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Updated: Jun 20, 2026

Phage-Mediated Genetic Manipulation of the Lyme Disease Spirochete Borrelia burgdorferi
Published on: September 28, 2022
Genic incompatibilities in two hybrid bacteriophages
Darin R Rokyta1, Holly A Wichman
1Department of Biological Science, Florida State University, USA. drokyta@bio.fsu.edu
Recombinant phages with exchanged coat protein genes initially lost fitness but rapidly recovered through compensatory evolution. This rapid recovery, involving multiple gene substitutions, highlights the genome-wide impact of epistatic interactions in evolution.
Area of Science:
- Evolutionary Biology
- Microbial Genetics
Background:
- Horizontal gene transfer and recombination are key drivers of microbial evolution.
- Epistatic interactions (gene-gene interactions) influence the fitness of recombinant genotypes.
Purpose of the Study:
- To investigate the role of epistatic interactions in the evolutionary viability of homologous recombination.
- To assess the impact of exchanging coat protein genes on phage fitness and subsequent recovery.
Main Methods:
- Constructed recombinant microvirid bacteriophages by interchanging coat protein genes between diverged ancestral phages.
- Subjected replicate lines of recombinant phages to selection to observe fitness recovery.
- Analyzed genetic substitutions and their contribution to fitness restoration.
Main Results:
- Recombinant phages exhibited drastically reduced fitness.
- All lineages recovered ancestral fitness levels within 60 generations through compensatory evolution.
- Three to five genetic substitutions were required for fitness recovery, involving eight of nine essential phage genes.
- Proteins with strong physical interactions with the exchanged coat protein showed limited involvement in recovery.
Conclusions:
- Epistatic interactions throughout the genome are crucial for mitigating fitness costs of recombination.
- Rapid fitness recovery suggests that weaker, transient epistatic interactions are more significant than strong, conserved ones in driving compensatory evolution.
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