The evolutionary dynamics of variant antigen genes in Babesia reveal a history of genomic innovation underlying host–parasite interaction
Identifieur interne : 002652 ( Pmc/Curation ); précédent : 002651; suivant : 002653The evolutionary dynamics of variant antigen genes in Babesia reveal a history of genomic innovation underlying host–parasite interaction
Auteurs : Andrew P. Jackson [Royaume-Uni] ; Thomas D. Otto [Royaume-Uni] ; Alistair Darby [Royaume-Uni] ; Abhinay Ramaprasad [Arabie saoudite] ; Dong Xia [Royaume-Uni] ; Ignacio Eduardo Echaide [Argentine] ; Marisa Farber [Argentine] ; Sunayna Gahlot [Inde] ; John Gamble [Royaume-Uni] ; Dinesh Gupta [Inde] ; Yask Gupta [Inde] ; Louise Jackson [Australie] ; Laurence Malandrin [France] ; Tareq B. Malas [Arabie saoudite] ; Ehab Moussa [Arabie saoudite] ; Mridul Nair [Arabie saoudite] ; Adam J. Reid [Royaume-Uni] ; Mandy Sanders [Royaume-Uni] ; Jyotsna Sharma [Allemagne] ; Alan Tracey [Royaume-Uni] ; Mike A. Quail [Royaume-Uni] ; William Weir [Allemagne] ; Jonathan M. Wastling [Royaume-Uni] ; Neil Hall [Royaume-Uni] ; Peter Willadsen [Australie] ; Klaus Lingelbach [Allemagne] ; Brian Shiels [Royaume-Uni] ; Andy Tait [Royaume-Uni] ; Matt Berriman [Royaume-Uni] ; David R. Allred [États-Unis] ; Arnab Pain [Arabie saoudite]Source :
- Nucleic Acids Research [ 0305-1048 ] ; 2014.
Abstract
Url:
DOI: 10.1093/nar/gku322
PubMed: 24799432
PubMed Central: 4066756
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reveal a history of genomic innovation underlying host–parasite interaction</title>
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<author><name sortKey="Sanders, Mandy" sort="Sanders, Mandy" uniqKey="Sanders M" first="Mandy" last="Sanders">Mandy Sanders</name>
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<author><name sortKey="Hall, Neil" sort="Hall, Neil" uniqKey="Hall N" first="Neil" last="Hall">Neil Hall</name>
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<author><name sortKey="Willadsen, Peter" sort="Willadsen, Peter" uniqKey="Willadsen P" first="Peter" last="Willadsen">Peter Willadsen</name>
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<author><name sortKey="Lingelbach, Klaus" sort="Lingelbach, Klaus" uniqKey="Lingelbach K" first="Klaus" last="Lingelbach">Klaus Lingelbach</name>
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<author><name sortKey="Shiels, Brian" sort="Shiels, Brian" uniqKey="Shiels B" first="Brian" last="Shiels">Brian Shiels</name>
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<wicri:regionArea>Institute of Biodiversity, Animal Health and Comparative Medicine, University of Glasgow, 464 Bearsden Road, Glasgow G61 1QH</wicri:regionArea>
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<author><name sortKey="Tait, Andy" sort="Tait, Andy" uniqKey="Tait A" first="Andy" last="Tait">Andy Tait</name>
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<author><name sortKey="Berriman, Matt" sort="Berriman, Matt" uniqKey="Berriman M" first="Matt" last="Berriman">Matt Berriman</name>
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<author><name sortKey="Allred, David R" sort="Allred, David R" uniqKey="Allred D" first="David R." last="Allred">David R. Allred</name>
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<country xml:lang="fr">États-Unis</country>
<wicri:regionArea>Department of Infectious Diseases and Pathology, and Genetics Institute, University of Florida, PO Box 110880, 2015 SW 16th Avenue, Gainesville FL 33611-0880</wicri:regionArea>
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<author><name sortKey="Pain, Arnab" sort="Pain, Arnab" uniqKey="Pain A" first="Arnab" last="Pain">Arnab Pain</name>
