Nested DNA inversion as a paradigm of programmed gene rearrangement

Programmed gene rearrangements are employed by a variety of microorganisms, including viruses, prokaryotes, and simple eukaryotes, to control gene expression. In most instances in which organisms mediate host evasion by large families of homologous gene cassettes, the mechanism of variation is not thought to involve DNA inversion. Here we report that Campylobacter fetus, a pathogenic Gram-negative bacterium, reassorts a single promoter, controlling surface-layer protein expression, and one or more complete ORFs strictly by DNA inversion. Rearrangements were independent of the distance between sites of inversion. These rearrangements permit variation in protein expression from the large surface-layer protein gene family and suggest an expanding paradigm of programmed DNA rearrangements among microorganisms.

包括病毒、原核生物及简单真核生物在内的多种微生物，均会利用程序性基因重排来调控基因表达。在多数借助同源基因盒大家族介导宿主逃逸的生物体中，学界此前认为其变异机制并不涉及DNA倒位。本研究发现，致病性革兰氏阴性菌胎儿弯曲菌（Campylobacter fetus）仅通过DNA倒位，即可对调控表面层蛋白表达的单个启动子以及一个或多个完整开放阅读框（Open Reading Frame, ORF）进行重排。此类重排不受倒位位点间距离的限制。这类重排可实现大型表面层蛋白基因家族的蛋白表达变异，同时提示微生物界的程序性DNA重排范式正不断扩展。