PT - JOURNAL ARTICLE AU - Alpay, Berk A. AU - Desai, Michael M. TI - Effects of selection stringency on the outcomes of directed evolution AID - 10.1101/2024.06.09.598029 DP - 2024 Jan 01 TA - bioRxiv PG - 2024.06.09.598029 4099 - http://biorxiv.org/content/early/2024/06/09/2024.06.09.598029.short 4100 - http://biorxiv.org/content/early/2024/06/09/2024.06.09.598029.full AB - Directed evolution makes mutant lineages compete in climbing complicated sequence-function landscapes. Given this underlying complexity it is unclear how selection stringency, a ubiquitous parameter of directed evolution, impacts the outcome. Here we approach this question in terms of the fitnesses of the candidate variants at each round and the heterogeneity of their distributions of fitness effects. We show that even if the fittest mutant is most likely to yield the fittest mutants in the next round of selection, diversification can improve outcomes by sampling a larger variety of fitness effects. We find that heterogeneity in fitness effects between variants, larger population sizes, and evolution over a greater number of rounds all encourage diversification.Competing Interest StatementThe authors have declared no competing interest.