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<country xml:lang="fr">Arabie saoudite</country>
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<sourceDesc><biblStruct><analytic><title xml:lang="en" level="a" type="main">The evolutionary dynamics of variant antigen genes in <italic>Babesia</italic>
reveal a history of genomic innovation underlying host–parasite interaction</title>
<author><name sortKey="Jackson, Andrew P" sort="Jackson, Andrew P" uniqKey="Jackson A" first="Andrew P." last="Jackson">Andrew P. Jackson</name>
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<author><name sortKey="Otto, Thomas D" sort="Otto, Thomas D" uniqKey="Otto T" first="Thomas D." last="Otto">Thomas D. Otto</name>
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<author><name sortKey="Darby, Alistair" sort="Darby, Alistair" uniqKey="Darby A" first="Alistair" last="Darby">Alistair Darby</name>
<affiliation wicri:level="1"><nlm:aff id="AFF3">Department of Functional and Comparative Genomics, Institute of Integrative Biology, University of Liverpool, Crown Street, Liverpool L69 7ZB, UK</nlm:aff>
<country xml:lang="fr">Royaume-Uni</country>
<wicri:regionArea>Department of Functional and Comparative Genomics, Institute of Integrative Biology, University of Liverpool, Crown Street, Liverpool L69 7ZB</wicri:regionArea>
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<author><name sortKey="Ramaprasad, Abhinay" sort="Ramaprasad, Abhinay" uniqKey="Ramaprasad A" first="Abhinay" last="Ramaprasad">Abhinay Ramaprasad</name>
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<author><name sortKey="Xia, Dong" sort="Xia, Dong" uniqKey="Xia D" first="Dong" last="Xia">Dong Xia</name>
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<author><name sortKey="Echaide, Ignacio Eduardo" sort="Echaide, Ignacio Eduardo" uniqKey="Echaide I" first="Ignacio Eduardo" last="Echaide">Ignacio Eduardo Echaide</name>
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<country xml:lang="fr">Argentine</country>
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<author><name sortKey="Farber, Marisa" sort="Farber, Marisa" uniqKey="Farber M" first="Marisa" last="Farber">Marisa Farber</name>
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<country xml:lang="fr">Argentine</country>
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<author><name sortKey="Gahlot, Sunayna" sort="Gahlot, Sunayna" uniqKey="Gahlot S" first="Sunayna" last="Gahlot">Sunayna Gahlot</name>
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<country xml:lang="fr">Inde</country>
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<author><name sortKey="Gamble, John" sort="Gamble, John" uniqKey="Gamble J" first="John" last="Gamble">John Gamble</name>
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<country xml:lang="fr">Royaume-Uni</country>
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<author><name sortKey="Gupta, Dinesh" sort="Gupta, Dinesh" uniqKey="Gupta D" first="Dinesh" last="Gupta">Dinesh Gupta</name>
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<country xml:lang="fr">Inde</country>
<wicri:regionArea>Bioinformatics Laboratory, Structural and Computational Biology Group, International Centre for Genetic Engineering and Biotechnology, Aruna Asaf Ali Marg, New Delhi 110 067</wicri:regionArea>
</affiliation>
</author>
<author><name sortKey="Gupta, Yask" sort="Gupta, Yask" uniqKey="Gupta Y" first="Yask" last="Gupta">Yask Gupta</name>
<affiliation wicri:level="1"><nlm:aff id="AFF7">Bioinformatics Laboratory, Structural and Computational Biology Group, International Centre for Genetic Engineering and Biotechnology, Aruna Asaf Ali Marg, New Delhi 110 067, India</nlm:aff>
