A re-assessment of gene-tag classification approaches for describing var gene expression patterns during human Plasmodium falciparum malaria parasite infections

PfEMP1 are variant parasite antigens that are inserted on the surface of infected erythrocytes (IE). Through interactions with various host molecules, PfEMP1 mediate IE sequestration in tissues and play a key role in the pathology of severe malaria. PfEMP1 is encoded by a diverse multi-gene family called . Previous studies have shown that that expression of specific subsets of genes are associated with low levels of host immunity and severe malaria. However, in most clinical studies to date, full-length gene sequences were unavailable and various approaches have been used to make comparisons between gene expression profiles in different parasite isolates using limited information. Several studies have relied on the classification of a 300 - 500 base-pair "DBLα tag" region in the DBLα domain located at the 5' end of most genes. We assessed the relationship between various DBLα tag classification methods, and sequence features that are only fully assessable through full-length gene sequences. We compared these different sequence features in full-length gene from six fully sequenced laboratory isolates. These comparisons show that despite a long history of recombination, DBLα sequence tag classification can provide functional information on important features of full-length genes. Notably, a specific subset of DBLα tags previously defined as "group A-like" is associated with CIDRα1 domains proposed to bind to endothelial protein C receptor. This analysis helps to bring together different sources of data that have been used to assess var gene expression in clinical parasite isolates.