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

TY - JOUR

T1 - Population size mediates the contribution of high-rate and large-benefit mutations to parallel evolution

AU - Schenk, Martijn F.

AU - Zwart, Mark

AU - Hwang, Sungmin

AU - Ruelens, Philip

AU - Severing, Edouard

AU - Krug, Joachim

AU - de Visser, J. Arjan G. M.

PY - 2022

Y1 - 2022

N2 - 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.

AB - 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.

U2 - 10.1038/s41559-022-01669-3

DO - 10.1038/s41559-022-01669-3

M3 - Article

SN - 2397-334X

VL - 6

SP - 439

EP - 447

JO - Nature Ecology and Evolution

JF - Nature Ecology and Evolution

IS - 4

ER -