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Updated: Jan 23, 2026

Measuring Microbial Mutation Rates with the Fluctuation Assay
Published on: November 28, 2019
Disentangling strictly self-serving mutations from win-win mutations in a mutualistic microbial community
Samuel Frederick Mock Hart1, Jose Mario Bello Pineda1, Chi-Chun Chen1
1Division of Basic Sciences, Fred Hutchinson Cancer Research Center, Seattle, United States.
Abstract:
Mutualisms can be promoted by pleiotropic win-win mutations which directly benefit self (self-serving) and partner (partner-serving). Intuitively, partner-serving phenotype could be quantified as an individual's benefit supply rate to partners. Here, we demonstrate the inadequacy of this thinking, and propose an alternative. Specifically, we evolved well-mixed mutualistic communities where two engineered yeast strains exchanged essential metabolites lysine and hypoxanthine. Among cells that consumed lysine and released hypoxanthine, a chromosome duplication mutation seemed win-win: it improved cell's affinity for lysine (self-serving), and increased hypoxanthine release rate per cell (partner-serving). However, increased release rate was due to increased cell size accompanied by increased lysine utilization per birth. Consequently, total hypoxanthine release rate per lysine utilization (defined as 'exchange ratio') remained unchanged. Indeed, this mutation did not increase the steady state growth rate of partner, and is thus solely self-serving during long-term growth. By extension, reduced benefit production rate by an individual may not imply cheating.
Insights
Win-win mutations in mutualisms may not benefit partners. A yeast study showed a mutation improving self-benefit also increased resource use, leaving partner benefit unchanged. This redefines how we assess cooperation.
Area of Science:
- Evolutionary biology
- Microbial ecology
- Systems biology
Background:
- Mutualisms, symbiotic relationships benefiting all partners, can be enhanced by pleiotropic mutations.
- These mutations offer direct benefits to the individual (self-serving) and its partner (partner-serving).
- Partner-serving benefits are often quantified by an individual's benefit supply rate to partners.
Purpose of the Study:
- To challenge the conventional quantification of partner-serving phenotypes in mutualisms.
- To propose and test an alternative metric for evaluating mutualistic interactions under genetic variation.
- To investigate the long-term effects of seemingly beneficial mutations on cooperative dynamics.
Main Methods:
- Evolving well-mixed mutualistic communities of two engineered yeast strains.
- Utilizing yeast strains engineered to exchange essential metabolites: lysine and hypoxanthine.
- Analyzing a specific chromosome duplication mutation affecting lysine affinity and hypoxanthine release.
Main Results:
- A chromosome duplication mutation improved yeast's lysine affinity (self-serving benefit).
- The mutation increased hypoxanthine release rate per cell, but also increased cell size and lysine utilization per birth.
- The exchange ratio (total hypoxanthine release per lysine utilization) remained unchanged, indicating no net benefit to the partner.
- The mutation did not increase the partner's steady-state growth rate, classifying it as solely self-serving in the long term.
Conclusions:
- The direct measure of benefit supply rate is insufficient for quantifying partner-serving phenotypes in mutualisms.
- An individual's increased benefit production rate does not automatically imply a net benefit to the partner.
- Reduced benefit production rate by an individual does not necessarily equate to cheating within a mutualistic system.
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