Evidence for the importance of genetic structuring to the structural and functional specialization of the Plasmodium falciparum var gene family
Summary The var gene family encodes Plasmodium falciparum erythrocyte membrane 1 (PfEMP1) proteins that act as virulence factors responsible for both antigenic variation and cytoadherence of infected erythrocytes. These proteins orchestrate infected erythrocyte sequestration from blood circulation a...
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| Veröffentlicht in: | Molecular microbiology 2003-12, Vol.50 (5), p.1527-1538 |
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| container_title | Molecular microbiology |
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| creator | Kraemer, Susan M. Smith, Joseph D. |
| description | Summary
The var gene family encodes Plasmodium falciparum erythrocyte membrane 1 (PfEMP1) proteins that act as virulence factors responsible for both antigenic variation and cytoadherence of infected erythrocytes. These proteins orchestrate infected erythrocyte sequestration from blood circulation and contribute to adhesion‐based complications of P. falciparum malaria infections. For this study, we analysed the genetic organization and strain structure of var genes and present evidence for three separately evolving groups that have, in part, functionally diverged and differ between subtelomeric and central chromosomal locations. Our analyses suggest that a recombination hierarchy limits reassortment between groups and may explain why some var genes are unusually conserved between parasite strains. This recombination hierarchy, coupled with binding and immune selection, shapes the variant antigen repertoire and has structural, functional and evolutionary consequences for the PfEMP1 protein family that are directly relevant to malaria pathogenesis. |
| doi_str_mv | 10.1046/j.1365-2958.2003.03814.x |
| format | Article |
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The var gene family encodes Plasmodium falciparum erythrocyte membrane 1 (PfEMP1) proteins that act as virulence factors responsible for both antigenic variation and cytoadherence of infected erythrocytes. These proteins orchestrate infected erythrocyte sequestration from blood circulation and contribute to adhesion‐based complications of P. falciparum malaria infections. For this study, we analysed the genetic organization and strain structure of var genes and present evidence for three separately evolving groups that have, in part, functionally diverged and differ between subtelomeric and central chromosomal locations. Our analyses suggest that a recombination hierarchy limits reassortment between groups and may explain why some var genes are unusually conserved between parasite strains. This recombination hierarchy, coupled with binding and immune selection, shapes the variant antigen repertoire and has structural, functional and evolutionary consequences for the PfEMP1 protein family that are directly relevant to malaria pathogenesis.</description><identifier>ISSN: 0950-382X</identifier><identifier>EISSN: 1365-2958</identifier><identifier>DOI: 10.1046/j.1365-2958.2003.03814.x</identifier><identifier>PMID: 14651636</identifier><language>eng</language><publisher>Oxford, UK: Blackwell Science Ltd</publisher><subject>Animals ; CD36 Antigens - metabolism ; Cell Adhesion ; EMP1 protein ; Erythrocytes - parasitology ; Evolution, Molecular ; Genome, Protozoan ; Molecular Sequence Data ; Multigene Family ; Phylogeny ; Plasmodium falciparum ; Plasmodium falciparum - classification ; Plasmodium falciparum - genetics ; Plasmodium falciparum - metabolism ; Protozoan Proteins - chemistry ; Protozoan Proteins - genetics ; Protozoan Proteins - metabolism ; Recombination, Genetic ; Sequence Analysis, DNA ; Structure-Activity Relationship ; Telomere - genetics ; var gene</subject><ispartof>Molecular microbiology, 2003-12, Vol.50 (5), p.1527-1538</ispartof><rights>Copyright Blackwell Scientific Publications Ltd. Dec 2003</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c5394-efc5bf9b6294b28c61befa5307aa2abd4a57ffdae9ad4ff9bde9d7d5dead92573</citedby><cites>FETCH-LOGICAL-c5394-efc5bf9b6294b28c61befa5307aa2abd4a57ffdae9ad4ff9bde9d7d5dead92573</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://onlinelibrary.wiley.com/doi/pdf/10.1046%2Fj.1365-2958.2003.03814.x$$EPDF$$P50$$Gwiley$$H</linktopdf><linktohtml>$$Uhttps://onlinelibrary.wiley.com/doi/full/10.1046%2Fj.1365-2958.2003.03814.x$$EHTML$$P50$$Gwiley$$H</linktohtml><link.rule.ids>314,776,780,1411,1427,27901,27902,45550,45551,46384,46808</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/14651636$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Kraemer, Susan M.