Papkou, AndreiGarcía Pastor, LucíaEscudero García-Calderón, José AntonioWagner, Andreas2024-01-242024-01-242023Andrei Papkou et al. ,A rugged yet easily navigable fitness landscape.Science382,eadh3860(2023).DOI:10.1126/science.adh38600036-807510.1126/science.adh3860https://hdl.handle.net/20.500.14352/95057Author contributions: A.P. and A.W. conceived the study and designed the experiments. A.P., L.G.-P. and J.A.E. carried out the experiments. A.P. and A.W. analyzed data. A.P. wrote computer code to carry out bioinformatic work, simulations, and analysis. A.W. and A.P. wrote the paper, which was edited by all authors.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.engAttribution-NonCommercial-NoDerivatives 4.0 Internationalhttp://creativecommons.org/licenses/by-nc-nd/4.0/journal article1095-9203https://doi.org/10.1126/science.adh3860restricted access636.09Veterinaria24 Ciencias de la Vida