title: Fitness landscape for nucleosome positioning.
abstract: Histone-DNA complexes, so-called nucleosomes, are the building blocks of DNA packaging in eukaryotic cells. The histone-binding affinity of a local DNA segment depends on its elastic properties and determines its accessibility within the nucleus, which plays an important role in the regulation of gene expression. Here, we derive a fitness landscape for intergenic DNA segments in yeast as a function of two molecular phenotypes: their elasticity-dependent histone affinity and their coverage with transcription factor binding sites. This landscape reveals substantial selection against nucleosome formation over a wide range of both phenotypes. We use it as the core component of a quantitative evolutionary model for intergenic DNA segments. This model consistently predicts the observed diversity of histone affinities within wild Saccharomyces paradoxus populations, as well as the affinity divergence between neighboring Saccharomyces species. Our analysis establishes histone binding and transcription factor binding as two separable modes of sequence evolution, each of which is a direct target of natural selection.
authors.affiliation: Institute for Theoretical Physics, University of Cologne, 50937 Cologne, Germany.
authors.forename: Donate
authors.initials: D
authors.lastname: Weghorn
authors.forename: Michael
authors.initials: M
authors.lastname: Lässig
mesh_terms: D005075:Biological Evolution; D055592:Biophysical Phenomena; D004271:DNA, Fungal / Q000737:chemistry / Q000378:metabolism; D004548:Elasticity; D005656:Fungal Proteins / Q000737:chemistry / Q000378:metabolism; D006657:Histones / Q000737:chemistry / Q000378:metabolism; D009707:Nucleosomes / Q000737:chemistry / Q000378:metabolism*; D010641:Phenotype; D012440:Saccharomyces / Q000235:genetics / Q000378:metabolism; D014157:Transcription Factors / Q000378:metabolism
chemical_list: D004271:DNA, Fungal; D005656:Fungal Proteins; D006657:Histones; D009707:Nucleosomes; D014157:Transcription Factors
keywords: biophysics; evolution of regulation; inference of selection; nucleosome-depleted regions; quantitative traits