The evolutionary dynamics of variant antigen genes in Babesia reveal a history of genomic innovation underlying host-parasite interaction

Handle URI:
http://hdl.handle.net/10754/325457
Title:
The evolutionary dynamics of variant antigen genes in Babesia reveal a history of genomic innovation underlying host-parasite interaction
Authors:
Jackson, Andrew P.; Otto, Thomas D.; Darby, Alistair; Ramaprasad, Abhinay ( 0000-0001-9372-5526 ) ; Xia, Dong; Echaide, Ignacio Eduardo; Farber, Marisa; Gahlot, Sunayna; Gamble, John; Gupta, Dinesh; Gupta, Yask; Jackson, Louise; Malandrin, Laurence; Malas, Tareq B.; Moussa, Ehab; Nair, Mridul; Reid, Adam J.; Sanders, Mandy; Sharma, Jyotsna; Tracey, Alan; Quail, Mike A.; Weir, William; Wastling, Jonathan M.; Hall, Neil; Willadsen, Peter; Lingelbach, Klaus; Shiels, Brian; Tait, Andy; Berriman, Matt; Allred, David R.; Pain, Arnab ( 0000-0002-1755-2819 )
Abstract:
Babesia spp. are tick-borne, intraerythrocytic hemoparasites that use antigenic variation to resist host immunity, through sequential modification of the parasite-derived variant erythrocyte surface antigen (VESA) expressed on the infected red blood cell surface. We identified the genomic processes driving antigenic diversity in genes encoding VESA (ves1) through comparative analysis within and between three Babesia species, (B. bigemina, B. divergens and B. bovis). Ves1 structure diverges rapidly after speciation, notably through the evolution of shortened forms (ves2) from 5? ends of canonical ves1 genes. Phylogenetic analyses show that ves1 genes are transposed between loci routinely, whereas ves2 genes are not. Similarly, analysis of sequence mosaicism shows that recombination drives variation in ves1 sequences, but less so for ves2, indicating the adoption of different mechanisms for variation of the two families. Proteomic analysis of the B. bigemina PR isolate shows that two dominant VESA1 proteins are expressed in the population, whereas numerous VESA2 proteins are co-expressed, consistent with differential transcriptional regulation of each family. Hence, VESA2 proteins are abundant and previously unrecognized elements of Babesia biology, with evolutionary dynamics consistently different to those of VESA1, suggesting that their functions are distinct. 2014 The Author(s) 2014.
KAUST Department:
Computational Bioscience Research Center (CBRC)
Citation:
Jackson AP, Otto TD, Darby A, Ramaprasad A, Xia D, et al. (2014) The evolutionary dynamics of variant antigen genes in Babesia reveal a history of genomic innovation underlying host-parasite interaction. Nucleic Acids Research 42: 7113-7131. doi:10.1093/nar/gku322.
Publisher:
Oxford University Press (OUP)
Journal:
Nucleic Acids Research
Issue Date:
5-May-2014
DOI:
10.1093/nar/gku322
PubMed ID:
24799432
PubMed Central ID:
PMC4066756
Type:
Article
ISSN:
13624962
Appears in Collections:
Articles; Computational Bioscience Research Center (CBRC)

