期刊
GENOME BIOLOGY AND EVOLUTION
卷 11, 期 10, 页码 3022-3034出版社
OXFORD UNIV PRESS
DOI: 10.1093/gbe/evz197
关键词
adaptation; experimental evolution; duplex sequencing; plasmids
资金
- Eberly College of Science at the Pennsylvania State University
- NIH [U41 HG006620, R01 AI134384-01, R35 GM128590]
- NSF ABI grant [1661497]
- Alfred P. Sloan Foundation
Coadaptation between bacterial hosts and plasmids frequently results in adaptive changes restricted exclusively to host genome leaving plasmids unchanged. To better understand this remarkable stability, we transformed naive Escherichia coil cells with a plasmid carrying an antibiotic-resistance gene and forced them to adapt in a turbidostat environment. We then drew population samples at regular intervals and subjected them to duplex sequencing a technique specifically designed for identification of lowfrequency mutations. Variants at ten sites implicated in plasmid copy number control emerged almost immediately, tracked consistently across the experiment's time points, and faded below detectable frequencies toward the end. This variation crash coincided with the emergence of mutations on the host chromosome. Mathematical modeling of trajectories for adaptive changes affecting plasmid copy number showed that such mutations cannot readily fix or even reach appreciable frequencies. We conclude that there is a strong selection against alterations of copy number even if it can provide a degree of growth advantage. This incentive is likely rooted in the complex interplay between mutated and wild-type plasmids constrained within a single cell and underscores the importance of understanding of intracellular plasmid variability.
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