Unravelling complexity: Relationship between DBLα types and genes in .

The enormous diversity and complexity of genes that diversify rapidly by recombination has led to the exclusion of assembly of these genes from major genome initiatives (e.g., Pf6). A scalable solution in epidemiological surveillance of genes is to use a small 'tag' region encoding the immunogenic DBLα domain as a marker to estimate diversity. As genes diversify by recombination, it is not clear the extent to which the same tag can appear in multiple genes. This relationship between marker and gene has not been investigated in natural populations. Analyses of recombination within and between genes have suggested that this relationship would not be exclusive. Using a dataset of publicly-available assembled sequences, we test this hypothesis by studying DBLα- relationships for four study sites in four countries: Pursat (Cambodia) and Mae Sot (Thailand), representing low malaria transmission, and Navrongo (Ghana) and Chikwawa (Malawi), representing high malaria transmission. In all study sites, DBLα- relationships were shown to be predominantly 1-to-1, followed by a second largest proportion of 1-to-2 DBLα- relationships. This finding indicates that DBLα tags can be used to estimate not just DBLα diversity but gene diversity when applied in a local endemic area. Epidemiological applications of this result are discussed.