title: The Valley-of-Death: reciprocal sign epistasis constrains adaptive trajectories in a constant, nutrient limiting environment.
abstract: The fitness landscape is a powerful metaphor for describing the relationship between genotype and phenotype for a population under selection. However, empirical data as to the topography of fitness landscapes are limited, owing to difficulties in measuring fitness for large numbers of genotypes under any condition. We previously reported a case of reciprocal sign epistasis (RSE), where two mutations individually increased yeast fitness in a glucose-limited environment, but reduced fitness when combined, suggesting the existence of two peaks on the fitness landscape. We sought to determine whether a ridge connected these peaks so that populations founded by one mutant could reach the peak created by the other, avoiding the low-fitness "Valley-of-Death" between them. Sequencing clones after 250 generations of further evolution provided no evidence for such a ridge, but did reveal many presumptive beneficial mutations, adding to a growing body of evidence that clonal interference pervades evolving microbial populations.
authors.affiliation: Division of Biological Sciences, University of Montana, Missoula, MT, USA.
authors.forename: Kami E
authors.initials: KE
authors.lastname: Chiotti
authors.affiliation: Department of Genetics, Stanford University, Stanford, CA 94305-5120, USA.
authors.forename: Daniel J
authors.initials: DJ
authors.lastname: Kvitek
authors.affiliation: Division of Biological Sciences, University of Montana, Missoula, MT, USA.
authors.forename: Karen H
authors.initials: KH
authors.lastname: Schmidt
authors.affiliation: Division of Biological Sciences, University of Montana, Missoula, MT, USA.
authors.forename: Gregory
authors.initials: G
authors.lastname: Koniges
authors.affiliation: Department of Genetics, Stanford University, Stanford, CA 94305-5120, USA.
authors.forename: Katja
authors.initials: K
authors.lastname: Schwartz
authors.affiliation: Department of Genetics, Stanford University, Stanford, CA 94305-5120, USA.
authors.forename: Elizabeth A
authors.initials: EA
authors.lastname: Donckels
authors.affiliation: Division of Biological Sciences, University of Montana, Missoula, MT, USA. Electronic address: Frank.Rosenzweig@mso.umt.edu.
authors.forename: Frank
authors.initials: F
authors.lastname: Rosenzweig
authors.affiliation: Department of Genetics, Stanford University, Stanford, CA 94305-5120, USA. Electronic address: gsherloc@stanford.edu.
authors.forename: Gavin
authors.initials: G
authors.lastname: Sherlock
mesh_terms: D000220:Adaptation, Biological; D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics* / Q000378:metabolism; D003470:Culture Media / Q000737:chemistry; D019020:Directed Molecular Evolution; D004843:Epistasis, Genetic; D019143:Evolution, Molecular; D018628:Gene Dosage; D056084:Genetic Fitness; D005947:Glucose / Q000737:chemistry / Q000378:metabolism; D009154:Mutation; D012441:Saccharomyces cerevisiae / Q000235:genetics* / Q000378:metabolism; D029701:Saccharomyces cerevisiae Proteins / Q000235:genetics* / Q000378:metabolism; D012641:Selection, Genetic
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D003470:Culture Media; C118806:MTH1 protein, S cerevisiae; D029701:Saccharomyces cerevisiae Proteins; D005947:Glucose
keywords: Epistasis; Evolution; Genomics; Yeast