MULTIDRUG-RESISTANT TRANSPORT PROTEINS IN YEAST - COMPLETE INVENTORY AND PHYLOGENETIC CHARACTERIZATION OF YEAST OPEN READING FRAMES WITHIN THE MAJOR FACILITATOR SUPERFAMILY

Screening of the complete genome sequence from the yeast Saccharomyces cerevisiae reveals that 28 open reading frames (ORFs) are homologous to each other and to established bacterial members of the drug-resista nt subfamily of the major facilitator superfamily. The phylogenesis of these protein sequences shows that they fall into three major cluster s. Cluster I contains 12 ORFs, cluster II contains ten ORFs and cluste r III contains six ORFs. Hydropathy analyses indicate that in clusters II and III ORFs, 14 transmembrane spans are predicted whereas only 12 transmembrane spans are predicted in cluster I ORFs. Three ORFs that have known functions as multidrug-resistance pumps in other yeast spec ies such as Schizosaccharomyces pombe (CAR1), Candida albicans (BMRP) or C. maltosa (CYHR), also fall into cluster I. Two S. cerevisiae ORFs of known multidrug-resistance function (ATR1, SGE1) fall into cluster II. Cluster III consists exclusively of ORFs of unknown function but binary sequence comparisons show homology to ORFs from cluster II. Ana lysis of the multiple alignment for these proteins leads to the identi fication of characteristic signature sequences for each of the three c lusters.