The more, the merrier? : Population genetics theory for bacteria carrying multicopy replicons

Many bacteria carry multiple copies of a replicon per cell, such as plasmids or polyploid chromosomes. Multicopy plasmids play an important role in bacterial adaptation, e.g., in the evolution of antibiotic resistance. Predicting the evolution of bacteria carrying a multicopy replicon is non-trivial since the random distribution of replicon copies at cell division can lead to daughter cells that are genotypically different from their mother cell. Theoretical models that describe the allele dynamics on multicopy replicons are largely lacking. In this thesis, I present population genetic models for bacteria carrying multicopy replicons that are applied to study evolutionary processes important for bacterial adaptation, such as the establishment and fixation of alleles.

In the first chapter, we investigate the establishment process of beneficial mutations on multicopy plasmids using the theory of branching processes and examine the influence of the plasmid copy number on the establishment probability in an evolutionary rescue scenario. Our results reveal that the dominance of resistance mutations is a key parameter to determine if smaller or higher plasmid copy numbers maximize the probability of successful bacterial adaptation. The second chapter provides a mathematical model to study the fixation process of dominant beneficial alleles on multicopy replicons. In the third chapter, we present empirical results of the allele dynamics on a multicopy plasmid that initially carries a novel allele in single copies. We find good agreement between the experimental dynamics with simulations confirming our theory of allele dynamics on multicopy replicons. In the fourth chapter, we present our research activities beyond the scope of multicopy replicon dynamics. We introduce a mathematical model to study the interplay of collective resistance and the evolution of genetic resistance against bacteriophages, a potential alternative to  antibiotics.


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