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Peer-reviewedCC BY-NCScience Advances

Frequency-dependent fitness effects are ubiquitous in rapidly adapting microbial populations

  • Joao A. Ascensao1
  • Keon D. Abedi2
  • Aditya N. Prasad2
  • Oskar Hallatschek2,3,4
4 affiliations
  1. 1Department of Bioengineering, University of California, Berkeley, Berkeley, CA, USA.
  2. 2Department of Physics, University of California, Berkeley, Berkeley, CA, USA.
  3. 3Department of Integrative Biology, University of California, Berkeley, Berkeley, CA, USA.
  4. 4Peter Debye Institute for Soft Matter Physics, Leipzig University, Leipzig, Germany.
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Abstract

In simple microbial populations, the fitness effects of selected mutations are typically assumed to be constant, regardless of mutant frequency. This assumption underpins predictions about evolutionary dynamics, epistasis, and the maintenance of genetic diversity. Here, we systematically test this assumption using beneficial mutations from early generations of the Escherichia coli long-term evolution experiment (LTEE). Using flow cytometry-based competition assays, we find that frequency-dependent fitness effects are the norm rather than the exception, occurring in ∼80% of strain pairs tested. Most competitions exhibit negative frequency dependence, where fitness advantages decline as mutant frequency increases. We demonstrate that the strength of frequency dependence is predictable from invasion fitness measurements, which explain approximately half of the biological variation in frequency-dependent slopes. We also observe violations of fitness transitivity in several strain combinations, indicating that competitive outcomes cannot always be predicted from fitness measured against a single reference strain. High-resolution measurements reveal that frequency dependence changes substantially within the growth cycle, with the net per-cycle effect reflecting the balance of opposing dynamics at different growth phases. Our results demonstrate that, even in a model system designed to minimize ecological complexity, subtle interactions between closely related genotypes create frequency-dependent selection that can fundamentally alter evolutionary trajectories.

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Cite

BibTeXRIS
BibTeX
@article{ascensao2026frequencydependent,
  title = {{Frequency-dependent fitness effects are ubiquitous in rapidly adapting microbial populations}},
  author = {Joao A. Ascensao and Keon D. Abedi and Aditya N. Prasad and Oskar Hallatschek},
  journal = {Science Advances},
  year = {2026},
  month = oct,
  doi = {10.1126/sciadv.aeh3295},
  url = {https://www.science.org/doi/10.1126/sciadv.aeh3295},
  note = {CC BY-NC},
}
RIS
TY  - JOUR
TI  - Frequency-dependent fitness effects are ubiquitous in rapidly adapting microbial populations
AU  - Joao A. Ascensao
AU  - Keon D. Abedi
AU  - Aditya N. Prasad
AU  - Oskar Hallatschek
PY  - 2026
DA  - 2026/10/23
JO  - Science Advances
DO  - 10.1126/sciadv.aeh3295
UR  - https://www.science.org/doi/10.1126/sciadv.aeh3295
AB  - In simple microbial populations, the fitness effects of selected mutations are typically assumed to be constant, regardless of mutant frequency. This assumption underpins predictions about evolutionary dynamics, epistasis, and the maintenance of genetic diversity. Here, we systematically test this assumption using beneficial mutations from early generations of the Escherichia coli long-term evolution experiment (LTEE). Using flow cytometry-based competition assays, we find that frequency-dependent fitness effects are the norm rather than the exception, occurring in ∼80% of strain pairs tested. Most competitions exhibit negative frequency dependence, where fitness advantages decline as mutant frequency increases. We demonstrate that the strength of frequency dependence is predictable from invasion fitness measurements, which explain approximately half of the biological variation in frequency-dependent slopes. We also observe violations of fitness transitivity in several strain combinations, indicating that competitive outcomes cannot always be predicted from fitness measured against a single reference strain. High-resolution measurements reveal that frequency dependence changes substantially within the growth cycle, with the net per-cycle effect reflecting the balance of opposing dynamics at different growth phases. Our results demonstrate that, even in a model system designed to minimize ecological complexity, subtle interactions between closely related genotypes create frequency-dependent selection that can fundamentally alter evolutionary trajectories.
SN  - 2375-2548
ER  -