<country xml:lang="fr">Inde</country>
<wicri:regionArea>Bioinformatics Laboratory, Structural and Computational Biology Group, International Centre for Genetic Engineering and Biotechnology, Aruna Asaf Ali Marg, New Delhi 110 067</wicri:regionArea>
</affiliation>
</author>
<author><name sortKey="Jackson, Louise" sort="Jackson, Louise" uniqKey="Jackson L" first="Louise" last="Jackson">Louise Jackson</name>
<affiliation wicri:level="1"><nlm:aff id="AFF8">Department of Agriculture, Fisheries and Forestry, Biosecurity Sciences Laboratory, 39 Kessels Road, Coopers Plains, Queensland 4108, Australia</nlm:aff>
<country xml:lang="fr">Australie</country>
<wicri:regionArea>Department of Agriculture, Fisheries and Forestry, Biosecurity Sciences Laboratory, 39 Kessels Road, Coopers Plains, Queensland 4108</wicri:regionArea>
</affiliation>
</author>
<author><name sortKey="Malandrin, Laurence" sort="Malandrin, Laurence" uniqKey="Malandrin L" first="Laurence" last="Malandrin">Laurence Malandrin</name>
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<country xml:lang="fr">France</country>
<wicri:regionArea>UMR1300 INRA/Oniris Biology, Epidemiology and Risk Analysis in Animal Health, BP 40706, F-44307 Nantes</wicri:regionArea>
</affiliation>
</author>
<author><name sortKey="Malas, Tareq B" sort="Malas, Tareq B" uniqKey="Malas T" first="Tareq B." last="Malas">Tareq B. Malas</name>
<affiliation wicri:level="1"><nlm:aff id="AFF4">Computational Bioscience Research Center, King Abdullah University of Science and Technology, Thuwal 23955-6900, Saudi Arabia</nlm:aff>
<country xml:lang="fr">Arabie saoudite</country>
<wicri:regionArea>Computational Bioscience Research Center, King Abdullah University of Science and Technology, Thuwal 23955-6900</wicri:regionArea>
</affiliation>
</author>
<author><name sortKey="Moussa, Ehab" sort="Moussa, Ehab" uniqKey="Moussa E" first="Ehab" last="Moussa">Ehab Moussa</name>
<affiliation wicri:level="1"><nlm:aff id="AFF4">Computational Bioscience Research Center, King Abdullah University of Science and Technology, Thuwal 23955-6900, Saudi Arabia</nlm:aff>
<country xml:lang="fr">Arabie saoudite</country>
<wicri:regionArea>Computational Bioscience Research Center, King Abdullah University of Science and Technology, Thuwal 23955-6900</wicri:regionArea>
</affiliation>
</author>
<author><name sortKey="Nair, Mridul" sort="Nair, Mridul" uniqKey="Nair M" first="Mridul" last="Nair">Mridul Nair</name>
<affiliation wicri:level="1"><nlm:aff id="AFF4">Computational Bioscience Research Center, King Abdullah University of Science and Technology, Thuwal 23955-6900, Saudi Arabia</nlm:aff>
<country xml:lang="fr">Arabie saoudite</country>
<wicri:regionArea>Computational Bioscience Research Center, King Abdullah University of Science and Technology, Thuwal 23955-6900</wicri:regionArea>
</affiliation>
</author>
<author><name sortKey="Reid, Adam J" sort="Reid, Adam J" uniqKey="Reid A" first="Adam J." last="Reid">Adam J. Reid</name>
<affiliation wicri:level="1"><nlm:aff id="AFF2">Pathogen Genomics Group, Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Hinxton, Cambridge CB10 1SA, UK</nlm:aff>
<country xml:lang="fr">Royaume-Uni</country>
<wicri:regionArea>Pathogen Genomics Group, Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Hinxton, Cambridge CB10 1SA</wicri:regionArea>
</affiliation>
</author>
<author><name sortKey="Sanders, Mandy" sort="Sanders, Mandy" uniqKey="Sanders M" first="Mandy" last="Sanders">Mandy Sanders</name>
