Plasmid stability in fluctuating environments: population genetics of
multi-copy plasmids
Abstract
Plasmids are extra-chromosomal genetic elements that encode a wide
variety of phenotypes and can be maintained in bacterial populations
through vertical and horizontal transmission, thus increasing bacterial
adaptation to hostile environmental conditions like those imposed by
antimicrobial substances. To circumvent the segregational instability
resulting from randomly distributing plasmids between daughter cells
upon division, non-transmissible plasmids tend to be carried in multiple
copies per cell, which also results in a metabolic burden to the
bacterial host, therefore reducing the overall fitness. This trade-off
poses an existential question for plasmids: What is the optimal plasmid
copy number? We address this question using a combination of population
genetics modeling with microbiology experiments consisting of
Escherichia coli K12 bearing a multi-copy plasmid encoding for blaTEM-1,
a gene conferring resistance to b-lactam antibiotics. We use a
Wright-Fisher model to evaluate the interaction between the above
mentioned opposing forces. By numerically determining the optimal
plasmid copy number for constant and fluctuating selection regimes, we
conclude that plasmid copy number is an optimized evolutionary trait
that depends on the rate of environmental fluctuation and balances the
benefit between increased stability in the absence of selection with the
burden associated with carrying multiple copies of the plasmid.