</creatorcontrib><creatorcontrib>Smith, Joseph D.</creatorcontrib><title>Evidence for the importance of genetic structuring to the structural and functional specialization of the Plasmodium falciparum var gene family</title><title>Molecular microbiology</title><addtitle>Mol Microbiol</addtitle><description>Summary
The var gene family encodes Plasmodium falciparum erythrocyte membrane 1 (PfEMP1) proteins that act as virulence factors responsible for both antigenic variation and cytoadherence of infected erythrocytes. These proteins orchestrate infected erythrocyte sequestration from blood circulation and contribute to adhesion‐based complications of P. falciparum malaria infections. For this study, we analysed the genetic organization and strain structure of var genes and present evidence for three separately evolving groups that have, in part, functionally diverged and differ between subtelomeric and central chromosomal locations. Our analyses suggest that a recombination hierarchy limits reassortment between groups and may explain why some var genes are unusually conserved between parasite strains. This recombination hierarchy, coupled with binding and immune selection, shapes the variant antigen repertoire and has structural, functional and evolutionary consequences for the PfEMP1 protein family that are directly relevant to malaria pathogenesis.</description><subject>Animals</subject><subject>CD36 Antigens - metabolism</subject><subject>Cell Adhesion</subject><subject>EMP1 protein</subject><subject>Erythrocytes - parasitology</subject><subject>Evolution, Molecular</subject><subject>Genome, Protozoan</subject><subject>Molecular Sequence Data</subject><subject>Multigene Family</subject><subject>Phylogeny</subject><subject>Plasmodium falciparum</subject><subject>Plasmodium falciparum - classification</subject><subject>Plasmodium falciparum - genetics</subject><subject>Plasmodium falciparum - metabolism</subject><subject>Protozoan Proteins - chemistry</subject><subject>Protozoan Proteins - genetics</subject><subject>Protozoan Proteins - metabolism</subject><subject>Recombination, Genetic</subject><subject>Sequence Analysis, DNA</subject><subject>Structure-Activity Relationship</subject><subject>Telomere - genetics</subject><subject>var gene</subject><issn>0950-382X</issn><issn>1365-2958</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2003</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqNkc1u1DAUhS0EosPAKyCLBbsE_8ROsmCBqgKVWsECJHbWjX-KR0kc7KTt8BK8MvHMABIbkCz53nO_eyz5IIQpKSmp5KtdSbkUBWtFUzJCeEl4Q6vy_gHa_B48RBvSClLwhn05Q09S2hFCOZH8MTqjlRRUcrlBPy5uvbGjttiFiOevFvthCnGGLAWHb-xoZ69xmuOi5yX68QbP4QD-kqDHMBrsllHPPoxrmyarPfT-O2Qh22T-Yw9pCMYvA3bQaz9BXMtbiIdHVm3w_f4perQOk312urfo89uLT-fvi6sP7y7P31wVWvC2KqzTonNtJ1lbdazRknbWgeCkBmDQmQpE7ZwB24Kp3Aoa25raCGPBtEzUfIteHn2nGL4tNs1q8EnbvofRhiWpmlaskTX7J0hbRjlfzxa9-AvchSWu35EZKUgjeHZrjpCOIaVonZqiHyDuFSUqR6t2KieocoIqR6sO0ar7dfX5yX_pBmv-LJ6yXIHXR-DO93b_38bq-voyV_wne523Fg</recordid><startdate>200312</startdate><enddate>200312</enddate><creator>Kraemer, Susan M.</creator><creator>Smith, Joseph D.</creator><general>Blackwell Science Ltd</general><general>Blackwell Publishing Ltd</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7QL</scope><scope>7QP</scope><scope>7QR</scope><scope>7TK</scope><scope>7TM</scope><scope>7U9</scope><scope>8FD</scope><scope>C1K</scope><scope>FR3</scope><scope>H94</scope><scope>M7N</scope><scope>P64</scope><scope>RC3</scope><scope>7X8</scope></search><sort><creationdate>200312</creationdate><title>Evidence for the importance of genetic structuring to the structural and functional specialization of the Plasmodium falciparum var gene family</title><author>Kraemer, Susan M. ; Smith, Joseph D.