A rugged yet easily navigable fitness landscape

Science. 2023 Nov 24;382(6673):eadh3860. doi: 10.1126/science.adh3860. Epub 2023 Nov 24.

Abstract

Fitness landscape theory predicts that rugged landscapes with multiple peaks impair Darwinian evolution, but experimental evidence is limited. In this study, we used genome editing to map the fitness of >260,000 genotypes of the key metabolic enzyme dihydrofolate reductase in the presence of the antibiotic trimethoprim, which targets this enzyme. The resulting landscape is highly rugged and harbors 514 fitness peaks. However, its highest peaks are accessible to evolving populations via abundant fitness-increasing paths. Different peaks share large basins of attraction that render the outcome of adaptive evolution highly contingent on chance events. Our work shows that ruggedness need not be an obstacle to Darwinian evolution but can reduce its predictability. If true in general, the complexity of optimization problems on realistic landscapes may require reappraisal.

MeSH terms

  • CRISPR-Cas Systems
  • Computer Simulation
  • Escherichia coli Proteins* / chemistry
  • Escherichia coli Proteins* / genetics
  • Gene Editing
  • Genetic Fitness*
  • Models, Genetic
  • Mutation
  • Selection, Genetic
  • Tetrahydrofolate Dehydrogenase* / chemistry
  • Tetrahydrofolate Dehydrogenase* / genetics

Substances

  • Tetrahydrofolate Dehydrogenase
  • Escherichia coli Proteins