Intracellular competition shapes plasmid population dynamics

Conflicts between levels of biological organization are central to evolution, from populations of multicellular organisms to selfish genetic elements. Plasmids—extrachromosomal, self-replicating genetic elements that face selective pressures on their hosts, but also compete within the cell for replication—are an ideal system for studying multilevel selection. While theory indicates that within-cell selection matters for plasmid evolution, experimental measurement of these dynamics has remained elusive. Here we measure the within-cell fitness of competing plasmids and characterize drift and selective dynamics. We achieve this by the controlled splitting of synthetic plasmid dimers, creating balanced competition experiments. We find that incompatible plasmids co-occur for longer than expected due to methylation-based plasmid eclipsing. Moreover, low-transcription plasmids display a within-cell advantage over their competition and fix preferentially. Critically, fixation depends non-trivially on gene dominance. Taken together, our results show that plasmid evolution is driven by dynamics at two levels, with a transient—but critical—contribution of within-cell fitness.

生物组织层级间的冲突是进化研究的核心议题，从多细胞生物种群直至自私遗传因子（selfish genetic elements）皆是如此。质粒（plasmids）——即染色体外、可自我复制的遗传因子，其宿主面临选择压力，同时又在细胞内竞争复制资源——是研究多级选择（multilevel selection）的理想模型系统。尽管理论研究表明细胞内选择对质粒进化具有重要意义，但对这些动态过程的实验测量长期以来一直难以实现。本研究通过可控拆分合成质粒二聚体（synthetic plasmid dimers）构建平衡竞争实验体系，实现了对竞争性质粒的细胞内适合度（within-cell fitness）的定量测量，并对遗传漂变（drift）与选择动态进行了系统表征。研究发现，不相容性质粒（incompatible plasmids）的共存时长超出预期，这源于基于甲基化的质粒遮蔽（methylation-based plasmid eclipsing）效应。此外，低转录质粒（low-transcription plasmids）相较于其竞争对象展现出细胞内优势，并会优先实现种群固定。尤为关键的是，种群固定过程与基因显性（gene dominance）之间的关联并非简单直观。综上，本研究结果表明，质粒进化由两个层级的动态过程共同驱动，其中细胞内适合度的贡献虽短暂却至关重要。