The role of plasmids in bacterial adaptation

质粒酶在细菌进化中起着关键作用。特别是，它们可以携带抗生素抗性基因，使这些基因具有高度移动的，并允许它们跨越物种界限。虽然临床相关的耐药往往是质粒编码，大多数的理论模型集中在染色体耐药。为了缩小这一差距，我将开发数学模型来解决两个主要的开放性问题-多拷贝质粒的进化潜力（项目1和2）和大肠杆菌作为耐药基因库的作用，可以被病原体（项目3）。现有的模型，包括质粒传播的阻力通常是基于确定性微分方程，类似于流行病学模型（与质粒的寄生虫的作用）。相比之下，我们将主要使用随机方法，遵循进化拯救的群体遗传学模型的建模框架。分析的主要部分将基于分支过程理论。随机过程的解析近似将通过确定性微分方程的分析和随机计算机模拟来补充。在项目4中，我们将远离耐药性，探索质粒介导的接合对染色体适应的影响。目的是评估在多大程度上称接合为一种“细菌性别”是合理的，这个问题到目前为止在理论研究中只得到了很少的解决。为了这个目的，我们将建立类似于那些用来描述有性生殖过程中重组的群体遗传学模型，并比较结果。

Plasmids play a key role in bacterial evolution. In particular, they can carry antibiotic resistance genes, making these genes highly mobile and allowing them to cross species boundaries. Although clinically relevant resistance is often encoded on plasmids, the majority of theoretical models focuses on chromosomal resistance. In order to close this gap, I will develop mathematical models to address two major open questions - the evolutionary potential of multicopy plasmids (Projects 1 and 2) and the role of commensal bacteria as a reservoir of resistance genes that can be picked up by pathogens (Project 3). Existing models incorporating plasmid-borne resistance are usually based on deterministic differential equations, similar to epidemiological models (with the plasmid taking the role of the parasite). In contrast, we will mainly use stochastic approaches, following the modeling framework from population genetics models of evolutionary rescue. Major parts of the analysis will be based on branching process theory. Analytical approximations of the stochastic process will be complemented by the analysis of deterministic differential equations and by stochastic computer simulations.In Project 4, we will turn away from drug resistance and explore the effect of plasmidmediated conjugation on chromosomal adaptation. The goal is to assess up to which extent it is justified to call conjugation a form of "bacterial sex", a question that has only marginally been addressed in theoretical studies so far. To this purpose, we will set up population genetics models analogous to those used to describe recombination during sexual reproduction and compare the results.