<affiliation wicri:level="1"><nlm:aff id="AFF2">Pathogen Genomics Group, Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Hinxton, Cambridge CB10 1SA, UK</nlm:aff>
<country xml:lang="fr">Royaume-Uni</country>
<wicri:regionArea>Pathogen Genomics Group, Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Hinxton, Cambridge CB10 1SA</wicri:regionArea>
</affiliation>
</author>
<author><name sortKey="Sharma, Jyotsna" sort="Sharma, Jyotsna" uniqKey="Sharma J" first="Jyotsna" last="Sharma">Jyotsna Sharma</name>
<affiliation wicri:level="1"><nlm:aff id="AFF10">FG Parasitologie, Philipps Universität Marburg, Karl von Frisch Strasse 8, 35043 Marburg, Germany</nlm:aff>
<country xml:lang="fr">Allemagne</country>
<wicri:regionArea>FG Parasitologie, Philipps Universität Marburg, Karl von Frisch Strasse 8, 35043 Marburg</wicri:regionArea>
</affiliation>
</author>
<author><name sortKey="Tracey, Alan" sort="Tracey, Alan" uniqKey="Tracey A" first="Alan" last="Tracey">Alan Tracey</name>
<affiliation wicri:level="1"><nlm:aff id="AFF2">Pathogen Genomics Group, Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Hinxton, Cambridge CB10 1SA, UK</nlm:aff>
<country xml:lang="fr">Royaume-Uni</country>
<wicri:regionArea>Pathogen Genomics Group, Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Hinxton, Cambridge CB10 1SA</wicri:regionArea>
</affiliation>
</author>
<author><name sortKey="Quail, Mike A" sort="Quail, Mike A" uniqKey="Quail M" first="Mike A." last="Quail">Mike A. Quail</name>
<affiliation wicri:level="1"><nlm:aff id="AFF2">Pathogen Genomics Group, Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Hinxton, Cambridge CB10 1SA, UK</nlm:aff>
<country xml:lang="fr">Royaume-Uni</country>
<wicri:regionArea>Pathogen Genomics Group, Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Hinxton, Cambridge CB10 1SA</wicri:regionArea>
</affiliation>
</author>
<author><name sortKey="Weir, William" sort="Weir, William" uniqKey="Weir W" first="William" last="Weir">William Weir</name>
<affiliation wicri:level="1"><nlm:aff id="AFF10">FG Parasitologie, Philipps Universität Marburg, Karl von Frisch Strasse 8, 35043 Marburg, Germany</nlm:aff>
<country xml:lang="fr">Allemagne</country>
<wicri:regionArea>FG Parasitologie, Philipps Universität Marburg, Karl von Frisch Strasse 8, 35043 Marburg</wicri:regionArea>
</affiliation>
</author>
<author><name sortKey="Wastling, Jonathan M" sort="Wastling, Jonathan M" uniqKey="Wastling J" first="Jonathan M." last="Wastling">Jonathan M. Wastling</name>
<affiliation wicri:level="1"><nlm:aff id="AFF1">Department of Infection Biology, Institute of Infection and Global Health, University of Liverpool, Liverpool Science Park Ic2, 146 Brownlow Hill, Liverpool L3 5RF, UK</nlm:aff>
<country xml:lang="fr">Royaume-Uni</country>
<wicri:regionArea>Department of Infection Biology, Institute of Infection and Global Health, University of Liverpool, Liverpool Science Park Ic2, 146 Brownlow Hill, Liverpool L3 5RF</wicri:regionArea>
</affiliation>
</author>
<author><name sortKey="Hall, Neil" sort="Hall, Neil" uniqKey="Hall N" first="Neil" last="Hall">Neil Hall</name>
<affiliation wicri:level="1"><nlm:aff id="AFF3">Department of Functional and Comparative Genomics, Institute of Integrative Biology, University of Liverpool, Crown Street, Liverpool L69 7ZB, UK</nlm:aff>
<country xml:lang="fr">Royaume-Uni</country>
<wicri:regionArea>Department of Functional and Comparative Genomics, Institute of Integrative Biology, University of Liverpool, Crown Street, Liverpool L69 7ZB</wicri:regionArea>
</affiliation>
</author>
<author><name sortKey="Willadsen, Peter" sort="Willadsen, Peter" uniqKey="Willadsen P" first="Peter" last="Willadsen">Peter Willadsen</name>
