Competition for nutritional resources masks the true frequency of bacterial mutants

Henrique Iglesias Neves, Gabriella Trombini Machado, Taíssa Cristina dos Santos Ramos, Hyun Mo Yang, Ezra Yagil, Beny Spira*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review


Background: It is widely assumed that all mutant microorganisms present in a culture are able to grow and form colonies, provided that they express the features required for selection. Unlike wild-type Escherichia coli, PHO-constitutive mutants overexpress alkaline phosphatase and hence can hydrolyze glycerol-2-phosphate (G2P) to glycerol and form colonies on plates having G2P as the sole carbon source. These mutations mostly occur in the pst operon. However, the frequency of PHO-constitutive colonies on the G2P selective plate is exceptionally low. Results: We show that the rate in which spontaneous PHO-constitutive mutations emerge is about 8.0 × 10−6/generation, a relatively high rate, but the growth of most existing mutants is inhibited by their neighboring wild-type cells. This inhibition is elicited only by non-mutant viable bacteria that can take up and metabolize glycerol formed by the mutants. Evidence indicates that the few mutants that do form colonies derive from microclusters of mutants on the selective plate. A mathematical model that describes the fate of the wild-type and mutant populations under these circumstances supports these results. Conclusion: This scenario in which neither the wild-type nor the majority of the mutants are able to grow resembles an unavoidable “tragedy of the commons” case which results in the collapse of the majority of the population. Cooperation between rare adjacent mutants enables them to overcome the competition and eventually form mutant colonies. The inhibition of PHO-constitutive mutants provides an example of mutant frequency masked by orders of magnitude due to a competition between mutants and their ancestral wild-type cells. Similar “tragedy of the commons-like” cases may occur in other settings and should be taken into consideration while estimating true mutant frequencies and mutation rates.

Original languageEnglish
Article number194
JournalBMC Biology
Issue number1
StatePublished - Dec 2020


FundersFunder number
Fundação de Amparo à Pesquisa do Estado de São Paulo
Coordenação de Aperfeiçoamento de Pessoal de Nível Superior
Conselho Nacional de Desenvolvimento Científico e Tecnológico
Centros de Pesquisa, Inovação e Difusão, Fundação Amazônia Paraense de Amparo à Pesquisa2018/16219-5


    • Glycerol-2-phosphate
    • Mutagenesis
    • Mutant frequency
    • Mutation rate
    • PHO regulon
    • Tragedy of the commons
    • pst operon


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