Malaria parasites when they live in human red blood cells can rapidly change the proteins on the surface of their host cells during the course of a single infection in order to hide from the immune system, researchers said.

In the study, Plasmodium falciparum parasites were kept dividing in human blood for over a year in the laboratory, with the full parasite genome being sequenced regularly.

This gave the scientists snapshots of the parasite's genome at multiple time points, allowing them to track evolution as it unfolded in the lab.
They found that the 60 or so genes that control proteins on the surface of infected human blood cells, known as var genes, swapped genetic information regularly, creating around a million new and unrecognisable surface proteins in every infected human every two days.

"These genes are like decks of cards constantly being shuffled," said William Hamilton, a first author from the Wellcome Trust Sanger Institute.

"The use of whole genome sequencing and the sheer number of samples we collected gave us a detailed picture of how the var gene repertoire changes continuously within red blood cells," Hamilton said.

The results show, for the first time, that the process of swapping genetic information, known as recombination, happens not when the malaria parasite is inside the mosquito, as previously thought, but during the asexual stage of the parasite's lifecycle inside human blood cells.

This may go some way to explaining how chronic asymptomatic infection, a crucial problem for malaria elimination, is possible.
"It's very likely that mosquitoes are re-infected with Plasmodium falciparum parasites at the beginning of each wet season by biting humans who have carried the parasites, often asymptomatically, for up to eight months during the dry season," said Dr Antoine Claessens, a first author from the Malaria Programme at the Wellcome Trust Sanger Institute.

"During those months the parasite's var genes are busy recombining to create millions of different versions – cunning disguises that mean they remain safe from the immune system and ready for the new malarial season," Claessens said.

Scientists found that var gene recombination takes place in about 0.2 percent of parasites after each 48-hour life cycle in the red blood cell.

With about a billion parasites living inside a typical infected human, there is huge potential for the parasite to create new, recombined var genes inside each person with malaria, researchers said.

The study was published in the journal PLOS Genetics.

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