Abstract
BackgroundMalaria parasites of the genus Plasmodium possess large hyper-variable families of antigen-encoding genes. These are often variantly-expressed and are major virulence factors for immune evasion and the maintenance of chronic infections. Recombination and diversification of these gene families occurs readily, and may be promoted by G-quadruplex (G4) DNA motifs within and close to the variant genes. G4s have been shown to cause replication fork stalling, DNA breakage and recombination in model systems, but these motifs remain largely unstudied in Plasmodium.ResultsWe examined the nature and distribution of putative G4-forming sequences in multiple Plasmodium genomes, finding that their co-distribution with variant gene families is conserved across different Plasmodium species that have different types of variant gene families. In P. falciparum, where a large set of recombination events that occurred over time in cultured parasites has been mapped, we found a strong spatial association between these recombination events and putative G4-forming sequences. Finally, we searched Plasmodium genomes for the three classes of helicase that can unwind G4s: Plasmodium spp. have no identifiable homologue of the highly efficient G4 helicase PIF1, but they do encode two putative RecQ helicases and one homologue of the RAD3-family helicase FANCJ.ConclusionsOur analyses, conducted at the whole-genome level in multiple species of Plasmodium, support the concept that G4s are likely to be involved in recombination and diversification of antigen-encoding gene families in this important protozoan pathogen.Electronic supplementary materialThe online version of this article (doi:10.1186/s12864-016-3183-3) contains supplementary material, which is available to authorized users.
Highlights
Malaria parasites of the genus Plasmodium possess large hyper-variable families of antigen-encoding genes
G-quadruplex-forming motifs in the P. falciparum genome are strongly associated with var genes A search for Putative quadruplex sequence (PQS) in the genome of the reference strain of P. falciparum, 3D7, was previously published in 2009, finding 63 PQSs [17]
By searching the updated ‘version 3’ assembly of this genome [34], we found 80 PQSs (Additional file 1: Table S1), of which 35 were var-gene-associated, i.e. the PQS was either within a var coding sequence or the nearest predicted gene, within 2 kb of the PQS, was a var gene. 19 of these PQSs were inside a var coding sequence and 16 were within 2 kb of a var gene start site, with this latter group being exclusively in the upsB type of upstream region [17]
Summary
Malaria parasites of the genus Plasmodium possess large hyper-variable families of antigen-encoding genes. These are often variantly-expressed and are major virulence factors for immune evasion and the maintenance of chronic infections. Human malaria gives rise to widespread morbidity and more than half a million deaths each year [1]. It is caused by protozoan Plasmodium parasites, with most of the mortality being due to the species Plasmodium falciparum. These parasites cause illness via the cyclical infection of erythrocytes They multiply inside these cells and modify their surfaces with proteins called P. falciparum Erythrocyte Membrane Protein 1 (PfEMP1) [2], which bind to the walls of blood vessels.
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