<affiliation wicri:level="1"><nlm:aff id="AFF8">Department of Agriculture, Fisheries and Forestry, Biosecurity Sciences Laboratory, 39 Kessels Road, Coopers Plains, Queensland 4108, Australia</nlm:aff>
<country xml:lang="fr">Australie</country>
<wicri:regionArea>Department of Agriculture, Fisheries and Forestry, Biosecurity Sciences Laboratory, 39 Kessels Road, Coopers Plains, Queensland 4108</wicri:regionArea>
</affiliation>
</author>
<author><name sortKey="Lingelbach, Klaus" sort="Lingelbach, Klaus" uniqKey="Lingelbach K" first="Klaus" last="Lingelbach">Klaus Lingelbach</name>
<affiliation wicri:level="1"><nlm:aff id="AFF10">FG Parasitologie, Philipps Universität Marburg, Karl von Frisch Strasse 8, 35043 Marburg, Germany</nlm:aff>
<country xml:lang="fr">Allemagne</country>
<wicri:regionArea>FG Parasitologie, Philipps Universität Marburg, Karl von Frisch Strasse 8, 35043 Marburg</wicri:regionArea>
</affiliation>
</author>
<author><name sortKey="Shiels, Brian" sort="Shiels, Brian" uniqKey="Shiels B" first="Brian" last="Shiels">Brian Shiels</name>
<affiliation wicri:level="1"><nlm:aff id="AFF11">Institute of Biodiversity, Animal Health and Comparative Medicine, University of Glasgow, 464 Bearsden Road, Glasgow G61 1QH, UK</nlm:aff>
<country xml:lang="fr">Royaume-Uni</country>
<wicri:regionArea>Institute of Biodiversity, Animal Health and Comparative Medicine, University of Glasgow, 464 Bearsden Road, Glasgow G61 1QH</wicri:regionArea>
</affiliation>
</author>
<author><name sortKey="Tait, Andy" sort="Tait, Andy" uniqKey="Tait A" first="Andy" last="Tait">Andy Tait</name>
<affiliation wicri:level="1"><nlm:aff id="AFF11">Institute of Biodiversity, Animal Health and Comparative Medicine, University of Glasgow, 464 Bearsden Road, Glasgow G61 1QH, UK</nlm:aff>
<country xml:lang="fr">Royaume-Uni</country>
<wicri:regionArea>Institute of Biodiversity, Animal Health and Comparative Medicine, University of Glasgow, 464 Bearsden Road, Glasgow G61 1QH</wicri:regionArea>
</affiliation>
</author>
<author><name sortKey="Berriman, Matt" sort="Berriman, Matt" uniqKey="Berriman M" first="Matt" last="Berriman">Matt Berriman</name>
<affiliation wicri:level="1"><nlm:aff id="AFF2">Pathogen Genomics Group, Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Hinxton, Cambridge CB10 1SA, UK</nlm:aff>
<country xml:lang="fr">Royaume-Uni</country>
<wicri:regionArea>Pathogen Genomics Group, Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Hinxton, Cambridge CB10 1SA</wicri:regionArea>
</affiliation>
</author>
<author><name sortKey="Allred, David R" sort="Allred, David R" uniqKey="Allred D" first="David R." last="Allred">David R. Allred</name>
<affiliation wicri:level="1"><nlm:aff id="AFF12">Department of Infectious Diseases and Pathology, and Genetics Institute, University of Florida, PO Box 110880, 2015 SW 16th Avenue, Gainesville FL 33611-0880, USA</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea>Department of Infectious Diseases and Pathology, and Genetics Institute, University of Florida, PO Box 110880, 2015 SW 16th Avenue, Gainesville FL 33611-0880</wicri:regionArea>
</affiliation>
</author>
<author><name sortKey="Pain, Arnab" sort="Pain, Arnab" uniqKey="Pain A" first="Arnab" last="Pain">Arnab Pain</name>
<affiliation wicri:level="1"><nlm:aff id="AFF4">Computational Bioscience Research Center, King Abdullah University of Science and Technology, Thuwal 23955-6900, Saudi Arabia</nlm:aff>
<country xml:lang="fr">Arabie saoudite</country>
<wicri:regionArea>Computational Bioscience Research Center, King Abdullah University of Science and Technology, Thuwal 23955-6900</wicri:regionArea>
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</analytic>
