Work

Effects of selection stringency on the outcomes of directed evolution

Year: 2024

Type: article

Abstract: 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.

Source: PLoS ONE

DOI: 10.1371/journal.pone.0311438

Authors: Berk A. Alpay, Michael M. Desai

Institution: Harvard University

Language: English

Topic: Evolution and Genetic Dynamics

Subfield: Genetics

Field: Biochemistry, Genetics and Molecular Biology

Domain: Life Sciences

Open Access status: gold

Estimated APC paid: $2,290

Funders: National Science Foundation, National Institutes of Health, National Institute of General Medical Sciences, National Science Foundation Graduate Research Fellowship Program