</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c5394-efc5bf9b6294b28c61befa5307aa2abd4a57ffdae9ad4ff9bde9d7d5dead92573</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2003</creationdate><topic>Animals</topic><topic>CD36 Antigens - metabolism</topic><topic>Cell Adhesion</topic><topic>EMP1 protein</topic><topic>Erythrocytes - parasitology</topic><topic>Evolution, Molecular</topic><topic>Genome, Protozoan</topic><topic>Molecular Sequence Data</topic><topic>Multigene Family</topic><topic>Phylogeny</topic><topic>Plasmodium falciparum</topic><topic>Plasmodium falciparum - classification</topic><topic>Plasmodium falciparum - genetics</topic><topic>Plasmodium falciparum - metabolism</topic><topic>Protozoan Proteins - chemistry</topic><topic>Protozoan Proteins - genetics</topic><topic>Protozoan Proteins - metabolism</topic><topic>Recombination, Genetic</topic><topic>Sequence Analysis, DNA</topic><topic>Structure-Activity Relationship</topic><topic>Telomere - genetics</topic><topic>var gene</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Kraemer, Susan M.</creatorcontrib><creatorcontrib>Smith, Joseph D.</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Bacteriology Abstracts (Microbiology B)</collection><collection>Calcium & Calcified Tissue Abstracts</collection><collection>Chemoreception Abstracts</collection><collection>Neurosciences Abstracts</collection><collection>Nucleic Acids Abstracts</collection><collection>Virology and AIDS Abstracts</collection><collection>Technology Research Database</collection><collection>Environmental Sciences and Pollution Management</collection><collection>Engineering Research Database</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>Algology Mycology and Protozoology Abstracts (Microbiology C)</collection><collection>Biotechnology and BioEngineering Abstracts</collection><collection>Genetics Abstracts</collection><collection>MEDLINE - Academic</collection><jtitle>Molecular microbiology</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Kraemer, Susan M.</au><au>Smith, Joseph D.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Evidence for the importance of genetic structuring to the structural and functional specialization of the Plasmodium falciparum var gene family</atitle><jtitle>Molecular microbiology</jtitle><addtitle>Mol Microbiol</addtitle><date>2003-12</date><risdate>2003</risdate><volume>50</volume><issue>5</issue><spage>1527</spage><epage>1538</epage><pages>1527-1538</pages><issn>0950-382X</issn><eissn>1365-2958</eissn><abstract>Summary
The var gene family encodes Plasmodium falciparum erythrocyte membrane 1 (PfEMP1) proteins that act as virulence factors responsible for both antigenic variation and cytoadherence of infected erythrocytes. These proteins orchestrate infected erythrocyte sequestration from blood circulation and contribute to adhesion‐based complications of P. falciparum malaria infections. For this study, we analysed the genetic organization and strain structure of var genes and present evidence for three separately evolving groups that have, in part, functionally diverged and differ between subtelomeric and central chromosomal locations. Our analyses suggest that a recombination hierarchy limits reassortment between groups and may explain why some var genes are unusually conserved between parasite strains. This recombination hierarchy, coupled with binding and immune selection, shapes the variant antigen repertoire and has structural, functional and evolutionary consequences for the PfEMP1 protein family that are directly relevant to malaria pathogenesis.</abstract><cop>Oxford, UK</cop><pub>Blackwell Science Ltd</pub><pmid>14651636</pmid><doi>10.1046/j.1365-2958.2003.03814.x</doi><tpages>12</tpages><oa>free_for_read</oa></addata></record> |
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| subjects | Animals CD36 Antigens - metabolism Cell Adhesion EMP1 protein Erythrocytes - parasitology Evolution, Molecular Genome, Protozoan Molecular Sequence Data Multigene Family Phylogeny Plasmodium falciparum Plasmodium falciparum - classification Plasmodium falciparum - genetics Plasmodium falciparum - metabolism Protozoan Proteins - chemistry Protozoan Proteins - genetics Protozoan Proteins - metabolism Recombination, Genetic Sequence Analysis, DNA Structure-Activity Relationship Telomere - genetics var gene |
| title | Evidence for the importance of genetic structuring to the structural and functional specialization of the Plasmodium falciparum var gene family |
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