<series><title level="j">Nucleic Acids Research</title>
<idno type="ISSN">0305-1048</idno>
<idno type="eISSN">1362-4962</idno>
<imprint><date when="2014">2014</date>
</imprint>
</series>
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</teiHeader>
<front><div type="abstract" xml:lang="en"><p><italic>Babesia</italic>
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 (<italic>ves1</italic>
) through comparative analysis within and between three <italic>Babesia</italic>
species, (<italic>B. bigemina</italic>
, <italic>B. divergens</italic>
and <italic>B. bovis</italic>
). <italic>Ves1</italic>
structure diverges rapidly after speciation, notably through the evolution of shortened forms (<italic>ves2</italic>
) from 5′ ends of canonical <italic>ves1</italic>
genes. Phylogenetic analyses show that <italic>ves1</italic>
genes are transposed between loci routinely, whereas <italic>ves2</italic>
genes are not. Similarly, analysis of sequence mosaicism shows that recombination drives variation in <italic>ves1</italic>
sequences, but less so for <italic>ves2</italic>
, indicating the adoption of different mechanisms for variation of the two families. Proteomic analysis of the <italic>B. bigemina</italic>
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 <italic>Babesia</italic>
biology, with evolutionary dynamics consistently different to those of VESA1, suggesting that their functions are distinct.</p>
</div>
</front>
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<pmc article-type="research-article"><pmc-dir>properties open_access</pmc-dir>
<front><journal-meta><journal-id journal-id-type="nlm-ta">Nucleic Acids Res</journal-id>
<journal-id journal-id-type="iso-abbrev">Nucleic Acids Res</journal-id>
<journal-id journal-id-type="hwp">nar</journal-id>
<journal-id journal-id-type="publisher-id">nar</journal-id>
<journal-title-group><journal-title>Nucleic Acids Research</journal-title>
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<issn pub-type="ppub">0305-1048</issn>
<issn pub-type="epub">1362-4962</issn>
<publisher><publisher-name>Oxford University Press</publisher-name>
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</journal-meta>
<article-meta><article-id pub-id-type="pmid">24799432</article-id>
<article-id pub-id-type="pmc">4066756</article-id>
<article-id pub-id-type="doi">10.1093/nar/gku322</article-id>
<article-categories><subj-group subj-group-type="heading"><subject>Gene regulation, Chromatin and Epigenetics</subject>
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<title-group><article-title>The evolutionary dynamics of variant antigen genes in <italic>Babesia</italic>
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<xref ref-type="aff" rid="AFF1"><sup>1</sup>
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<xref ref-type="corresp" rid="COR1">*</xref>
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<xref ref-type="aff" rid="AFF2"><sup>2</sup>
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<xref ref-type="aff" rid="AFF3"><sup>3</sup>
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<xref ref-type="aff" rid="AFF4"><sup>4</sup>
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<xref ref-type="aff" rid="AFF1"><sup>1</sup>
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<xref ref-type="aff" rid="AFF5"><sup>5</sup>
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<xref ref-type="aff" rid="AFF2"><sup>2</sup>
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<xref ref-type="aff" rid="AFF7"><sup>7</sup>
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<xref ref-type="aff" rid="AFF7"><sup>7</sup>
