The antigenic switching network of Plasmodium falciparum and its implications for the immuno-epidemiology of malaria

Antigenic variation in the human malaria parasite Plasmodium falciparum involves sequential and mutually exclusive expression of members of the var multi-gene family and appears to follow a non-random pattern. In this study, using a detailed in vitro gene transcription analysis of the culture-adapte...

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Published ineLife Vol. 2; p. e01074
Main Authors Noble, Robert, Christodoulou, Zóe, Kyes, Sue, Pinches, Robert, Newbold, Chris I, Recker, Mario
Format Journal Article
LanguageEnglish
Published England eLife Sciences Publications Ltd 17.09.2013
eLife Sciences Publications, Ltd
Subjects
Algorithms
Animals
Antigenic Variation
Chromosome Mapping
Epidemiology
Estimates
Gene expression
Genomics and Evolutionary Biology
Growth rate
Humans
Infections
Malaria
Malaria, Falciparum - epidemiology
Malaria, Falciparum - immunology
Microbiology and Infectious Disease
Parameter estimation
Parasites
Plasmodium falciparum
Plasmodium falciparum - genetics
Plasmodium falciparum - immunology
Promoter Regions, Genetic
Reproductive fitness
Transcription
Transcription, Genetic
var genevar genes
Plasmodium falciparum
antigenic variation
malaria
var genes
Other
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Summary:Antigenic variation in the human malaria parasite Plasmodium falciparum involves sequential and mutually exclusive expression of members of the var multi-gene family and appears to follow a non-random pattern. In this study, using a detailed in vitro gene transcription analysis of the culture-adapted HB3 strain of P. falciparum, we show that antigenic switching is governed by a global activation hierarchy favouring short and highly diverse genes in central chromosomal location. Longer and more conserved genes, which have previously been associated with severe infection in immunologically naive hosts, are rarely activated, however, implying an in vivo fitness advantage possibly through adhesion-dependent survival rates. We further show that a gene's activation rate is positively associated sequence diversity, which could offer important new insights into the evolution and maintenance of antigenic diversity in P. falciparum malaria. DOI:http://dx.doi.org/10.7554/eLife.01074.001.
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These authors contributed equally to this work.
ISSN:2050-084X
2050-084X
DOI:10.7554/eLife.01074