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Open Access Research article

Characterization and gene expression analysis of the cir multi-gene family of plasmodium chabaudi chabaudi (AS)

Jennifer Lawton1, Thibaut Brugat1, Yam Xue Yan2, Adam James Reid3, Ulrike Böhme3, Thomas Dan Otto3, Arnab Pain34, Andrew Jackson3, Matthew Berriman3, Deirdre Cunningham1, Peter Preiser2 and Jean Langhorne1*

Author Affiliations

1 Division of Parasitology, MRC National Institute for Medical Research, London, UK

2 Division of Genomics and Genetics, Nanyang Technological University Singapore, Singapore

3 Parasite Genomics, Wellcome Trust Sanger Institute, Hinxton, UK

4 Pathogen Genomics Group, Computational Bioscience Research Center, Chemical Life Sciences and Engineering Division, 4700 King Abdullah University of Science and Technology, Thuwal 23955-6900, Kingdom of Saudi Arabia

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BMC Genomics 2012, 13:125  doi:10.1186/1471-2164-13-125

Published: 29 March 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.


The cir 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.