Expression of the Plasmodium falciparum Clonally Variant clag3 Genes in Human Infections

<span class="paragraphSection"><div class="boxTitle">Abstract</div><div class="boxTitle">Background.</div>Many genes of the malaria parasite <span style="font-style:italic;">Plasmodium falciparum</span> 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 <span style="font-style:italic;">clag3</span> genes, <span style="font-style:italic;">clag3.1</span> and <span style="font-style:italic;">clag3.2</span>, which mediate nutrient uptake and are linked to resistance to some toxic compounds.<div class="boxTitle">Methods.</div>We developed a procedure to characterize the expression of <span style="font-style:italic;">clag3</span> genes in naturally infected patients and in experimentally infected human volunteers.<div class="boxTitle">Results.</div>We provide the first description of <span style="font-style:italic;">clag3</span> 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 <span style="font-style:italic;">clag3</span> expression. We also found that <span style="font-style:italic;">clag3</span> expression patterns were reset during transmission stages.<div class="boxTitle">Conclusions.</div>Different environment conditions select for parasites with different <span style="font-style:italic;">clag3</span> 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.</span>

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