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<xref ref-type="aff" rid="AFF8"><sup>8</sup>
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<xref ref-type="aff" rid="AFF9"><sup>9</sup>
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<xref ref-type="aff" rid="AFF4"><sup>4</sup>
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<xref ref-type="aff" rid="AFF4"><sup>4</sup>
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<xref ref-type="aff" rid="AFF2"><sup>2</sup>
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<xref ref-type="aff" rid="AFF10"><sup>10</sup>
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</contrib>
<contrib contrib-type="author"><name><surname>Wastling</surname>
<given-names>Jonathan M.</given-names>
</name>
<xref ref-type="aff" rid="AFF1"><sup>1</sup>
</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Hall</surname>
<given-names>Neil</given-names>
</name>
<xref ref-type="aff" rid="AFF3"><sup>3</sup>
</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Willadsen</surname>
<given-names>Peter</given-names>
</name>
<xref ref-type="aff" rid="AFF8"><sup>8</sup>
</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Lingelbach</surname>
<given-names>Klaus</given-names>
</name>
<xref ref-type="aff" rid="AFF10"><sup>10</sup>
</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Shiels</surname>
<given-names>Brian</given-names>
</name>
<xref ref-type="aff" rid="AFF11"><sup>11</sup>
</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Tait</surname>
<given-names>Andy</given-names>
</name>
<xref ref-type="aff" rid="AFF11"><sup>11</sup>
</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Berriman</surname>
<given-names>Matt</given-names>
</name>
<xref ref-type="aff" rid="AFF2"><sup>2</sup>
</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Allred</surname>
<given-names>David R.</given-names>
</name>
<xref ref-type="aff" rid="AFF12"><sup>12</sup>
</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Pain</surname>
<given-names>Arnab</given-names>
</name>
<xref ref-type="aff" rid="AFF4"><sup>4</sup>
</xref>
</contrib>
<aff id="AFF1"><label>1</label>
Department of Infection Biology, Institute of Infection and Global Health, University of Liverpool, Liverpool Science Park Ic2, 146 Brownlow Hill, Liverpool L3 5RF, UK</aff>
<aff id="AFF2"><label>2</label>
Pathogen Genomics Group, Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Hinxton, Cambridge CB10 1SA, UK</aff>
<aff id="AFF3"><label>3</label>
Department of Functional and Comparative Genomics, Institute of Integrative Biology, University of Liverpool, Crown Street, Liverpool L69 7ZB, UK</aff>
<aff id="AFF4"><label>4</label>
Computational Bioscience Research Center, King Abdullah University of Science and Technology, Thuwal 23955-6900, Saudi Arabia</aff>
<aff id="AFF5"><label>5</label>
Laboratorio de Inmunología y , EEA-INTA CC 22, 2300 Rafaela Santa Fe, Argentina</aff>
<aff id="AFF6"><label>6</label>
Centro Nacional de Investigaciones Agropecuarias, Instituto de Biotecnología INTA, Buenos Aires, Argentina</aff>
<aff id="AFF7"><label>7</label>
Bioinformatics Laboratory, Structural and Computational Biology Group, International Centre for Genetic Engineering and Biotechnology, Aruna Asaf Ali Marg, New Delhi 110 067, India</aff>
<aff id="AFF8"><label>8</label>
Department of Agriculture, Fisheries and Forestry, Biosecurity Sciences Laboratory, 39 Kessels Road, Coopers Plains, Queensland 4108, Australia</aff>
<aff id="AFF9"><label>9</label>
UMR1300 INRA/Oniris Biology, Epidemiology and Risk Analysis in Animal Health, BP 40706, F-44307 Nantes, France</aff>
<aff id="AFF10"><label>10</label>
