Genetic diversity of the DBLα region in Plasmodiumfalciparumvar genes among Asia-Pacific isolates

Abstract

In Plasmodium falciparum a highly polymorphic multi-copy gene family, var, encodes the variant surface antigen P. falciparum erythrocyte membrane protein 1 (PfEMP1), which has an important role in cytoadherence and immune evasion. Using previously described universal PCR primers for the first Duffy binding-like domain (DBLα) of var we analysed the DBLα repertoires of Dd2 (originally from Thailand) and eight isolates from the Solomon Islands ( n=4), Philippines ( n=2), Papua New Guinea ( n=1) and Africa ( n=1). We found 15–32 unique DBLα sequence types among these isolates and estimated detectable DBLα repertoire sizes ranging from 33–38 to 52–57 copies per genome. Our data suggest that var gene repertoires generally consist of 40–50 copies per genome. Eighteen DBLα sequences appeared in more than one Asia-Pacific isolate with the number of sequences shared between any two isolates ranging from 0 to 6 (mea n=2.0±1.6). At the amino acid level DBLα sequence similarity within isolates ranged from 45.2±7.1 to 50.2±6.9%, and was not significantly different from the DBLα amino acid sequence similarity among isolates ( P>0.1). Comparisons with published sequences also revealed little overlap among DBLα sequences from different regions. High DBLα sequence diversity and minimal overlap among these isolates suggest that the global var gene repertoire is immense, and may potentially be selected for by the host's protective immune response to the var gene products, PfEMP1.