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Phages use contingency loci as a bet-hedging strategy
Jasper B Gomez1, Jeffrey E Barrick2, Christopher M Waters1
1Department of Microbiology, Genetics, & Immunology, Michigan State University, East Lansing, Michigan, USA.
Biorxiv : the Preprint Server for Biology
|November 24, 2025
Summary
Bacteriophages possess contingency loci (CL), hypermutable DNA regions enabling rapid evolution. These genetic elements drive diversification and population heterogeneity, enhancing phage adaptation and survival against host defenses.
Area of Science:
- Microbiology
- Genetics
- Evolutionary Biology
Background:
- Bacteriophages are viruses that infect bacteria and are abundant in most environments.
- Contingency loci (CL) are known mutable DNA regions in bacteria, archaea, and eukaryotes, facilitating adaptation.
- CL have not been previously identified or characterized in bacteriophages.
Purpose of the Study:
- To investigate the presence and function of contingency loci (CL) in bacteriophage genomes.
- To determine if CL contribute to genomic and phenotypic diversity in phage progeny.
- To explore the evolutionary implications of CL in bacteriophage populations.
Main Methods:
- Whole genome sequencing of coliphages T2 and T4.
- Bioinformatic analysis of multiple phage genomes including T6, T7, Secφ27, ICP1, and ICP2.
- Examination of the BASEL phage collection for the presence of putative CL.
Main Results:
- Contingency loci (CL) were identified in coliphage T2 and T4 genomes, promoting reversible frameshift mutations.
- CL were found to generate genomic and phenotypic diversity in phage progeny, supporting bet-hedging strategies.
- Putative CL are widespread across diverse bacteriophages and are present in genes across all functional classes.
Conclusions:
- Bacteriophages harbor contingency loci (CL) that drive genetic diversification and population heterogeneity.
- CL represent a significant mechanism for rapid evolution and adaptation in bacteriophages.
- The discovery of CL in phages introduces a new paradigm for understanding phage replication and evolution.
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