Mira Martínez, SofíaSchuppen, Evi vanAmambua-Ngwa, AlfredBottieau, EmmanuelAffara, MunaEsbroeck, Marjan vanVlieghe, ErikaGuetens, PieterRovira Graells, NúriaGomez-Perez, Gloria P.Alonso, PedroD'Alessandro, UmbertoRosanas Urgell, AnnaCortés, Alfred2017-05-122018-02-072017-02-070022-1899https://hdl.handle.net/2445/110938Background.: 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.8 p.application/pdfeng(c) Mira-Martinez et al., 2017MalàriaPlasmodium falciparumMalariaPlasmodium falciparuminfo:eu-repo/semantics/article2017-05-03info:eu-repo/semantics/openAccess28419281