Data from: Plasmid and clonal interference during post-horizontal gene transfer evolution

Plasmids are nucleic acid molecules that can drive their own replication in a living cell. They can be transmitted horizontally and can thrive in the host cell to high copy numbers. Plasmid replication and gene expression consume cellular resources and cells carrying plasmids incur fitness costs. But many plasmids carry genes that can be beneficial under certain conditions, allowing the cell to endure in the presence of antibiotics, toxins, competitors or parasites. Horizontal transfer of plasmid-encoded genes can thus instantaneously confer differential adaptation to local or transient selection conditions. This conflict between cellular fitness and plasmid spread sets the scene for multilevel selection processes. We have engineered a system to study the short term evolutionary impact of different synonymous versions of a plasmid-encoded antibiotic resistance gene. Applying experimental evolution under different selection conditions and deep sequencing allowed us to show rapid local adaptation to the presence of antibiotic and to the specific version of the resistance gene transferred. We describe the presence of clonal interference at two different levels: at the within-cell level, because a single cell can carry several plasmids, and at the between-cell level, because a bacterial population may contain several clones carrying different plasmids and displaying different fitness in the presence|absence of antibiotic. Understanding the within-cell and between-cell dynamics of plasmids after horizontal gene transfer is essential to unravel the dense network of mobile elements underlying the worldwide threat to public health of antibiotic resistance.

质粒（plasmid）是一类可在活细胞内自主驱动自身复制的核酸分子。其可通过水平基因转移（horizontal gene transfer）途径传播，并能在宿主细胞内增殖至较高拷贝数。质粒的复制与基因表达会消耗细胞固有资源，携带质粒的宿主细胞将付出相应的适合度代价。但诸多质粒携带的基因可在特定条件下发挥有益功能，使宿主细胞能够耐受抗生素、毒素、竞争者或寄生物的胁迫。因此，质粒编码基因的水平转移可快速赋予宿主细胞针对局部或瞬时选择压力的差异化适应性。宿主细胞适合度与质粒扩散之间的这种冲突，为多水平选择过程搭建了典型研究场景。
我们构建了一套实验系统，用于研究质粒编码的抗生素抗性基因的不同同义变体所产生的短期进化效应。通过在不同选择条件下开展实验进化实验，并结合深度测序（deep sequencing）技术，我们证实宿主细胞可快速适应当地的抗生素环境，以及所转移的抗性基因的特定同义变体。我们观察到克隆干扰（clonal interference）现象存在于两个不同层面：在细胞内层面，单个细胞可携带多个质粒；在细胞间层面，细菌种群中可能存在多个携带不同质粒的克隆，且在有/无抗生素的环境中展现出不同的适合度。
解析水平基因转移后质粒的细胞内与细胞间动态，对于阐明抗生素耐药性这一全球公共卫生威胁背后的移动遗传元件复杂网络至关重要。