Abstract

Plasmids are extrachromosomal DNA elements of microorganisms encoding beneficial genetic information. They were thought to be equally distributed to daughter cells during cell division. Here we use mathematical modeling to investigate the evolutionary stability of plasmid segregation for high-copy plasmids—plasmids that are present in up to several hundred copies per cell—carrying antibiotic resistance genes. Evolutionary stable strategies (ESS) are determined by numerical analysis of a plasmid-load structured population model. The theory predicts that the evolutionary stable segregation strategy of a cell depends on the plasmid copy number: For low and medium plasmid load, both daughters receive in average an equal share of plasmids, while in case of high plasmid load, one daughter obtains distinctively and systematically more plasmids. These findings are in good agreement with recent experimental results. We discuss the interpretation and practical consequences.

Highlights

  • Plasmids are circular or linear pieces of DNA of different size encoding beneficial genetic information for their microbial hosts replicated independently from the chromosome(s) [4]

  • It becomes more and more clear that heterogeneity in isogenic bacterial populations is rather the rule than the exception. This observation is interesting as it reveals the complex social life of bacteria, and because of tremendous practical implications in medicine, biotechnology, and ecology

  • The central questions in this field are the identification of the underlying proximate causes on the one hand and on the other hand the identification of ultimate causes that shape the social life of bacteria

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Summary

Introduction

Plasmids are circular or linear pieces of DNA of different size (several 1000 to 100,000 bp) encoding beneficial genetic information for their microbial hosts replicated independently from the chromosome(s) [4]. In contrast to lowcopy plasmids that often incorporate a distinct active mechanism of segregation ensuring that during cell division each daughter inherits at least one copy [9,10,11], high-copy plasmids are mainly segregated by random diffusion [12,13,14]. A few years ago equal distribution of plasmids between daughter cells during cell division was assumed. We know that at least some high-copy plasmids are distributed unequally between their production hosts [15]. Unequal plasmid segregation may lead to the commercially important factor of cost-intensive feeding of non-productive microbial cells. Experimental and theoretical approaches are required to elucidate the underlying evolutionary and molecular mechanisms as a foundation for their directed improvement

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