AUTHOR=Tan Mun Hua , Shim Heejung , Chan Yao-ban , Day Karen P. 

TITLE=Unravelling var complexity: Relationship between DBLα types and var genes in Plasmodium falciparum

JOURNAL=Frontiers in Parasitology

VOLUME=1

YEAR=2023

URL=https://www.frontiersin.org/journals/parasitology/articles/10.3389/fpara.2022.1006341

DOI=10.3389/fpara.2022.1006341

ISSN=2813-2424

ABSTRACT=<p>The enormous diversity and complexity of <italic>var</italic> 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 <italic>var</italic> genes is to use a small ‘tag’ region encoding the immunogenic DBLα domain as a marker to estimate <italic>var</italic> diversity. As <italic>var</italic> genes diversify by recombination, it is not clear the extent to which the same tag can appear in multiple <italic>var</italic> genes. This relationship between marker and gene has not been investigated in natural populations. Analyses of <italic>in vitro</italic> recombination within and between <italic>var</italic> genes have suggested that this relationship would not be exclusive. Using a dataset of publicly-available assembled <italic>var</italic> sequences, we test this hypothesis by studying DBLα-<italic>var</italic> 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-<italic>var</italic> relationships were shown to be predominantly 1-to-1, followed by a second largest proportion of 1-to-2 DBLα-<italic>var</italic> relationships. This finding indicates that DBLα tags can be used to estimate not just DBLα diversity but <italic>var</italic> gene diversity when applied in a local endemic area. Epidemiological applications of this result are discussed.</p>