title: Experimental illumination of a fitness landscape.
abstract: The genes of all organisms have been shaped by selective pressures. The relationship between gene sequence and fitness has tremendous implications for understanding both evolutionary processes and functional constraints on the encoded proteins. Here, we have exploited deep sequencing technology to experimentally determine the fitness of all possible individual point mutants under controlled conditions for a nine-amino acid region of Hsp90. Over the past five decades, limited glimpses into the relationship between gene sequence and function have sparked a long debate regarding the distribution, relative proportion, and evolutionary significance of deleterious, neutral, and advantageous mutations. Our systematic experimental measurement of fitness effects of Hsp90 mutants in yeast, evaluated in the light of existing population genetic theory, are remarkably consistent with a nearly neutral model of molecular evolution.
authors.affiliation: Department of Biochemistry and Molecular Pharmacology, University of Massachusetts Medical School, Worcester, MA 01605, USA.
authors.forename: Ryan T
authors.initials: RT
authors.lastname: Hietpas
authors.forename: Jeffrey D
authors.initials: JD
authors.lastname: Jensen
authors.forename: Daniel N A
authors.initials: DN
authors.lastname: Bolon
mesh_terms: D019943:Amino Acid Substitution; D003062:Codon / Q000235:genetics; D003198:Computer Simulation; D004271:DNA, Fungal / Q000235:genetics; D019143:Evolution, Molecular; D005800:Genes, Fungal; D018841:HSP90 Heat-Shock Proteins / Q000737:chemistry / Q000235:genetics; D008957:Models, Genetic; D008958:Models, Molecular; D010802:Phylogeny; D017354:Point Mutation; D012441:Saccharomyces cerevisiae / Q000235:genetics; D029701:Saccharomyces cerevisiae Proteins / Q000737:chemistry / Q000235:genetics; D012641:Selection, Genetic
chemical_list: D003062:Codon; D004271:DNA, Fungal; C074510:HSP82 protein, S cerevisiae; D018841:HSP90 Heat-Shock Proteins; D029701:Saccharomyces cerevisiae Proteins