A rugged yet easily navigable fitness landscape

• 成果类型: Article
• 署名作者: Papkou, Andrei; Garcia-Pastor, Lucia; Escudero, Jose Antonio; Wagner, Andreas
• 署名单位: University of Zurich; Complutense University of Madrid; Complutense University of Madrid; Swiss Institute of Bioinformatics; The Santa Fe Institute
• 刊物名称: SCIENCE
• ISSN/ISSBN: 0036-14067
• DOI: 10.1126/science.adh3860
• 发表日期: 2023-11-24
• 关键词: beneficial mutations; sign epistasis; key innovation; adaptation; EVOLUTION; selection; peaks; predictability; populations; contingency

摘要

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.