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Publication Details
AFRICAN RESEARCH NEXUS
SHINING A SPOTLIGHT ON AFRICAN RESEARCH
agricultural and biological sciences
Evolutionary analyses of the major variant surface antigen-encoding genes reveal population structure of Plasmodium falciparum within and between continents
PLoS Genetics, Volume 17, No. 2, Article e1009269, Year 2021
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Description
Malaria remains a major public health problem in many countries. Unlike influenza and HIV, where diversity in immunodominant surface antigens is understood geographically to inform disease surveillance, relatively little is known about the global population structure of PfEMP1, the major variant surface antigen of the malaria parasite Plasmodium falciparum. The complexity of the var multigene family that encodes PfEMP1 and that diversifies by recombination, has so far precluded its use in malaria surveillance. Recent studies have demonstrated that cost-effective deep sequencing of the region of var genes encoding the PfEMP1 DBLα domain and subsequent classification of within host sequences at 96% identity to define unique DBLα types, can reveal structure and strain dynamics within countries. However, to date there has not been a comprehensive comparison of these DBLα types between countries. By leveraging a bioinformatic approach (jumping hidden Markov model) designed specifically for the analysis of recombination within var genes and applying it to a dataset of DBLα types from 10 countries, we are able to describe population structure of DBLα types at the global scale. The sensitivity of the approach allows for the comparison of the global dataset to ape samples of Plasmodium Laverania species. Our analyses show that the evolution of the parasite population emerging out of Africa underlies current patterns of DBLα type diversity. Most importantly, we can distinguish geographic population structure within Africa between Gabon and Ghana in West Africa and Uganda in East Africa. Our evolutionary findings have translational implications in the context of globalization. Firstly, DBLα type diversity can provide a simple diagnostic framework for geographic surveillance of the rapidly evolving transmission dynamics of P. falciparum. It can also inform efforts to understand the presence or absence of global, regional and local population immunity to major surface antigen variants. Additionally, we identify a number of highly conserved DBLα types that are present globally that may be of biological significance and warrant further characterization. © 2021 Tonkin-Hill et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Available Materials
https://efashare.b-cdn.net/share/pmc/articles/PMC7906310/bin/pgen.1009269.s001.pdf
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https://efashare.b-cdn.net/share/pmc/articles/PMC7906310/bin/pgen.1009269.s021.csv
https://efashare.b-cdn.net/share/pmc/articles/PMC7906310/bin/pgen.1009269.s022.csv
https://efashare.b-cdn.net/share/pmc/articles/PMC7906310/bin/pgen.1009269.s023.csv
https://efashare.b-cdn.net/share/pmc/articles/PMC7906310/bin/pgen.1009269.s024.csv
https://efashare.b-cdn.net/share/pmc/articles/PMC7906310/bin/pgen.1009269.s025.docx
Authors & Co-Authors
Tonkin-Hill, Gerry Q.
Australia, Melbourne
University of Melbourne
Australia, Melbourne
Walter and Eliza Hall Institute of Medical Research
United Kingdom, Hinxton
Wellcome Sanger Institute
Ruybal-Pesantez, Shazia
Australia, Melbourne
University of Melbourne
Tiedje, Kathryn E.
Australia, Melbourne
University of Melbourne
Australia, Melbourne
The Peter Doherty Institute for Infection and Immunity
Rougeron, Virginie
France, Montpellier
Maladies Infectieuses et Vecteurs : Écologie, Génétique, Évolution et Contrôle
Duffy, Michael F.
Australia, Melbourne
University of Melbourne
Australia, Melbourne
The Peter Doherty Institute for Infection and Immunity
Zakeri, Sedigheh
Iran, Tehran
Pasteur Institute of Iran
Pumpaibool, Tepanata
Thailand, Bangkok
Chulalongkorn University
Harnyuttanakorn, Pongchai
Thailand, Bangkok
Chulalongkorn University
Branch, Ora Lee H.
Peru, Iquitos
Universidad Nacional de la Amazonia Peruana
Ruiz, Lastenia
Peru, Iquitos
Universidad Nacional de la Amazonia Peruana
Rask, Thomas S.
Australia, Melbourne
University of Melbourne
Prugnolle, Franck
France, Montpellier
Maladies Infectieuses et Vecteurs : Écologie, Génétique, Évolution et Contrôle
Papenfuss, Anthony T.
Australia, Melbourne
Walter and Eliza Hall Institute of Medical Research
Australia, Melbourne
University of Melbourne
Australia, Melbourne
Peter Maccallum Cancer Centre
Day, Karen P.
Australia, Melbourne
University of Melbourne
Australia, Melbourne
The Peter Doherty Institute for Infection and Immunity
Statistics
Citations: 19
Authors: 14
Affiliations: 9
Identifiers
Doi:
10.1371/journal.pgen.1009269
ISSN:
15537390
Research Areas
Health System And Policy
Infectious Diseases
Study Design
Cross Sectional Study
Study Locations
Multi-countries
Gabon
Ghana
Uganda