Identifying functional groups among the diverse, recombining antigenic < i > var < /i > genes of the malaria parasite < i > Plasmodium falciparum < /i > from a local community in Ghana

by Mary M. Rorick, Edward B. Baskerville, Thomas S. Rask, Karen P. Day, Mercedes Pascual A challenge in studying diverse multi-copy gene families is deciphering distinct functional types within immense sequence variation. Functional changes can in some cases be tracked through the evolutionary history of a gene family; however phylogenetic approaches are not possible in cases where ge ne families diversify primarily by recombination. We take a network theoretical approach to functionally classify the highly recombiningvar antigenic gene family of the malaria parasitePlasmodium falciparum. We samplevar DBL α sequence types from a local population in Ghana, and classify 9,276 of these variants into just 48 functional types. Our approach is to first decompose each sequence type into its constituent, recombining parts; we then use a stochastic block model to identify functional groups among the parts; f inally, we classify the sequence types based on which functional groups they contain. This method for functional classification does not rely on an inferred phylogenetic history, nor does it rely on inferring function based on conserved sequence features. Instead, it infers functional similarity amo ng recombining parts based on the sharing of similar co-occurrence interactions with other parts. This method can therefore group sequences that have undetectable sequence homology or even distinct origination. Describing these 48var functional types allows us to simplify the antigen...
Source: PLoS Computational Biology - Category: Biology Authors: Source Type: research