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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  Pf  EMP1 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 DBLα 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  DBLα repertoire. Despite extensive  var  DBLα diversity and minimal overlap between repertoires, specific DBLα 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.

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