The Valley-of-Death: reciprocal sign epistasis constrains adaptive trajectories in a constant, nutrient limiting environment. Academic Article uri icon

start page

  • 431

end page

  • 437


  • 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.Copyright © 2014 Elsevier Inc. All rights reserved.

date/time value

  • December 2014

Digital Object Identifier (DOI)

  • 10.1016/j.ygeno.2014.10.011

PubMed Identifier

  • 25449178


  • 104


  • 6 Pt A


  • Adaptation, Biological
  • Adaptor Proteins, Signal Transducing
  • Culture Media
  • Directed Molecular Evolution
  • Epistasis, Genetic
  • Evolution, Molecular
  • Gene Dosage
  • Genetic Fitness
  • Glucose
  • Mutation
  • Saccharomyces cerevisiae
  • Saccharomyces cerevisiae Proteins
  • Selection, Genetic