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Global genetic diversity and evolution of var genes associated with placental and severe childhood malaria
Abstract
In Plasmodium falciparum, var genes encode adhesive proteins that are transported to the surface of infected erythrocytes and act as major virulence determinants for infected erythrocyte binding and immune evasion. Var genes are highly diverse and can be classified into five major groups (UpsA, B, C, D, and E). Previous serological studies have suggested that the UpsA var group may contain common antigenic types that have important roles in severe childhood malaria. Here, our analysis found that UpsA vars are highly diverse between 22 world-wide parasite isolates, although they could be grouped into two broad clusters that may be separately recombining. By comparison, orthologs of the UpsA-linked Type 3 var and UpsE-linked var2csa were detected in nearly all parasite isolates, and a var2csa ortholog was also present in a chimpanzee malaria P. reichenowi that diverged from P. falciparum approximately 5-7 million years ago. Although the specific function of Type 3 var genes is unknown, var2csa is a leading candidate for a pregnancy associated malaria vaccine. Compared to typical var genes, var2csa is unusually conserved but still had only 54-94% amino acid identity in extracellular binding regions. However, var2csa alleles have extensive gene mosaicism within polymorphic blocks that are shared between world-wide parasite isolates and recognizable in P. rechenowi suggesting a high rate of self-self recombination and an ancient and globally-related pool of var2csa polymorphism. T…
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“VAR2CSA show substantial sequence and structure conservation between isolates (Trimnell et al. , 2006), which could explain the geographical independence of antibody responses to the VSA expressed by iEs from pregnant women.”
From Towards a vaccine against pregnancy-associated malaria (2008) · cites this paper as Trimnell et al., 2006
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“but analysis of var2csa from field isolates has revealed alternating areas of substantial interclonal polymorphism (Dahlback et al. , 2006; Trimnell et al. , 2006).”
From Towards a vaccine against pregnancy-associated malaria (2008) · cites this paper as Trimnell et al., 2006
Citations
Cites
Genome sequence of the human malaria parasite Plasmodium falciparum
Gardner, M. J., Hall, N., Fung, E., White, O., Berriman, M., Hyman, R. W., Carlton, J. M., Pain, A., Nelson, K. E., Bowman, S., et al. (2002) · Nature · doi:10.1038/nature01097 · Cited by 4,407
Antibody neutralization and escape by HIV-1
Wei, X., Decker, J. M., Wang, S., Hui, H., Kappes, J. C., Wu, X., Salazar-Gonzalez, J. F., Salazar, M. G., Kilby, J. M., Saag, M. S., et al. (2003) · Nature · doi:10.1038/nature01470 · Cited by 2,421
The pathogenic basis of malaria
Miller, L. H., Baruch, D. I., Marsh, K., & Doumbo, O. K. (2002) · Nature · doi:10.1038/415673a · Cited by 1,804
A Test of Neutral Molecular Evolution Based on Nucleotide Data
Hudson, R. R., Kreitman, M., & Aguadé, M. (1987) · Genetics · doi:10.1093/genetics/116.1.153 · Cited by 1,759
Su, X.-Z., Heatwole, V. M., Wertheimer, S. P., Guinet, F., Herrfeldt, J. A., Peterson, D. S., Ravetch, J. A., & Wellems, T. E. (1995) · Cell · doi:10.1016/0092-8674(95)90055-1 · Cited by 1,219
Self-citationAdherence of Plasmodium falciparum to Chondroitin Sulfate A in the Human Placenta
Fried, M., & Duffy, P. E. (1996) · Science · doi:10.1126/science.272.5267.1502 · Cited by 1,108
