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Updated: Jul 13, 2026

Identifying DNA Mutations in Purified Hematopoietic Stem/Progenitor Cells
Published on: February 24, 2014
Amplification of mutator cells in a population as a result of horizontal transfer
P Funchain1, A Yeung, J Stewart
1Department of Microbiology and Molecular Genetics, University of California, Los Angeles, California 90095, USA.
Abstract:
Mutator cells that lack the mismatch repair system (MMR(-)) occur at rates of 10(-5) or less in laboratory populations started from wild-type cells. We show that after selection for recombinants in an interspecies mating between Salmonella enterica serovar Typhimurium and Escherichia coli, the percentage of MMR(-) cells rises to several percent of the recombinant population, and after a second successive mating and selection, greater than 95% of the recombinants are MMR(-). Coupling a single cross and selection with either mutagenesis or selection for spontaneous mutants also results in a dramatic increase in MMR(-) cells. We discuss how horizontal transfer can result in mutator strains during adaptive evolution.
Insights
Mutator cells lacking mismatch repair (MMR(-)) dramatically increase after interspecies mating and selection. This suggests horizontal gene transfer can drive the evolution of mutator strains during adaptation.
Area of Science:
- Microbiology
- Evolutionary Biology
- Genetics
Background:
- Mutator cells, deficient in the mismatch repair system (MMR(-)), are rare in wild-type populations.
- Understanding the evolutionary dynamics of mutator cells is crucial for comprehending adaptation and genome stability.
Purpose of the Study:
- To investigate the frequency and evolution of mismatch repair deficient (MMR(-)) cells under specific selective conditions.
- To explore the role of horizontal gene transfer in the proliferation of mutator strains.
Main Methods:
- Interspecies bacterial mating (Salmonella enterica serovar Typhimurium and Escherichia coli) followed by selection for recombinants.
- Serial mating and selection experiments.
- Coupling of bacterial crosses with mutagenesis or selection for spontaneous mutants.
Main Results:
- The percentage of MMR(-) cells increased significantly (to several percent) after a single interspecies mating and selection.
- Following a second successive mating and selection, MMR(-) cells constituted over 95% of the recombinant population.
- Combining bacterial crosses with mutagenesis or mutant selection also led to a substantial rise in MMR(-) cells.
Conclusions:
- Interspecies horizontal gene transfer, coupled with selection, strongly favors the proliferation of mismatch repair deficient (MMR(-)) cells.
- These findings indicate that horizontal gene transfer can be a significant mechanism driving the emergence and dominance of mutator strains during adaptive evolution.
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