Evolution of antigen variation in the tick-borne pathogen Anaplasma phagocytophilum.
Evolution of antigen variation in the tick-borne pathogen Anaplasma phagocytophilum.
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蜱传病原体嗜吞噬细胞无形体抗原变异的进化。
DOI：
10.1093/molbev/msr229
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发表时间：
2012
影响因子：
10.7
通讯作者：
Foley,Janet
中科院分区：
文献类型：
--
作者：
Rejmanek,Daniel;Foley,Patrick;Barbet,Anthony;Foley,Janet
嗜吞噬细胞无浆体是一种专性细胞内蜱传病原体。在感染过程中，A.嗜吞噬细胞菌利用基因转换将100个功能假基因改组到它们的sp2（p44）基因的单个表达盒中，所述p44基因编码主要表面抗原和主要表面蛋白2（MSP 2）。msp2（p44）重组的作用和程度，特别是在只经历急性感染的宿主中，尚不清楚。本研究探讨了A.在连续感染的小鼠模型中，尽管这种细菌在小鼠中迅速传播，使宿主产生适应性免疫的机会最小化，但我们检测到34种p44表达盒变体的出现。msp2（p44）假基因的表达在不同组的小鼠中并不遵循一致的模式，尽管某些假基因的表达比其他假基因更频繁。此外，在263个表达的假基因中，鉴定出3个嵌合序列，每个嵌合序列由2个不同的假基因组成。群体遗传分析表明，遗传多样性和亚群分化往往会随着时间的推移而增加，直到达到平稳，但观察到的等位基因（表达的假基因）频率的方差可能会发生漂移，只有在细菌繁殖的高方差可以假设。这些发现表明，进化力量影响抗原变异在A。嗜吞噬细胞菌可能包括随机遗传漂变以及一些先天的，但显然是非净化选择之前的强频率依赖性选择，发生周期后，主机发展强大的适应性免疫。
Anaplasma phagocytophilumis an obligately intracellular tick-transmitted bacterial pathogen of humans and other animals. During the course of infection,A. phagocytophilumutilizes gene conversion to shuffle ∼100 functional pseudogenes into a single expression cassette of themsp2(p44)gene, which codes for the major surface antigen and major surface protein 2 (MSP2). The role and extent ofmsp2(p44)recombination, particularly in hosts that only experience acute infections, is not clear. In the present study, we explored patterns of recombination and expression of themsp2(p44)gene ofA. phagocytophilumin a serially infected mouse model. Even though the bacterium was passed rapidly among mice, minimizing the opportunities for the host to develop adaptive immunity, we detected the emergence of 34 uniquemsp2(p44)expression cassette variants. The expression ofmsp2(p44)pseudogenes did not follow a consistent pattern among different groups of mice, although some pseudogenes were expressed more frequently than others. In addition, among 263 expressed pseudogenes, 3 mosaic sequences each consisting of 2 different pseudogenes were identified. Population genetic analysis showed that genetic diversity and subpopulation differentiation tended to increase over time until stationarity was reached but that the variance that was observed in allele (expressed pseudogene) frequency could occur by drift alone only if a high variance in bacterial reproduction could be assumed. These findings suggest that evolutionary forces influencing antigen variation inA. phagocytophilummay comprise random genetic drift as well as some innate but apparently nonpurifying selection prior to the strong frequency-dependent selection that occurs cyclically after hosts develop strong adaptive immunity.