Institute for Glycomics, Griffith University, Gold Coast, Queensland 4215, Australia.
Institute for Glycomics, Griffith University, Gold Coast, Queensland 4215, Australia
Biochem Soc Trans. 2019 Aug 30;47(4):1131-1141. doi: 10.1042/BST20180633. Epub 2019 Jul 24.
Phase-variation of genes is defined as the rapid and reversible switching of expression - either ON-OFF switching or the expression of multiple allelic variants. Switching of expression can be achieved by a number of different mechanisms. Phase-variable genes typically encode bacterial surface structures, such as adhesins, pili, and lipooligosaccharide, and provide an extra contingency strategy in small-genome pathogens that may lack the plethora of 'sense-and-respond' gene regulation systems found in other organisms. Many bacterial pathogens also encode phase-variable DNA methyltransferases that control the expression of multiple genes in systems called phasevarions (phase-variable regulons). The presence of phase-variable genes allows a population of bacteria to generate a number of phenotypic variants, some of which may be better suited to either colonising certain host niches, surviving a particular environmental condition and/or evading an immune response. The presence of phase-variable genes complicates the determination of an organism's stably expressed antigenic repertoire; many phase-variable genes are highly immunogenic, and so would be ideal vaccine candidates, but unstable expression due to phase-variation may allow vaccine escape. This review will summarise our current understanding of phase-variable genes that switch expression by a variety of mechanisms, and describe their role in disease and pathobiology.
基因的表型转换被定义为表达的快速和可逆切换——无论是开-关切换还是多个等位基因变体的表达。表达的切换可以通过许多不同的机制来实现。表型转换基因通常编码细菌表面结构，如黏附素、菌毛和脂寡糖，为小基因组病原体提供了额外的应急策略，这些病原体可能缺乏其他生物体中存在的大量“感知-响应”基因调控系统。许多细菌病原体还编码可控制多个基因表达的表型转换 DNA 甲基转移酶，这些基因在称为表型变异子（表型转换调控子）的系统中表达。表型转换基因的存在允许细菌群体产生许多表型变体，其中一些可能更适合在特定的宿主小生境中定殖、在特定的环境条件下存活和/或逃避免疫反应。表型转换基因的存在使确定生物体稳定表达的抗原库变得复杂；许多表型转换基因具有高度免疫原性，因此是理想的疫苗候选物，但由于表型转换导致的不稳定表达可能允许疫苗逃逸。本文将总结我们目前对通过各种机制切换表达的表型转换基因的理解，并描述它们在疾病和病理生物学中的作用。
