Reconstruction of the evolutionary history of the DHA1 family of yeast multidrug resistance transporters of the major facilitator superfamily

Multidrug resistance (MDR) is frequently mediated by the action of drug-efflux pumps, which are able to catalyze the active expulsion of several unrelated cytotoxic compounds out of the cell or their intracellular partitioning. A group of transporters involved in MDR belongs to the major facilitator superfamily (MFS) which, based on protein topology, phylogeny and function, divides into two families: 12-spanner drug:H⁺ antiporter-1 (DHA1) and 14-spanner drug:H⁺ antiporter-2 (DHA2). The evolutionary history of 422 DHA1 proteins identified in twenty-four hemiascomycetous genomes was reconstructed. The phylogenetic tree divided the DHA1 genes into 21 clusters, twelve containing no Saccharomyces cerevisiae members. Inclusion of gene neighbourhood data allowed to scrutinize the orthologous, paralogous, and ohnologous status of these genes, and also to identify ten main DHA1 gene lineages, spanning the whole hemiascomycetes clade. The DHA1 proteins of seven pathogenic Candida spp. were phylogenetically characterized.