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

Handle URI:
http://hdl.handle.net/10754/325241
Title:
Characterization and gene expression analysis of the cir multi-gene family of plasmodium chabaudi chabaudi (AS)
Authors:
Lawton, Jennifer; Brugat, Thibaut; Yan, Yam Xue; Reid, Adam James; Böhme, Ulrike; Otto, Thomas Dan; Pain, Arnab ( 0000-0002-1755-2819 ) ; Jackson, Andrew; Berriman, Matthew; Cunningham, Deirdre; Preiser, Peter; Langhorne, Jean
Abstract:
Background: 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.Results: 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.Conclusions: 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. 2012 Lawton et al; licensee BioMed Central Ltd.
KAUST Department:
Biological and Environmental Sciences and Engineering (BESE) Division; Computational Bioscience Research Center (CBRC); Pathogen Genomics Laboratory
Citation:
Lawton J, Brugat T, Yan Y, Reid A, Böhme U, et al. (2012) Characterization and gene expression analysis of the cir multi-gene family of plasmodium chabaudi chabaudi (AS). BMC Genomics 13: 125. doi:10.1186/1471-2164-13-125.
Publisher:
BioMed Central
Journal:
BMC Genomics
Issue Date:
29-Mar-2012
DOI:
10.1186/1471-2164-13-125
PubMed ID:
22458863
PubMed Central ID:
PMC3384456
Type:
Article
ISSN:
14712164
Appears in Collections:
Articles; Computational Bioscience Research Center (CBRC); Biological and Environmental Sciences and Engineering (BESE) Division

Full metadata record

DC FieldValue Language
dc.contributor.authorLawton, Jenniferen
dc.contributor.authorBrugat, Thibauten
dc.contributor.authorYan, Yam Xueen
dc.contributor.authorReid, Adam Jamesen
dc.contributor.authorBöhme, Ulrikeen
dc.contributor.authorOtto, Thomas Danen
dc.contributor.authorPain, Arnaben
dc.contributor.authorJackson, Andrewen
dc.contributor.authorBerriman, Matthewen
dc.contributor.authorCunningham, Deirdreen
dc.contributor.authorPreiser, Peteren
dc.contributor.authorLanghorne, Jeanen
dc.date.accessioned2014-08-27T09:41:51Z-
dc.date.available2014-08-27T09:41:51Z-
dc.date.issued2012-03-29en
dc.identifier.citationLawton J, Brugat T, Yan Y, Reid A, Böhme U, et al. (2012) Characterization and gene expression analysis of the cir multi-gene family of plasmodium chabaudi chabaudi (AS). BMC Genomics 13: 125. doi:10.1186/1471-2164-13-125.en
dc.identifier.issn14712164en
dc.identifier.pmid22458863en
dc.identifier.doi10.1186/1471-2164-13-125en
dc.identifier.urihttp://hdl.handle.net/10754/325241en
dc.description.abstractBackground: 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.Results: 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.Conclusions: 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. 2012 Lawton et al; licensee BioMed Central Ltd.en
dc.language.isoenen
dc.publisherBioMed Centralen
dc.rightsThis is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.en
dc.rights.urihttp://creativecommons.org/licenses/by/2.0en
dc.subjectamino aciden
dc.subjectCIR proteinen
dc.subjectproteinen
dc.subjectRNAen
dc.subjectunclassified drugen
dc.subjectmessenger RNAen
dc.subjectprotozoal proteinen
dc.subjectprotozoal RNAen
dc.subjectantigenic variationen
dc.subjectbacterial geneticsen
dc.subjectCIR geneen
dc.subjectcontrolled studyen
dc.subjectgeneen
dc.subjectgene expressionen
dc.subjectgenetic analysisen
dc.subjectgenetic variabilityen
dc.subjectimmune evasionen
dc.subjectmicroarray analysisen
dc.subjectmouseen
dc.subjectmultigene familyen
dc.subjectnucleotide sequenceen
dc.subjectparasite survivalen
dc.subjectPlasmodium chabaudien
dc.subjectprotein analysisen
dc.subjectprotein expressionen
dc.subjectprotein functionen
dc.subjectprotein motifen
dc.subjectRNA sequenceen
dc.subjectamino acid sequenceen
dc.subjectbiologyen
dc.subjectchemistryen
dc.subjectDNA microarrayen
dc.subjectgeneen
dc.subjectgene expression profilingen
dc.subjectgeneticsen
dc.subjectgrowth, development and agingen
dc.subjecthost pathogen interactionen
dc.subjectlife cycle stageen
dc.subjectmetabolismen
dc.subjectmethodologyen
dc.subjectpathogenicityen
dc.subjectphysiologyen
dc.subjectsequence analysisen
dc.subjectsequence homologyen
dc.subjectMusen
dc.subjectPlasmodium chabaudien
dc.subjectPlasmodium chabaudi chabaudien
dc.subjectPlasmodium knowlesien
dc.subjectPlasmodium vivaxen
dc.subjectRodentiaen
dc.subjectAmino Acid Motifsen
dc.subjectAmino Acid Sequenceen
dc.subjectComputational Biologyen
dc.subjectConserved Sequenceen
dc.subjectGene Expression Profilingen
dc.subjectGenes, Protozoanen
dc.subjectHost-Pathogen Interactionsen
dc.subjectLife Cycle Stagesen
dc.subjectMiceen
dc.subjectMultigene Familyen
dc.subjectOligonucleotide Array Sequence Analysisen
dc.subjectPlasmodium chabaudien
dc.subjectProtozoan Proteinsen
dc.subjectRNA, Messengeren
dc.subjectRNA, Protozoanen
dc.subjectSequence Analysis, RNAen
dc.subjectSequence Homology, Amino Aciden
dc.titleCharacterization and gene expression analysis of the cir multi-gene family of plasmodium chabaudi chabaudi (AS)en
dc.typeArticleen
dc.contributor.departmentBiological and Environmental Sciences and Engineering (BESE) Divisionen
dc.contributor.departmentComputational Bioscience Research Center (CBRC)en
dc.contributor.departmentPathogen Genomics Laboratoryen
dc.identifier.journalBMC Genomicsen
dc.identifier.pmcidPMC3384456en
dc.eprint.versionPublisher's Version/PDFen
dc.contributor.institutionDivision of Parasitology, MRC National Institute for Medical Research, London, United Kingdomen
dc.contributor.institutionDivision of Genomics and Genetics, Nanyang Technological University Singapore, Singaporeen
dc.contributor.institutionParasite Genomics, Wellcome Trust Sanger Institute, Hinxton, United Kingdomen
dc.contributor.affiliationKing Abdullah University of Science and Technology (KAUST)en
kaust.authorPain, Arnaben
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