Abstract
Anaplasma phagocytophilum
is an obligately intracellular tick-transmitted bacterial pathogen of humans and other animals. During the course of infection,
A. phagocytophilum
utilizes gene conversion to shuffle ∼100 functional pseudogenes into a single expression cassette of the
msp2(p44)
gene, which codes for the major surface antigen and major surface protein 2 (MSP2). The role and extent of
msp2(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 the
msp2(p44)
gene of
A. phagocytophilum
in 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 unique
msp2(p44)
expression cassette variants. The expression of
msp2(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 in
A. phagocytophilum
may 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.