Raw data corresponding to Fig 3.

Integrons are adaptive devices that capture, stockpile, shuffle and express gene cassettes thereby sampling combinatorial phenotypic diversity. Some integrons called sedentary chromosomal integrons (SCIs) can be massive structures containing hundreds of cassettes. Since most of these cassettes are non-expressed, it is not clear how they remain stable over long evolutionary timescales. Recently, it was found that the experimental inversion of the SCI of Vibrio cholerae led to a dramatic increase of the cassette excision rate associated with a fitness defect. Here, we question the evolutionary sustainability of this apparently counter selected genetic context. Through experimental evolution, we find that the integrase is rapidly inactivated and that the inverted SCI can recover its original orientation by homologous recombination between two insertion sequences (ISs) present in the array. These two outcomes of SCI inversion restore the normal growth and prevent the loss of cassettes, enabling SCIs to retain their roles as reservoirs of functions. These results illustrate a nice interplay between gene orientation, genome rearrangement, bacterial fitness and demonstrate how integrons can benefit from their embedded ISs.

整合子（Integrons）是一类能够捕获、储存、重排并表达基因盒（gene cassettes）的适应性元件，借此实现组合表型多样性的遴选。部分被称为静止型染色体整合子（sedentary chromosomal integrons, SCIs）的整合子可形成包含数百个基因盒的庞大结构。由于这类基因盒中的大多数均不表达，目前尚不清楚它们如何在漫长的进化时间尺度上保持稳定。近期有研究发现，对霍乱弧菌（Vibrio cholerae）的静止型染色体整合子进行实验性倒位后，其基因盒的切除率会显著升高，并伴随适合度缺陷。本研究针对这一显然处于负选择压力下的遗传背景的进化可持续性提出质疑。通过实验进化实验，我们发现整合酶（integrase）会快速失活，且倒位后的静止型染色体整合子可通过该基因盒阵列中两段插入序列（insertion sequences, ISs）之间的同源重组恢复其原始方向。上述静止型染色体整合子倒位的两种结局均可恢复正常生长状态，并阻止基因盒的丢失，从而使静止型染色体整合子能够维持其作为功能储备库的角色。本研究结果清晰展现了基因方向、基因组重排与细菌适合度之间的精妙互作关系，并阐释了整合子如何借助其内嵌的插入序列获益。