Baruch, D., Pasloske, B., Singh, H. B., Bi, X., Ma, X. C., Feldman, M., Taraschi, T., & Howard, R. J. (1995) · Cell · doi:10.1016/0092-8674(95)90054-3 · Cited by 1,087
Smith, J. D., Chitnis, C. E., Craig, A. G., Roberts, D. J., Hudson-Taylor, D. E., Peterson, D. S., Pinches, R., Newbold, C. I., & Miller, L. H. (1995) · Cell · doi:10.1016/0092-8674(95)90056-x · Cited by 1,005
Self-citationMalaria parasites and other haemosporidia
Garnhám, P. C. C. (1966) · Medical Entomology and Zoology · Cited by 960
Diversity Considerations in HIV-1 Vaccine Selection
Gaschen, B. K., Taylor, J., Yusim, K., Foley, B. T., Gao, F., Lang, D. M., Novitsky, V., Haynes, B. F., Hahn, B. H., Tanmoy Bhattacharya, A., et al. (2002) · Science · doi:10.1126/science.1070441 · Cited by 811
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- Hudson, 1987, A test of neutral molecular evolution based on nucleotide data, Genetics, 116, 153, 10.1093/genetics/116.1.153 · DOI
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Items 101–165 of 165
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Towards a vaccine against pregnancy-associated malaria
Tuikue Ndam, N., & Deloron, P. (2008) · Parasite · doi:10.1051/parasite/2008153515 · Cited by 14
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Rovira-Vallbona, E., Monteiro, I. F., Bardají, A., Serra‐Casas, E., Neafsey, D. E., Quelhas, D., Valim, C., Alonso, P. L., Dobaño, C., Ordï, J., et al. (2013) · PLoS ONE · doi:10.1371/journal.pone.0069753 · Cited by 14
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Fonseca, A. M., Quintó, L., Jiménez, A., González, R., Bardají, A., Maculuve, S. A., Dobaño, C., Rupérez, M., Valá, A., Aponte, J. J., et al. (2017) · PLoS ONE · doi:10.1371/journal.pone.0181150 · Cited by 12
Hadjimichael, E., & Deitsch, K. (2025) · Microbiology and Molecular Biology Reviews · doi:10.1128/mmbr.00114-23 · Cited by 13
Talundzic, E., Shah, S., Fawole, O., Owino, S. O., Moore, J. M., & Peterson, D. S. (2012) · PLoS ONE · doi:10.1371/journal.pone.0031565 · Cited by 13
Plasmodium falciparum genetic variation of var2csa in the Democratic Republic of the Congo
Verity, R., Hathaway, N. J., Waltmann, A., Doctor, S. M., Watson, O. J., Patel, J. C., Mwandagalirwa, K., Tshefu, A. K., Bailey, J. A., Ghani, A. C., et al. (2018) · Malaria Journal · doi:10.1186/s12936-018-2193-9 · Cited by 13
Blythe, J. E., Niang, M., Marsh, K., Holder, A. A., Langhorne, J., & Preiser, P. R. (2009) · Malaria Journal · doi:10.1186/1475-2875-8-140 · Cited by 13
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Ditlev, S. B., Nielsen, M. A., Resende, M., Agerbæk, M. Ø., Pinto, V. V., Andersen, P. H., Magistrado, P., Lusingu, J., Dahlbäck, M., Theander, T. G., et al. (2012) · PLoS ONE · doi:10.1371/journal.pone.0043663 · Cited by 11
Gross, M., Hsu, R., & Deitsch, K. (2021) · BMC Ecology and Evolution · doi:10.1186/s12862-021-01872-z · Cited by 11
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Duffy, P. E., & Fried, M. (2011) · Memórias do Instituto Oswaldo Cruz · doi:10.1590/s0074-02762011000900008 · Cited by 11
van Noort, S. P., Nunes, M. C., Weedall, G. D., Hviid, L., & Gomes, M. G. M. (2010) · PLoS ONE · doi:10.1371/journal.pone.0009778 · Cited by 11
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Zhang, Y., Jiang, N., Chang, Z., Wang, H., Lu, H., Wahlgren, M., & Chen, Q. (2014) · Parasite · doi:10.1051/parasite/2014019 · Cited by 10
Malaria vaccines: immunity, models and monoclonal antibodies
