Understanding the mechanisms governing innovation is a central element of evolutionary theory. Novel traits usually arise through mutations in existing genes, but trade-offs between new and ancestral protein functions are pervasive and constrain the evolution of innovation. Classical models posit that evolutionary innovation circumvents the constraints imposed by trade-offs through genetic amplifications, which provide functional redundancy. Bacterial multicopy plasmids provide a paradigmatic example of genetic amplification, yet their role in evolutionary innovation remains largely unexplored. Here, we reconstructed the evolution of a new trait encoded in a multicopy plasmid using TEM-1 β-lactamase as a model system. Through a combination of theory and experimentation, we show that multicopy plasmids promote the coexistence of ancestral and novel traits for dozens of generations, allowing bacteria to escape the evolutionary constraints imposed by trade-offs. Our results suggest that multicopy plasmids are excellent platforms for evolutionary innovation, contributing to explain their extreme abundance in bacteria.
With plasmid-mediated antibiotic resistance thriving and threatening to become a serious public health problem, it is paramount to increase our understanding of the forces that enable the spread and maintenance of drug resistance genes encoded in mobile genetic elements. The relevance of plasmids as vehicles for the dissemination of antibiotic resistance genes, in addition to the extensive use of plasmid-derived vectors for biotechnological and industrial purposes, has promoted the in-depth study of the molecular mechanisms controlling multiple aspects of a plasmids’ life cycle. This body of experimental work has been paralleled by the development of a wealth of mathematical models aimed at understanding the interplay between transmission, replication, and segregation, as well as their consequences in the ecological and evolutionary dynamics of plasmid-bearing bacterial populations. In this review, we discuss theoretical models of plasmid dynamics that span from the molecular mechanisms of plasmid partition and copy-number control occurring at a cellular level, to their consequences in the population dynamics of complex microbial communities. We conclude by discussing future directions for this exciting research topic.
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, nontransmissible plasmids tend to be carried in multiple copies per cell, with the added benefit of exhibiting increased gene dosage and resistance levels. But carrying multiple copies also results in a high metabolic burden to the bacterial host, therefore reducing the overall fitness of the population. This trade‐off poses an existential question for plasmids: What is the optimal plasmid copy number? In this manuscript, we address this question by postulating and analyzing a population genetics model to evaluate the interaction between selective pressure, the number of plasmid copies carried by each cell, and the metabolic burden associated with plasmid bearing in the absence of selection for plasmid‐encoded traits. Parameter values of the model were estimated experimentally using Escherichia coli K12 carrying a multicopy plasmid encoding for a fluorescent protein and bla TEM‐1 , a gene conferring resistance to β ‐lactam antibiotics. By numerically determining the optimal plasmid copy number for constant and fluctuating selection regimes, we show that plasmid copy number is a highly 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.
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