Population genomics of virulence genes of Plasmodium falciparum in clinical isolates from Uganda

Abstract

Plasmodium falciparum causes a spectrum of malarial disease from asymptomatic to uncomplicated through to severe. Investigations of parasite virulence have associated the expression of distinct variants of the major surface antigen of the blood stages known as PfEMP1 encoded by up to 60 var genes per genome. Looking at the population genomics of var genes in cases of uncomplicated malaria, we set out to determine if there was any evidence of a selective sweep of specific var genes or clonal epidemic structure related to the incidence of uncomplicated disease in children. By sequencing the conserved DBL alpha domain of var genes from six sentinel sites in Uganda we found that the parasites causing uncomplicated P. falciparum disease in children were highly diverse and that every child had a unique var DBLa repertoire. Despite extensive var DBLa diversity and minimal overlap between repertoires, specific DBLa types and groups were conserved at the population level across Uganda. This pattern was the same regardless of the geographic distance or malaria transmission intensity. These data lead us to propose that any parasite can cause uncomplicated malarial disease and that these diverse parasite repertoires are composed of both upsA and non-upsA var gene groups.