Hviid, L., & Barfod, L. K. (2008) · Trends in Parasitology · doi:10.1016/j.pt.2008.05.007 · Cited by 9
Beeson, J. G., Fowkes, F. J. I., Reiling, L., Osier, F. H. A., Drew, D. R., & Brown, G. V. (2014) · doi:10.2217/fmeb2013.13.144 · Cited by 9
Akhouri, R. R., Goel, S., & Skoglund, U. (2023) · Nature Communications · doi:10.1038/s41467-023-41838-x · Cited by 8
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Recker, M., Bouma, M. J., Bamford, P., Gupta, S., & Dobson, A. P. (2009) · Malaria Journal · doi:10.1186/1475-2875-8-245 · Cited by 8
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Bittencourt, N. C., Bertolla, L. P., & Albrecht, L. (2021) · Current Clinical Microbiology Reports · doi:10.1007/s40588-020-00155-3 · Cited by 8
Panneerselvam, P., Bawankar, P., Kulkarni, S. S., & Patankar, S. (2011) · Evolutionary Bioinformatics · doi:10.4137/ebo.s8162 · Cited by 8
Agrawal, M., Ozarkar, A., Gupta, S., Deobagkar, D. N., & Deobagkar, D. D. (2014) · Molecular BioSystems · doi:10.1039/c4mb00274a · Cited by 8
Gangnard, S., Chêne, A., Dechavanne, S., Srivastava, A., Avril, M., Smith, J. D., & Gamain, B. (2019) · Scientific Reports · doi:10.1038/s41598-019-53334-8 · Cited by 8
Self-citationApproaches to Malaria Vaccine Development Using the Retrospectroscope
Sardá, V., Kaslow, D. C., & Williamson, K. C. (2009) · Infection and Immunity · doi:10.1128/iai.00122-09 · Cited by 11
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Gervassi, A. L., Collins, L. J., & Britschgi, T. B. (2010) · PLoS ONE · doi:10.1371/journal.pone.0013814 · Cited by 7
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Smith, J. D., & Deitsch, K. (2012) · Wiley eBooks · doi:10.1002/9781118308165.ch18 · Cited by 6
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Using Population Genetics to Guide Malaria Vaccine Design
Alyssa, E., Beeson, J. G., John, C. F., Freya, J. I., & Arnott, A. (2012) · InTech eBooks · doi:10.5772/34031 · Cited by 5
Cernetich, A., Daly, T. M., Vaidya, A. B., Bergman, L. W., & Burns, J. M. (2012) · Malaria Journal · doi:10.1186/1475-2875-11-265 · Cited by 5
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Talundzic, E., Scott, S., Owino, S. O., Campo, D. S., Lucchi, N. W., Udhayakumar, V., Moore, J. M., & Peterson, D. S. (2022) · Pathogens · doi:10.3390/pathogens11050520 · Cited by 4
Rajwani, J., Klinger, C. M., Arango, E., Arroyo-Arroyo, M. I., Sabbagh, A., Maestre, A., Dacks, J. B., Gnidehou, S., & Yanow, S. K. (2017) · Infection Genetics and Evolution · doi:10.1016/j.meegid.2017.09.003 · Cited by 4
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Hoffmann-Veltung, H., Anabire, N. G., Ofori, M. F., Janhmatz, P., Ahlborg, N., Hviid, L., & Quintana, M. D. P. (2022) · eLife · doi:10.7554/elife.79245 · Cited by 3
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Ozarkar, A., Prakash, D., Deobagkar, D. N., & Deobagkar, D. (2009) · Scholarly Research Exchange · doi:10.3814/2009/824949 · Cited by 3
Winterberg, M., Przyborski, J. M., & Lingelbach, K. R. (2009) · doi:10.1002/9783527629176.ch33 · Cited by 3
van Noort, S. P. (2014) · Portuguese National Funding Agency for Science, Research and Technology (RCAAP Project by FCT) · Cited by 2
Tembo, D. L. (2014) · University of Liverpool · doi:10.17638/00011453 · Cited by 1
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Quintana, M. D. P. (2021) · mSphere · doi:10.1128/msphere.00391-21 · Cited by 1
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Ismail, H. A. (2013) · Figshare · Cited by 1
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Su, X., & Joy, D. A. (2014) · ASM Press eBooks · doi:10.1128/9781555817213.ch16