Full metadata record

DC FieldValue Language
dc.contributor.authorJackson, Andrew P.en
dc.contributor.authorOtto, Thomas D.en
dc.contributor.authorDarby, Alistairen
dc.contributor.authorRamaprasad, Abhinayen
dc.contributor.authorXia, Dongen
dc.contributor.authorEchaide, Ignacio Eduardoen
dc.contributor.authorFarber, Marisaen
dc.contributor.authorGahlot, Sunaynaen
dc.contributor.authorGamble, Johnen
dc.contributor.authorGupta, Dineshen
dc.contributor.authorGupta, Yasken
dc.contributor.authorJackson, Louiseen
dc.contributor.authorMalandrin, Laurenceen
dc.contributor.authorMalas, Tareq B.en
dc.contributor.authorMoussa, Ehaben
dc.contributor.authorNair, Mridulen
dc.contributor.authorReid, Adam J.en
dc.contributor.authorSanders, Mandyen
dc.contributor.authorSharma, Jyotsnaen
dc.contributor.authorTracey, Alanen
dc.contributor.authorQuail, Mike A.en
dc.contributor.authorWeir, Williamen
dc.contributor.authorWastling, Jonathan M.en
dc.contributor.authorHall, Neilen
dc.contributor.authorWilladsen, Peteren
dc.contributor.authorLingelbach, Klausen
dc.contributor.authorShiels, Brianen
dc.contributor.authorTait, Andyen
dc.contributor.authorBerriman, Matten
dc.contributor.authorAllred, David R.en
dc.contributor.authorPain, Arnaben
dc.date.accessioned2014-08-27T09:52:10Zen
dc.date.available2014-08-27T09:52:10Zen
dc.date.issued2014-05-05en
dc.identifier.citationJackson AP, Otto TD, Darby A, Ramaprasad A, Xia D, et al. (2014) The evolutionary dynamics of variant antigen genes in Babesia reveal a history of genomic innovation underlying host-parasite interaction. Nucleic Acids Research 42: 7113-7131. doi:10.1093/nar/gku322.en
dc.identifier.issn13624962en
dc.identifier.pmid24799432en
dc.identifier.doi10.1093/nar/gku322en
dc.identifier.urihttp://hdl.handle.net/10754/325457en
dc.description.abstractBabesia spp. are tick-borne, intraerythrocytic hemoparasites that use antigenic variation to resist host immunity, through sequential modification of the parasite-derived variant erythrocyte surface antigen (VESA) expressed on the infected red blood cell surface. We identified the genomic processes driving antigenic diversity in genes encoding VESA (ves1) through comparative analysis within and between three Babesia species, (B. bigemina, B. divergens and B. bovis). Ves1 structure diverges rapidly after speciation, notably through the evolution of shortened forms (ves2) from 5? ends of canonical ves1 genes. Phylogenetic analyses show that ves1 genes are transposed between loci routinely, whereas ves2 genes are not. Similarly, analysis of sequence mosaicism shows that recombination drives variation in ves1 sequences, but less so for ves2, indicating the adoption of different mechanisms for variation of the two families. Proteomic analysis of the B. bigemina PR isolate shows that two dominant VESA1 proteins are expressed in the population, whereas numerous VESA2 proteins are co-expressed, consistent with differential transcriptional regulation of each family. Hence, VESA2 proteins are abundant and previously unrecognized elements of Babesia biology, with evolutionary dynamics consistently different to those of VESA1, suggesting that their functions are distinct. 2014 The Author(s) 2014.en
dc.language.isoenen
dc.publisherOxford University Press (OUP)en
dc.rightsThis is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0/), which permits unrestricted reuse, distribution, and reproduction in any medium, provided the original work is properly cited.en
dc.rights.urihttp://creativecommons.org/licenses/by/3.0/en
dc.subjectmembrane antigenen
dc.subjectunclassified drugen
dc.subjectvariant erythrocyte surface antigen 1en
dc.subjectvariant erythrocyte surface antigen 2en
dc.subjectantigenic variationen
dc.subjectBabesiaen
dc.subjectBabesia bigeminaen
dc.subjectBabesia bovisen
dc.subjectBabesia divergensen
dc.subjectcomparative studyen
dc.subjectcontrolled studyen
dc.subjectDNA transpositionen
dc.subjectgeneen
dc.subjectgene locusen
dc.subjectgene rearrangementen
dc.subjectgene sequenceen
dc.subjectgene structureen
dc.subjectgenetic recombinationen
dc.subjectgenetic variabilityen
dc.subjecthost parasite interactionen
dc.subjectin vitro studyen
dc.subjectmolecular evolutionen
dc.subjectmosaicismen
dc.subjectphylogenyen
dc.subjectprotein expressionen
dc.subjectprotein functionen
dc.subjectproteomicsen
dc.subjectspecies comparisonen
dc.subjectspecies differentiationen
dc.subjecttranscription regulationen
dc.subjectves1 geneen
dc.subjectves2 geneen
dc.titleThe evolutionary dynamics of variant antigen genes in Babesia reveal a history of genomic innovation underlying host-parasite interactionen
dc.typeArticleen
dc.contributor.departmentComputational Bioscience Research Center (CBRC)en
dc.identifier.journalNucleic Acids Researchen
dc.identifier.pmcidPMC4066756en
dc.eprint.versionPublisher's Version/PDFen
dc.contributor.institutionDepartment of Infection Biology, Institute of Infection and Global Health, University of Liverpool, Liverpool Science Park Ic2, 146 Brownlow Hill, Liverpool L3 5RF, United Kingdomen
dc.contributor.institutionPathogen Genomics Group, Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Hinxton, Cambridge CB10 1SA, United Kingdomen
dc.contributor.institutionDepartment of Functional and Comparative Genomics, Institute of Integrative Biology, University of Liverpool, Crown Street, Liverpool L69 7ZB, United Kingdomen
dc.contributor.institutionLaboratorio de Inmunologa y, EEA-INTA CC 22, 2300 Rafaela Santa Fe, Argentinaen
dc.contributor.institutionCentro Nacional de Investigaciones Agropecuarias, Instituto de Biotecnologa INTA, Buenos Aires, Argentinaen
dc.contributor.institutionBioinformatics Laboratory, Structural and Computational Biology Group, International Centre for Genetic Engineering and Biotechnology, Aruna Asaf Ali Marg, New Delhi 110 067, Indiaen
dc.contributor.institutionDepartment of Agriculture, Fisheries and Forestry, Biosecurity Sciences Laboratory, 39 Kessels Road, Coopers Plains, QLD 4108, Australiaen
dc.contributor.institutionUMR1300 INRA/Oniris Biology, Epidemiology and Risk Analysis in Animal Health, BP 40706, F-44307 Nantes, Franceen
dc.contributor.institutionFG Parasitologie, Philipps Universitt Marburg, Karl von Frisch Strasse 8, 35043 Marburg, Germanyen
dc.contributor.institutionInstitute of Biodiversity, Animal Health and Comparative Medicine, University of Glasgow, 464 Bearsden Road, Glasgow G61 1QH, United Kingdomen
dc.contributor.institutionDepartment of Infectious Diseases and Pathology, Genetics Institute, University of Florida, 2015 SW 16th Avenue, Gainesville FL 33611-0880, United Statesen
dc.contributor.affiliationKing Abdullah University of Science and Technology (KAUST)en
kaust.authorRamaprasad, Abhinayen
kaust.authorMalas, Tareq Majed Yasinen
kaust.authorMoussa, Ehaben
kaust.authorNair, Mridulen
kaust.authorPain, Arnaben

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