FG Parasitologie, Philipps Universität Marburg, Karl von Frisch Strasse 8, 35043 Marburg, Germany</aff>
<aff id="AFF11"><label>11</label>
Institute of Biodiversity, Animal Health and Comparative Medicine, University of Glasgow, 464 Bearsden Road, Glasgow G61 1QH, UK</aff>
<aff id="AFF12"><label>12</label>
Department of Infectious Diseases and Pathology, and Genetics Institute, University of Florida, PO Box 110880, 2015 SW 16th Avenue, Gainesville FL 33611-0880, USA</aff>
</contrib-group>
<author-notes><corresp id="COR1"><label>*</label>
To whom correspondence should be addressed. Tel: +44 151 7950225; Fax: +44 151 7955529; Email: <email>a.p.jackson@liv.ac.uk</email>
</corresp>
</author-notes>
<pub-date pub-type="ppub"><day>01</day>
<month>7</month>
<year>2014</year>
</pub-date>
<pub-date pub-type="epub"><day>05</day>
<month>5</month>
<year>2014</year>
</pub-date>
<pub-date pub-type="pmc-release"><day>05</day>
<month>5</month>
<year>2014</year>
</pub-date>
<pmc-comment> PMC Release delay is 0 months and 0 days and was based on the
. </pmc-comment>
<volume>42</volume>
<issue>11</issue>
<fpage>7113</fpage>
<lpage>7131</lpage>
<history><date date-type="accepted"><day>4</day>
<month>4</month>
<year>2014</year>
</date>
<date date-type="rev-recd"><day>3</day>
<month>4</month>
<year>2014</year>
</date>
<date date-type="received"><day>3</day>
<month>1</month>
<year>2014</year>
</date>
</history>
<permissions><copyright-statement>© The Author(s) 2014. Published by Oxford University Press on behalf of Nucleic Acids Research.</copyright-statement>
<copyright-year>2014</copyright-year>
<license license-type="creative-commons" xlink:href="http://creativecommons.org/licenses/by/3.0/"><license-p>This is an Open Access article distributed under the terms of the Creative Commons Attribution License (<ext-link ext-link-type="uri" xlink:href="http://creativecommons.org/licenses/by/3.0/">http://creativecommons.org/licenses/by/3.0/</ext-link>
), which permits unrestricted reuse, distribution, and reproduction in any medium, provided the original work is properly cited.</license-p>
</license>
</permissions>
<self-uri xlink:title="pdf" xlink:type="simple" xlink:href="gku322.pdf"></self-uri>
<abstract><p><italic>Babesia</italic>
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 (<italic>ves1</italic>
) through comparative analysis within and between three <italic>Babesia</italic>
species, (<italic>B. bigemina</italic>
, <italic>B. divergens</italic>
and <italic>B. bovis</italic>
). <italic>Ves1</italic>
structure diverges rapidly after speciation, notably through the evolution of shortened forms (<italic>ves2</italic>
) from 5′ ends of canonical <italic>ves1</italic>
genes. Phylogenetic analyses show that <italic>ves1</italic>
genes are transposed between loci routinely, whereas <italic>ves2</italic>
genes are not. Similarly, analysis of sequence mosaicism shows that recombination drives variation in <italic>ves1</italic>
sequences, but less so for <italic>ves2</italic>
, indicating the adoption of different mechanisms for variation of the two families. Proteomic analysis of the <italic>B. bigemina</italic>
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 <italic>Babesia</italic>
biology, with evolutionary dynamics consistently different to those of VESA1, suggesting that their functions are distinct.</p>
</abstract>
<counts><page-count count="19"></page-count>
</counts>
<custom-meta-group><custom-meta><meta-name>cover-date</meta-name>
<meta-value>2014</meta-value>
</custom-meta>
</custom-meta-group>
</article-meta>
</front>
</pmc>
</record>
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