Population size mediates the contribution of high-rate and large-benefit mutations to parallel evolution

Martijn F. Schenk, Mark P. Zwart*, Sungmin Hwang, Philip Ruelens, Edouard Severing, Joachim Krug, J.A.G.M. de Visser*

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

5 Citations (Scopus)


Mutations with large fitness benefits and mutations occurring at high rates may both cause parallel evolution, but their contribution is predicted to depend on population size. Moreover, high-rate and large-benefit mutations may have different long-term adaptive consequences. We show that small and 100-fold larger bacterial populations evolve resistance to a β-lactam antibiotic by using similar numbers, but different types of mutations. Small populations frequently substitute similar high-rate structural variants and loss-of-function point mutations, including the deletion of a low-activity β-lactamase, and evolve modest resistance levels. Large populations more often use low-rate, large-benefit point mutations affecting the same targets, including mutations activating the β-lactamase and other gain-of-function mutations, leading to much higher resistance levels. Our results demonstrate the separation by clonal interference of mutation classes with divergent adaptive consequences, causing a shift from high-rate to large-benefit mutations with increases in population size.

Original languageEnglish
Pages (from-to)439-447
JournalNature Ecology and Evolution
Issue number4
Early online date3 Mar 2022
Publication statusPublished - Apr 2022


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