J. Lawton, T. Brugat, X.Y. Yam, A.J. Reid, U. Boehme, T.D. Otto, A .Pain, A. Jackson, M. Berriman, D. Cunningham, P. Preiser, J. Langhorne
BMC Genomics, 13(1):125, (2012)
The pir genes comprise the largest multi-gene family in Plasmodium, with members found in P. vivax, P. knowlesi
and the rodent malaria species. Despite comprising up to 5% of the
genome, little is known about the functions of the proteins encoded by pir genes. P. chabaudi causes chronic infection in mice, which may be due to antigenic variation. In this model, pir genes are called cirs
and may be involved in this mechanism, allowing evasion of host immune
responses. In order to fully understand the role(s) of CIR proteins
during P. chabaudi infection, a detailed characterization of the cir gene family was required.
repertoire was annotated and a detailed bioinformatic characterization
of the encoded CIR proteins was performed. Two major sub-families were
identified, which have been named A and B. Members of each sub-family
displayed different amino acid motifs, and were thus predicted to have
undergone functional divergence. In addition, the expression of the
entire cir repertoire was analyzed via RNA sequencing and microarray. Up to 40% of the cir gene repertoire was expressed in the parasite population during infection, and dominant cir transcripts could be identified. In addition, some differences were observed in the pattern of expression between the cir subgroups at the peak of P. chabaudi infection. Finally, specific cir genes were expressed at different time points during asexual blood stages.
In conclusion, the large number of cir
genes and their expression throughout the intraerythrocytic cycle of
development indicates that CIR proteins are likely to be important for
parasite survival. In particular, the detection of dominant cir transcripts at the peak of P. chabaudi
infection supports the idea that CIR proteins are expressed, and could
perform important functions in the biology of this parasite. Further
application of the methodologies described here may allow the
elucidation of CIR sub-family A and B protein functions, including their
contribution to antigenic variation and immune evasion.