Generation of Antigenic Diversity in by Structured Rearrangement of Genes During Mitosis

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Malaria kills >600,000 people each year, with most deaths caused by Plasmodium falciparum. A family of proteins known as P. falciparum erythrocyte membrane protein 1, PfEMP1, is expressed on the surface of infected erythrocytes and plays an important role in pathogenesis. Each P. falciparum genome contains approximately 60 highly polymorphic var genes encoding the PfEMP1 proteins, and monoallelic expression with periodic switching results in immune evasion. Var gene polymorphism is thus critical to this survival strategy. We investigated how var gene diversity is generated by performing an in vitro evolution experiment, tracking var gene mutation in ‘real-time’ with whole genome sequencing. We found that genome structural variation is focused in and around var genes. These genetic rearrangements created new ‘chimeric’ var gene sequences during the mitotic part of the life cycle, and were consistent with processes of mitotic non-allelic homologous recombination. The recombinant var genes were always in frame and with conserved overall var gene architecture, and the recombination rate implies that many millions of rearranged var gene sequences are produced every 48-hour life cycle within infected individuals. In conclusion, we provide a detailed description of how new var gene sequences are continuously generated in the parasite genome, helping to explain long-term parasite survival within infected human hosts.

Vyšlo v časopise: Generation of Antigenic Diversity in by Structured Rearrangement of Genes During Mitosis. PLoS Genet 10(12): e32767. doi:10.1371/journal.pgen.1004812
Kategorie: Research Article
prolekare.web.journal.doi_sk: https://doi.org/10.1371/journal.pgen.1004812

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