellular process or pathway. Here we assess the prevalence of polygenic evolution in pathways in the yeasts Saccharomyces cerevisiae and S. bayanus. We first established short-read sequencing methods to detect cis-regulatory variation in a diploid hybrid between the species. We then tested for the scenario in which selective pressure in one species to increase or decrease the activity of a pathway has driven the accumulation of cis-regulatory variants that act in the same direction on gene expression. Application of this test revealed a variety of yeast pathways with evidence for directional regulatory evolution. In parallel, we also used population genomic sequencing data to compare protein and cis-regulatory variation within and between species. We identified pathways with evidence for divergence within S. cerevisiae, and we detected signatures of positive selection between S. cerevisiae and S. bayanus. Our results point to polygenic, pathway-level change as a common evolutionary mechanism among yeasts. We suggest that pathway analyses, including our test for directional regulatory evolution, will prove to be a relevant and powerful strategy in many evolutionary genomic applications.
authors.affiliation: Division of Biostatistics, Department of Molecular and Cell Biology, University of California, Berkeley, CA 94720, USA.
authors.forename: James H
authors.initials: JH
authors.lastname: Bullard
authors.forename: Yulia
authors.initials: Y
authors.lastname: Mostovoy
authors.forename: Sandrine
authors.initials: S
authors.lastname: Dudoit
authors.forename: Rachel B
authors.initials: RB
authors.lastname: Brem
mesh_terms: D000483:Alleles; D001483:Base Sequence; D005075:Biological Evolution; D055354:Exosomes / Q000378:metabolism; D015966:Gene Expression Regulation, Fungal; D014644:Genetic Variation; D006824:Hybridization, Genetic; D053858:Metabolic Networks and Pathways / Q000235:genetics*; D020412:Multifactorial Inheritance / Q000235:genetics*; D012331:RNA, Fungal / Q000235:genetics; D012045:Regulatory Sequences, Nucleic Acid / Q000235:genetics; D012440:Saccharomyces / Q000235:genetics*; D012641:Selection, Genetic; D013045:Species Specificity
chemical_list: D012331:RNA, Fungal