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Duffy, P. E. (2006) · doi:10.21236/ada451342
Blomqvist, K. (2011) · Figshare
Albrecht, L. (2008) · Digital Library of Theses and Dissertations (Universidade de São Paulo) · doi:10.11606/t.42.2008.tde-23092008-153317
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Falk, N. (2008) · edoc (University of Basel) · doi:10.5451/unibas-004823177
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Nys, H. M. D. (2015) · Ghent University Academic Bibliography (Ghent University)
Costa, F. T. M., Albrecht, L., & Ndam, N. T. (2015) · Springer eBooks · doi:10.1007/978-1-4614-8326-7_66
Rovira-Vallbona, E. (2011) · Dipòsit Digital de la Universitat de Barcelona (Universitat de Barcelona)
Sherman, I. W. (2008) · Advances in Parasitology/Advances in parasitology · doi:10.1016/s0065-308x(08)00430-2
Shokoohi, G., Saadatnia, A., & Abolghazi, A. (2022) · Infection Epidemiology and Microbiology · doi:10.52547/iem.8.2.177
Lenz, T., Zhang, X., Chakraborty, A., Ardakany, A. R., Prudhomme, J. G., Ay, F., Deitsch, K., & Roch, K. G. L. (2024) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2024.02.13.580059
Hawadak, J., Arya, A., Chaudhry, S., & Singh, V. (2024) · Genomics & Informatics · doi:10.1186/s44342-024-00009-0
Gross, M., Hsu, R., & Deitsch, K. (2021) · Figshare · doi:10.6084/m9.figshare.14936190
Chaikitgosiyakul, S., Kuamsab, N., Tia, T., Putaporntip, C., & Jongwutiwes, S. (2026) · Infection Genetics and Evolution · doi:10.1016/j.meegid.2026.105916
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Patil, P. (2011) · theses.fr (ABES) · doi:10.70675/1c21a6eaz0cf8z454fz9b42z330bc52a95ea
Metadata
- Authors
- Trimnell, A. R., Kraemer, S. M., Mukherjee, S., Phippard, D. J., Janes, J. H., Flamoe, E., Su, X.-Z., Awadalla, P., & Smith, J. D.
- Affiliations
- Center for Infectious Disease Research (US)
- National Institutes of Health (US)
- North Carolina State University (US)
- Corresponding author
- Awadalla, Philip
- Smith, Joseph D.
- Venue
- Molecular and Biochemical Parasitology
- Publisher
- Elsevier BV
- Published
- 2006-08
- Volume
- 148
- Issue
- 2
- Pages
- 169-180
- ISSN
- 0166-6851 (ISSN-L)
- OpenAlex
- W1996773860
- Cited by
- 165
- References
- 57
- Citations by year
- 2026: 1 · 2025: 1 · 2024: 2 · 2023: 4 · 2022: 3 · 2021: 6 · 2020: 2 · 2019: 3 · 2018: 3 · 2017: 8 · 2016: 1 · 2015: 8 · 2014: 14 · 2013: 11 · 2012: 14
- FWCI
- 19.64
- Type
- journal article
- Language
- en
- Open access
- closed
- Licence
- Locations
- Molecular and Biochemical Parasitology (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Wellcome Trust
- European Commission
- National Institute of Allergy and Infectious Diseases (R01AI047953, R01 AI4795301A1)
- Topics
- Health Sciences › Medicine › Public Health, Environmental and Occupational Health › Malaria Research and Control
- Health Sciences › Medicine › Hematology › Blood groups and transfusion
- Life Sciences › Immunology and Microbiology › Parasitology › Bird parasitology and diseases
- Keywords
- Plasmodium falciparum, var genes, VAR2CSA, placental malaria, Plasmodium reichenowi, erythrocyte adhesion, immune evasion
- MeSH terms
- Amino Acid Sequence, Animals, Antigenic Variation, Child, Female, Humans, Molecular Sequence Data, Placenta, Placenta Diseases, Plasmodium falciparum, Pregnancy, Severity of Illness Index, Genetic Variation, Pregnancy Complications, Parasitic, Malaria, Falciparum, Genes, Protozoan, Sequence Analysis, DNA, Evolution, Molecular
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