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)

Abstract

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
Volume6
Issue number4
Early online date3 Mar 2022
DOIs
Publication statusPublished - Apr 2022

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