Expression of the Plasmodium falciparum clonally variant clag3 genes in human infections

Sofía Mira-Martínez, Evi van Schuppen, Alfred Amambua-Ngwa, Emmanuel Bottieau, Muna Affara, Marjan Van Esbroeck, Erika Vlieghe, Pieter Guetens, Núria Rovira-Graells, Gloria P Gómez-Pérez, Pedro L Alonso, Umberto D'Alessandro, Anna Rosanas-Urgell, Alfred Cortés

Research output: Contribution to journalA1: Web of Science-articlepeer-review


Background.: Many genes of the malaria parasite Plasmodium falciparum show clonally variant expression regulated at the epigenetic level. These genes participate in fundamental host-parasite interactions and contribute to adaptive processes. However, little is known about their expression patterns during human infections. A peculiar case of clonally variant genes are the 2 nearly identical clag3 genes, clag3.1 and clag3.2, which mediate nutrient uptake and are linked to resistance to some toxic compounds.

Methods.: We developed a procedure to characterize the expression of clag3 genes in naturally infected patients and in experimentally infected human volunteers.

Results.: We provide the first description of clag3 expression during human infections, which revealed mutually exclusive expression and identified the gene predominantly expressed. Adaptation to culture conditions or selection with a toxic compound resulted in isolate-dependent changes in clag3 expression. We also found that clag3 expression patterns were reset during transmission stages.

Conclusions.: Different environment conditions select for parasites with different clag3 expression patterns, implying functional differences between the proteins encoded. The epigenetic memory is likely erased before parasites start infection of a new human host. Altogether, our findings support the idea that clonally variant genes facilitate the adaptation of parasite populations to changing conditions through bet-hedging strategies.

Original languageEnglish
JournalJournal of Infectious Diseases
Issue number6
Pages (from-to)938-945
Number of pages8
Publication statusPublished - 2017


  • Journal Article


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